Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood.

BACKGROUND: The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. METHODS: A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. RESULTS: The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was < or =5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between -5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to 582 micromol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L), biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175 ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140-165 muL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. CONCLUSIONS: The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting.     

Left inferior parietal cortex integrates time and space during collision judgments

Left inferior parietal lobe lesions can cause perturbation of the space-time plans underlying skilled actions. But does the perceptual integration of spatiotemporal information use the same neural substrate or is the role of the left inferior parietal cortex restricted to visuomotor transformations? We use fMRI and a collision judgment paradigm to examine whether the left inferior parietal cortex integrates temporal and spatial variables in situations in which no complex action and no visuomotor transformation is required. We used a perceptual task in which healthy subjects indicated by simple button presses whether two moving objects (of the same or different size) would or would not collide with each other. This task of interest was contrasted with a control task that employed the same stimuli and identical motor responses but in which the size of the two moving objects had to be compared. To assess putative differential eye-movement effects both tasks were performed with and without central fixation. Analysis of the fMRI data (employing a random-effects model and SPM99) showed that collision judgments (relative to size judgments) provoked a significant increase in neural activity in the left inferior parietal cortex (supramarginal gyrus) only. These results show that left inferior parietal cortex is involved in the integration of perceptual spatiotemporal information and thus provide a neural correlate for the use of space-time plans (whose perturbation can lead to apraxia as originally hypothesized by Liepmann). Furthermore, the data suggest that the left supramarginal gyrus combines temporal and spatial variables more widely than previously supposed.     

The right temporoparietal junction in attention and social interaction: A transcranial magnetic stimulation study

The right temporoparietal junction (rTPJ) has been associated with the ability to reorient attention to unexpected stimuli and the capacity to understand others' mental states (theory of mind [ToM]/false belief). Using activation likelihood estimation meta‐analysis we previously unraveled that the anterior rTPJ is involved in both, reorienting of attention and ToM, possibly indicating a more general role in attention shifting. Here, we used neuronavigated transcranial magnetic stimulation to directly probe the role of the rTPJ across attentional reorienting and false belief. Task performance in a visual cueing paradigm and false belief cartoon task was investigated after application of continuous theta burst stimulation (cTBS) over anterior rTPJ (versus vertex, for control). We found that attentional reorienting was significantly impaired after rTPJ cTBS compared with control. For the false belief task, error rates in trials demanding a shift in mental state significantly increased. Of note, a significant positive correlation indicated a close relation between the stimulation effect on attentional reorienting and false belief trials. Our findings extend previous neuroimaging evidence by indicating an essential overarching role of the anterior rTPJ for both cognitive functions, reorienting of attention and ToM. Hum Brain Mapp 37:796–807, 2016. © 2015 Wiley Periodicals, Inc .     

Causality between local field potentials of the subthalamic nucleus and electromyograms of forearm muscles in Parkinson’s disease

Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease, although its precise mechanisms remain poorly understood. To gain further insight into the mechanisms underlying deep brain stimulation, we analysed the causal relationship between forearm muscle activity and local field potentials derived from the subthalamic nucleus. In 19 patients suffering from Parkinson’s disease of the akinetic‐rigid subtype, we calculated the squared partial directed coherence between muscles of the contralateral forearm and the subthalamic nucleus or zona incerta during both a rest and a hold condition of the arm. For both recording regions, data analysis revealed that, during the rest condition, electromyographic activity was significantly more often ‘Granger‐causal’ for the local field potentials than the opposite causation. In contrast, during the hold condition, no significant difference was found in the occurrence of causalities. Contrary to the existing basal ganglia model and the current concept of Parkinson’s disease pathophysiology, we found the subthalamic nucleus to receive more ‘afferences’ than it emitted ‘efferences’, suggesting that its role is more complex than a simple driving nucleus in the basal ganglia loop. Therefore, the effect of deep brain stimulation in the subthalamic nucleus could, at least in part, result from a blockade of pathological afferent input.     

Functional interactions during the retrieval of conceptual action knowledge: an fMRI study

Impaired retrieval of conceptual knowledge for actions has been associated with lesions of left premotor, left parietal, and left middle temporal areas [Tranel, D., Kemmerer, D., Adolphs, R., Damasio, H., & Damasio, A. R. Neural correlates of conceptual knowledge for actions. Cognitive Neuropsychology, 409-432, 2003]. Here we aimed at characterizing the differential contribution of these areas to the retrieval of conceptual knowledge about actions. During functional magnetic resonance imaging (fMRI), different categories of pictograms (whole-body actions, manipulable and nonmanipulable objects) were presented to healthy subjects. fMRI data were analyzed using SPM2. A conjunction analysis of the neural activations elicited by all pictograms revealed ( p<.05, corrected) a bilateral inferior occipito-temporal neural network with strong activations in the right and left fusiform gyri. Action pictograms contrasted to object pictograms showed differential activation of area MT+, the inferior and superior parietal cortex, and the premotor cortex bilaterally. An analysis of psychophysiological interactions identified contribution-dependent changes in the neural responses when pictograms triggered the retrieval of conceptual action knowledge: Processing of action pictograms specifically enhanced the neural interaction between the right and left fusiform gyri, the right and left middle temporal cortices (MT+), and the left superior and inferior parietal cortex. These results complement and extend previous neuropsychological and neuroimaging studies by showing that knowledge about action concepts results from an increased coupling between areas concerned with semantic processing (fusiform gyrus), movement perception (MT+), and temporospatial movement control (left parietal cortex).     

Predictive force programming in the grip-lift task: the role of memory links between arbitrary cues and object weight

We tested the ability of healthy participants to learn an association between arbitrary sensory cues and the weight of an object to be lifted using a precision grip between the index finger and thumb. Right-handed participants performed a series of grip-lift tasks with each hand. In a first experiment, participants lifted two objects of equal visual appearance which unexpectedly and randomly changed their weight. In two subsequent experiments, the change in object weight was indicated by cues, which were presented (i) visually or (ii) auditorily. When no cue about the weight of the object to be lifted was presented, participants programmed grip force according to the most recent lift, regardless of the hand used. In contrast, participants were able to rapidly establish an association between a particular sensory cue with a given weight and scaled grip force precisely to the actual weight thereafter, regardless of the hand used or the sensory modality of the cue. We discuss our data within the theoretical concept of internal models.     

Differential processing of hierarchical visual stimuli in young and older healthy adults: implications for pathology

Hierarchical figures in which large (global) forms are constructed from smaller (local) forms (Navon, 1977) have proved valuable in studies of perceptual organisation and hemispheric specialisation in both healthy volunteers and a wide range of neurological and psychiatric patients. In studies using Navon figures, normal young adults typically identify global forms faster than local forms. When the global and local forms are incongruent (e.g., a large E made of smaller Rs), global forms often interfere with local form identification more than vice versa. In two conditions on the same subjects, we contrasted the performance of young (mean age 22 years) and older (mean age 58 years) healthy volunteers on global and local processing. In the directed attention task, subjects were instructed to detect a target letter that occurred at the prespecified local or global level. The young subjects showed, as expected, faster reaction times (RTs) to detect global targets. In contrast, the older subjects showed significantly faster RTs to the local targets. Likewise, in a divided attention task, in which subjects were instructed to detect a target letter that could occur at either the local or the global level, the young adults were slightly quicker to detect the global targets and the older subjects were significantly quicker to detect the local targets. Error rates were generally low and there was no significant speed/accuracy trade-off in either condition. The observed local precedence effects in healthy older subjects were unexpected and are discussed in reference to previous work on differential hemispheric aging. That work has suggested that the left hemisphere is preferentially biased toward local processing and ages relatively slowly while the right hemisphere is biased toward global processing and ages relatively quickly. The implications of such putative differential aging for the interpretation of pathological local/global processing in neurological and psychiatric diseases are also emphasised.     

Dose-adjusted EPOCH-R is a safe and well tolerated outpatient treatment regimen in double-hit lymphoma

Background

Double-hit lymphoma (DHL) is an aggressive subtype of high-grade B-cell lymphoma with inferior prognosis using standard dose chemotherapy. Controversy remains whether more intensive chemotherapy regimens such as dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) provide better outcomes in this cohort.

Aims

To review consecutive cases of DHL treated with DA-EPOCH-R at our institution in comparison to available literature.

Methods

We conducted a retrospective study of 13 consecutive patients with DHL treated with DA-EPOCH-R at our institution. Primary endpoints included complete response (CR), event-free survival (EFS) and overall survival (OS).

Results

CR rate with DA-EPOCH-R in DHL was 69% in our cohort. Median EFS and OS duration was 61 months (95% CI: 41–86 months) and 64 months (95% CI: 42–86 months) respectively. One patient discontinued DA-EPOCH-R due to recurrent febrile neutropenia and there were no treatment or infection-related deaths during the study.

Conclusions

This study suggests that DA-EPOCH-R is a well tolerated outpatient regimen for DHL and should be considered for initial treatment in medically fit patients. Further prospective studies are warranted to confirm these findings.     

Developmental changes in neural activation and psychophysiological interaction patterns of brain regions associated with interference control and time perception

Interference control and time perception are mediated by common neural networks, including the frontal and parietal lobes, the cerebellum and the basal ganglia. Previous studies have shown that while time perception develops early in life, interference control seems to follow a protracted course of maturation into late adolescence. Thus, the current study examined developmental changes in neural activation and functional interaction between brain regions during a combined time discrimination and interference control task using fMRI. Thirty-four participants, aged 8-15 years, were scanned while performing a spatial stimulus response compatibility (SRC) task and a time discrimination (TD) task using identical stimuli. We found shared neural activation in a fronto-parieto-cerebellar network as well as task-specific patterns of psychophysiological interaction with positive coupling between the right inferior frontal gyrus (IFG), the superior parietal lobes bilaterally, the contralateral IFG and the thalamus during interference control and positive interactions between the right IFG and bilateral cerebellar activity and the thalamus during time discrimination. Developmental changes in task performance and brain activation patterns were only observed during the SRC task, with increased neural activity in the left inferior parietal gyrus and positive coupling between fronto-parietal brain regions that was only observed in the adolescents group. These results suggest that although both cognitive tasks rely on a shared neural network, distinct developmental curves of brain activation and connectivity could be observed associated with differential maturation patterns underlying cognitive development.