Comparison of cardiac, hepatic, and renal effects of arginine vasopressin and noradrenaline during porcine fecal peritonitis: a randomized controlled trial

INTRODUCTION: Infusing arginine vasopressin (AVP) in vasodilatory shock usually decreases cardiac output and thus systemic oxygen transport. It is still a matter of debate whether this vasoconstriction impedes visceral organ blood flow and thereby causes organ dysfunction and injury. Therefore, we tested the hypothesis whether low-dose AVP is safe with respect to liver, kidney, and heart function and organ injury during resuscitated septic shock. METHODS: After intraperitoneal inoculation of autologous feces, 24 anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned to noradrenaline alone (increments of 0.05 microg/kg/min until maximal heart rate of 160 beats/min; n = 12) or AVP (1 to 5 ng/kg/min; supplemented by noradrenaline if the maximal AVP dosage failed to maintain mean blood pressure; n = 12) to treat sepsis-associated hypotension. Parameters of systemic and regional hemodynamics (ultrasound flow probes on the portal vein and hepatic artery), oxygen transport, metabolism (endogenous glucose production and whole body glucose oxidation derived from blood glucose isotope and expiratory 13CO2/12CO2 enrichment during 1,2,3,4,5,6-13C6-glucose infusion), visceral organ function (blood transaminase activities, bilirubin and creatinine concentrations, creatinine clearance, fractional Na+ excretion), nitric oxide (exhaled NO and blood nitrate + nitrite levels) and cytokine production (interleukin-6 and tumor necrosis factor-alpha blood levels), and myocardial function (left ventricular dp/dtmax and dp/dtmin) and injury (troponin I blood levels) were measured before and 12, 18, and 24 hours after peritonitis induction. Immediate post mortem liver and kidney biopsies were analysed for histomorphology (hematoxylin eosin staining) and apoptosis (TUNEL staining). RESULTS: AVP decreased heart rate and cardiac output without otherwise affecting heart function and significantly decreased troponin I blood levels. AVP increased the rate of direct, aerobic glucose oxidation and reduced hyperlactatemia, which coincided with less severe kidney dysfunction and liver injury, attenuated systemic inflammation, and decreased kidney tubular apoptosis. CONCLUSIONS: During well-resuscitated septic shock low-dose AVP appears to be safe with respect to myocardial function and heart injury and reduces kidney and liver damage. It remains to be elucidated whether this is due to the treatment per se and/or to the decreased exogenous catecholamine requirements

Risk stratification for venous thromboembolism in patients with testicular germ cell tumors

BACKGROUND:Patients with testicular germ cell tumors (TGCT) have an increased risk for venous thromboembolism (VTE). We identified risk factors for VTE in this patient cohort and developed a clinical risk model. METHODS:In this retrospective cohort study at the Medical University of Graz we included 657 consecutive TGCT patients across all clinical stages. A predictive model for VTE was developed and externally validated in 349 TGCT patients treated at the University Hospital Zurich. RESULTS:Venous thromboembolic events occurred in 34 (5.2%) patients in the Graz cohort. In univariable competing risk analysis, higher clinical stage (cS) and a retroperitoneal lymphadenopathy (RPLN) were the strongest predictors of VTE (p<0.0001). As the presence of a RPLN with more than 5cm in greatest dimension without coexisting visceral metastases is classified as cS IIC, we constructed an empirical VTE risk model with the following four categories (12-month-cumulative incidence): cS IA-B 8/463 patients (1.7%), cS IS-IIB 5/86 patients (5.9%), cS IIC 3/21 patients (14.3%) and cS IIIA-C 15/70 patients (21.4%). This risk model was externally validated in the Zurich cohort (12-month-cumulative incidence): cS IA-B (0.5%), cS IS-IIB (6.0%), cS IIC (11.1%) and cS IIIA-C (19.1%). Our model had a significantly higher discriminatory performance than a previously published classifier (RPLN-VTE-risk-classifier) which is based on the size of RPLN alone (AUC-ROC: 0.75 vs. 0.63, p = 0.007). CONCLUSIONS:According to our risk stratification, TGCT patients with cS IIC and cS III disease have a very high risk of VTE and may benefit from primary thromboprophylaxis for the duration of chemotherapy

Potenziale der schwachen künstlichen Intelligenz für die betriebliche Ressourceneffizienz

POTENZIALE DER SCHWACHEN KÜNSTLICHEN INTELLIGENZ FÜR DIE BETRIEBLICHE RESSOURCENEFFIZIENZ Potenziale der schwachen künstlichen Intelligenz für die betriebliche Ressourceneffizienz / Friedrich, Robert (Rights reserved) ( -

Impaired Representation of Geometric Relationships in Humans with Damage to the Hippocampal Formation

The pivotal role of the hippocampus for spatial memory is well-established. However, while neurophysiological and imaging studies suggest a specialization of the hippocampus for viewpoint-independent or allocentric memory, results from human lesion studies have been less conclusive. It is currently unclear whether disproportionate impairment in allocentric memory tasks reflects impairment of cognitive functions that are not sufficiently supported by regions outside the medial temporal lobe or whether the deficits observed in some studies are due to experimental factors. Here, we have investigated whether hippocampal contributions to spatial memory depend on the spatial references that are available in a certain behavioral context. Patients with medial temporal lobe lesions affecting systematically the right hippocampal formation performed a series of three oculomotor tasks that required memory of a spatial cue either in retinal coordinates or relative to a single environmental reference across a delay of 5000 ms. Stimulus displays varied the availability of spatial references and contained no complex visuo-spatial associations. Patients showed a selective impairment in a condition that critically depended on memory of the geometric relationship between spatial cue and environmental reference. We infer that regions of the medial temporal lobe, most likely the hippocampal formation, contribute to behavior in conditions that exceed the potential of viewpoint-dependent or egocentric representations. Apparently, this already applies to short-term memory of simple geometric relationships and does not necessarily depend on task difficulty or integration of landmarks into more complex representations. Deficient memory of basic geometric relationships may represent a core deficit that contributes to impaired performance in allocentric spatial memory tasks

A role of the human thalamus in predicting the perceptual consequences of eye movements

Internal monitoring of oculomotor commands may help to anticipate and keep track of changes in perceptual input imposed by our eye movements. Neurophysiological studies in non-human primates identified corollary discharge signals of oculomotor commands that are conveyed via thalamus to frontal cortices. We tested whether disruption of these monitoring pathways on the thalamic level impairs the perceptual matching of visual input before and after an eye movement in human subjects. Fourteen patients with focal thalamic stroke and twenty healthy control subjects performed a task requiring a perceptual judgment across eye movements. Subjects reported the apparent displacement of a target cue that jumped unpredictably in sync with a saccadic eye movement. In a critical condition of this task, six patients exhibited clearly asymmetric perceptual performance for rightward versus leftward saccade direction. Furthermore, perceptual judgments in seven patients systematically depended on oculomotor targeting errors, with self-generated targeting errors erroneously attributed to external stimulus jumps. Voxel-based lesion-symptom mapping identified an area in right central thalamus as critical for the perceptual matching of visual space across eye movements. Our findings suggest that trans-thalamic corollary discharge transmission decisively contributes to a correct prediction of the perceptual consequences of oculomotor actions

Advanced motion tracking for interactive mass spectrometry imaging (IMSI)

Mass spectrometry imaging (MSI) is a powerful analytical technique for the two-dimensional (2D) localization of chemicals on surfaces. Conventional MSI experiments require to predefine the surface of interest based on photographic or microscopic images. Typically, these boundaries can no longer be changed or adjusted once the experiment has been started. In terms of a more interactive approach we recently developed a pen-like ionization interface which is directly connected to the mass spectrometer. The device allows the user to ionize chemicals by desorption electrospray ionization (DESI) and to freely move the interface over a surface of interest. A mini camera, which is mounted on the tip of the pen, magnifies the desorption area and enables a simple positioning of the pen. The combination of optical data from the camera module and chemical data obtained by mass analysis facilitates a novel type of imaging experiment: interactive mass spectrometry imaging (IMSI). For this application, we present a novel approach for a robust, optical flow-based motion detection. While the live video stream from the camera is used to track the pen's motion across the surface a post-acquisition algorithm correlates the coordinates of the pen trajectory with respective mass spectra obtained from a simultaneous mass spectrometric data acquisition. This algorithm is no longer dependent on a single, manually applied optical marker on the sample surface, which has to be visible on all video frames throughout the analysis. The advanced DESI-IMSI method was successfully tested on inkjet-printed letters as well as mouse brain tissue samples. Validation of the results was done by comparing DESI-IMSI with standard DESI-MSI data

Schematic of the tasks.

<p>EGO task: Subjects were presented a memory cue while fixating on a central fixation cross. After an unfilled delay of 5000 ms, subjects performed an eye movement to the remembered cue position (‘memory-guided saccade’). ALLO-EGO: While fixating on a central fixation cross, subjects were presented a bar, followed by presentation of a memory cue together with the bar. After an unfilled delay of 5000 ms, the bar re-appeared and subjects performed an eye movement to the remembered cue position. ALLO: This task was identical to the ALLO-EGO task until the end of the delay. Then, the bar re-appeared at a new location. Subjects performed an eye movement to the relative position of the cue with respect to the bar (i.e. to the position of the memory cue if it had been displaced together with the bar).</p

Example lesion, patient H.N.

<p>Top: coronal MRI section perpendicular to the line connecting the anterior and posterior commissures (AC-PC line), at the level of amygdala, hippocampal head, rostral entorhinal cortex, rostral perirhinal cortex and infero-temporal cortex. Bottom: Axial MRI section parallel below the AC-PC line, at the level of amygdala, rostral hippocampus, entorhinal cortex, perirhinal cortex and infero-temporal cortex. Note damage to rostral hippocampus and adjacent MTL structures on the right.</p