Glucose-potassium-insulin in hypodynamic septic shock

Haemodynamic and metabolic effects of glucose-potassium-insulin (GKI) were studied in 14 patients with peritonitis. Study entry criteria were: hypodynamic septic shock (mean arterial pressure less than 50 mmHg and cardiac index less than 3.5 l/min) despite a highly positive fluid balance (greater than +2,000 ml during the last 12 h) and use of catecholamines (greater than 15 mcg/kg/min Dobutamine). GKI (glucose 70% 1 g/kg + potassium 10 mval + insulin 1.5 U/kg) was infused within 15 min via a central venous catheter. Before and 10 min after GKI haemodynamic and metabolic measurements were performed. GKI led to significant increases in systolic (+53%) and mean (+61%) arterial pressures, cardiac index (+50%), right (+60%) and left (+109%) ventricular stroke work indices, and oxygen consumption index (+18%). Heart rate remained unchanged, pulmonary shunt fraction increased slightly, systemic and pulmonary vascular resistances showed an insignificant decline. Serum glucose (p less than 0.01) and pCO2 (p less than 0.1) increased. The haemodynamic improvement lasted from 30 min or less (n = 3; 21%) to several hours. Nine patients (64%) survived more than 2 days, and two patients (14%) were eventually discharged from the hospital. We conclude, that in hypodynamic septic shock refractory to volume loading and catecholamine treatment GKI may be beneficial, although the mechanism of action remains unclear.     

Repeated immunization with plasmid DNA formulated in poly(lactide-co-glycolide) microparticles is well tolerated and stimulates durable T cell responses to the tumor-associated antigen cytochrome P450 1B1

Injection of microparticle-encapsulated DNA elicits immune responses to plasmid-encoded antigens in mice and humans. Cytochrome P450 CYP1B1 (CYP1B1) is a member of the CYP1 P450 enzyme family that is overexpressed in a variety of solid tumors. The work described herein was performed to study the kinetics of stimulating T cell responsiveness with an encapsulated DNA encoding CYP1B1 and provides support for the clinical development of this formulation. Immunization of HLA-A2/Kb transgenic mice with human CYP1B1 encoding plasmid DNA formulated in poly(lactide-co-glycolide) (PLG) microparticles elicits CD8+ T cells that respond to human CYP1B1-positive target cells. The duration of the immune response, the effect on the immune response of multiple injections, and the safety of repeated injections were studied. These results show that the PLG-encapsulated DNA therapeutic elicits durable immune responses to CYP1B1, the responses are dependent on repeat immunization, and that the formulation is well tolerated.     

Serum vasopressin (AVP) levels in polyuric brain-dead organ donors

Summary Hydromineral metabolism and serum arginine-vasopressin (AVP) levels were investigated in 11 patients who sustained brain death. They showed various degrees of polyuria with low osmolality and low fractional sodium excretion. Urine osmolality was always below that of serum, and AVP levels were between 1.3 and 50.0 pg/ml vs 0.7–8.0 pg/ml in ten normal subjects. Thus central diabetes insipidus was excluded. A renal mechanism inducing water diuresis has to be assumed. The type of renal lesion, however, remains unclear.This work was supported by the Fonds zur Förderung der wissenschaftlichen Forschung, project no. 3100, Vienna     

Motor rehabilitation after traumatic brain injury and stroke - Advances in assessment and therapy

A long-term goal in motor rehabilitation is that treatment is not selected on the basis of 'schools of thought', but rather, based on knowledge about efficacy and effectiveness of specific interventions for specific situations (e.g. functional syndromes). Motor dysfunction after stroke or TBI can be caused by many different functional syndromes such as paresis, ataxia, deafferentaion, visuo-perceptual deficits, or apraxia. Examples are provided showing that theory-based analysis of motor behavior makes it possible to describe 'syndrome-specific motor deficits'. Its potential implications for motor rehabilitation are that our understanding of altered motor behavior as well as specific therapeutic approaches might be promoted. A methodological prerequisite for clinical trials in rehabilitation is knowledge about test properties of assessment tools in follow-up situations such as test-retest reliability and responsiveness to change. Test-retest reliability assesses whether a test can produce stable measures with test repetition, while sensitivity to change reflects whether a test detects changes that occur over time. Exemplifying these considerations, a reliability and validity study of a kinematic arm movement analysis is summarized. In terms of new therapeutic developments, two examples of clinical therapeutic studies are provided assessing the efficacy of specific inter-ventions for specific situations in arm and gait rehabilitation: the Arm Ability Training for high functioning hemiparetic stroke and TBI patients, and the treadmill training for non-ambulatory hemiparetic patients. In addition, a new technical development, a machine-controlled gait trainer ist introduced.     

Multimodal Functional Neuroimaging by Simultaneous BOLD fMRI and Fiber-Optic Calcium Recordings and Optogenetic Control

Recent developments of optogenetic tools and fluorescence-based calcium recording techniques enable the manipulation and monitoring of neural circuits on a cellular level. Non-invasive imaging of brain networks, however, requires the application of methods such as blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), which is commonly used for functional neuroimaging. While BOLD fMRI provides brain-wide non-invasive reading of the hemodynamic response, it is only an indirect measure of neural activity. Direct observation of neural responses requires electrophysiological or optical methods. The latter can be combined with optogenetic control of neuronal circuits and are MRI compatible. Yet, simultaneous optical recordings are still limited to fiber-optic-based approaches. Here, we review the integration of optical recordings and optogenetic manipulation into fMRI experiments. As a practical example, we describe how BOLD fMRI in a 9.4-T small animal MR scanner can be combined with in vivo fiber-optic calcium recordings and optogenetic control in a multimodal setup. We present simultaneous BOLD fMRI and calcium recordings under optogenetic control in rat. We outline details about MR coil configuration, choice, and usage of opsins and chemically and genetically encoded calcium sensors, fiber implantation, appropriate light power for stimulation, and calcium signal detection, to provide a glimpse into challenges and opportunities of this multimodal molecular neuroimaging approach.     

Impact of concomitant injuries on outcomes after traumatic brain injury

Background

Patients with traumatic brain injury (TBI) frequently have concomitant injuries; we aimed to investigate their impact on outcomes.

Methods

Between February 2002 and April 2010, 17 Austrian centers prospectively enrolled 863 patients with moderate and severe TBI into observational studies. Data on accident, treatment, and outcomes were collected. Patients who survived until intensive care unit (ICU) admission and had survivable TBI were selected, and were assigned to “isolated TBI” or “TBI + injury” groups. Six-month outcomes were classified as “favorable” if Glasgow Outcome Scale (GOS) scores were five or four, and were classified as “unfavorable” if GOS scores were three or less. Univariate statistics (Fisher’s exact test, t test, χ²-test) and logistic regression were used to identify factors associated with hospital mortality and unfavorable outcome.

Results

Of the 767 patients, 403 (52.5 %) had isolated TBI, 364 (47.5 %) had concomitant injuries. Patients with isolated TBI had higher mean age (53 vs. 44 years, P = 0.001); hospital mortality (30.0 vs. 27.2 %, P = 0.42) and rate of unfavorable outcome (50.4 vs. 41.8 %, P = 0.02) were higher, too. There were no significant mortality differences for factors like age groups, trauma mechanisms, neurologic status, CT findings, or treatment factors. Concomitant injuries were associated with higher mortality (33.3 vs. 12.5 %, P = 0.05) in patients with moderate TBI, and were significantly associated with more ventilation, ICU, and hospitals days. Logistic regression revealed that age, Glasgow Coma Scale score, pupillary reactivity, severity of TBI and CT score were the main factors that influenced outcomes.

Conclusions

Concomitant injuries have a significant effect upon the mortality of patients with moderate TBI. They do not affect the mortality in patients with severe TBI.

Level of evidence and study type

Evidence level 2; prospective, observational prognostic study.     

Outcome after severe brain trauma associated with epidural hematoma

Objective

The aim of this study was to identify factors contributing to outcomes after severe traumatic brain injury (TBI) associated with epidural hematoma (EDH).

Methods

Between 02/2002 and 4/2010 17 Austrian centers prospectively enrolled 863 patients with moderate and severe TBI into observational studies. Data on accident, treatment, and outcomes were collected. Data sets from patients who had severe TBI (=Glasgow Coma Scale score <9) and EDH were selected. Six-month outcomes were classified as “favorable” if Glasgow Outcome Scale (GOS) scores were 5 or 4, and were classified as “unfavorable” if GOS scores were 3 or less. The Rotterdam score was used to classify computed tomography (CT) findings; the scores published by Hukkelhoven et al. (J Neurotrauma 22:1025–1039, 2005) were used to estimate predicted rates of death and of unfavorable outcomes. Univariate (Fisher’s exact test, t test, Chi²-test) and multivariate (logistic regression) statistics were used to identify factors associated with hospital mortality and favorable outcome.

Results

Of the 738 patients with severe TBI 159 (21.5 %) had EDH. Of these, 49 (30.8 %) died in the hospital, 21 (13.2 %) survived with unfavorable outcome, 82 (51.6 %) with favorable outcome; long-term outcome was unknown in 7 survivors (4.4 %). Mortality rates predicted by the Rotterdam score showed good correlation with observed mortality rates. According to the Hukkelhoven scores, observed/predicted ratios for mortality and unfavorable outcome were 0.94 and 0.97, respectively. Age, severity of TBI, and neurological status were the main factors influencing outcomes after severe TBI associated with EDH. We were unable to demonstrate significant effects of treatment factors.