Omeprazole significantly reduced the morbidity of stress-related UGI bleeding in patients with ICH due to its effective prophylactic effect without increasing the risk of nosocomial pneumonia, but it did not reduce the 1-month mortality or ICU stay. Further evaluation of high-dose omeprazole as the drug of choice for patients presenting with UGI bleeding is warranted. Clinical trial registration no.: ChiCTR-TRC-12001871, registered at the Chinese clinical trial registry (http://www.chictr.org/en/proj/show.aspx?proj=2384).
ObjectiveVariations of conductive fluid content in brain tissue (e.g. cerebral edema) change tissue impedance and can potentially be measured by Electrical Impedance Tomography (EIT), an emerging medical imaging technique. The objective of this work is to establish the feasibility of using EIT as an imaging tool for monitoring brain fluid content.Designa prospective study.SettingIn this study EIT was used, for the first time, to monitor variations in cerebral fluid content in a clinical model with patients undergoing clinical dehydration treatment. The EIT system was developed in house and its imaging sensitivity and spatial resolution were evaluated on a saline-filled tank.Patients23 patients with brain edema.InterventionsThe patients were continuously imaged by EIT for two hours after initiation of dehydration treatment using 0.5 g/kg intravenous infusion of mannitol for 20 minutes.Measurement and Main ResultsOverall impedance across the brain increased significantly before and after mannitol dehydration treatment (p = 0.0027). Of the all 23 patients, 14 showed high-level impedance increase and maintained this around 4 hours after the dehydration treatment whereas the other 9 also showed great impedance gain during the treatment but it gradually decreased after the treatment. Further analysis of the regions of interest in the EIT images revealed that diseased regions, identified on corresponding CT images, showed significantly less impedance changes than normal regions during the monitoring period, indicating variations in different patients' responses to such treatment.ConclusionsEIT shows potential promise as an imaging tool for real-time and non-invasive monitoring of brain edema patients.
Intracranial bleeding is one of the most severe medical emergencies in neurosurgery. Early detection or diagnosis would largely reduce the rate of disability and mortality, and improve the prognosis of the patients. Electrical Impedance Tomography (EIT) can non-invasively image the internal resistivity distribution within a human body using a ring of external electrodes, and is thus a promising technique to promptly detect the occurrence of intracranial bleedings because blood differs from other brain tissues in resistivity. However, so far there is no experimental study that has determined whether the intracranial resistivity changes in humans could be repeatedly detected and imaged by EIT. Hence, we for the first time attempt to clinically validate this by in vivo imaging the influx and efflux of irrigating fluid (5% dextrose in water, D5W) during the twist-drill drainage operation for the patients with subdural hematoma (SDH). In this study, six patients (four male, two female) with subacute or chronic SDH received the surgical operation in order to evacuate the hematoma around subdural region, and EIT measurements were performed simultaneously on each patient’s head. The results showed that the resistivity significantly increased on the corresponding position of EIT images during the influx of D5W and gradually decreased back to baseline during the efflux. In the quantitative analysis, the average resistivity values demonstrated the similar results and had highly linear correlation (R2 = 0.93±0.06) with the injected D5W volumes, as well as the area of the resistivity gain(R2 = 0.94±0.05). In conclusion, it was clinically validated that intracranial resistivity changes in humans were detectable and quantifiable by the EIT method. After further technical improvements, EIT has the great potential of being a routine neuroimaging tool for early detection of intracranial bleedings.
Glioblastoma (GBM) is still one of the most lethal forms of brain tumor despite of the improvements in treatments. TRAIL (TNF-related apoptosis-inducing ligand) is a promising anticancer agent that can be potentially used as an alternative or complementary therapy because of its specific antitumor activity. To define the novel pathways that regulate susceptibility to TRAIL in GBM cells, we performed a genome-wide expression profiling of microRNAs in GBM cell lines with the distinct sensitivity to TRAIL-induced apoptosis. We found that the expression pattern of miR-7 is closely correlated with sensitivity of GBM cells to TRAIL. Furthermore, our gain and loss of function experiments showed that miR-7 is a potential sensitizer for TRAIL-induced apoptosis in GBM cells. In the mechanistic study, we identified XIAP is a direct downstream gene of miR-7. Additionally, this regulatory axis could also exert in other types of tumor cells like hepatocellular carcinoma cells. More importantly, in the xenograft model, enforced expression of miR-7 in TRAIL-overexpressed mesenchymal stem cells increased apoptosis and suppressed tumor growth in an exosome dependent manner. In conclusion, we identify that miR-7 is a critical sensitizer for TRAIL-induced apoptosis, thus making it as a promising therapeutic candidate for TRAIL resistance in GBM cells.
Cerebral edema after brain injury can lead to brain damage and death if diagnosis and treatment are delayed. This study investigates the feasibility of employing electrical impedance tomography (EIT) as a non-invasive imaging tool for monitoring the development of cerebral edema, in which impedance imaging of the brain related to brain water content is compared with intracranial pressure (ICP). We enrolled forty patients with cerebral hemorrhage who underwent lateral external ventricular drain with intraventricular ICP and EIT monitoring for 3 h after initiation of dehydration treatment. The average reconstructed impedance value (ARV) calculated from EIT images was compared with ICP. Dehydration effects induced changes in ARV and ICP showed a close negative correlation in all patients, and the mean correlation reached
R
2
= 0.78 ± 0.16 (
p
< .001). A regression equation (
R
2
= 0.62,
p
< .001) was formulated from the total of measurement data. The 95% limits of agreement were − 6.13 to 6.13 mmHg. Adaptive clustering and variance analysis of normalized changes in ARV and ICP showed 92.5% similarity and no statistically significant differences (
p
> .05). Moreover, the sensitivity, specificity and area under the curve of changes in ICP >10 mmHg were 0.65, 0.73 and 0.70 respectively. The findings show that EIT can monitor changes in brain water content associated with cerebral edema, which could provide a real-time and non-invasive imaging tool for early identification of cerebral edema and the evaluation of mannitol dehydration.
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