Fully automated preoperative liver volumetry incorporating the anatomical location of the central hepatic vein

The precise preoperative calculation of functional liver volumes is essential prior major liver resections, as well as for the evaluation of a suitable donor for living donor liver transplantation. The aim of this study was to develop a fully automated, reproducible, and quantitative 3D volumetry of the liver from standard CT examinations of the abdomen as part of routine clinical imaging. Therefore, an in-house dataset of 100 venous phase CT examinations for training and 30 venous phase ex-house CT examinations with a slice thickness of 5 mm for testing and validating were fully annotated with right and left liver lobe. Multi-Resolution U-Net 3D neural networks were employed for segmenting these liver regions. The Sorensen-Dice coefficient was greater than 0.9726 +/- 0.0058, 0.9639 +/- 0.0088, and 0.9223 +/- 0.0187 and a mean volume difference of 32.12 +/- 19.40 ml, 22.68 +/- 21.67 ml, and 9.44 +/- 27.08 ml compared to the standard of reference (SoR) liver, right lobe, and left lobe annotation was achieved. Our results show that fully automated 3D volumetry of the liver on routine CT imaging can provide reproducible, quantitative, fast and accurate results without needing any examiner in the preoperative work-up for hepatobiliary surgery and especially for living donor liver transplantation.Projekt DEA

siRNA-mediated knockdown of the serotonin transporter in the adult mouse brain.

Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressant drugs that increase the extracellular levels of serotonin by blocking the reuptake activity of the serotonin transporter (SERT). Although SSRIs elevate brain serotonergic neurotransmission acutely, their full therapeutic effects involve neurochemical adaptations that emerge following chronic drug administration. The adaptive downregulation of SERT has recently been implicated in the therapeutic response of SSRIs. Interestingly, studies using SERT-knockout mice reveal somewhat paradoxical depression-related effects, probably specific to the downregulation of SERT during early development. However, the behavioral significance of SSRI-mediated downregulation of SERT during adulthood is still unknown. We investigated whether somatic gene manipulation, triggered by infusing short interfering RNA (siRNA) into the ventricular system, would enable the downregulation of SERT in the adult mouse brain. Infusing the SERT-targeting siRNA, for 2 weeks, significantly reduced the mRNA levels of SERT in raphe nuclei. Further, a significant, specific and widespread downregulation of SERT-binding sites was achieved in the brain. In contrast, 2-week infusion of the SSRI, citalopram, produced a widespread downregulation of SERT-binding sites, independent of any alterations at the mRNA level. Irrespective of their mechanisms for downregulating SERT in the brain, infusions of SERT-siRNA or citalopram elicited a similar antidepressant-related behavioral response in the forced swim test. These results signify a role for the downregulation of SERT in mediating the antidepressant action of SSRIs in adults. Further, these data demonstrate that siRNA-induced widespread knockdown of gene expression serves as a powerful tool for assessing the function of endogenous genes in the adult brain

Neurochemical and behavioral consequences of widespread gene knockdown in the adult mouse brain by using nonviral RNA interference.

Gene expression analysis implicates an increasing number of novel genes in the brain as potential targets for the treatment of neurological and psychiatric disorders. Frequently, these genes are ubiquitously expressed in the brain and, thus, may contribute to a pathophysiological state through actions in several brain nuclei. Current strategies employing genetically modified animals for in vivo validation of such targets are time-consuming and often limited by developmental adaptations. Somatic gene manipulation using viral-mediated RNA interference (RNAi) has emerged recently, although restricting the target validation to specific brain nuclei. We investigated whether nonviral infusion of short interfering RNA (siRNA) into the ventricular system would enable a sequence-specific gene knockdown. The temporality and extent of siRNA-induced down-regulation were analyzed by targeting a transgene, EGFP, in mice overexpressing EGFP. Extensive knockdown of EGFP was observed, especially in regions adjacent or dorsoventrally and mediolaterally distant to the infusion site (dorsal third ventricle), with lesser knockdown in more distal regions. We challenged our RNAi approach to generate a specific knockdown of an endogenous gene, encoding the dopamine transporter (DAT) in regions (ventral midbrain) far distal to the infusion site. DAT-siRNA infusion in adult mice produced a significant down-regulation of DAT mRNA and protein in the brain and also elicited a temporal hyperlocomotor response similar to that (but delayed) obtained upon infusion of GBR-12909, a pharmacologically selective DAT inhibitor. Application of this nonviral RNAi approach may accelerate target validation for neuropsychiatric disorders that involve a complex interplay of gene(s) from various brain regions

High MELD score and extended operating time predict prolonged initial ICU stay after liver transplantation and influence the outcome

<div><p>Background</p><p>The aim of the present study is to determine the incidence of a prolonged (>3 days) initial ICU-stay after liver transplantation (LT) and to identify risk factors for it.</p><p>Patients and methods</p><p>We retrospectively analyzed data of adult recipients who underwent deceased donor first-LT at the University Hospital Essen between 11/2003 and 07/2012 and showed a primary graft function.</p><p>Results</p><p>Of the 374 recipients, 225 (60.16%) had prolonged ICU-stay. On univariate analysis, donor INR, high doses of vasopressors, “rescue-offer” grafts, being hospitalized at transplant, high urgency cases, labMELD, alcoholic cirrhosis, being on renal dialysis and length of surgery were associated with prolonged ICU-stay. After multivariate analysis, only the labMELD and the operation’s length were independently correlated with prolonged ICU-stay. Cut-off values for these variables were 19 and 293.5 min, respectively. Hospital stay was longer for patients with a prolonged initial ICU-stay (p<0.001). Survival rates differed significantly between the two groups at 3 months, 1-year and 5-years after LT (p<0.001).</p><p>Conclusions</p><p>LabMELD and duration of LT were identified as independent predictors for prolonged ICU-stay after LT. Identification of recipients in need of longer ICU-stay could contribute to a more evidenced-based and cost-effective use of ICU facilities in transplant centers.</p></div

Univariate Cox proportional hazard regression analysis for prolonged ICU stay after LT.

<p>Univariate Cox proportional hazard regression analysis for prolonged ICU stay after LT.</p

Receiver Operating Characteristic curve (ROC) curve associated with the logistic regression model.

<p>Receiver Operating Characteristic curve (ROC) curve associated with the logistic regression model.</p

Number of recipients in each MELD group.

<p>Number of recipients in each MELD group.</p

Box-Whisker-Plot depicting the influence of labMELD score on the length of ICU stay.

<p>Box-Whisker-Plot depicting the influence of labMELD score on the length of ICU stay.</p

Flow diagram of patients included in the study.

<p>Flow diagram of patients included in the study.</p