Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection

Background Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection. Methods Markers of hepatocyte injury (AST, GSTα, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with and without intermittent inflow occlusion. To study the separate involvement of the intestines and the liver in systemic L-FABP release, arteriovenous concentration differences for L-FABP were measured. Results During liver manipulation, liver injury markers increased significantly. Arterial plasma levels and transhepatic and transintestinal concentration gradients of L-FABP indicated that this increase was exclusively due to hepatic and not due to intestinal release. Intermittent hepatic inflow occlusion, anesthesia, and liver transection did not further enhance arterial L-FABP and GSTα levels. Hepatocyte injury was followed by an inflammatory response. Conclusions This study shows that liver manipulation is a leading cause of hepatocyte injury during liver surgery. A potential causal relation between liver manipulation and systemic inflammation remains to be established; but since the inflammatory response is apparently initiated early during major abdominal surgery, interventions aimed at reducing postoperative inflammation and related complications should be started early during surgery or beforehand. Marcel C. G. van de Poll, Joep P. M. Derikx contributed equally to this work.     

Motor and sensory dissociative phenomena associated with induced catalepsy: A brief communication

The purpose of this study was to investigate dissociative symptoms that may occur as an epiphenomenon of tactile-induced catalepsy. In 15 participants, catalepsy was induced in the right arm, and dissociative symptoms were evaluated using a self-report questionnaire. In comparison with the left, noncataleptic arm, the right cataleptic arm was perceived differently. In addition to increased rigidity, the cataleptic arm was characterized by the presence of paresthesias, a decreased perception of sense and a decreased awareness of the arm. Moreover, the self-reported changes in perception were significantly correlated to the hypnotically induced arm-immobilization part of the Stanford Hypnotic Susceptibility Scale. In conclusion, catalepsy induction elicits a variety of dissociative symptoms and provides a useful research paradigm for the study of motor-perceptual dissociative phenomena.     

The effects of social stress and cortisol responses on the preconscious selective attention to social threat

The purpose of the present study was to investigate the effects of social stress and stress-induced cortisol on the preconscious selective attention to social threat. Twenty healthy participants were administered a masked emotional Stroop task (comparing color-naming latencies for angry, neutral and happy faces) in conditions of rest and social stress. Stress was induced by means of the Trier social stress test. Based on the stress-induced increase in cortisol levels, participants were allocated post hoc (median-split) to a high and low responders group. In contrast to low responders, high responders showed a negative or avoidant attentional bias to threat (i.e. shorter latencies for angry than neutral faces) in the rest condition. Most importantly, although low responders became avoidant, the high responders became vigilant to the angry faces after stress induction. There were no such effects for happy faces. Our findings are in line with previous studies in both animals and humans, that associate high glucocorticoid stress-responsiveness with diminished avoidance and prolonged freezing reactions during stress.     

Detection and characterization of usability problems in structured data entry interfaces in dentistry

BackgroundPoor usability is one of the major barriers for optimally using electronic health records (EHRs). Dentists are increasingly adopting EHRs, and are using structured data entry interfaces to enter data such that the data can be easily retrieved and exchanged. Until recently, dentists have lacked a standardized terminology to consistently represent oral health diagnoses.ObjectivesIn this study we evaluated the usability of a widely used EHR interface that allow the entry of diagnostic terms, using multi-faceted methods to identify problems and work with the vendor to correct them using an iterative design method.MethodsFieldwork was undertaken at two clinical sites, and dental providers as subjects participated in user testing (n = 32), interviews (n = 36) and observations (n = 24).ResultsUser testing revealed that only 22–41% of users were able to successfully complete a simple task of entering one diagnosis, while no user was able to complete a more complex task. We identified and characterized 24 high-level usability problems reducing efficiency and causing user errors. Interface-related problems included unexpected approaches for displaying diagnosis, lack of visibility, and inconsistent use of UI widgets. Terminology related issues included missing and mis-categorized concepts. Work domain issues involved both absent and superfluous functions. In collaboration with the vendor, each usability problem was prioritized and a timeline set to resolve the concerns.DiscussionMixed methods evaluations identified a number of critical usability issues relating to the user interface, underlying terminology of the work domain. The usability challenges were found to prevent most users from successfully completing the tasks. Our further work we will determine if changes to the interface, terminology and work domain do result in improved usability.     

Pretreatment with interferon-γ enhances the therapeutic activity of mesenchymal stromal cells in animal models of colitis

Mesenchymal stromal cells (MSCs) are currently under investigation for the treatment of inflammatory disorders, including Crohn's disease. MSCs are pluripotent cells with immunosuppressive properties. Recent data suggest that resting MSCs do not have significant immunomodulatory activity, but that the immunosuppressive function of MSCs has to be elicited by interferon-γ (IFN-γ). In this article, we assessed the effects of IFN-γ prestimulation of MSCs (IMSCs) on their immunosuppressive properties in vitro and in vivo. To this end, we pretreated MSCs with IFN-γ and assessed their therapeutic effects in dextran sodium sulfate (DSS)- and trinitrobenzene sulfonate (TNBS)-induced colitis in mice. We found that mice treated with IMSCs (but not MSCs) showed a significantly attenuated development of DSS-induced colitis. Furthermore, IMSCs alleviated symptoms of TNBS-induced colitis. IMSC-treated mice displayed an increase in body weight, lower colitis scores, and better survival rates compared with untreated mice. In addition, serum amyloid A protein levels and local proinflammatory cytokine levels in colonic tissues were significantly suppressed after administration of IMSC. We also observed that IMSCs showed greater migration potential than unstimulated MSCs to sites within the inflamed intestine. In conclusion, we show that prestimulation of MSCs with IFN-γ enhances their capacity to inhibit Th1 inflammatory responses, resulting in diminished mucosal damage in experimental colitis. These data demonstrate that IFN-γ activation of MSCs increases their immunosuppresive capacities and importantly, their therapeutic efficacy in vivo.