To cite this article: Hugenholtz GCG, Macrae F, Adelmeijer J, Dulfer S, Porte RJ, Lisman T, Ari€ ens RAS. Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen. J Thromb Haemost 2016; 14: 1054-66. Essentials Patients with cirrhosis have hemostatic changes, which may contribute to a risk of thrombosis. This in vitro study compares clot formation and structure between patients and healthy subjects. Clot formation is delayed in patients; ultimately, however , clot permeability is decreased. The thrombogenic structure of fibrin clots may contribute to the thrombotic risk in cirrhosis. Abstract. Background and Objectives: Patients with cirrho-sis can be at risk of thrombotic complications due to an imbalance between hemostatic components. However, little is known on how the disease affects clot generation or how alterations in the structure of fibrin clots may affect the hemostatic function of these patients. Methods: We investigated the formation and structure of clots generated with plasma and purified fibrinogen of 42 patients with cirrhosis. Clots generated with plasma and fibrino-gen of 29 healthy volunteers were studied for comparison. Clot formation and structure were assessed by turbidity, permeation studies, confocal laser and scanning electron microscopy (SEM). The extent of fibrinogen oxidation was assessed by measuring the carbonyl content of purified fibrinogen samples. Results: Tissue factor and throm-bin-induced clotting of plasma was delayed in patients. The clotting rate was also decreased, but change in tur-bidity, fibrin density and fiber thickness were largely comparable to healthy volunteers. Conversely, clot perme-ability was significantly decreased in patients. When clots were generated with purified fibrinogen, differences in clot formation and structure similar to those in plasma were found. The carbonyl content was increased in patient fibrinogen and correlated with disease severity and clot permeability. Conclusions: Delayed clot formation in cir-rhosis ultimately results in decreased clot permeability. Similar alterations in clots generated with purified fibrino-gen suggest that modifications of the molecule are (partly) responsible. Taken together, these findings are indicative of hypercoagulable features of clots of patients with cirrhosis, which may explain the increased risk of thrombosis associated with this condition.

Purpose of reviewWe will explain the basic principles of intraoperative neurophysiological monitoring (IONM) during spinal surgery. Thereafter we highlight the significant impact that general anesthesia can have on the efficacy of the IONM and provide an overview of the essential pharmacological and physiological factors that need to be optimized to enable IONM. Lastly, we stress the importance of teamwork between the anesthesiologist, the neurophysiologist, and the surgeon to improve clinical outcome after spinal surgery. Recent findingsIn recent years, the use of IONM has increased significantly. It has developed into a mature discipline, enabling neurosurgical procedures of ever-increasing complexity. It is thus of growing importance for the anesthesiologist to appreciate the interplay between IONM and anesthesia and to build up experience working in a team with the neurosurgeon and the neurophysiologist. SummarySafety measures, cooperation, careful choice of drugs, titration of drugs, and maintenance of physiological homeostasis are essential for effective IONM.

Muscle-recorded transcranial electrical stimulation motor-evoked potentials (mTc-MEPs) are used to assess the spinal cord integrity. They are commonly recorded with subcutaneous needle or surface electrodes, but the different characteristics of mTc-MEP signals recorded with the two types of electrodes have not been formally compared yet. In this study, mTc-MEPs were simultaneously recorded from the tibialis anterior (TA) muscles using surface and subcutaneous needle electrodes in 242 consecutive patients. Elicitability, motor thresholds, amplitude, area under the curve (AUC), signal-to-noise ratio (SNR), and the variability between mTc-MEP amplitudes were compared. Whereas amplitude and AUC were significantly higher in subcutaneous needle recordings (p < 0.01), motor thresholds and elicitability were similar for surface and subcutaneous needle recordings. Moreover, the SNRs were >2 in more than 99.5% of the surface and subcutaneous needle recordings, and the variability between consecutive amplitudes was not significantly different between the two recording electrode types (p = 0.34). Surface electrodes appear to be a good alternative to needle electrodes for spinal cord monitoring. They are non-invasive, can record signals at similar threshold intensities, have adequately high SNRs, and record signals with equivalent variability. Whether surface electrodes are non-inferior to subcutaneous needle electrodes in detecting motor warnings is investigated in part II of the NERFACE study.