Abnormal gamma-band oscillations (GBO) have been frequently associated with the pathophysiology of schizophrenia. GBO are modulated by glutamate, a neurotransmitter, which is continuously discussed to shape the complex symptom spectrum in schizophrenia. The current study examined the effects of ketamine, a glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist, on the auditory-evoked gamma-band response (aeGBR) and psychopathological outcomes in healthy volunteers to investigate neuronal mechanisms of psychotic behavior. In a placebo-controlled, randomized crossover design, the aeGBR power, phase-locking factor (PLF) during a choice reaction task, the Positive and Negative Syndrome Scale (PANSS) and the Altered State of Consciousness (5D-ASC) Rating Scale were assessed in 25 healthy subjects. Ketamine was applied in a subanaesthetic dose. Lowresolution brain electromagnetic tomography was used for EEG source localization. Significant reductions of the aeGBR power and PLF were identified under ketamine administration compared to placebo (p < 0.01). Source-space analysis of aeGBR generators revealed significantly reduced current source density (CSD) within the anterior cingulate cortex during ketamine administration. Ketamine induced an increase in all PANSS (p < 0.001) as well as 5D-ASC scores (p < 0.01) and increased response times (p < 0.001) and error rates (p < 0.01). Only negative symptoms were significantly associated with an aeGBR power decrease (p = 0.033) as revealed by multiple linear regression. These findings argue for a substantial role of the glutamate system in the mediation of dysfunctional gamma band responses and negative symptomatology of schizophrenia and are compatible with the NMDAR hypofunction hypothesis of schizophrenia.

Background: Due to medical advances, an increasing number of patients are surviving the acute critical illness. However, some patients require a prolonged critical care treatment. Data on outcome and functional status of patients with an ICU-stay >= 90 days are scarce. Methods: Single-center retrospective study including all adult patients with ICU stay >= 90 days treated at the department of intensive care medicine at the university medical center Hamburg-Eppendorf, Germany, between January 1st 2008 and December 31st 2016. Results: Out of 65,249 patients, we identified 96 (0.1%) patients with a very prolonged ICU stay. Median age was 61 (49.8-67) years, 30 (31%) patients were female. Patients were admitted to ICU due to abdominal (28%) reasons, followed by sepsis (23%) and transplantation (15%). Fourteen patients received organ-transplantation: 9 received liver-, 4 lung- and 1 heart-transplantation. All patients needed mechanical ventilation (MV), median duration was 74.1 (55-95.1) days. Sixty-Three (66%) patients survived the ICU-stay and 1-Year survival rate was 28%. Overall eight (8%) patients had a favourable outcome after 1-Year. Severity of illness (SOFA, SAPS II) on admission were comparable. Length of MV, use of renal replacement therapy (both p < .01) and maximum lactate (5.3 vs 11.5 mmol/l; p < .001) were significantly higher in ICU non-survivors. ICU-stay was significantly longer in ICU non-survivors (137 vs 107 days; p < .05). Cox-regression-model revealed age (HR 1.02, 95% CI 1.00-1.04, p < .05) and surgical admission (HR 0.50, 95% CI 0.28-0.90, p < .05) as independent predictors of 1-year mortality. Conclusions: Only a small number of patients requires a very prolonged ICU stay. Two-third of patients survive the ICU stay and about one-third 1-Year. However, about 10% of patients have a remarkable recovery with a favourable overall outcome after 1-Year.

For critically ill patients, effective airway management with a high first-attempt success rate for endotracheal intubation is essential to prevent hypoxic complications during securing of the airway. Video guidance may improve first-attempt success rate over direct laryngoscopy (DL).

Percutaneous dilatational tracheotomy (PDT) may lead to transient impairment of pulmonary function due to suboptimal ventilation, loss of positive end-expiratory pressure (PEEP) and repetitive suction maneuvers during the procedure. Possible changes in regional lung aeration were investigated using electrical impedance tomography (EIT), an increasingly implied instrument for bedside monitoring of pulmonary aeration.

We thank Xue et al. for their comments [1] regarding our article on the peri-interventional visualization of percutaneous dilatational tracheostomy (PDT) [2].The authors noted that we did not provide diameters for the endotracheal tubes used in the bronchoscopy group.The endotracheal tubes had an inner diameter of 7.5 mm for female and 8.0 or 8.5 mm for male patients.Therefore, the differences between the inner tubes' diameter and the 4.9 mm bronchoscopes used in our study were always ≥ 2.0 mm as recommended [3] to maintain minute ventilation during bronchoscopy.The crosssectional areas of endotracheal tubes with an inner diameter of 7.5, 8.0, and 8.5 mm are 44.2,50.3, and 56.7 mm 2 , respectively.The effective cross-sectional area with a 4.9 mm bronchoscope inserted decreases to 25.3, 31.4,and 37.9 mm 2 and to 36.6, 42.7, and 49.2 mm 2 for a 3.1 mm bronchoscope, respectively.Although the decrease of the cross-sectional area is less pronounced when using a 3.1 mm bronchoscope potentially offering improved ventilation with less hypercarbia, it must be noted that the channel width of the Olympus LF-DP bronchoscope is only 1.2 mm compared to 2.2 mm in the Olympus BF-P60 used in our study.Regarding the respective cross-sectional areas of 1.1 and 3.8 mm 2 , it becomes clear that suctioning of secretions and especially blood from the trachea is nearly impossible with the smaller bronchoscope.Concerning the fresh gas flow, we used critical care ventilators (Evita V500, Drägerwerk AG, Lübeck, Germany) with a semi-open breathing circuit.In semi-

μ-Opioid receptor agonists are widely used within the contemporary treatment of pain, but abrupt opioid suspension, even after short-term infusion, can paradoxically increase the sensitivity to noxious stimuli, a phenomenon that has been, for example, reported after application of the fast-acting μ-opioid receptor agonist remifentanil. To investigate the mechanisms underlying the effects of discontinuation of remifentanil application on pain processing in the human CNS, we analyzed neuronal responses to thermal stimuli before and after a short-term infusion of remifentanil (30 min 0.1 μg/kg body weight/min) compared with control in the brain, brainstem, and spinal cord in drug-naive male volunteers using fMRI. Subsequent to remifentanil suspension, we observed reduced heat pain thresholds and increased neuronal responses in pain-encoding as well as in key regions of the descending pain-modulatory system, such as the periaqueductal gray matter, the nucleus cuneiformis, and the rostral ventromedial medulla. Moreover, the spinal pain-related multivoxel activity pattern showed an opioid-specific change after drug suspension. Importantly, remifentanil suspension increased the functional coupling between the nucleus cuneiformis and the rostral anterior cingulate cortex, and the coupling strength between the rostral anterior cingulate cortex and the nucleus cuneiformis correlated negatively with the individual pain threshold after opioid suspension. These findings demonstrate that, already subsequent to a short-term infusion of the μ-opioid receptor agonist remifentanil, signaling in the descending pain-modulatory system is fundamentally altered and that these changes are directly related to the behavioral sensitivity to pain. SIGNIFICANCE STATEMENT Opioids are widely used in modern medicine, but, in addition to their known side effects, it is increasingly recognized that opioids can also increase sensitivity to pain subsequent to their use. Using the fast-acting μ-opioid receptor agonist remifentanil and fMRI in healthy male volunteers, this study demonstrates how signaling changes occur along the entire descending pain-modulatory pathway after opioid discontinuation and how these alterations are closely linked to increased behavioral pain sensitivity. Particularly by revealing modified responses in pain-modulatory brainstem regions that have been previously demonstrated to be causally involved in acute opioid withdrawal effects in rodents, the data provide a plausible neuronal mechanism by which the increased sensitivity to pain after opioid suspension is mediated in humans.

Auditory verbal hallucinations (AVH) are a common positive symptom of schizophrenia. Excitatory-to-inhibitory (E/I) imbalance related to disturbed N-methyl-d-aspartate receptor (NMDAR) functioning has been suggested as a possible mechanism underlying altered connectivity and AVH in schizophrenia. The current study examined the effects of ketamine, a NMDAR antagonist, on glutamate-related mechanisms underlying interhemispheric gamma-band connectivity, conscious auditory perception during dichotic listening (DL), and the emergence of auditory verbal distortions and hallucinations (AVD/AVH) in healthy volunteers. In a single-blind, pseudo-randomized, placebo-controlled crossover design, nineteen male, right-handed volunteers were measured using 64 channel electroencephalography (EEG). Psychopathology was assessed with the PANSS interview and the 5D-ASC questionnaire, including a subscale to detect auditory alterations with regard to AVD/AVH (AUA-AVD/AVH). Interhemispheric connectivity analysis was performed using eLORETA source estimation and lagged phase synchronization (LPS) in the gamma-band range (30–100 Hz). Ketamine induced positive symptoms such as hallucinations in a subgroup of healthy subjects. In addition, interhemispheric gamma-band connectivity was found to be altered under ketamine compared to placebo, and subjects with AUA-AVD/AVH under ketamine showed significantly higher interhemispheric gamma-band connectivity than subjects without AUA-AVD/AVH. These findings demonstrate a relationship between NMDAR functioning, interhemispheric connectivity in the gamma-band frequency range between bilateral auditory cortices and the emergence of AVD/AVH in healthy subjects. The result is in accordance with the interhemispheric miscommunication hypothesis of AVH and argues for a possible role of glutamate in AVH in schizophrenia.

Die perkutane Dilatationstracheotomie (PDT) ist eine bei langzeitbeatmeten Intensivpatienten häufige Intervention, zur Erleichterung des Weanings. Bei der Bronchoskopie nimmt das Atemminutenvolumen (AMV) häufig ab, daraus resultiert die Zunahme des Kohlenstoffdioxidpartialdruckes und die Gefahr einer Azidose. Die Verwendung eines VivaSightTM-SL-Tubus (VST, ETView Ltd., Misgav, Israel) mit integrierter Kamera ermöglicht eine kontinuierliche Darstellung der Trachea. Es wird untersucht, ob die optische Kontrolle bei der PDT mittels VST durchführbar ist.

Percutaneous dilatational tracheostomy (PDT) in critically ill patients often involves bronchoscopic optical guidance. However, this procedure is not without disadvantages. Therefore, we aimed to study a recently introduced endotracheal tube-mounted camera (VivaSightTM-SL tube [VST]; ETView, Misgav, Israel) for guiding PDT.

BACKGROUND:Targeting the N-methyl-D-aspartate receptor (NMDAR) is a major translational approach for treating negative symptoms of schizophrenia. Ketamine comprehensively produces schizophrenia-like symptoms, such as positive, cognitive and negative symptoms in healthy volunteers. The amplitude of the mismatch negativity (MMN) is known to be significantly reduced not only in patients with schizophrenia, but also in healthy controls receiving ketamine. Accordingly, it was the aim of the present study to investigate whether changes of MMN amplitudes during ketamine administration are associated with the emergence of schizophrenia-like negative symptoms in healthy volunteers. METHODS:We examined the impact of ketamine during an MMN paradigm with 64-channel electroencephalography (EEG) and assessed the psychopathological status using the Positive and Negative Syndrome Scale (PANSS) in healthy male volunteers using a single-blind, randomized, placebo-controlled crossover design. Low-resolution brain electromagnetic tomography was used for source localization. RESULTS:Twenty-four men were included in our analysis. Significant reductions of MMN amplitudes and an increase in all PANSS scores were identified under the ketamine condition. Smaller MMN amplitudes were specifically associated with more pronounced negative symptoms. Source analysis of MMN generators indicated a significantly reduced current source density (CSD) under the ketamine condition in the primary auditory cortex, the posterior cingulate and the middle frontal gyrus. LIMITATIONS:The sample included only men within a tight age range of 20-32 years. CONCLUSION:The MMN might represent a biomarker for negative symptoms in schizophrenia related to an insufficient NMDAR system and could be used to identify patients with schizophrenia with negative symptoms due to NMDAR dysfunction.

In waking and sleeping states, thalamocortical system generates a variety of oscillations ranging from 0.1 Hz to hundreds of Hz. Most of them are present during NREM sleep, but slower activities prevail in this state of vigilance. Thalamocortical network is organized in a loop in which thalamocortical cells excite reticular thalamic and neocortical cells, reticular thalamic cells inhibit thalamocortical cells and corticothalamic cells excite thalamocortical and reticular thalamic cells. Despite stable anatomical connectivity, different types of oscillations preferentially originate either in neocortex or in thalamus. During sleep stage 2, spindle oscillation (9–15 Hz) is a dominant type of activity. It is well accepted that spindles originate in the thalamus via interplay of firing of reticular thalamic and thalamocortical neurons, but neocortex controls spindle generation. Spindles can be divided on fast and slow. Several properties of slow spindles do not match known mechanisms of their thalamic origin. Slow oscillation (about 1 Hz) dominates slow-wave sleep stage. Each slow wave is composed of hyperpolarized or silent and depolarized and active state. Active states may be accompanied by spindles and higher frequency activities. Slow waves originate mainly in deep cortical layers from which they propagate to more superficial layers and they also propagate horizontally. Full expression of slow wave activities requires the presence of thalamus, although slow oscillation can be recorded in athalamic preparations. Therefore, despite the fact of preferential origin of different sleep oscillations in either neocortex or in thalamus, only the full thalamocortical network can generate sleep activities with known properties. Support: CIHR and NSERC.

Background Percutaneous dilatational tracheostomy (PDT) in critically ill patients is often led by optical guidance with a bronchoscope. This is not without its disadvantages. Therefore, we aimed to study the feasibility of a recently introduced endotracheal tube‐mounted camera (VivaSight™‐SL, ET View, Misgav, Israel) in the guidance of PDT. Methods We studied 10 critically ill patients who received PDT with a VivaSight‐SL tube that was inserted prior to tracheostomy for optical guidance. Visualization of the tracheal structures (i.e., identification and monitoring of the thyroid, cricoid, and tracheal cartilage and the posterior wall) and the quality of ventilation (before puncture and during the tracheostomy) were rated on four‐point Likert scales. Respiratory variables were recorded, and blood gases were sampled before the interventions, before the puncture and before the insertion of the tracheal cannula. Results Visualization of the tracheal landmarks was rated as ‘very good’ or ‘good’ in all but one case. Monitoring during the puncture and dilatation was also rated as ‘very good’ or ‘good’ in all but one. In the cases that were rated ‘difficult’, the visualization and monitoring of the posterior wall of the trachea were the main concerns. No changes in the respiratory variables or blood gases occurred between the puncture and the insertion of the tracheal cannula. Conclusion Percutaneous dilatational tracheostomy with optical guidance from a tube‐mounted camera is feasible. Further studies comparing the camera tube with bronchoscopy as the standard approach should be performed.

Im Rahmen einer bronchoskopisch kontrollierten perkutanen Dilatationstracheotomie erlitt eine 71-jährige Patientin eine langstreckige gedeckte Perforation der Trachealhinterwand. Die Schädigung trat vermutlich durch stumpfes Trauma im Rahmen der Dilatation bzw. Kanüleninsertion auf und wurde möglicherweise durch eine exzessive Blockung des Cuffs weiter aufgespreizt. Da die Verletzung bis 0,5 cm vor die Hauptkarina reichte, ließ sich der Defekt nicht mit einem blockbaren Endotrachealtubus überbrücken. Wir entschieden uns dennoch für einen konservativen Behandlungsansatz mittels bronchoskopisch kontrollierter Platzierung des geblockten Trachealtubus direkt kranial des Defekts. Im Verlauf mehrerer Wochen kam es zu einer komplikationslosen Abheilung, die in regelmäßigen Abständen bronchoskopisch kontrolliert und dokumentiert wurde

Bariatric surgery has proven a successful approach in the treatment of morbid obesity and its concomitant diseases such as diabetes mellitus and arterial hypertension. Aiming for optimal management of this challenging patient cohort, tailored concepts directly guided by individual patient physiology may outperform standardized care. Implying esophageal pressure measurement and electrical impedance tomography—increasingly applied monitoring approaches to individually adjust mechanical ventilation in challenging circumstances like acute respiratory distress syndrome (ARDS) and intraabdominal hypertension—we compared our institutions standard ventilator regimen with an individually adjusted positive end expiratory pressure (PEEP) level aiming for a positive transpulmonary pressure (P L) throughout the respiratory cycle.

Esophageal pressure (Pes) is a surrogate for intrapleural pressure. Measuring Pes during mechanical ventilation allows for positive end-expiratory pressure adjustments by transpulmonary pressure (PL), which has been shown to improve oxygenation and outcome in acute respiratory distress syndrome patients. In morbidly obese patients, we saw progressively increasing PL measurements, although airway pressure (Paw), intra-abdominal pressure, and patient position did not change. On further examination, we determined that the gradual increases of PL were artifacts caused by a leak in the pressure probes, which resulted in underestimation of Pes and overestimation of PL as derived from the equation Paw - Pes = PL.