Effects of NMDA-receptor blockade by ketamine on mentalizing and its neural correlates in humans: a randomized control trial.

Schizophrenia is associated with various deficits in social cognition that remain relatively unaltered by antipsychotic treatment. While faulty glutamate signaling has been associated with general cognitive deficits as well as negative symptoms of schizophrenia, no direct link between manipulation of glutamate signaling and deficits in mentalizing has been demonstrated thus far. Here, we experimentally investigated whether ketamine, an uncompetitive N-methyl-D-aspartate receptor antagonist known to induce psychotomimetic effects, influences mentalizing and its neural correlates. In a randomized, placebo-controlled between-subjects experiment, we intravenously administered ketamine or placebo to healthy participants performing a video-based social cognition task during functional magnetic resonance imaging. Psychotomimetic effects of ketamine were assessed using the Positive and Negative Syndrome Scale. Compared to placebo, ketamine led to significantly more psychotic symptoms and reduced mentalizing performance (more "no mentalizing" errors). Ketamine also influenced blood oxygen level dependent (BOLD) response during mentalizing compared to placebo. Specifically, ketamine increased BOLD in right posterior superior temporal sulcus (pSTS) and increased connectivity between pSTS and anterior precuneus. These increases may reflect a dysfunctional shift of attention induced by ketamine that leads to mentalizing deficits. Our findings show that a psychotomimetic dose of ketamine impairs mentalizing and influences its neural correlates, a result compatible with the notion that deficient glutamate signaling may contribute to deficits in mentalizing in schizophrenia. The results also support efforts to seek novel psychopharmacological treatments for psychosis and schizophrenia targeting glutamatergic transmission.

Effects of Different Hemoglobin Levels on Near-Infrared Spectroscopy-Derived Cerebral Oxygen Saturation in Elderly Patients Undergoing Noncardiac Surgery.

Background: Near-infrared spectroscopy (NIRS) is a commonly used technique to evaluate tissue oxygenation and prevent harmful cerebral desaturation in the perioperative setting. The aims of the present study were to assess whether surgery-related anemia can be detected via NIRS of cerebral oxygen saturation and to investigate the effects of different perioperative transfusion strategies on cerebral oxygenation, potentially affecting transfusion decision-making. Study Design and Methods: Data from the ongoing multicenter LIBERAL-Trial (liberal transfusion strategy to prevent mortality and anemia-associated ischemic events in elderly noncardiac surgical patients, LIBERAL) were used. In this single-center sub-study, regional cerebral oxygenation saturation (rSO2) was evaluated by NIRS at baseline, pre-, and post-RBC transfusion. The obtained values were correlated with blood gas analysis-measured Hb concentrations. Results: rSO2 correlated with Hb decline during surgery (r = 0.35, p < 0.0001). Different RBC transfusion strategies impacted rSO2 such that higher Hb values resulted in higher rSO2. Cerebral desaturation occurred at lower Hb values more often. Discussion: Cerebral oxygenation monitoring using NIRS provides noninvasive rapid and continuous information regarding perioperative alterations in Hb concentration without the utilization of patients' blood for blood sampling. Further investigations are required to demonstrate if cerebral rSO2 may be included in future individualized transfusion decision strategies.

Digital Online Patient Informed Consent for Anesthesia before Elective Surgery-Recent Practice in Europe.

BACKGROUND: Digitalization in the health system is a topic that is rapidly gaining popularity, and not only because of the current pandemic. As in many areas of daily life, digitalization is becoming increasingly important in the medical field amid the exponential rise in the use of computers and smartphones. This opens up new possibilities for optimizing patient education in the context of anesthesia. The main aim of this study was to assess the implementation of remote consent in Europe. METHODS: An online survey entitled "Digital online Patient Informed Consent for Anesthesia before Elective Surgery. Recent practice in Europe," with a total of 27 questions, was sent by the European Society of Anesthesiology and Intensive Care (ESAIC) to their members in 47 European countries. To assess the effect of the economy on digitalization and legal status with regard to anesthesia consent, data were stratified based on gross domestic product per capita (GDPPC). RESULTS: In total, 23.1% and 37.2% of the 930 participants indicated that it was possible to obtain consent online or via telephone, respectively. This observation was more often reported in countries with high GDPPC levels than in countries with low GDPPC levels. Furthermore, 27.3% of the responses for simple anesthesia, 18.7% of the responses for complex anesthesia, and 32.2% of the responses for repeated anesthesia indicated that remote consent was in accordance with the law, and this was especially prevalent in countries with high GDPPC. Concerning the timing of consent, patients were informed at least one day before in 67.1% of cases for simple procedures and in 85.2% of cases for complex procedures. CONCLUSION: Even European countries with high GDPPC use remote informed consent only in a minority of cases, and most of the time for repeated anesthetic procedures. This might reflect the inconsistent legal situation and inhomogeneous medical technical structures across Europe.

Whole body irradiation with intensity-modulated helical tomotherapy prior to haematopoietic stem cell transplantation: analysis of organs at risk by dose and its effect on blood kinetics.

BACKGROUND: Intensity-modulated helical tomotherapy (HT) is a promising technique in preparation for bone marrow transplantation. Nevertheless, radiation-sensitive organs can be substantially compromised due to suboptimal delivery techniques of total body irradiation (TBI). To reduce the potential burden of radiation toxicity to organs at risk (OAR), high-quality coverage and homogeneity are essential. We investigated dosimetric data from kidney, lung and thorax, liver, and spleen in relation to peripheral blood kinetics. To further advance intensity-modulated total body irradiation (TBI), the potential for dose reduction to lung and kidney was considered in the analysis. PATIENTS AND METHODS: 46 patients undergoing TBI were included in this analysis, partially divided into dose groups (2, 4, 8, and 12 Gy). HT was performed using a rotating gantry to ensuring optimal reduction of radiation to the lungs and kidneys and to provide optimal coverage of other OAR. Common dosimetric parameters, such as D05, D95, and D50, were calculated and analysed. Leukocytes, neutrophils, platelets, creatinine, GFR, haemoglobin, overall survival, and graft-versus-host disease were related to the dosimetric evaluation using statistical tests. RESULTS: The mean D95 of the lung is 48.23%, less than half the prescribed and unreduced dose. The D95 of the chest is almost twice as high at 84.95%. Overall liver coverage values ranged from 96.79% for D95 to 107% for D05. The average dose sparing of all patients analysed resulted in an average D95 of 68.64% in the right kidney and 69.31% in the left kidney. Average D95 in the spleen was 94.28% and D05 was 107.05%. Homogeneity indexes ranged from 1.12 for liver to 2.28 for lung. The additional significance analyses conducted on these blood kinetics showed a significant difference between the 2 Gray group and the other three groups for leukocyte counts. Further statistical comparisons of the dose groups showed no significant differences. However, there were significant changes in the dose of OAR prescribed with dose sparing (e.g., lung vs. rib and kidney). CONCLUSION: Using intensity-modulated helical tomotherapy to deliver TBI is a feasible method in preparation for haematopoietic stem cell transplantation. Significant dose sparing in radiosensitive organs such as the lungs and kidneys is achievable with good overall quality of coverage. Peripheral blood kinetics support the positive impact of HT and its advantages strongly encourage its implementation within clinical routine.

Ketamine increases fronto-posterior functional connectivity during meta-perceptual confidence ratings.

Recent advances in the neuropsychopharmacology of metacognition indicate a constituent role of glutamate for the integrity of metamnestic processes. However, the extent to which previous results can be generalized across functional domains to characterize the relationship between glutamate and metacognition remains unclear. Here, in a randomized, double-blind, placebo-controlled, preregistered fMRI study, we tested the effects of a psychotomimetic dose (target plasma concentration 100 ng/mL) of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine on metacognition in a perceptual decision-making framework. We collected trial-by-trial metacognitive reports as participants performed a two-alternative forced-choice perceptual task during functional magnetic resonance imaging (fMRI). Results indicated ketamine-induced deterioration in metacognitive performance, whereas no significant effects were observed for perceptual performance, response times and - unexpectedly - metacognitive bias. Whilst there were no detectable ketamine effects on mean BOLD activation, exploratory psychophysiological interaction (PPI) analysis revealed alterations in functional connectivity during metacognitive confidence ratings under ketamine. Specifically, there was increased task-specific connectivity for ketamine compared to placebo between right anterior dorsolateral prefrontal cortex and left middle temporal, supramarginal and precentral gyrus, as well as between right insula/inferior frontal gyrus and left lingual gyrus, possibly indicating re-representations of object-level features supplied for metacognitive evaluations. Overall, these findings contribute towards the emerging picture of the substructures underlying metacognitive operations at the neurotransmitter level and may shed light on a neural pattern characteristic of pharmacologically challenged metacognition.

Effects of ketamine on brain function during metacognition of episodic memory.

Only little research has been conducted on the pharmacological underpinnings of metacognition. Here, we tested the modulatory effects of a single intravenous dose (100 ng/ml) of the N-methyl-D-aspartate-glutamate-receptor antagonist ketamine, a compound known to induce altered states of consciousness, on metacognition and its neural correlates. Fifty-three young, healthy adults completed two study phases of an episodic memory task involving both encoding and retrieval in a double-blind, placebo-controlled fMRI study. Trial-by-trial confidence ratings were collected during retrieval. Effects on the subjective state of consciousness were assessed using the 5D-ASC questionnaire. Confirming that the drug elicited a psychedelic state, there were effects of ketamine on all 5D-ASC scales. Acute ketamine administration during retrieval had deleterious effects on metacognitive sensitivity (meta-d') and led to larger metacognitive bias, with retrieval performance (d') and reaction times remaining unaffected. However, there was no ketamine effect on metacognitive efficiency (meta-d'/d'). Measures of the BOLD signal revealed that ketamine compared to placebo elicited higher activation of posterior cortical brain areas, including superior and inferior parietal lobe, calcarine gyrus, and lingual gyrus, albeit not specific to metacognitive confidence ratings. Ketamine administered during encoding did not significantly affect performance or brain activation. Overall, our findings suggest that ketamine impacts metacognition, leading to significantly larger metacognitive bias and deterioration of metacognitive sensitivity as well as unspecific activation increases in posterior hot zone areas of the neural correlates of consciousness.

Cognitive bias in professional hand hygiene and feedback: A national online-survey on overconfidence in Germany.

To evaluate learning motivation barriers in infection control and feedback competences, we conducted a national online survey in Germany. Among 767 healthcare workers, overconfidence effects could be detected independent from age, gender, profession, education, and hospital-size. The identified effects may impair learning motivation relevant for supervisors and educators in infection control.

Age-related differences of intraischemic gap junction uncoupling in hearts during ischemia.

OBJECTIVE: Myocardial ischemia leads to energetic, morphologic, metabolic, and functional alterations. To evaluate differences in ischemia tolerance between neonatal and adult hearts, we investigated gap junction uncoupling (GJU) and its correlation to myocardial intracellular edema formation during normothermic ischemia. METHODS: Hearts of landrace piglets (neonates, 7.4 ± 1.9 days of age, body weight 2.9 ± 0.5 kg, n = 5 and adults, 84 ± 9 days of age, body weight 30.5 ± 3.9 kg, n = 5) were investigated. After we harvested the hearts, the bioelectrical impedance spectra were measured continuously during normothermic global ischemia (35°C). Spectra of the dielectric permittivity, ε'(frequency), and conductivity, σ(frequency), were calculated from the impedance measurements, and GJU was identified in the sigmoidal time course of ε' (13 kHz). The extracellular volume was estimated by the ratio σ (100Hz)/σ (1MHz). Dielectric data were correlated with electron-microscopical images. RESULTS: Intraischemic GJU was observed in neonates after 54 ± 9 minutes of ischemia and thus significantly earlier than in adults (90 ± 7 minutes, P < .05). A more than 20% increase of intercalated water was found in tissue samples of neonates after 20 ± 2 minutes, in contrast to adults after 137 ± 8 minutes (P < .05). CONCLUSIONS: Intraischemic formation of edema and earlier GJU indicate faster intraischemic changes in neonates compared with adults. Intraischemic GJU and determination of intracellular water shifts are an experimental approach to establish the period of life-threatening damage. Because both parameters are linked and occur significantly earlier in neonates, they distinctly demonstrate the lower ischemia tolerance of neonatal hearts as both events interact.

Manually controlled total intravenous anesthesia augmented by electrophysiologic monitoring for complex stereotactic neurosurgical procedures.

Stereotactically guided procedures are performed for an ever extending range of conditions. They present a unique anesthetic challenge. In our institution, a standardized anesthetic protocol for total intravenous anesthesia (TIVA) augmented by electrophysiologic monitoring with BIS or AEP monitors was introduced. We conducted a retrospective study of 21 patients (ASA status 2-3) presenting for stereotactically guided procedures who were anesthetized according to the protocol. Median duration of anesthesia was 260 minutes (222 to 325 min); on average 3.0 (1.0 to 4.2) adjustments to the TIVA-protocol were made per patient. Highest and lowest mean arterial blood pressures in relation to baselines were 100% (87.5% to 109.8%) and 68.7% (64.0% to 72.6%), respectively. Likewise highest and lowest heart rates recorded were 106.7% (98.5% to 119.0%) and 75.0% (68.2% to 83.3%). After discontinuation of TIVA, spontaneous breathing returned after 5.0 minutes (4.0 to 8.0 min), extubation was possible after 6.0 minutes (5.0 to 10.0 min) and patients were ready for discharge to the ward after 15.0 minutes (12.0 to 18.0 min). There were no cases of postoperative nausea or vomiting. We found that manually controlled TIVA, augmented by electrophysiologic monitoring, facilitated maintenance of an appropriate depth of anesthesia with stable hemodynamics and excellent recovery times.

The continuous epidural infusion of ropivacaine 0.1% with 0.5 microg x mL(-1) sufentanil provides effective postoperative analgesia after total hip replacement: a pilot study.

PURPOSE: To assess the analgesic efficacy and functional outcome of postoperative epidural infusion of ropivacaine combined with sufentanil in a randomized, controlled trial. METHODS: Thirty-two ASA I-III patients undergoing elective total hip replacement (THR) were included. Lumbar epidural block using 0.75% ropivacaine was combined with either propofol sedation or general anesthesia for surgery. On arrival in the recovery room, the epidural infusion was commenced at a rate in mL calculated as follows: (height in cm - 100) x 0.1. Eleven patients received an epidural infusion of ropivacaine 0.1% with 0.5 microg x mL(-1) sufentanil (Group R+S0.5), ten patients ropivacaine 0.1% with 0.75 microg x mL(-1) sufentanil (Group R+S0.75), and 11 patients ropivacaine 0.1% with 1 microg x mL(-1) sufentanil (Group R+S1) over a postoperative study period of 44 hr. All patients had access to iv piritramide via a patient-controlled analgesia (PCA) device. Postel-Merle-d'Aubigné scoring system (PMA score) was assessed preoperatively, three weeks after surgery, and three months after surgery by an orthopedic surgeon blinded to study group. RESULTS: Motor block was negligible in all three groups. After eight hours of epidural infusion, sensory block had regressed completely in all patients. There was no significant difference with regard to visual analogue scale (VAS) scores (at rest: P = 0.55, on movement: P = 0.63), consumption of rescue medication (P = 0.99), patient satisfaction (P = 0.22), and the incidence of adverse events. All treatment regimens provided effective postoperative analgesia with only a minimal use of supplemental opioid PCA. There was no difference between groups regarding orthopedic PMA score (pain: P = 0.24, mobility: P = 0.65, and ability to walk: P = 0.44). CONCLUSION: Ropivacaine 0.1% with 0.5 microg x mL(-1) sufentanil for postoperative analgesia after THR provides efficient pain relief and, compared with 0.75 and 1 microg x mL(-1) sufentanil, reduces sufentanil consumption without compromise in patient satisfaction, VAS scores, and functional outcome.