Herzfrequenz-Variabilität unter postoperativer thorakaler Periduralanalgesie : Vergleich mit i.v. PCA

Herzfrequenzvariabilität ist der Betrag der Abweichung um die mittlere Herzfrequenz, die sogenannte Varianz der RR-Abstände. Sie wird als kardio-respiratorisches Kontrollsystem gesehen.97 Die Berechnung der Herzfrequenzvariabilität erlaubt es, die Aktivität des autonomen Nervensystems im Rahmen von physiologischen und patho-physiologischen Geschehnissen zu untersuchen und zu überwachen. Sie lässt sich mit nicht invasiver Untersuchungstechnik ableiten und kann das Gleichgewicht zwischen sympathischem und parasympathischem Einfluss auf das Herz beurteilen. Ein wichtiger Anwendungsbereich ist die Überwachung von Patienten nach Myokard-infarkt. Diese Patienten sind in der frühen Krankheitsphase stark gefährdet, einen plötzlichen Herztod zu erleiden. Ein sympathovagales Ungleichgewicht kann aber auch in der Herzfrequenzvariabilitätsanalyse von Patienten beobachtet werden, die an koronarer Herzkrankheit und arterieller Hypertonie leiden. Zu weiteren beein-flussenden Faktoren zählen Diabetes mellitus, neurologische Krankheiten, insbe-sondere Verletzungen des zentralen Nervensystems. Verschiedene Medikamente haben einen interagierenden Einfluss. Dieser Einfluss kann auch eine protektive Wirkung auf die Herzfrequenzvariabilität entfalten. Die Periduralanästhesie zeichnet sich durch die Ausschaltung von sympathisch afferenten und efferenten neuralen Übertragungsmechanismen aus. Damit integriert sie sich ins Konzept der balancierten Analgesie bei der Behandlung postoperativer Schmerzen. Entsprechend angewendet, werden thorakale Anteile des Sympathikus blockiert, die eine Efferenz zum Herz leiten. Das Ziel der Studie ist es, den Einfluss der postoperativen thorakalen Peridural-anästhesie (PDA) auf die Herzfrequenzvariabilität eingehender zu untersuchen und dem postoperativen Verlauf mit i.v. Patient controlled Analgesia (i.v. PCA) gegenüber zu stellen. Dazu werden drei Patientengruppen gebildet, die diese postoperativen Analgesiemethoden in Anspruch nehmen. Patienten nach elektiver Hüftprothesen-operation mit i.v. PCA, Patienten nach Nephrektomie mit thorakaler PDA oder i.v. PCA. Mit Hilfe der Regressionsanalyse werden die Verläufe der Herzfrequenz-variabilität im Vergleich prä- und postoperativ und innerhalb der Gruppen evaluiert. Die Risikosituation eines postoperativen O2-Sättigungsabfalls und die Zeit nach den Demands, den selbstausgelösten Bolusgaben im i.v. PCA System werden speziell herausgearbeitet. Die Verläufe der Powerspektren innerhalb der Patientengruppen und der Patienten-gruppen zu einander zeigen Unterschiede. Die Powerspektren der Patientengruppen Hüft-PCA und Neph-PDA mit systemischen und locoregionalen Analgesieverfahren zeigen in beiden postoperativen Nächten eine signifikante Abnahme im Low und High Bereich. Dabei fällt die Unterscheidung zwischen hüftoperierten und nephrektomierten Patienten nicht signifikant aus, wobei sich tendenzmässig nicht so sehr die postoperativen Analgesieverfahren, sondern die intraoperative Anwendung eines neuroaxialen Verfahrens als determinierender Faktor zeigt. Ein Grund dafür mögen die niedrig konzentrierten Lokalanästhetikalösungen sein. Das höhere Alter spielt einen wesentlichen Einfluss. Während postoperativer O2-Entsättigungsevents zeigen die Veränderungen in den Powerspektren im Vergleich zur ganzen Nacht sich ausgleichende Abweichungen im positiven und negativen Bereich. Das männliche Geschlecht hat einen dominanten Effekt. Die Zeitperiode nach den Demands bei i.v. PCA zeigt trotz signifikanten Änderungen der Powerspektren keine Unterschiede im Bereich Low/High Frequency. PCA-Boli reduzieren die Powerspektren und zeigen damit indirekt die günstige Wirkung einer postoperativen Analgesie. Die Patienten sind kardial akut nicht vorbelastet. Besondere klinische Risiko-situationen treten nicht auf. Durch die Powerspektrumanalyse kann eine zusätzliche klinisch unerkannte Risikosituation in unserem Kollektiv nicht beobachtet werden. Ob durch das postoperativ verminderte Powerspektrum eine verstärkte Gefährdung von Risikopatienten vorhergesagt werden kann, lässt sich anhand der hier erhobenen Daten nicht belegen. Die Anästhesieführung intraoperativ hat in dieser Studie keinen direkten Einfluss gezeigt.63 Die Wahl der postoperativen Analgesie richtet sich nach dem für den Operationsort und der Operationsart sowie der Lokalisation am Körper besten Verfahren

Feasibility of transesophageal phrenic nerve stimulation

Background Every year, more than 2.5 million critically ill patients in the ICU are dependent on mechanical ventilation. The positive pressure in the lungs generated by the ventilator keeps the diaphragm passive, which can lead to a loss of myofibers within a short time. To prevent ventilator-induced diaphragmatic dysfunction (VIDD), phrenic nerve stimulation may be used. Objective The goal of this study is to show the feasibility of transesophageal phrenic nerve stimulation (TEPNS). We hypothesize that selective phrenic nerve stimulation can efficiently activate the diaphragm with reduced co-stimulations. Methods An in vitro study in saline solution combined with anatomical findings was performed to investigate relevant stimulation parameters such as inter-electrode spacing, range to target site, or omnidirectional vs. sectioned electrodes. Subsequently, dedicated esophageal electrodes were inserted into a pig and single stimulation pulses were delivered simultaneously with mechanical ventilation. Various stimulation sites and response parameters such as transdiaphragmatic pressure or airway flow were analyzed to establish an appropriate stimulation setting. Results Phrenic nerve stimulation with esophageal electrodes has been demonstrated. With a current amplitude of 40 mA, similar response figures of the diaphragm activation as compared to conventional stimulation with needle electrodes at 10mA were observed. Directed electrodes best aligned with the phrenic nerve resulted in up to 16.9 % higher amplitude at the target site in vitro and up to 6 cmH20 higher transdiaphragmatic pressure in vivo as compared to omnidirectional electrodes. The activation efficiency was more sensitive to the stimulation level inside the esophagus than to the inter-electrode spacing. Most effective and selective stimulation was achieved at the level of rib 1 using sectioned electrodes 40 mm apart. Conclusion Directed transesophageal phrenic nerve stimulation with single stimuli enabled diaphragm activation. In the future, this method might keep the diaphragm active during, and even support, artificial ventilation. Meanwhile, dedicated sectioned electrodes could be integrated into gastric feeding tubes

Intravascular stenting for stenosis of aortocoronary venous bypass grafts

AbstractTo test the ability of endoluminal stents to prevent saphenous vein graft restenosis after balloon angioplasty, 13 patients with angina and previous coronary bypass surgery underwent implantation of one or more stents into 14 stenosed grafts. Implantation was technically successful in all cases and there were no major in-hospital complications. During a median follow-up interval of 7 months (range 2 to 26), 10 patients (77%) underwent follow-up angiography. Seven patients remained asymptomatic or in improved condition without further intervention; three patients had further angioplasty with stent implantation for a new stenosis in the same graft. Two patients (20%) developed within-stent restenosis. There was one death from progressive congestive heart failure 7 months after implantation. No patient had a myocardial infarction or needed surgical revascularization during the follow-up period.In selected cases, stent implantation appears to be a promising new technique that may decrease the incidence of restenosis after balloon angioplasty in venous bypass grafts. The rate of complications is low. Further experience and longer follow-up will be needed before definite recommendations can be made about its use

Ice nucleation efficiency of natural dust samples in the immersion mode

A total of 12 natural surface dust samples, which were surface-collected on four continents, most of them in dust source regions, were investigated with respect to their ice nucleation activity. Dust collection sites were distributed across Africa, South America, the Middle East, and Antarctica. Mineralogical composition has been determined by means of X-ray diffraction. All samples proved to be mixtures of minerals, with major contributions from quartz, calcite, clay minerals, K-feldspars, and (Na, Ca)-feldspars. Reference samples of these minerals were investigated with the same methods as the natural dust samples. Furthermore, Arizona test dust (ATD) was re-evaluated as a benchmark. Immersion freezing of emulsion and bulk samples was investigated by differential scanning calorimetry. For emulsion measurements, water droplets with a size distribution peaking at about 2 µm, containing different amounts of dust between 0.5 and 50 wt % were cooled until all droplets were frozen. These measurements characterize the average freezing behaviour of particles, as they are sensitive to the average active sites present in a dust sample. In addition, bulk measurements were conducted with one single 2 mg droplet consisting of a 5 wt % aqueous suspension of the dusts/minerals. These measurements allow the investigation of the best ice-nucleating particles/sites available in a dust sample. All natural dusts, except for the Antarctica and ATD samples, froze in a remarkably narrow temperature range with the heterogeneously frozen fraction reaching 10 % between 244 and 250 K, 25 % between 242 and 246 K, and 50 % between 239 and 244 K. Bulk freezing occurred between 255 and 265 K. In contrast to the natural dusts, the reference minerals revealed ice nucleation temperatures with 2–3 times larger scatter. Calcite, dolomite, dolostone, and muscovite can be considered ice nucleation inactive. For microcline samples, a 50 % heterogeneously frozen fraction occurred above 245 K for all tested suspension concentrations, and a microcline mineral showed bulk freezing temperatures even above 270 K. This makes microcline (KAlSi3O8) an exceptionally good ice-nucleating mineral, superior to all other analysed K-feldspars, (Na, Ca)-feldspars, and the clay minerals. In summary, the mineralogical composition can explain the observed freezing behaviour of 5 of the investigated 12 natural dust samples, and partly for 6 samples, leaving the freezing efficiency of only 1 sample not easily explained in terms of its mineral reference components. While this suggests that mineralogical composition is a major determinant of ice-nucleating ability, in practice, most natural samples consist of a mixture of minerals, and this mixture seems to lead to remarkably similar ice nucleation abilities, regardless of their exact composition, so that global models, in a first approximation, may represent mineral dust as a single species with respect to ice nucleation activity. However, more sophisticated representations of ice nucleation by mineral dusts should rely on the mineralogical composition based on a source scheme of dust emissions

Feasibility of transesophageal phrenic nerve stimulation.

BACKGROUND Every year, more than 2.5 million critically ill patients in the ICU are dependent on mechanical ventilation. The positive pressure in the lungs generated by the ventilator keeps the diaphragm passive, which can lead to a loss of myofibers within a short time. To prevent ventilator-induced diaphragmatic dysfunction (VIDD), phrenic nerve stimulation may be used. OBJECTIVE The goal of this study is to show the feasibility of transesophageal phrenic nerve stimulation (TEPNS). We hypothesize that selective phrenic nerve stimulation can efficiently activate the diaphragm with reduced co-stimulations. METHODS An in vitro study in saline solution combined with anatomical findings was performed to investigate relevant stimulation parameters such as inter-electrode spacing, range to target site, or omnidirectional vs. sectioned electrodes. Subsequently, dedicated esophageal electrodes were inserted into a pig and single stimulation pulses were delivered simultaneously with mechanical ventilation. Various stimulation sites and response parameters such as transdiaphragmatic pressure or airway flow were analyzed to establish an appropriate stimulation setting. RESULTS Phrenic nerve stimulation with esophageal electrodes has been demonstrated. With a current amplitude of 40 mA, similar response figures of the diaphragm activation as compared to conventional stimulation with needle electrodes at 10mA were observed. Directed electrodes best aligned with the phrenic nerve resulted in up to 16.9 % higher amplitude at the target site in vitro and up to 6 cmH20 higher transdiaphragmatic pressure in vivo as compared to omnidirectional electrodes. The activation efficiency was more sensitive to the stimulation level inside the esophagus than to the inter-electrode spacing. Most effective and selective stimulation was achieved at the level of rib 1 using sectioned electrodes 40 mm apart. CONCLUSION Directed transesophageal phrenic nerve stimulation with single stimuli enabled diaphragm activation. In the future, this method might keep the diaphragm active during, and even support, artificial ventilation. Meanwhile, dedicated sectioned electrodes could be integrated into gastric feeding tubes

The Reversal Curse: LLMs trained on "A is B" fail to learn "B is A"

We expose a surprising failure of generalization in auto-regressive large language models (LLMs). If a model is trained on a sentence of the form "A is B", it will not automatically generalize to the reverse direction "B is A". This is the Reversal Curse. For instance, if a model is trained on "Olaf Scholz was the ninth Chancellor of Germany", it will not automatically be able to answer the question, "Who was the ninth Chancellor of Germany?". Moreover, the likelihood of the correct answer ("Olaf Scholz") will not be higher than for a random name. Thus, models exhibit a basic failure of logical deduction and do not generalize a prevalent pattern in their training set (i.e. if "A is B'' occurs, "B is A" is more likely to occur). We provide evidence for the Reversal Curse by finetuning GPT-3 and Llama-1 on fictitious statements such as "Uriah Hawthorne is the composer of 'Abyssal Melodies'" and showing that they fail to correctly answer "Who composed 'Abyssal Melodies?'". The Reversal Curse is robust across model sizes and model families and is not alleviated by data augmentation. We also evaluate ChatGPT (GPT-3.5 and GPT-4) on questions about real-world celebrities, such as "Who is Tom Cruise's mother? [A: Mary Lee Pfeiffer]" and the reverse "Who is Mary Lee Pfeiffer's son?". GPT-4 correctly answers questions like the former 79% of the time, compared to 33% for the latter. This shows a failure of logical deduction that we hypothesize is caused by the Reversal Curse. Code is available at https://github.com/lukasberglund/reversal_curse.Comment: 18 pages, 10 figure

Taken out of context: On measuring situational awareness in LLMs

We aim to better understand the emergence of `situational awareness' in large language models (LLMs). A model is situationally aware if it's aware that it's a model and can recognize whether it's currently in testing or deployment. Today's LLMs are tested for safety and alignment before they are deployed. An LLM could exploit situational awareness to achieve a high score on safety tests, while taking harmful actions after deployment. Situational awareness may emerge unexpectedly as a byproduct of model scaling. One way to better foresee this emergence is to run scaling experiments on abilities necessary for situational awareness. As such an ability, we propose `out-of-context reasoning' (in contrast to in-context learning). We study out-of-context reasoning experimentally. First, we finetune an LLM on a description of a test while providing no examples or demonstrations. At test time, we assess whether the model can pass the test. To our surprise, we find that LLMs succeed on this out-of-context reasoning task. Their success is sensitive to the training setup and only works when we apply data augmentation. For both GPT-3 and LLaMA-1, performance improves with model size. These findings offer a foundation for further empirical study, towards predicting and potentially controlling the emergence of situational awareness in LLMs. Code is available at: https://github.com/AsaCooperStickland/situational-awareness-evals

Post-hoc motion correction for coronary computed tomography angiography without additional radiation dose - Improved image quality and interpretability for “free”

Objective To evaluate the impact of a motion-correction (MC) algorithm, applicable post-hoc and not dependent on extended padding, on the image quality and interpretability of coronary computed tomography angiography (CCTA). Methods Ninety consecutive patients undergoing CCTA on a latest-generation 256-slice CT device were prospectively included. CCTA was performed with prospective electrocardiogram-triggering and the shortest possible acquisition window (without padding) at 75% of the R-R-interval. All datasets were reconstructed without and with MC of the coronaries. The latter exploits the minimal padding inherent in cardiac CT scans with this device due to data acquisition also during the short time interval needed for the tube to reach target currents and voltage (“free” multiphase). Two blinded readers independently assessed image quality on a 4-point Likert scale for all segments. Results A total of 1,030 coronary segments were evaluated. Application of MC both with automatic and manual coronary centerline tracking resulted in a significant improvement in image quality as compared to the standard reconstruction without MC (mean Likert score 3.67 [3.50;3.81] vs 3.58 [3.40;3.73], P = 0.005, and 3.7 [3.55;3.82] vs 3.58 [3.40;3.73], P < 0.001, respectively). Furthermore, MC significantly reduced the proportion of non-evaluable segments and patients with at least one non-evaluable coronary segment from 2% to as low as 0.3%, and from 14% to as low as 3%. Reduction of motion artifacts was predominantly observed in the right coronary artery. Conclusions A post-hoc device-specific MC algorithm improves image quality and interpretability of prospectively electrocardiogram-triggered CCTA and reduces the proportion of non-evaluable scans without any additional radiation dose exposure

European Expert Opinion on ANT-DBS therapy for patients with drug-resistant epilepsy (a Delphi consensus)

Introduction: Although deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) represents an established third-line therapy for patients with drug-resistant focal epilepsy, guiding reports on practical treatment principles remain scarce. Methods: An Expert Panel (EP) of 10 European neurologists and 4 neurosurgeons was assembled to share their experience with ANT-DBS therapy. The process included a review of the current literature, which served as a basis for an online survey completed by the EP prior to and following a face-to-face meeting (Delphi method). An agreement level of >= 71 % was considered as consensus. Results: Out of 86 reviewed studies, 46 (53 %) were selected to extract information on the most reported criteria for patient selection, management, and outcome. The Delphi process yielded EP consensus on 4 parameters for selection of good candidates and patient management as well as 7 reasons of concern for this therapy. Since it was not possible to give strict device programming advice due to low levels of evidence, the experts shared their clinical practice: all of them start with monopolar stimulation, 79 % using the cycling mode. Most (93 %) EP members set the initial stimulation frequency and pulse width according to the SANTE parameters, while there is more variability in the amplitudes used. Further agreement was achieved on a list of 7 patient outcome parameters to be monitored during the follow-up. Conclusions: Although current evidence is too low for definite practical guidelines, this EP report could support the selection and management of patients with ANT-DBS