Ultrafast Exciton Dynamics in the Atomically Thin van der Waals Magnet CrSBr.

Among atomically thin semiconductors, CrSBr stands out as both its bulk and monolayer forms host tightly bound, quasi-one-dimensional excitons in a magnetic environment. Despite its pivotal importance for solid-state research, the exciton lifetime has remained unknown. While terahertz polarization probing can directly trace all excitons, independently of interband selection rules, the corresponding large far-field foci substantially exceed the lateral sample dimensions. Here, we combine terahertz polarization spectroscopy with near-field microscopy to reveal a femtosecond decay of paramagnetic excitons in a monolayer of CrSBr, which is 30 times shorter than the bulk lifetime. We unveil low-energy fingerprints of bound and unbound electron-hole pairs in bulk CrSBr and extract the nonequilibrium dielectric function of the monolayer in a model-free manner. Our results demonstrate the first direct access to the ultrafast dielectric response of quasi-one-dimensional excitons in CrSBr, potentially advancing the development of quantum devices based on ultrathin van der Waals magnets.

Apnoeic oxygenation during paediatric tracheal intubation: a systematic review and meta-analysis.

BACKGROUND: Supplemental oxygen administration by apnoeic oxygenation during laryngoscopy for tracheal intubation is intended to prolong safe apnoea time, reduce the risk of hypoxaemia, and increase the success rate of first-attempt tracheal intubation under general anaesthesia. This systematic review examined the efficacy and effectiveness of apnoeic oxygenation during tracheal intubation in children. METHODS: This systematic review and meta-analysis included randomised controlled trials and non-randomised studies in paediatric patients requiring tracheal intubation, evaluating apnoeic oxygenation by any method compared with patients without apnoeic oxygenation. Searched databases were MEDLINE, Embase, Cochrane Library, CINAHL, ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), Scopus, and Web of Science from inception to March 22, 2023. Data extraction and risk of bias assessment followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) recommendation. RESULTS: After initial selection of 40 708 articles, 15 studies summarising 9802 children were included (10 randomised controlled trials, four pre-post studies, one prospective observational study) published between 1988 and 2023. Eight randomised controlled trials were included for meta-analysis (n=1070 children; 803 from operating theatres, 267 from neonatal intensive care units). Apnoeic oxygenation increased intubation first-pass success with no physiological instability (risk ratio [RR] 1.27, 95% confidence interval [CI] 1.03-1.57, P=0.04, I2=0), higher oxygen saturation during intubation (mean difference 3.6%, 95% CI 0.8-6.5%, P=0.02, I2=63%), and decreased incidence of hypoxaemia (RR 0.24, 95% CI 0.17-0.33, P<0.01, I2=51%) compared with no supplementary oxygen administration. CONCLUSION: This systematic review with meta-analysis confirms that apnoeic oxygenation during tracheal intubation of children significantly increases first-pass intubation success rate. Furthermore, apnoeic oxygenation enables stable physiological conditions by maintaining oxygen saturation within the normal range. CLINICAL TRIAL REGISTRATION: Protocol registered prospectively on PROSPERO (registration number: CRD42022369000) on December 2, 2022.

Decision Curve Analysis of In-Hospital Mortality Prediction Models: The Relative Value of Pre- and Intraoperative Data For Decision-Making.

BACKGROUND: Clinical prediction modeling plays a pivotal part in modern clinical care, particularly in predicting the risk of in-hospital mortality. Recent modeling efforts have focused on leveraging intraoperative data sources to improve model performance. However, the individual and collective benefit of pre- and intraoperative data for clinical decision-making remains unknown. We hypothesized that pre- and intraoperative predictors contribute equally to the net benefit in a decision curve analysis (DCA) of in-hospital mortality prediction models that include pre- and intraoperative predictors. METHODS: Data from the VitalDB database featuring a subcohort of 6043 patients were used. A total of 141 predictors for in-hospital mortality were grouped into preoperative (demographics, intervention characteristics, and laboratory measurements) and intraoperative (laboratory and monitor data, drugs, and fluids) data. Prediction models using either preoperative, intraoperative, or all data were developed with multiple methods (logistic regression, neural network, random forest, gradient boosting machine, and a stacked learner). Predictive performance was evaluated by the area under the receiver-operating characteristic curve (AUROC) and under the precision-recall curve (AUPRC). Clinical utility was examined with a DCA in the predefined risk preference range (denoted by so-called treatment threshold probabilities) between 0% and 20%. RESULTS: AUROC performance of the prediction models ranged from 0.53 to 0.78. AUPRC values ranged from 0.02 to 0.25 (compared to the incidence of 0.09 in our dataset) and high AUPRC values resulted from prediction models based on preoperative laboratory values. A DCA of pre- and intraoperative prediction models highlighted that preoperative data provide the largest overall benefit for decision-making, whereas intraoperative values provide only limited benefit for decision-making compared to preoperative data. While preoperative demographics, comorbidities, and surgery-related data provide the largest benefit for low treatment thresholds up to 5% to 10%, preoperative laboratory measurements become the dominant source for decision support for higher thresholds. CONCLUSIONS: When it comes to predicting in-hospital mortality and subsequent decision-making, preoperative demographics, comorbidities, and surgery-related data provide the largest benefit for clinicians with risk-averse preferences, whereas preoperative laboratory values provide the largest benefit for decision-makers with more moderate risk preferences. Our decision-analytic investigation of different predictor categories moves beyond the question of whether certain predictors provide a benefit in traditional performance metrics (eg, AUROC). It offers a nuanced perspective on for whom these predictors might be beneficial in clinical decision-making. Follow-up studies requiring larger datasets and dedicated deep-learning models to handle continuous intraoperative data are essential to examine the robustness of our results.

In Vitro Investigation of Insulin Dynamics During 4 Hours of Simulated Cardiopulmonary Bypass.

BACKGROUND: Hyperglycemia is common in patients undergoing cardiovascular surgery with cardiopulmonary bypass. We hypothesize that intraoperative hyperglycemia may be, at least partially, attributable to insulin loss due to adhesion on artificial surfaces and/or degradation by hemolysis. Thus, our primary aim was to investigate the loss of insulin in 2 different isolated extracorporeal circulation circuits (ECCs), that is, a conventional ECC (cECC) with a roller pump, and a mini-ECC (MiECC) system with a centrifugal pump. The secondary aim was to assess and compare the relationship between changes in insulin concentration and the degree of hemolysis in our 2 ECC models. METHODS: Six cECC and 6 MiECC systems were primed with red packed blood cells and thawed fresh-frozen plasma (1:1). Four additional experiments were performed in cECC using only thawed fresh-frozen plasma. Human insulin (Actrapid) was added, targeting a plasma insulin concentration of 400 mU/L. Insulin concentration and hemolysis index were measured at baseline and hourly thereafter. The end points were the change in insulin level after 4 hours compared to baseline and hemolysis index after 4 hours. The insulin concentration and hemolysis index were analyzed by means of a saturated linear mixed-effect regression model with a random offset for each experiment to account for the repeated measure design of the study, resulting in mean estimates and 95% confidence intervals (CIs) of the primary end points as well as of pairwise contrasts with respect to ECC type. RESULTS: Insulin concentration decreased by 63% (95% CI, 48%-77%) in the MiECC and 92% (95% CI, 77%-106%) in the cECC system that contained red blood cells. Insulin loss was significantly higher in the cECC system compared to the MiECC (P = .022). In the cECC with only plasma, insulin did not significantly decrease (-4%; 95% CI, -21% to 14%). Hemolysis index in MiECC increased from 68 (95% CI, 46-91) to 76 (95% CI, 54-98) after 4 hours, in cECC from 81 (95% CI, 59-103) to 121 (95% CI, 99-143). Hemolysis index and percent change of insulin showed an excellent relationship (r = -0.99, P < .01). CONCLUSIONS: Our data showed that insulin levels substantially decreased during 4 hours of simulated cardiopulmonary bypass only in the ECC that contained hemoglobin. The decrease was more pronounced in the cECC, which also exhibited a greater degree of hemolysis. Our results suggest that insulin degradation by hemolysis products may be a stronger contributor to insulin loss than adhesion of insulin molecules to circuit surfaces.

Emergency front-of-neck access in infants: A pragmatic crossover randomized control trial comparing two approaches on a simulated rabbit model.

BACKGROUND: Rapid-sequence tracheotomy and scalpel-bougie tracheotomy are two published approaches for establishing emergency front-of-neck access in infants. It is unknown whether there is a difference in performance times and success rates between the two approaches. AIMS: The aim of this cross-over randomized control trial study was to investigate whether the two approaches were equivalent for establishing tracheal access in rabbit cadavers. The underlying hypothesis was that the time to achieve the tracheal access is the same with both techniques. METHODS: Between May and September 2022, thirty physicians (pediatric anesthesiologists and intensivists) were randomized to perform front-of-neck access using one and then the other technique: rapid-sequence tracheotomy and scalpel-bougie tracheotomy. After watching training videos, each technique was practiced four times followed by a final tracheotomy during which study measurements were obtained. Based on existing data, an equivalence margin was set at ∆ = ±10 s for the duration of the procedure. The primary outcome was defined as the duration until tracheal tube placement was achieved successfully. Secondary outcomes included success rate, structural injuries, and subjective participant self-evaluation. RESULTS: The median duration of the scalpel-bougie tracheotomy was 48 s (95% CI: 37-57), while the duration of the rapid-sequence tracheotomy was 59 s (95% CI: 49-66, p = .07). The difference in the median duration between the two approaches was 11 s (95% CI: -4.9 to 29). The overall success rate was 93.3% (95% CI: 83.8%-98.2%). The scalpel-bougie tracheotomy resulted in significantly fewer damaged tracheal rings and was preferred among participants. CONCLUSIONS: The scalpel-bougie tracheotomy was slightly faster than the rapid-sequence tracheotomy and favored by participants, with fewer tracheal injuries. Therefore, we propose the scalpel-bougie tracheostomy as a rescue approach favoring the similarity to the adult approach for small children. The use of a comparable equipment kit for both children and adults facilitates standardization, performance, and logistics. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05499273.

Structural basis for selective AMPylation of Rac-subfamily GTPases by Bartonella effector protein 1 (Bep1).

Small GTPases of the Ras-homology (Rho) family are conserved molecular switches that control fundamental cellular activities in eukaryotic cells. As such, they are targeted by numerous bacterial toxins and effector proteins, which have been intensively investigated regarding their biochemical activities and discrete target spectra; however, the molecular mechanism of target selectivity has remained largely elusive. Here we report a bacterial effector protein that selectively targets members of the Rac subfamily in the Rho family of small GTPases but none in the closely related Cdc42 or RhoA subfamilies. This exquisite target selectivity of the FIC domain AMP-transferase Bep1 from Bartonella rochalimae is based on electrostatic interactions with a subfamily-specific pair of residues in the nucleotide-binding G4 motif and the Rho insert helix. Residue substitutions at the identified positions in Cdc42 enable modification by Bep1, while corresponding Cdc42-like substitutions in Rac1 greatly diminish modification. Our study establishes a structural understanding of target selectivity toward Rac-subfamily GTPases and provides a highly selective tool for their functional analysis.

Flow cytometry-based high-throughput RNAi screening for miRNAs regulating MHC class II HLA-DR surface expression.

HLA-DR isotype is a MHC-II cell-surface receptor found on APCs and plays a key role in initiating immune responses. In severely immunocompromised patients with conditions like sepsis, the number of HLA-DR molecules expressed on leukocytes is considered to correlate with infectious complications and patients' probability of survival. The underlying regulatory mechanisms of HLA-DR expression remain largely unknown. One probable path to regulation is through microRNAs (miRNAs), which have been implicated as regulatory elements of both innate and adaptive immune system development and function. In our study, flow cytometry-based high-throughput miRNA screening was performed in a stable HLA-DR-expressing human melanoma cell line, MelJuSo, for either up- or downregulating miRNAs of the surface HLA-DR expression. By the end of the screening, the top ten upregulators and top five downregulators were identified, and both the HLA-DR protein and mRNA regulations were further verified and validated. In-silico approaches were applied for functional miRNA-mRNA interaction prediction. The potential underlying gene regulations of different miRNAs were proposed. Our results promote the study of miRNA-mediated HLA-DR regulation under both physiological and pathological conditions, and may pave the way for potential clinical applications.

Risk patterns of consecutive adverse events in airway management: a Bayesian network analysis.

BACKGROUND: Minor adverse airway events play a pivotal role in the safety of airway management. Changes in airway management strategies can reduce such events, but the broader impact on airway management remains unclear. METHODS: Minor, frequently occurring adverse airway events were audited before and after implementation of changes to airway management strategies. We used two Bayesian networks to examine conditional probabilities of subsequent airway events and to compute the likelihood of certain events given that certain previous events occurred. RESULTS: Independent of sex, age, and American Society of Anesthesiologists physical status, targeted changes to airway management strategies reduced the risk of a first event. Obese patients were an exception, in whom no risk reduction was achieved. Frequently occurring event sequences were identified, for example the most likely event to follow difficult bag-mask ventilation was a Cormack-Lehane grade ≥3, with a risk of 14.3% (95% credible interval [CI], 11.4-17.2%). An impact of the targeted changes was detected on the likelihood of some event sequences, for example the likelihood of no consecutive event after a tracheal tube-related event increased from 43.3% (95% CI, 39.4-47.6%) to 56.4% (95% CI, 52.0-60.5%). CONCLUSIONS: Identification of risk patterns and typical structures of event sequences provides a clinically relevant perspective on airway incidents. It further provides a means to quantify the impact of targeted airway management changes. These targeted changes can influence some event sequences, but overall, the benefit results from the cumulative effect of improvements in multiple events. Targeted airway management changes with knowledge of risk patterns and event sequences can potentially further improve patient safety in airway management. CLINICAL TRIAL REGISTRATION: NCT02743767.

A Pilot Investigation Evaluating Relative Changes in Fronto-Occipital Alpha and Beta Spectral Power as Measurement of Anesthesia Hypnotic Depth.

BACKGROUND: Other than clinical observation of a patient's vegetative response to nociception, monitoring the hypnotic component of general anesthesia (GA) and unconsciousness relies on electroencephalography (EEG)-based indices. These indices exclusively based on frontal EEG activity neglect an important observation. One of the main hallmarks of transitions from wakefulness to GA is a shift in alpha oscillations (7.5-12.5 Hz activity) from occipital brain regions toward anterior brain regions ("alpha anteriorization"). Monitoring the degree of this alpha anteriorization may help to guide induction and maintenance of hypnotic depth and prevent intraoperative awareness. However, the occipital region of the brain is completely disregarded and occipital alpha as characteristic of wakefulness and its posterior-to-anterior shift during induction are missed. Here, we propose an application of Narcotrend's reduced power alpha beta (RPAB) index, originally developed to monitor differences in hemispheric perfusion, for determining the ratio of alpha and beta activity in the anterior-posterior axis. METHODS: Perioperative EEG data of 32 patients undergoing GA in the ophthalmic surgery department of Bern University Hospital were retrospectively analyzed. EEG was recorded with the Narcotrend® monitor using a frontal (Fp1-Fp2) and a posterior (T9-Oz) bipolar derivation with reference electrode over A2. The RPAB index was computed between both bipolar signals, defining the fronto-occipital RPAB (FO-RPAB). FO-RPAB was analyzed during wakefulness, GA maintenance, and emergence, as well as before and after the intraoperative administration of a ketamine bolus. FO-RPAB was compared with a classical quantitative EEG measure-the spectral edge frequency 95% (SEF-95). RESULTS: A significant shift of the FO-RPAB was observed during both induction of and emergence from GA ( P < .001). Interestingly, the additional administration of ketamine during GA did not lead to a significant change in FO-RPAB ( P = 0.81). In contrast, a significant increase in the SEF-95 in the frontal channel was observed during the 10-minute period after ketamine administration ( P < .001). CONCLUSIONS: FO-RPAB appears to qualify as a marker of unconsciousness, reflecting physiological fronto-occipital activity differences during GA. In contrast to frontal SEF-95, it is not disturbed by additional administration of ketamine for analgesia.

Relevance of spirituality and perceived social support to mental health of people with pre-existing mental health disorders during the COVID-19 pandemic: a longitudinal investigation.

BACKGROUND: The COVID-19 pandemic and related measures have negatively impacted mental health worldwide. The main objective of the present longitudinal study was to investigate mental health in people living in Tyrol (Austria) and South Tyrol (Italy) during the COVID-19 pandemic and to report the prevalence of psychological distress among individuals with versus those without pre-existing mental health disorders (MHD) in the long-term (summer 2020-winter 2022). Here, we specifically focus on the relevance of spirituality and perceived social support in this regard. METHODS: 161 individuals who had been diagnosed with MHD and 446 reference subjects participated in this online survey. Electronic data capture was conducted using the Computer-based Health Evaluation System and included both sociodemographic and clinical aspects as well as standardized questionnaires on psychological distress, spirituality, and the perception of social support. RESULTS: The prevalence of psychological distress was significantly higher in individuals with MHD (36.6% vs. 12.3%) and remained unchanged among both groups over time. At baseline, the perception of social support was significantly higher in healthy control subjects, whereas the two groups were comparable in regards of the subjective relevance of faith. Reference subjects indicated significantly higher spiritual well-being in terms of the sense of meaning in life and peacefulness, which mediated in large part the between-group difference of psychological distress at follow-up. Notably, both faith and the perception of social support did not prove to be relevant in this context. CONCLUSIONS: These findings point to a consistently high prevalence of psychological distress among people suffering from MHD and underscore the prominent role of meaning in life and peacefulness as a protective factor in times of crisis. Therapeutic strategies that specifically target spirituality may have a beneficial impact on mental health.

Decision curve analysis confirms higher clinical utility of multi-domain versus single-domain prediction models in patients with open abdomen treatment for peritonitis.

BACKGROUND: Prediction modelling increasingly becomes an important risk assessment tool in perioperative systems approaches, e.g. in complex patients with open abdomen treatment for peritonitis. In this population, combining predictors from multiple medical domains (i.e. demographical, physiological and surgical variables) outperforms the prediction capabilities of single-domain prediction models. However, the benefit of these prediction models for clinical decision-making remains to be investigated. We therefore examined the clinical utility of mortality prediction models in patients suffering from peritonitis with a decision curve analysis. METHODS: In this secondary analysis of a large dataset, a traditional logistic regression approach, three machine learning methods and a stacked ensemble were employed to examine the predictive capability of demographic, physiological and surgical variables in predicting mortality under open abdomen treatment for peritonitis. Calibration was examined with calibration belts and predictive performance was assessed with the area both under the receiver operating characteristic curve (AUROC) and under the precision recall curve (AUPRC) and with the Brier Score. Clinical utility of the prediction models was examined by means of a decision curve analysis (DCA) within a treatment threshold range of interest of 0-30%, where threshold probabilities are traditionally defined as the minimum probability of disease at which further intervention would be warranted. RESULTS: Machine learning methods supported available evidence of a higher prediction performance of a multi- versus single-domain prediction models. Interestingly, their prediction performance was similar to a logistic regression model. The DCA demonstrated that the overall net benefit is largest for a multi-domain prediction model and that this benefit is larger compared to the default "treat all" strategy only for treatment threshold probabilities above about 10%. Importantly, the net benefit for low threshold probabilities is dominated by physiological predictors: surgical and demographics predictors provide only secondary decision-analytic benefit. CONCLUSIONS: DCA provides a valuable tool to compare single-domain and multi-domain prediction models and demonstrates overall higher decision-analytic value of the latter. Importantly, DCA provides a means to clinically differentiate the risks associated with each of these domains in more depth than with traditional performance metrics and highlighted the importance of physiological predictors for conservative intervention strategies for low treatment thresholds. Further, machine learning methods did not add significant benefit either in prediction performance or decision-analytic utility compared to logistic regression in these data.

Ultrafast Nanoscopy of High-Density Exciton Phases in WSe2.

The density-driven transition of an exciton gas into an electron-hole plasma remains a compelling question in condensed matter physics. In two-dimensional transition metal dichalcogenides, strongly bound excitons can undergo this phase change after transient injection of electron-hole pairs. Unfortunately, unavoidable nanoscale inhomogeneity in these materials has impeded quantitative investigation into this elusive transition. Here, we demonstrate how ultrafast polarization nanoscopy can capture the Mott transition through the density-dependent recombination dynamics of electron-hole pairs within a WSe2 homobilayer. For increasing carrier density, an initial monomolecular recombination of optically dark excitons transitions continuously into a bimolecular recombination of an unbound electron-hole plasma above 7 × 1012 cm-2. We resolve how the Mott transition modulates over nanometer length scales, directly evidencing the strong inhomogeneity in stacked monolayers. Our results demonstrate how ultrafast polarization nanoscopy could unveil the interplay of strong electronic correlations and interlayer coupling within a diverse range of stacked and twisted two-dimensional materials.

[Interrater reliability and concurrent validity of 4AT for the detection of postoperative delirium: A prospective cohort study]. / Interrater Reliabilität und Übereinstimmungsvalidität des 4AT zur Erfassung des postoperativen Delirs.

Interrater reliability and concurrent validity of 4AT for the detection of postoperative delirium: A prospective cohort study Abstract. Background: Numerous tools for detecting postoperative delirium are available. Guidelines recommend the 4 A's Test (4AT). However, there is little evidence on the validity and reliability of the German version of 4AT. Aim: To assess the interrater reliability of the German version of 4AT test for the detection of postoperative delirium in general surgical and orthopedic-traumatological patients, and the concurrent validity with the Delirium Observation Screening Scale (DOS). Methods: The present work is part of a prospective cohort study with a sample of 202 inpatients (≥ 65 years) who underwent surgery. The interrater reliability of the 4AT (intraclass coefficients) was determined with a subsample of 33 subjects who were rated by two nurses. Concurrent validity between the DOS scale and the 4AT was calculated using Pearson's correlation coefficient. Results: Interrater reliability for the 4AT total score and dichotomized total score were 0.92 (95% CI 0.84-0.96) and 0.98 (95% CI 0.95-0.98), respectively. The correlation between DOS and 4AT (Pearson) was 0.54 (p < 0.001). Conclusions: The 4A test can be used by nurses as a screening instrument for the detection of postoperative delirium in older patients on general surgery and orthopedic traumatology wards. In case of positive 4AT results further assessment by nurse experts or physicians is required.

Acquisition of enzymatic progress curves in real time by quenching-free ion exchange chromatography.

We describe a quenching-free, 'online' ion exchange chromatography (oIEC) method for the quantitative analysis of enzymatic reactions in real-time. We show that separate quenching of the ongoing reaction performed conventionally is not required, since enzymatic reactions are interrupted upon immobilization of the reaction compounds by binding to the stationary phase of the ion exchange column. The reaction mix samples are directly injected into the column, thereby improving data consistency and allowing automation of the process. The method allows reliable and efficient acquisition of enzymatic progress curves by automatic loading of aliquots of an ongoing reaction at predefined timepoints. We demonstrate the applicability of this method for a variety of enzymatic reactions. SUBJECT: Enzymatic assays and analysis.

Carbon Dioxide Changes during High-flow Nasal Oxygenation in Apneic Patients: A Single-center Randomized Controlled Noninferiority Trial.

BACKGROUND: Anesthesia studies using high-flow, humidified, heated oxygen delivered via nasal cannulas at flow rates of more than 50 l · min-1 postulated a ventilatory effect because carbon dioxide increased at lower levels as reported earlier. This study investigated the increase of arterial partial pressure of carbon dioxide between different flow rates of 100% oxygen in elective anesthetized and paralyzed surgical adults before intubation. METHODS: After preoxygenation and standardized anesthesia induction with nondepolarizing neuromuscular blockade, all patients received 100% oxygen (via high-flow nasal oxygenation system or circuit of the anesthesia machine), and continuous jaw thrust/laryngoscopy was applied throughout the 15-min period. In this single-center noninferiority trial, 25 patients each, were randomized to five groups: (1) minimal flow: 0.25 l · min-1, endotracheal tube; (2) low flow: 2 l · min-1, continuous jaw thrust; (3) medium flow: 10 l · min-1, continuous jaw thrust; (4) high flow: 70 l · min-1, continuous jaw thrust; and (5) control: 70 l · min-1, continuous laryngoscopy. Immediately after anesthesia induction, the 15-min apnea period started with oxygen delivered according to the randomized flow rate. Serial arterial blood gas analyses were drawn every 2 min. The study was terminated if either oxygen saturation measured by pulse oximetry was less than 92%, transcutaneous carbon dioxide was greater than 100 mmHg, pH was less than 7.1, potassium level was greater than 6 mmol · l-1, or apnea time was 15 min. The primary outcome was the linear rate of mean increase of arterial carbon dioxide during the 15-min apnea period computed from linear regressions. RESULTS: In total, 125 patients completed the study. Noninferiority with a predefined noninferiority margin of 0.3 mmHg · min-1 could be declared for all treatments with the following mean and 95% CI for the mean differences in the linear rate of arterial partial pressure of carbon dioxide with associated P values regarding noninferiority: high flow versus control, -0.0 mmHg · min-1 (-0.3, 0.3 mmHg · min-1, P = 0.030); medium flow versus control, -0.1 mmHg · min-1 (-0.4, 0.2 mmHg · min-1, P = 0.002); low flow versus control, -0.1 mmHg · min-1 (-0.4, 0.2 mmHg · min-1, P = 0.003); and minimal flow versus control, -0.1 mmHg · min-1 (-0.4, 0.2 mmHg · min-1, P = 0.004). CONCLUSIONS: Widely differing flow rates of humidified 100% oxygen during apnea resulted in comparable increases of arterial partial pressure of carbon dioxide, which does not support an additional ventilatory effect of high-flow nasal oxygenation.

Perioperative continuation of aspirin, oral anticoagulants or bridging with therapeutic low-molecular-weight heparin does not increase intraoperative blood loss and blood transfusion rate in cystectomy patients: an observational cohort study.

OBJECTIVE: To assess if uninterrupted anticoagulant agents' administration affects blood loss and blood transfusion during open radical cystectomy (RC) and urinary diversion. PATIENTS AND METHODS: We conducted an observational single-centre cohort study of a consecutive series of 1430 RC patients, between 2000 and 2020. Blood loss was depicted according to body weight and duration of surgery (mL/kg/h), and blood transfusion. The group 'with anticoagulant agents' was considered if surgery was performed with uninterrupted low-dose aspirin (ASS), oral anticoagulants (OAC) with an international normalised ratio (INR) goal of 2-2.5 or bridging with therapeutic low-molecular-weight heparin (LMWH). Outcomes were intraoperative blood loss, blood transfusion rate (separately analysed if administered within 24 h perioperatively or >24 h after surgery) and the 90-day major adverse cardiac events (MACE) rate. We used propensity score (PS)-matching analysis to adjust for imbalances between groups with or without anticoagulant agents. RESULTS: The PS-matched median (interquartile range [IQR]) blood loss was 2.10 (1.50-2.94) mL/kg/h in patients with anticoagulant agents vs 2.11 (1.47-2.94) mL/kg/h without anticoagulant agents (Padj > 0.99). The PS-matched blood transfusion rates were 26.2% vs 35.1% (Padj = 0.875) within 24 h perioperatively and 57.0% vs 55.0% (Padj = 0.680) if administered >24 h postoperatively. A sub-analysis of the three different anticoagulant agents could not detect any significance between ASS, OAC, or LMWH. The PS-matched incidence of MACE was 9.1% in the group with anticoagulant agents and 8.1% in those without anticoagulant agents (Padj > 0.99). Limitations include selection bias and retrospective analysis from prospectively assessed data. CONCLUSIONS: Perioperative continuation of ASS, uninterrupted OAC with low INR goal or bridging with LMWH had no impact on blood loss and transfusion rate in RC patients. Therefore, there might be no compulsory need for discontinuation of anticoagulant agents.

The impact of on-site cardiac rhythm on mortality in patients supported with extracorporeal cardiopulmonary resuscitation: A retrospective cohort study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used in patients with out-of-hospital or in-hospital cardiac arrest in whom conventional cardiopulmonary resuscitation remains unsuccessful. The aim of this study was to analyze the impact of initial cardiac rhythm-detected on-site of the cardiac arrest-on mortality. METHODS: We performed a retrospective cohort study of patients who received ECPR in our tertiary care cardiac arrest center. Patients were divided into three groups depending on their cardiac rhythm: shockable rhythm, pulseless electrical activity, and asystole. The primary endpoint was mortality within the first 7 days after ECPR deployment. Secondary endpoints were mortality within 28 days and the impact of pre-ECPR potassium, serum lactate, pH, and pCO2 on mortality. The association of the initial cardiac rhythm and the location of arrhythmia detection (patient monitored in hospital [category: monitored], not monitored but hospitalized [in-hospital], not monitored, not hospitalized [out-of hospital]) with the primary and secondary outcome was examined by means of univariable and multivariable logistic regression. RESULTS: Sixty-five patients could be included in the final analysis. Thirty-two patients (49.2%, 95%CI 36.6%-61.9%) died within the first 7 days. In terms of 7-day-mortality patients differed in the initial cardiac rhythm (p = 0.040) and with respect to the location of arrhythmia detection (p = 0.002). Shockable cardiac rhythm (crude OR 0.21; 95%CI 0.03-0.98) and pulseless electrical activity (0.13; 0.02-0.61) as the initial rhythm on-site showed better odds for survival compared to asystole. However, this association did neither persist in adjusted analysis nor pairwise comparison. DISCUSSION: The study could not demonstrate a better outcome with shockable rhythm after ECPR. More homogeneous and adequately powered cohorts are needed to better understand the impact of cardiac rhythm on patient outcomes after ECPR.

Age, minimum alveolar concentration and choice of depth of sedation monitor: examining the paradox of age when using the Narcotrend monitor: A secondary analysis of an observational study.

BACKGROUND: With an ageing global population, it is important to individualise titration of anaesthetics according to age and by measuring their effect on the brain. A recent study reported that during general surgery, the given concentration of volatile anaesthetics, expressed as a fraction of the minimum alveolar concentration (MAC fraction), decreases by around only 3% per age-decade, which is less than the 6% expected from age-adjusted MAC. Paradoxically, despite the excessive dosing, Bispectral index (BIS) values also increased. OBJECTIVE: We planned to investigate the paradox of age when using the Narcotrend depth of anaesthesia monitor. DESIGN: Secondary analyses of a prospective observational study. SETTING: Tertiary hospital in Switzerland, recordings took place during 2016 and 2017. PATIENTS: One thousand and seventy-two patients undergoing cardiac surgery entered the study, and 909 with noise-free recordings and isoflurane anaesthesia were included in this analysis. INTERVENTION: We calculated mean end-tidal MAC fraction and mean index value of the Narcotrend depth of sedation monitor used in the study during the prebypass period. Statistical associations were modelled using linear regression, local weighted regression (LOESS) and a generalised additive model (GAM). MAIN OUTCOME MEASURES: Primary endpoints in this study were the change in end-tidal MAC fraction and mean Narcotrend index values, both measured per age-decade. RESULTS: We observed a linear decrease in end-tidal MAC fraction of 3.2% per age-decade [95% confidence interval (CI) -3.97% to -2.38%, P < 0.001], consistent with previous findings. In contrast to the BIS, mean Narcotrend index values decreased with age at 3.0 index points per age-decade (95% CI, -3.55 points to -2.36 points, P < 0.001), a direction of change commensurate with the increasing age-adjusted MAC fraction with patient age. These relationships were consistent regardless of whether age-adjusted MAC was displayed on the anaesthetic machine. CONCLUSIONS: We caution that the 'paradox of age' may in part depend on the choice of depth of sedation monitor. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02976584.

Outcome in patients with open abdomen treatment for peritonitis: a multidomain approach outperforms single domain predictions.

Numerous patient-related clinical parameters and treatment-specific variables have been identified as causing or contributing to the severity of peritonitis. We postulated that a combination of clinical and surgical markers and scoring systems would outperform each of these predictors in isolation. To investigate this hypothesis, we developed a multivariable model to examine whether survival outcome can reliably be predicted in peritonitis patients treated with open abdomen. This single-center retrospective analysis used univariable and multivariable logistic regression modeling in combination with repeated random sub-sampling validation to examine the predictive capabilities of domain-specific predictors (i.e., demography, physiology, surgery). We analyzed data of 1,351 consecutive adult patients (55.7% male) who underwent open abdominal surgery in the study period (January 1998 to December 2018). Core variables included demographics, clinical scores, surgical indices and indicators of organ dysfunction, peritonitis index, incision type, fascia closure, wound healing, and fascial dehiscence. Postoperative complications were also added when available. A multidomain peritonitis prediction model (MPPM) was constructed to bridge the mortality predictions from individual domains (demographic, physiological and surgical). The MPPM is based on data of n = 597 patients, features high predictive capabilities (area under the receiver operating curve: 0.87 (0.85 to 0.90, 95% CI)) and is well calibrated. The surgical predictor "skin closure" was found to be the most important predictor of survival in our cohort, closely followed by the two physiological predictors SAPS-II and MPI. Marginal effects plots highlight the effect of individual outcomes on the prediction of survival outcome in patients undergoing staged laparotomies for treatment of peritonitis. Although most single indices exhibited moderate performance, we observed that the predictive performance was markedly increased when an integrative prediction model was applied. Our proposed MPPM integrative prediction model may outperform the predictive power of current models.

Quantitative terahertz emission nanoscopy with multiresonant near-field probes.

By sampling terahertz waveforms emitted from InAs surfaces, we reveal how the entire, realistic geometry of typical near-field probes drastically impacts the broadband electromagnetic fields. In the time domain, these modifications manifest as a shift in the carrier-envelope phase and emergence of a replica pulse with a time delay dictated by the length of the cantilever. This interpretation is fully corroborated by quantitative simulations of terahertz emission nanoscopy based on the finite element method. Our approach provides a solid theoretical framework for quantitative nanospectroscopy and sets the stage for a reliable description of subcycle, near-field microscopy at terahertz frequencies.