Teleconsultation for Preoperative Anesthesia Evaluation: Identifying Environmental Potentials by Life Cycle Assessment.

Introduction: Teleconsultations for preoperative evaluation in anesthesiology proved to be feasible during the COVID-19 pandemic. However, widespread implementation of teleconsultations has not yet occurred. Besides time savings and economic benefits, teleconsultations in anesthesia may have the potential to reduce CO2 emissions. Methods: We conducted a life cycle assessment based on prospective surveys to assess the potential environmental benefits of preoperative anesthesia teleconsultations in comparison to the status-quo in-person consultations. Within 1 month, all patients presenting at the preoperative anesthesia clinic at RWTH Aachen University Hospital were asked about the distance traveled and mode of transportation to the hospital. The main outcome measure was the potential environmental benefit resulting from the implementation of teleconsultations. Results: In total, 821 out of 981 patients presenting at the anesthesia clinic participated in the survey. Most patients visited on an outpatient basis (62.9%) and traveled by car (81.7%). The median travel distance was 25 km [interquartile range 12-40]. If patients who came to the hospital solely for the anesthesia appointment had scheduled virtual appointments, the emissions of 3.03-ton CO2 equivalents (CO2-eq) could be avoided in the first month after implementation. The environmental impact associated with the production of teleconsultation equipment is outweighed by the reduction in patient travel. If all outpatient appointments were performed virtually, these savings would triple. Within 10 years, more than 1,300 tons CO2-eq could be avoided. Conclusion: Teleconsultations can mitigate the environmental impact of in-person anesthesia consultations. Further research is essential to leverage teleconsultations for preoperative evaluation also across other medical specialties.

Telemedical support for prehospital emergency medical service in severe emergencies: an open-label randomised non-inferiority clinical trial.

BACKGROUND: A tele-emergency medical service with a remote emergency physician for severe prehospital emergencies may overcome the increasing number of emergency calls and shortage of emergency medical service providers. We analysed whether routine use of a tele-emergency medical service is non-inferior to a conventional physician-based one in the occurrence of intervention-related adverse events. METHODS: This open-label, randomised, controlled, parallel-group, non-inferiority trial included all routine severe emergency patients aged ≥ 18 years within the ground-based ambulance service of Aachen, Germany. Patients were randomised in a 1:1 allocation ratio to receive either tele-emergency medical service (n = 1764) or conventional physician-based emergency medical service (n = 1767). The primary outcome was the occurrence of intervention-related adverse events with suspected causality to the group assignment. The trial was registered with ClinicalTrials.gov (NCT02617875) on 30 November 2015 and is reported in accordance with the CONSORT statement for non-inferiority trials. RESULTS: Among 3531 randomised patients, 3220 were included in the primary analysis (mean age, 61.3 years; 53.8% female); 1676 were randomised to the conventional physician-based emergency medical service (control) group and 1544 to the tele-emergency medical service group. A physician was not deemed necessary in 108 of 1676 cases (6.4%) and 893 of 1544 cases (57.8%) in the control and tele-emergency medical service groups, respectively. The primary endpoint occurred only once in the tele-emergency medical service group. The Newcombe hybrid score method confirmed the non-inferiority of the tele-emergency medical service, as the non-inferiority margin of - 0.015 was not covered by the 97.5% confidence interval of - 0.0046 to 0.0025. CONCLUSIONS: Among severe emergency cases, tele-emergency medical service was non-inferior to conventional physician-based emergency medical service in terms of the occurrence of adverse events.

Poor reporting quality of observational clinical studies comparing treatments of COVID-19 - a retrospective cross-sectional study.

BACKGROUND: During the COVID-19 pandemic, the scientific world is in urgent need for new evidence on the treatment of COVID patients. The reporting quality is crucial for transparent scientific publication. Concerns of data integrity, methodology and transparency were raised. Here, we assessed the adherence of observational studies comparing treatments of COVID 19 to the STROBE checklist in 2020. METHODS: Design: We performed a retrospective, cross-sectional study. SETTING: We conducted a systematic literature search in the Medline database. This study was performed at the RWTH Aachen University Hospital, Department of Anaesthesiology Participants: We extracted all observational studies on the treatment of COVID-19 patients from the year 2020. MAIN OUTCOME MEASURES: The adherence of each publication to the STROBE checklist items was analysed. The journals' impact factor (IF), the country of origin, the kind of investigated treatment and the month of publication were assessed. RESULTS: We analysed 147 observational studies and found a mean adherence of 45.6% to the STROBE checklist items. The percentage adherence per publication correlated significantly with the journals' IF (point estimate for the difference between 1st and 4th quartile 11.07%, 95% CI 5.12 to 17.02, p < 0.001). U.S. American authors gained significantly higher adherence to the checklist than Chinese authors, mean difference 9.10% (SD 2.85%, p = 0.023). CONCLUSIONS: We conclude a poor reporting quality of observational studies on the treatment of COVID-19 throughout the year 2020. A considerable improvement is mandatory.

Effect of Intraoperative Handovers of Anesthesia Care on Mortality, Readmission, or Postoperative Complications Among Adults: The HandiCAP Randomized Clinical Trial.

Importance: Intraoperative handovers of anesthesia care are common. Handovers might improve care by reducing physician fatigue, but there is also an inherent risk of losing critical information. Large observational analyses report associations between handover of anesthesia care and adverse events, including higher mortality. Objective: To determine the effect of handovers of anesthesia care on postoperative morbidity and mortality. Design, Setting, and Participants: This was a parallel-group, randomized clinical trial conducted in 12 German centers with patients enrolled between June 2019 and June 2021 (final follow-up, July 31, 2021). Eligible participants had an American Society of Anesthesiologists physical status 3 or 4 and were scheduled for major inpatient surgery expected to last at least 2 hours. Interventions: A total of 1817 participants were randomized to receive either a complete handover to receive anesthesia care by another clinician (n = 908) or no handover of anesthesia care (n = 909). None of the participating institutions used a standardized handover protocol. Main Outcomes and Measures: The primary outcome was a 30-day composite of all-cause mortality, hospital readmission, or serious postoperative complications. There were 19 secondary outcomes, including the components of the primary composite, along with intensive care unit and hospital lengths of stay. Results: Among 1817 randomized patients, 1772 (98%; mean age, 66 [SD, 12] years; 997 men [56%]; and 1717 [97%] with an American Society of Anesthesiologists physical status of 3) completed the trial. The median total duration of anesthesia was 267 minutes (IQR, 206-351 minutes), and the median time from start of anesthesia to first handover was 144 minutes in the handover group (IQR, 105-213 minutes). The composite primary outcome occurred in 268 of 891 patients (30%) in the handover group and in 284 of 881 (33%) in the no handover group (absolute risk difference [RD], -2.5%; 95% CI, -6.8% to 1.9%; odds ratio [OR], 0.89; 95% CI, 0.72 to 1.10; P = .27). Nineteen of 889 patients (2.1%) in the handover group and 30 of 873 (3.4%) in the no handover group experienced all-cause 30-day mortality (absolute RD, -1.3%; 95% CI, -2.8% to 0.2%; OR, 0.61; 95% CI, 0.34 to 1.10; P = .11); 115 of 888 (13%) vs 136 of 872 (16%) were readmitted to the hospital (absolute RD, -2.7%; 95% CI, -5.9% to 0.6%; OR, 0.80; 95% CI, 0.61 to 1.05; P = .12); and 195 of 890 (22%) vs 189 of 874 (22%) experienced serious postoperative complications (absolute RD, 0.3%; 95% CI, -3.6% to 4.1%; odds ratio, 1.02; 95% CI, 0.81 to 1.28; P = .91). None of the 19 prespecified secondary end points differed significantly. Conclusions and Relevance: Among adults undergoing extended surgical procedures, there was no significant difference between the patients randomized to receive handover of anesthesia care from one clinician to another, compared with the no handover group, in the composite primary outcome of mortality, readmission, or serious postoperative complications within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04016454.

Acid sphingomyelinase regulates TH 2 cytokine release and bronchial asthma.

BACKGROUND: Allergic diseases and especially allergic asthma are widespread diseases with high prevalence in childhood, but also in adults. Acid sphingomyelinase (ASM) is a key regulator of the sphingolipid pathway. Previous studies defined the association of ASM with the pathogenesis of TH 1-directed lung diseases like cystic fibrosis and acute lung injury. Here, we define the role of ASM in TH 2-regulated allergic bronchial asthma. METHODS: To determine the role of Asm under baseline conditions, wild-type (WT) and Asm-/- mice were ventilated with a flexiVent setup and bronchial hyperresponsiveness was determined using acetylcholine. Flow cytometry and cytokine measurements in bronchoalveolar lavage fluid and lung tissue were followed by in vitro TH 2 differentiations with cells from WT and Asm-/- mice and blockade of Asm with amitriptyline. As proof of principle, we conducted an ovalbumin-induced model of asthma in WT- and Asm-/-  mice. RESULTS: At baseline, Asm-/- mice showed better lung mechanics, but unaltered bronchial hyperresponsiveness. Higher numbers of Asm-/- T cells in bronchoalveolar lavage fluid released lower levels of IL-4 and IL-5, and these results were paralleled by decreased production of typical TH 2 cytokines in Asm-/- T lymphocytes in vitro. This phenotype could be imitated by incubation of T cells with amitriptyline. In the ovalbumin asthma model, Asm-/- animals were protected from high disease activity and showed better lung functions and lower levels of eosinophils and TH 2 cytokines. CONCLUSION: Asm deficiency could induce higher numbers of TH 2 cells in the lung, but those cells release decreased TH 2 cytokine levels. Hereby, Asm-/- animals are protected from bronchial asthma, which possibly offers novel therapeutic strategies, for example, with ASM blockade.

Maize death acids, 9-lipoxygenase-derived cyclopente(a)nones, display activity as cytotoxic phytoalexins and transcriptional mediators.

Plant damage promotes the interaction of lipoxygenases (LOXs) with fatty acids yielding 9-hydroperoxides, 13-hydroperoxides, and complex arrays of oxylipins. The action of 13-LOX on linolenic acid enables production of 12-oxo-phytodienoic acid (12-OPDA) and its downstream products, termed "jasmonates." As signals, jasmonates have related yet distinct roles in the regulation of plant resistance against insect and pathogen attack. A similar pathway involving 9-LOX activity on linolenic and linoleic acid leads to the 12-OPDA positional isomer, 10-oxo-11-phytodienoic acid (10-OPDA) and 10-oxo-11-phytoenoic acid (10-OPEA), respectively; however, physiological roles for 9-LOX cyclopentenones have remained unclear. In developing maize (Zea mays) leaves, southern leaf blight (Cochliobolus heterostrophus) infection results in dying necrotic tissue and the localized accumulation of 10-OPEA, 10-OPDA, and a series of related 14- and 12-carbon metabolites, collectively termed "death acids." 10-OPEA accumulation becomes wound inducible within fungal-infected tissues and at physiologically relevant concentrations acts as a phytoalexin by suppressing the growth of fungi and herbivores including Aspergillus flavus, Fusarium verticillioides, and Helicoverpa zea. Unlike previously established maize phytoalexins, 10-OPEA and 10-OPDA display significant phytotoxicity. Both 12-OPDA and 10-OPEA promote the transcription of defense genes encoding glutathione S transferases, cytochrome P450s, and pathogenesis-related proteins. In contrast, 10-OPEA only weakly promotes the accumulation of multiple protease inhibitor transcripts. Consistent with a role in dying tissue, 10-OPEA application promotes cysteine protease activation and cell death, which is inhibited by overexpression of the cysteine protease inhibitor maize cystatin-9. Unlike jasmonates, functions for 10-OPEA and associated death acids are consistent with specialized roles in local defense reactions.

Compatibility in the Ustilago maydis-maize interaction requires inhibition of host cysteine proteases by the fungal effector Pit2.

The basidiomycete Ustilago maydis causes smut disease in maize, with large plant tumors being formed as the most prominent disease symptoms. During all steps of infection, U. maydis depends on a biotrophic interaction, which requires an efficient suppression of plant immunity. In a previous study, we identified the secreted effector protein Pit2, which is essential for maintenance of biotrophy and induction of tumors. Deletion mutants for pit2 successfully penetrate host cells but elicit various defense responses, which stops further fungal proliferation. We now show that Pit2 functions as an inhibitor of a set of apoplastic maize cysteine proteases, whose activity is directly linked with salicylic-acid-associated plant defenses. Consequently, protease inhibition by Pit2 is required for U. maydis virulence. Sequence comparisons with Pit2 orthologs from related smut fungi identified a conserved sequence motif. Mutation of this sequence caused loss of Pit2 function. Consequently, expression of the mutated protein in U. maydis could not restore virulence of the pit2 deletion mutant, indicating that the protease inhibition by Pit2 is essential for fungal virulence. Moreover, synthetic peptides of the conserved sequence motif showed full activity as protease inhibitor, which identifies this domain as a new, minimal protease inhibitor domain in plant-pathogenic fungi.

Easy-to-implement educational interventions to bring climate-smart actions to daily anesthesiologic practice: a cross-sectional before and after study.

BACKGROUND: Anesthesia contributes significantly to a hospital's carbon footprint. Climate-smart actions have the potential to reduce greenhouse gas emissions. Prerequisites for sustainable behavior of providers are knowledge and awareness. We aimed to assess the change in anesthesiologists' climate-friendly behavior before and after educational interventions in three areas that every anesthesiologist can address in their daily clinical routine: 1) energy use; 2) recycling opportunities; 3) consumption of volatile anesthetics. METHODS: We performed a cross-sectional before-and-after single center sub-study within the multicenter "Provider Education and Evaluation Project" at the Department of Anesthesiology, RWTH Aachen University hospital from May3 2021 to May 1 2022. Educational interventions consisted of stickers, posters and a presentation on climate-smart actions in anesthesiologists' work routine between the first and the second assessment. For each cross-sectional assessment, all central 28 ORs were observed for one week. During the before-and-after comparison we analyzed: 1) energy wasted in unoccupied ORs because of running computers and turned-on lights at 9 p.m.; 2) feasibility of recycling preoperative anesthesia plastic packaging by determining the difference between calculated weight of unseparated preoperative plastic waste in the first assessment and the weight of actual separated waste in the second assessment; 3) fresh gas flow in balanced anesthesia cases in steady state at 9 a.m., and purchased hypnotics converted to bottles/1000 general anesthesia cases in 2018-2022. RESULTS: We observed a reduction of wasted energy by 44% in unoccupied ORs. Usage of low fresh gas flow settings increased from 55% to 75%. The average of purchased desflurane in 2018-2020 decreased by 72% in 2022. We calculated 10.33 kg of preoperative plastic waste per week but were unable to implement waste separation for infrastructural and logistical reasons. CONCLUSIONS: We found that environment-friendly working behaviors increased after the implementation of educational interventions. The causality between the interventions and the observed improvements remains to be proven.

Preoperative Midazolam and Patient-Centered Outcomes of Older Patients: The I-PROMOTE Randomized Clinical Trial.

Importance: The effect of oral midazolam premedication on patient satisfaction in older patients undergoing surgery is unclear, despite its widespread use. Objective: To determine the differences in global perioperative satisfaction in patients with preoperative administration of oral midazolam compared with placebo. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial was conducted in 9 German hospitals between October 2017 and May 2019 (last follow-up, June 24, 2019). Eligible patients aged 65 to 80 years who were scheduled for elective inpatient surgery for at least 30 minutes under general anesthesia and with planned extubation were enrolled. Data were analyzed from November 2019 to December 2020. Interventions: Patients were randomized to receive oral midazolam, 3.75 mg (n = 309), or placebo (n = 307) 30 to 45 minutes prior to anesthesia induction. Main Outcomes and Measures: The primary outcome was global patient satisfaction evaluated using the self-reported Evaluation du Vécu de l'Anesthésie Generale (EVAN-G) questionnaire on the first postoperative day. Key secondary outcomes included sensitivity and subgroup analyses of the primary outcome, perioperative patient vital data, adverse events, serious complications, and cognitive and functional recovery up to 30 days postoperatively. Results: Among 616 randomized patients, 607 were included in the primary analysis. Of these, 377 (62.1%) were male, and the mean (SD) age was 71.9 (4.4) years. The mean (SD) global index of patient satisfaction did not differ between the midazolam and placebo groups (69.5 [10.7] vs 69.6 [10.8], respectively; mean difference, -0.2; 95% CI, -1.9 to 1.6; P = .85). Sensitivity (per-protocol population, multiple imputation) and subgroup analyses (anxiety, frailty, sex, and previous surgical experience) did not alter the primary results. Secondary outcomes did not differ, except for a higher proportion of patients with hypertension (systolic blood pressure ≥160 mm Hg) at anesthesia induction in the placebo group. Conclusion and Relevance: A single low dose of oral midazolam premedication did not alter the global perioperative patient satisfaction of older patients undergoing surgery or that of patients with anxiety. These results may be affected by the low dose of oral midazolam. Further trials-including a wider population with commonplace low-dose intravenous midazolam and plasma level measurements-are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03052660.

Poor reporting quality of randomized controlled trials comparing treatments of COVID-19-A retrospective cross-sectional study on the first year of publications.

INTRODUCTION: Transparent and complete reporting of randomized controlled trials (RCTs) is essential for critical scientific appraisal of the results. It has been argued whether publications during the COVID-19 pandemic have met reporting standards. In this study, we assessed reporting adherence of RCTs on treatment interventions in COVID-19 patients to the CONSORT checklist and discuss which lessons can be learned to improve reporting in the future. METHODS: This was a retrospective, cross-sectional study performed at the University Hospital RWTH Aachen, Germany. We conducted a pragmatic systematic literature search in the PubMed database to identify RCTs on treatment interventions in COVID-19 patients in the first year of publications on the topic (March 2020-February 2021). We investigated the adherence of each publication to the CONSORT checklist and assessed the association between specific predictors and percentage adherence in an exploratory multivariable regression model. RESULTS: We analyzed 127 RCTs and found that the median percentage adherence to the CONSORT checklist was 54.3% [IQR 38.9 to 65.7]. In the exploratory multivariable regression model, the impact factor (highest tertile of impact factor compared to lowest tertile ß = 21.77, 95% CI 13.89 to 29.66, p<0.001; middle tertile compared lowest tertile ß = 11.79, 95% CI 5.74 to 17.84, p<0.001)) and authors' referral to the CONSORT statement (ß = 9.29, 95% CI 2.98 to 15.60, p = 0.004) were associated with a higher percentage adherence to the CONSORT checklist. CONCLUSION: The reporting quality of RCTs on treatment interventions in COVID-19 patients during the first year of publications was poor. Measures to improve reporting quality are urgently needed.

Intraoperative transfusion practices and perioperative outcome in the European elderly: A secondary analysis of the observational ETPOS study.

The demographic development suggests a dramatic growth in the number of elderly patients undergoing surgery in Europe. Most red blood cell transfusions (RBCT) are administered to older people, but little is known about perioperative transfusion practices in this population. In this secondary analysis of the prospective observational multicentre European Transfusion Practice and Outcome Study (ETPOS), we specifically evaluated intraoperative transfusion practices and the related outcomes of 3149 patients aged 65 years and older. Enrolled patients underwent elective surgery in 123 European hospitals, received at least one RBCT intraoperatively and were followed up for 30 days maximum. The mean haemoglobin value at the beginning of surgery was 108 (21) g/l, 84 (15) g/l before transfusion and 101 (16) g/l at the end of surgery. A median of 2 [1-2] units of RBCT were administered. Mostly, more than one transfusion trigger was present, with physiological triggers being preeminent. We revealed a descriptive association between each intraoperatively administered RBCT and mortality and discharge respectively, within the first 10 postoperative days but not thereafter. In our unadjusted model the hazard ratio (HR) for mortality was 1.11 (95% CI: 1.08-1.15) and the HR for discharge was 0.78 (95% CI: 0.74-0.83). After adjustment for several variables, such as age, preoperative haemoglobin and blood loss, the HR for mortality was 1.10 (95% CI: 1.05-1.15) and HR for discharge was 0.82 (95% CI: 0.78-0.87). Pre-operative anaemia in European elderly surgical patients is undertreated. Various triggers seem to support the decision for RBCT. A closer monitoring of elderly patients receiving intraoperative RBCT for the first 10 postoperative days might be justifiable. Further research on the causal relationship between RBCT and outcomes and on optimal transfusion strategies in the elderly population is warranted. A thorough analysis of different time periods within the first 30 postoperative days is recommended.

Tele-EMS physicians improve life-threatening conditions during prehospital emergency missions.

Almost seven years ago, a telemedicine system was established as an additional component of the city of Aachen's emergency medical service (EMS). It allows paramedics to engage in an immediate consultation with an EMS physician at any time. The system is not meant to replace the EMS physician on the scene during life-threatening emergencies. The aim of this study was to analyze teleconsultations during life-threatening missions and evaluate whether they improve patient care. Telemedical EMS (tele-EMS) physician consultations that occurred over the course of four years were evaluated. Missions were classified as involving potentially life-threatening conditions based on at least one of the following criteria: documented patient severity score, life-threatening vital signs, the judgement of the onsite EMS physician involved in the mission, or definite life-threatening diagnoses. The proportion of vital signs indicating that the patient was in a life-threatening condition was analyzed as the primary outcome at the start and end of the tele-EMS consultation. The secondary outcome parameters were the administered drug doses, tracer diagnoses made by the onsite EMS physicians during the missions, and quality of the documentation of the missions. From January 2015 to December 2018, a total of 10,362 tele-EMS consultations occurred; in 4,293 (41.4%) of the missions, the patient was initially in a potentially life-threatening condition. Out of those, a total of 3,441 (80.2%) missions were performed without an EMS physician at the scene. Records of 2,007 patients revealed 2,234 life-threatening vital signs of which 1,465 (65.6%) were remedied during the teleconsultation. Significant improvement was detected for oxygen saturation, hypotonia, tachy- and bradycardia, vigilance states, and hypoglycemia. Teleconsultation during missions involving patients with life-threatening conditions can significantly improve those patients' vital signs. Many potentially life-threatening cases could be handled by a tele-EMS physician as they did not require any invasive interventions that needed to be performed by an onsite EMS physician. Diagnoses of myocardial infarction, cardiac pulmonary edema, or malignant dysrhythmias necessitate the presence of onsite EMS physicians. Even during missions involving patients with life-threatening conditions, teleconsultation was feasible and often accessed by the paramedics.

Proteases Underground: Analysis of the Maize Root Apoplast Identifies Organ Specific Papain-Like Cysteine Protease Activity.

Plant proteases are key regulators of plant cell processes such as seed development, immune responses, senescence and programmed cell death (PCD). Apoplastic papain-like cysteine proteases (PL) are hubs in plant-microbe interactions and play an important role during abiotic stresses. The apoplast is a crucial interface for the interaction between plant and microbes. So far, apoplastic maize PL and their function have been mostly described for aerial parts. In this study, we focused on apoplastic PLCPs in the roots of maize plants. We have analyzed the phylogeny of maize PLCPs and investigated their protein abundance after salicylic acid (SA) treatment. Using activity-based protein profiling (ABPP) we have identified a novel root-specific PLCP belonging to the RD21-like subfamily, as well as three SA activated PLCPs. The root specific PLCP CP1C shares sequence and structural similarities to known CP1-like proteases. Biochemical analysis of recombinant CP1C revealed different substrate specificities and inhibitor affinities compared to the related proteases. This study characterized a root-specific PLCP and identifies differences between the SA-dependent activation of PLCPs in roots and leaves.

An apoplastic peptide activates salicylic acid signalling in maize.

Localized control of cell death is crucial for the resistance of plants to pathogens. Papain-like cysteine proteases (PLCPs) regulate plant defence to drive cell death and protection against biotrophic pathogens. In maize (Zea mays), PLCPs are crucial in the orchestration of salicylic acid (SA)-dependent defence signalling. Despite this central role in immunity, it remains unknown how PLCPs are activated, and which downstream signals they induce to trigger plant immunity. Here, we discover an immune signalling peptide, Z. mays immune signalling peptide 1 (Zip1), which is produced after salicylic acid (SA) treatment. In vitro studies demonstrate that PLCPs are required to release bioactive Zip1 from its propeptide precursor. Conversely, Zip1 treatment strongly elicits SA accumulation in leaves. Moreover, transcriptome analyses revealed that Zip1 and SA induce highly overlapping transcriptional changes. Consequently, Zip1 promotes the infection of the necrotrophic fungus Botrytis cinerea, while it reduces virulence of the biotrophic fungus Ustilago maydis. Thus, Zip1 represents the previously missing signal that is released by PLCPs to activate SA defence signalling.