LOX-1 and MMP-9 Inhibition Attenuates the Detrimental Effects of Delayed rt-PA Therapy and Improves Outcomes After Acute Ischemic Stroke.

BACKGROUND: Acute ischemic stroke triggers endothelial activation that disrupts vascular integrity and increases hemorrhagic transformation leading to worsened stroke outcomes. rt-PA (recombinant tissue-type plasminogen activator) is an effective treatment; however, its use is limited due to a restricted time window and hemorrhagic transformation risk, which in part may involve activation of MMPs (matrix metalloproteinases) mediated through LOX-1 (lectin-like oxLDL [oxidized low-density lipoprotein] receptor 1). This study's overall aim was to evaluate the therapeutic potential of novel MMP-9 (matrix metalloproteinase 9) ± LOX-1 inhibitors in combination with rt-PA to improve stroke outcomes. METHODS: A rat thromboembolic stroke model was utilized to investigate the impact of rt-PA delivered 4 hours poststroke onset as well as selective MMP-9 (JNJ0966) ±LOX-1 (BI-0115) inhibitors given before rt-PA administration. Infarct size, perfusion, and hemorrhagic transformation were evaluated by 9.4-T magnetic resonance imaging, vascular and parenchymal MMP-9 activity via zymography, and neurological function was assessed using sensorimotor function testing. Human brain microvascular endothelial cells were exposed to hypoxia plus glucose deprivation/reperfusion (hypoxia plus glucose deprivation 3 hours/R 24 hours) and treated with ±tPA and ±MMP-9 ±LOX-1 inhibitors. Barrier function was assessed via transendothelial electrical resistance, MMP-9 activity was determined with zymography, and LOX-1 and barrier gene expression/levels were measured using qRT-PCR (quantitative reverse transcription PCR) and Western blot. RESULTS: Stroke and subsequent rt-PA treatment increased edema, hemorrhage, MMP-9 activity, LOX-1 expression, and worsened neurological outcomes. LOX-1 inhibition improved neurological function, reduced edema, and improved endothelial barrier integrity. Elevated MMP-9 activity correlated with increased edema, infarct volume, and decreased neurological function. MMP-9 inhibition reduced MMP-9 activity and LOX-1 expression. In human brain microvascular endothelial cells, LOX-1/MMP-9 inhibition differentially attenuated MMP-9 levels, inflammation, and activation following hypoxia plus glucose deprivation/R. CONCLUSIONS: Our findings indicate that LOX-1 inhibition and ± MMP-9 inhibition attenuate negative aspects of ischemic stroke with rt-PA therapy, thus resulting in improved neurological function. While no synergistic effect was observed with simultaneous LOX-1 and MMP-9 inhibition, a distinct interaction is evident.

Association between left ventricular systolic function parameters and myocardial injury, organ failure and mortality in patients with septic shock.

BACKGROUND: Left ventricular ejection fraction (LVEF) is inconsistently associated with poor outcomes in patients with sepsis. Newer parameters such as LV longitudinal strain (LVLS), mitral annular plane systolic excursion (MAPSE) and LV longitudinal wall fractional shortening (LV-LWFS) may be more sensitive indicators of LV dysfunction, but are sparsely investigated. Our objective was to evaluate the association between five traditional and novel echocardiographic parameters of LV systolic function (LVEF, peak tissue Doppler velocity at the mitral valve (s´), LVLS, MAPSE and LV-LWFS) and outcomes in patients admitted to the Intensive Care Unit (ICU) with septic shock. METHODS: A total of 152 patients admitted to the ICU with septic shock from two data repositories were included. Transthoracic echocardiograms were performed within 24 h of ICU admission. The primary outcome was myocardial injury, defined as high-sensitivity troponin T ≥ 45 ng/L on ICU admission. Secondary outcomes were organ support-free days (OSFD) and 30-day mortality. We also tested for the prognostic value of the systolic function parameters using multivariable analysis. RESULTS: LVLS, MAPSE and LV-LWFS, but not LVEF and s´, differed between patients with and without myocardial injury. After adjustment for age, pre-existing cardiac disease, Simplified Acute Physiology (SAPS3) score, Sequential Organ Failure Assessment (SOFA) score, plasma creatinine and presence of right ventricular dysfunction, only MAPSE and LV-LWFS were independently associated with myocardial injury. None of the systolic function parameters were associated with OSFD or 30-day mortality. CONCLUSIONS: MAPSE and LV-LWFS are independently associated with myocardial injury and outperform LVEF, s´ and LVLS. Whether these parameters are associated with clinical outcomes such as the need for organ support and short-term mortality is still unclear. Trial registration NCT01747187 and NCT04695119.

Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction.

BACKGROUND AND AIMS: The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD. METHODS: The relationship between plasma S100A8/A9 and cardiac dysfunction was assessed in a cohort of 62 patients with severe sepsis admitted to the intensive care unit of Linköping University Hospital, Sweden. We used S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 and S100A9-/- mice for therapeutic and mechanistic studies on endotoxemia-induced cardiac dysfunction in mice. RESULTS: In sepsis patients, elevated plasma S100A8/A9 was associated with left-ventricular (LV) systolic dysfunction and increased SOFA score. In wild-type mice, 5 mg/kg of bacterial lipopolysaccharide (LPS) induced rapid plasma S100A8/A9 increase and acute LV dysfunction. Two ABR-238901 doses (30 mg/kg) administered intraperitoneally with a 6 h interval, starting directly after LPS or at a later time-point when LV dysfunction is fully established, efficiently prevented and reversed the phenotype, respectively. In contrast, dexamethasone did not improve cardiac function compared to PBS-treated endotoxemic controls. S100A8/A9 inhibition potently reduced systemic levels of inflammatory mediators, prevented upregulation of inflammatory genes and restored mitochondrial function in the myocardium. The S100A9-/- mice were protected against LPS-induced LV dysfunction to an extent comparable with pharmacologic S100A8/A9 blockade. The ABR-238901 treatment did not induce an additional improvement of LV function in the S100A9-/- mice, confirming target specificity. CONCLUSION: Elevated S100A8/A9 is associated with the development of LV dysfunction in severe sepsis patients and in a mouse model of endotoxemia. Pharmacological blockade of S100A8/A9 with ABR-238901 has potent anti-inflammatory effects, mitigates myocardial dysfunction and might represent a novel therapeutic strategy for patients with severe sepsis.

Prediction of perioperative myocardial infarction/injury in high-risk patients after noncardiac surgery.

AIMS: Perioperative myocardial infarction/injury (PMI) is a surprisingly common yet difficult-to-predict cardiac complication in patients undergoing noncardiac surgery. We aimed to assess the incremental value of preoperative cardiac troponin (cTn) concentration in the prediction of PMI. METHODS AND RESULTS: Among prospectively recruited patients at high cardiovascular risk (age ≥65 years or ≥45 years with preexisting cardiovascular disease), PMI was defined as an absolute increase in high-sensitivity cTnT (hs-cTnT) concentration of ≥14 ng/L (the 99th percentile) above the preoperative concentration. Perioperative myocardial infarction/injury was centrally adjudicated by two independent cardiologists using serial measurements of hs-cTnT. Using logistic regression, three models were derived: Model 1 including patient- and procedure-related information, Model 2 adding routinely available laboratory values, and Model 3 further adding preoperative hs-cTnT concentration. Models were also compared vs. preoperative hs-cTnT alone. The findings were validated in two independent cohorts. Among 6944 patients, PMI occurred in 1058 patients (15.2%). The predictive accuracy as quantified by the area under the receiver operating characteristic curve was 0.73 [95% confidence interval (CI) 0.71-0.74] for Model 1, 0.75 (95% CI 0.74-0.77) for Model 2, 0.79 (95% CI 0.77-0.80) for Model 3, and 0.74 for hs-cTnT alone. Model 3 included 10 preoperative variables: age, body mass index, known coronary artery disease, metabolic equivalent >4, risk of surgery, emergency surgery, planned duration of surgery, haemoglobin, platelet count, and hs-cTnT. These findings were confirmed in both independent validation cohorts (n = 722 and n = 966). CONCLUSION: Preoperative cTn adds incremental value above patient- and procedure-related variables as well as routine laboratory variables in the prediction of PMI.

Image quality of spectral brain computed tomography angiography using halved dose of iodine contrast medium.

PURPOSE: Reduction in iodinated contrast medium (CM) dose is highly motivated. Our aim was to evaluate if a 50% reduction of CM, while preserving image quality, is possible in brain CT angiography (CTA) using virtual monoenergetic images (VMI) on spectral CT. As a secondary aim, we evaluated if VMI can salvage examinations with suboptimal CM timing. METHODS: Consecutive patients older than 18 years without intracranial stenosis/occlusion were included. Three imaging protocols were used: group 1, full CM dose; group 2, 50% CM dose suboptimal timing; and group 3, 50% CM dose optimized timing. Attenuation, noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured in the internal carotid artery, M2 segment of the middle cerebral artery, and white matter for conventional images (CI) and VMI (40-200 keV). Qualitative image quality for CI and VMI (50 and 60 keV) was rated by 4 experienced reviewers. RESULTS: Qualitatively and quantitatively, VMI (40-60 keV) improved image quality within each group. Significantly higher attenuation and CNR was found for group 3 VMI 40-50 keV, with unchanged SNR, compared to group 1 CI. Group 3 VMI 50 keV also received significantly higher rating scores than group 1 CI. Group 2 VMI (40-50 keV) had significantly higher CNR compared to group 3 CI, but the subjective image quality was similar. CONCLUSION: VMI of 50 keV with 50% CM dose increases qualitative and quantitative image quality over CI with full CM dose. Using VMI reduces non-diagnostic examinations and may salvage CTA examinations deemed non-diagnostic due to suboptimal timing.

The onset of sepsis as experienced by patients and family members: A qualitative interview study.

AIMS AND OBJECTIVES: To explore the onset of sepsis based on patients' and family members' experiences. BACKGROUND: Knowledge about the onset of sepsis is limited among patients and their families, which makes early recognition of sepsis difficult. Previous studies argue that their stories are important to recognising sepsis and reduced suffering and mortality. DESIGN: A descriptive design with a qualitative approach was used. METHODS: In total, 29 patients and family members participated in 24 interviews with open-ended questions, including five dyadic and 19 individual interviews. The interviews were conducted during 2021, and participants were recruited from a sepsis group on social media. A thematic analysis based on descriptive phenomenology was performed. The study followed the COREQ checklist. FINDINGS: Two themes emerged from the experiences: (1) When health changes into something unknown, including the two subthemes; Bodily symptoms and signs being vague but still tangible and Feelings of uncertainty, and (2) Turning points when warnings signs are deemed as serious, including the two subthemes Passing borders when feeling out of control and Difficulties understanding the seriousness. CONCLUSIONS: Patients' and family members' stories of the onset of sepsis indicate that symptoms and signs appeared insidiously and then noticeably worsen. The symptoms and signs seemed not be attributed to sepsis; instead, there was uncertainty about what the symptoms and signs meant. It was mainly family members who possibly understood the seriousness of the disease. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Patients' experiences of their symptoms and signs and family members' unique knowledge of the patient, indicate that healthcare professionals should listen and try to understand what the patient and family members are telling and take their concerns seriously. How the condition appears, and family members' concerns are important pieces of the assessment to recognise patients with sepsis. PATIENT OR PUBLIC CONTRIBUTION: Patients and family members contributed to the data collected.

Effects of Blended Simulation on Nursing Students' Critical Thinking Skills: A Quantitative Study.

Introduction: Critical thinking is regarded as imperative to healthcare quality and patient outcomes; therefore, effective strategies in nursing education are required to promote students' critical thinking abilities, leading to their success in clinical work. Accordingly, simulation-based education has been suggested as a measure for achieving this goal. Objective: The aim of this study was to explore whether a nursing education course with blended simulation activities (hands-on simulations with high-fidelity manikins and a web-based interactive simulation program) could increase nursing students' critical thinking skills. Method: A quasiexperimental, one-group pretest and post-test design was utilized. Data were collected through premeasurement and postmeasurement using a critical thinking questionnaire and were analyzed using paired sample t-tests, independent sample t-tests, and the nonparametric Wilcoxon signed-rank test. The effect size was calculated using Cohen's d formula. Results: Sixty-one nursing students (57 women and four men, mean age 30 years) participated in the study. Findings of the paired sample t-test showed a significantly higher mean score for posteducation than pre-education, indicating a significant change in nurses' critical thinking capabilities (p < .001). The results for Cohen's d formula ( - 0.87) of the mean scores between pre-education and posteducation indicated a large effect size. The Wilcoxon signed-rank test also showed a statistically significant increase in the students' critical thinking abilities between pre-education and posteducation measures (p < .001). No statistically significant differences were found in the mean score according to age or sex. Conclusion: This study concluded that blended simulation-based education can increase nursing students' critical thinking capabilities. As a result, this study builds on the use of simulation as a measure for developing and promoting critical thinking abilities during nursing education.

Prediction of the Risk of Sepsis by Using Analysis of Plasma Glucose and Serum Lactate in Ambulance Services: A Prospective Study.

INTRODUCTION: The early recognition of patients with sepsis is difficult and the initial assessment outside of hospitals is challenging for ambulance clinicians (ACs). Indicators that ACs can use to recognize sepsis early are beneficial for patient outcomes. Research suggests that elevated point-of-care (POC) plasma glucose and serum lactate levels may help to predict sepsis in the ambulance service (AS) setting. STUDY OBJECTIVE: The aim of this study was to test the hypothesis that the elevation of POC plasma glucose and serum lactate levels may help to predict Sepsis-3 in the AS. METHODS: A prospective observational study was performed in the AS setting of Gothenburg in Sweden from the beginning of March 2018 through the end of September 2019. The criteria for sampling POC plasma glucose and serum lactate levels in the AS setting were high or intermediate risk according to the Rapid Emergency Triage and Treatment System (RETTS), as red, orange, yellow, and green if the respiratory rate was >22 breaths/minutes. Sepsis-3 were identified retrospectively. A primary and secondary analyses were carried out. The primary analysis included patients cared for in the AS and emergency department (ED) and were hospitalized. In the secondary analysis, patients who were only cared for in the AS and ED without being hospitalized were also included. To evaluate the predictive ability of these biomarkers, the area under the curve (AUC), sensitivity, specificity, and predictive values were used. RESULTS: A total of 1,057 patients were included in the primary analysis and 1,841 patients were included in the secondary analysis. In total, 253 patients met the Sepsis-3 criteria (in both analyses). The AUC for POC plasma glucose and serum lactate levels showed low accuracy in predicting Sepsis-3 in both the primary and secondary analyses. Among all hospitalized patients, regardless of Sepsis-3, more than two-thirds had elevated plasma glucose and nearly one-half had elevated serum lactate when measured in the AS. CONCLUSIONS: As individual biomarkers, an elevated POC plasma glucose and serum lactate were not associated with an increased likelihood of Sepsis-3 when measured in the AS in this study. However, the high rate of elevation of these biomarkers before arrival in hospital highlights that their role in clinical decision making at this early stage needs further evaluation, including other endpoints than Sepsis-3.

A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles.

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.

Acute heart failure after non-cardiac surgery: incidence, phenotypes, determinants and outcomes.

AIMS: Primary acute heart failure (AHF) is a common cause of hospitalization. AHF may also develop postoperatively (pAHF). The aim of this study was to assess the incidence, phenotypes, determinants and outcomes of pAHF following non-cardiac surgery. METHODS AND RESULTS: A total of 9164 consecutive high-risk patients undergoing 11 262 non-cardiac inpatient surgeries were prospectively included. The incidence, phenotypes, determinants and outcome of pAHF, centrally adjudicated by independent cardiologists, were determined. The incidence of pAHF was 2.5% (95% confidence interval [CI] 2.2-2.8%); 51% of pAHF occurred in patients without known heart failure (de novo pAHF), and 49% in patients with chronic heart failure. Among patients with chronic heart failure, 10% developed pAHF, and among patients without a history of heart failure, 1.5% developed pAHF. Chronic heart failure, diabetes, urgent/emergent surgery, atrial fibrillation, cardiac troponin elevations above the 99th percentile, chronic obstructive pulmonary disease, anaemia, peripheral artery disease, coronary artery disease, and age, were independent predictors of pAHF in the logistic regression model. Patients with pAHF had significantly higher all-cause mortality (44% vs. 11%, p < 0.001) and AHF readmission (15% vs. 2%, p < 0.001) within 1 year than patients without pAHF. After Cox regression analysis, pAHF was an independent predictor of all-cause mortality (adjusted hazard ratio [aHR] 1.7 [95% CI 1.3-2.2]; p < 0.001) and AHF readmission (aHR 2.3 [95% CI 1.5-3.7]; p < 0.001). Findings were confirmed in an external validation cohort using a prospective multicentre cohort of 1250 patients (incidence of pAHF 2.4% [95% CI 1.6-3.3%]). CONCLUSIONS: Postoperative AHF frequently developed following non-cardiac surgery, being de novo in half of cases, and associated with a very high mortality.

Optimizing environmental and economic aspects of collaborative transportation and logistics related to infrastructure projects - A case study from Norway.

The main challenge addressed in this paper is how to handle and recycle the large amount of C&D waste that is generated from infrastructure projects. The study is motivated by Bærum Ressursbank in Norway and their aim of finding logistical solutions to an expected surplus of 15 million m3 of waste from infrastructure projects in the next decade. We identify the key decisions as the design of the distribution network for both surplus waste materials and new construction materials and the investments in processing machinery at each recycling facility, and we call the problem representing this situation the Infrastructure Waste Management Problem (IWMP). The methodologies used are mathematical programming and operations research. We formulate the IWMP as a mixed integer linear program and identify two objectives; to minimize transportation costs and to minimize the environmental impact of the operations. The description of the problem, assumptions, and data are based on cases that represent the situation of Bærum Ressursbank. A special emphasis in the analysis is to quantify the gains from collaboration. Comparing individual planning of each project with an ideal situation of complete collaboration gives a cost reduction of more than 29% and a reduction in emissions of more than 14%. The study supports the conjecture by Bærum Ressursbank that large cost savings and considerable reductions in environmental impact are possible through collaboration.

Comparison of image quality between a novel mobile CT scanner and current generation stationary CT scanners.

PURPOSE: Point-of-care imaging with mobile CT scanners offers several advantages, provided that the image quality is satisfactory. Our aim was to compare image quality of a novel mobile CT to stationary scanners for patients in a neurosurgical intensive care unit (ICU). METHODS: From November 2020 to April 2021, all patients above 18 years of age examined by a mobile CT scanner at a neurosurgical ICU were included if they also had a stationary head CT examination during the same hospitalization. Quantitative image quality parameters included attenuation and noise in six predefined regions of interest, as well as contrast-to-noise ratio between gray and white matter. Subjective image quality was rated on a 4-garde scale, by four radiologists blinded to scanner parameters. RESULTS: Fifty patients were included in the final study population. Radiation dose and image attenuation values were similar for mobCT and stationary CTs. There was a small statistically significant difference in subjective quality rating between mobCT and stationary CT images. Two radiologists favored the stationary CT images, one was neutral, and one favored mobCT images. For overall image quality, 14% of mobCT images were rated grade 1 (poor image quality) compared to 8% for stationary CT images. CONCLUSION: Point-of-care brain CT imaging was successfully performed on clinical neurosurgical ICU patients with small reduction in image quality, predominantly affecting the posterior fossa, compared to high-end stationary CT scanners.

The Olfactomedin-4-Defined Human Neutrophil Subsets Differ in Proteomic Profile in Healthy Individuals and Patients with Septic Shock.

The specific granule glycoprotein olfactomedin-4 (Olfm4) marks a subset (1-70%) of human neutrophils and the Olfm4-high (Olfm4-H) proportion has been found to correlate with septic shock severity. The aim of this study was to decipher proteomic differences between the subsets in healthy individuals, hypothesizing that Olfm4-H neutrophils have a proteomic profile distinct from that of Olfm4 low (Olfm4-L) neutrophils. We then extended the investigation to septic shock. A novel protocol for the preparation of fixed, antibody-stained, and sorted neutrophils for LC-MS/MS was developed. In healthy individuals, 39 proteins showed increased abundance in Olfm4-H, including the small GTPases Rab3d and Rab11a. In Olfm4-L, 52 proteins including neutrophil defensin alpha 4, CXCR1, Rab3a, and S100-A7 were more abundant. The data suggest differences in important neutrophil proteins that might impact immunological processes. However, in vitro experiments revealed no apparent difference in the ability to control bacteria nor produce oxygen radicals. In subsets isolated from patients with septic shock, 24 proteins including cytochrome b-245 chaperone 1 had significantly higher abundance in Olfm4-H and 30 in Olfm4-L, including Fc receptor proteins. There was no correlation between Olfm4-H proportion and septic shock severity, but plasma Olfm4 concentration was elevated in septic shock. Thus, the Olfm4-H and Olfm4-L neutrophils have different proteomic profiles, but there was no evident functional significance of the differences in septic shock.

Educational intervention in triage with the Swedish triage scale RETTS©, with focus on specialist nurse students in ambulance and emergency care - A cross-sectional study.

AIM: To determine the reliability of application of the RETTS© triage scale after an educational intervention using paper-based scenarios in emergency care education. BACKGROUND: Knowledge about and education in triage are important factors in triagescale implementation. Presenting students with a large number of triage scenarios is a common part of triage education. METHODS: In this prospective cross-sectional study at two universities students undergoing education in emergency care used RETTS© to assess triage level in 46 paper-based scenarios. RESULTS: 57 students in the study made 2590 final triage decisions. Fleiss Kappa for final triage was 0.411 which is in the lower range of moderate agreement. In 25 of 46 (53.4%) scenarios, final triage levels did not agree about whether the case was stable or unstable. CONCLUSION/IMPLICATIONS: Application of the RETTS© triage scale after an educational intervention with paper-based simulation in emergency care education resulted in moderate agreement about the final levels of triage.

Incidence of acute myocardial injury and its association with left and right ventricular systolic dysfunction in critically ill COVID-19 patients.

BACKGROUND: Previous studies have found an increase in cardiac troponins (cTns) and echocardiographic abnormalities in patients with COVID-19 and reported their association with poor clinical outcomes. Whether acute injury occurs during the course of critical care and if it is associated with cardiac function is unknown. The purpose of this study was to document the incidence of acute myocardial injury (AMInj) and echocardiographically defined left ventricular (LV) and right ventricular (RV) systolic dysfunction in consecutive patients admitted to an intensive care unit (ICU) for COVID-19. The relationship between AMInj and echocardiographic abnormalities during the first 14 days of ICU admission was studied. Finally, the association between echocardiographic findings, AMInj and clinical outcome was evaluated. METHODS: Seventy-four consecutive patients (≥18 years) admitted to the ICU at Linköping University Hospital between 19 Mar 2020 and 31 Dec 2020 for COVID-19 were included. High-sensitivity troponin-T (hsTnT) was measured daily for up to 14 days. Transthoracic echocardiography was conducted within 72 h of ICU admission. Acute myocardial injury was defined as an increased hsTnT > 14ng/l and a > 20% absolute change with or without ischaemic symptoms. LV and RV systolic dysfunction was defined as at least 2 abnormal indicators of systolic function specified by consensus guidelines. RESULTS: Increased hsTnT was observed in 59% of patients at ICU admission, and 82% developed AMInj with peak levels at 8 (3-13) days after ICU admission. AMInj was not statistically significantly associated with 30-day mortality but was associated with an increased duration of invasive mechanical ventilation (10 (3-13) vs. 5 days (0-9), p=0.001) as well as ICU length of stay (LOS) (19.5 (11-28) vs. 7 days (5-13), p=0.015). After adjustment for SAPS-3 and admission SOFA score, the effect of AMInj was significant only for the duration of mechanical ventilation (p=0.030). The incidence of LV and RV dysfunction was 28% and 22%, respectively. Only indices of LV and RV longitudinal contractility (mitral and tricuspid annular plane systolic excursion) were associated with AMInj. Echocardiographic parameters were not associated with clinical outcome. CONCLUSIONS: Myocardial injury is common in critically ill patients with COVID-19, with AMInj developing in more than 80% after ICU admission. In contrast, LV and RV dysfunction occurred in approximately one-quarter of patients. AMInj was associated with an increased need for mechanical ventilation and ICU LOS but neither AMInj nor ventricular dysfunction was significantly associated with mortality.

Ethics education to support ethical competence learning in healthcare: an integrative systematic review.

BACKGROUND: Ethical problems in everyday healthcare work emerge for many reasons and constitute threats to ethical values. If these threats are not managed appropriately, there is a risk that the patient may be inflicted with moral harm or injury, while healthcare professionals are at risk of feeling moral distress. Therefore, it is essential to support the learning and development of ethical competencies among healthcare professionals and students. The aim of this study was to explore the available literature regarding ethics education that promotes ethical competence learning for healthcare professionals and students undergoing training in healthcare professions. METHODS: In this integrative systematic review, literature was searched within the PubMed, CINAHL, and PsycInfo databases using the search terms 'health personnel', 'students', 'ethics', 'moral', 'simulation', and 'teaching'. In total, 40 articles were selected for review. These articles included professionals from various healthcare professions and students who trained in these professions as subjects. The articles described participation in various forms of ethics education. Data were extracted and synthesised using thematic analysis. RESULTS: The review identified the need for support to make ethical competence learning possible, which in the long run was considered to promote the ability to manage ethical problems. Ethical competence learning was found to be helpful to healthcare professionals and students in drawing attention to ethical problems that they were not previously aware of. Dealing with ethical problems is primarily about reasoning about what is right and in the patient's best interests, along with making decisions about what needs to be done in a specific situation. CONCLUSIONS: The review identified different designs and course content for ethics education to support ethical competence learning. The findings could be used to develop healthcare professionals' and students' readiness and capabilities to recognise as well as to respond appropriately to ethically problematic work situations.

A review of the advances in composites/nanocomposites for triboelectric nanogenerators.

Material development is essential when studying triboelectric nanogenerators (TENGs). This importance is because the performance of TENGs is highly dependent on the properties of the utilized triboelectric materials. To obtain more specific properties, composites have been developed that combine the features of their components. According to Google Scholar, 55% of published papers related to triboelectric nanogenerators have utilized or mentioned composites. This number is 34.5% if one searches with the keyword nanocomposites instead of composites. The importance of composites is because they can exhibit new dielectric properties, better mechanical strength, enhanced charge affinities, etc. Therefore, the development of new composites has great importance in TENG studies. In this paper, we review the production of nanocomposites, the types of nanocomposites, and their application in TENG studies. This review gives an overview of how nanocomposites boost the performance of TENGs and provides guidance for future studies.

Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience.

OBJECTIVES: To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. METHODS: Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens' MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen's κ (dichotomized data), Cohen's κw, and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as κ/κw ≥ 0.80 and ICC ≥ 0.80 (significance level at 95% CI ≥ 0.65). RESULTS: Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen's κ. All raters achieved adequate agreement expressed as Cohen's κw and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. CONCLUSION: We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences. KEY POINTS: • Radiologists with varying experience achieve adequate inter-modality agreement with similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. • Differences in rating styles might affect accuracy, this was most evident for senior neuroradiologists, and only junior radiologists achieved adequate agreement on dichotomized (abnormal/normal) ratings. • The use of an MTA scale template might compensate for varying clinical experience which could make it applicable for clinical use.

Ambulance clinicians' attitudes to older patients' self-determination when the patient has impaired decision-making ability: A Delphi study.

OBJECTIVE: The proportion of older people is increasing and reflects in the demand on ambulance services (AS). Patients can be more vulnerable and increasingly dependent, especially when their decision-making ability is impaired. Self-determination in older people has a positive relation to quality of life and can raise ethical conflicts in AS. Hence, the aim of this study was to empirically explore attitudes among Swedish ambulance clinicians (ACs) regarding older patients' self-determination in cases where patients have impaired decision-making ability, and who are in urgent need of care. MATERIALS AND METHODS: An explorative design was adopted. A Delphi technique was used, comprising four rounds, involving a group (N = 31) of prehospital emergency nurses (n = 14), registered nurses (n = 10) and emergency medical technicians (n = 7). Focus group conversations (Round 1) and questionnaires (Rounds 2-4) generated data. Round 1 was analysed using manifest content analysis, which ultimately resulted in the creation of discrete items. Each item was rated with a five-point Likert scale together with free-text answers. Consensus (≥70%) was calculated by trichotomising the Likert scale. RESULTS: Round 1 identified 108 items which were divided into four categories: (1) attitudes regarding the patient (n = 35), (2) attitudes regarding the patient relationship (n = 8), (3) attitudes regarding oneself and one's colleagues (n = 45), and (4) attitudes regarding other involved factors (n = 20). In Rounds 2-4, one item was identified in the free text from Round 2, generating a total of 109 items. After four rounds, 72 items (62%) reached consensus. CONCLUSIONS: The findings highlight the complexity of ACs' attitudes towards older patients' self-determination. The respect of older patients' self-determination is challenged by the patient, other healthcare personnel, significant others and/or colleagues. The study provided a unique opportunity to explore self-determination and shared decision-making. AS have to provide continued ethical training, for example to increase the use of simulation-based training or moral case deliberations in order to strengthen the ACs' moral abilities within their professional practice. IMPLICATIONS FOR PRACTICE: Ambulance services must develop opportunities to provide continued training within this topic. One option would be to increase the use of simulation-based training, focusing on ethical aspects of the care. Another option might be to facilitate moral case deliberations to strengthen the ACs' abilities to manage these issues while being able to share experiences with peers. These types of interventions should illuminate the importance of the topic for the individual AC, which, in turn, may strengthen and develop the caring abilities within an integrated care team.