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Activation of the kynurenine pathway (KP) has been shown to predict outcome in cardiac arrest (CA) patients. We validated these findings in a Swiss cohort.We measured admission tryptophan and kynurenine levels in 270 consecutive CA patients (38 in-hospital CA) and investigated associations with in-hospital mortality and neurological outcome at hospital discharge.120 of 270 (44%) patients died in the hospital. Compared to survivors, non-survivors showed higher median initial kynurenine levels (5.28 μmol/l [IQR 2.91 to 7.40] vs 3.58 μmol/l [IQR 2.47 to 5.46]; p 0.001) and a higher median kynurenine/tryptophan ratio (0.10 μmol/l [IQR 0.07 to 0.17] vs 0.07 μmol/l [IQR 0.05 to 0.1]; p 0.001). In a model adjusted for age, gender and comorbidities, kynurenine (OR 1.16, 95% CI 1.05 to 1.27; p = 0.001) and kynurenine/tryptophan ratio (OR 1.19, 95% CI 1.08 to 1.31; p = 0.003) were significantly associated with mortality. Results were similar for neurological outcome.Our findings validate a previous study and show associations of the activation of the KP with unfavorable outcomes after CA. Future studies should evaluate whether therapeutic modulation of the KP may impact clinical outcomes after CA.

Background A recent study found serum neurofilament light chain (NfL) levels to be strongly associated with poor neurological outcome in patients after cardiac arrest. Our aim was to confirm these findings in an independent validation study and to investigate whether NfL improves the prognostic value of two cardiac arrest-specific risk scores. Methods This prospective, single-center study included 164 consecutive adult after out-of-hospital cardiac arrest (OHCA) patients upon intensive care unit admission. We calculated two clinical risk scores (OHCA, CAHP) and measured NfL on admission within the first 24 h using the single molecule array NF-light® assay. The primary endpoint was neurological outcome at hospital discharge assessed with the cerebral performance category (CPC) score. Results Poor neurological outcome (CPC > 3) was found in 60% (98/164) of patients, with 55% (91/164) dying within 30 days of hospitalization. Compared to patients with favorable outcome, NfL was 14-times higher in patients with poor neurological outcome (685 ± 1787 vs. 49 ± 111 pg/mL), with an adjusted odds ratio of 3.4 (95% CI 2.1 to 5.6, p p p p p Conclusions Admission NfL was a strong outcome predictor and significantly improved two clinical risk scores regarding prognostication of neurological outcome in patients after cardiac arrest. When confirmed in future outcome studies, admission NfL should be considered as a standard laboratory measures in the evaluation of OHCA patients.

Background The understanding of vascular plasticity is key to defining the role of blood vessels in physiologic and pathogenic processes. In the present study, the impact of the vascular quiescence marker SPARCL1 on angiogenesis, capillary morphogenesis, and vessel integrity was evaluated. Methods Angiogenesis was studied using the metatarsal test, an ex vivo model of sprouting angiogenesis. In addition, acute and chronic dextran sodium sulfate colitis models with SPARCL1 knockout mice were applied. Results This approach indicated that SPARCL1 inhibits angiogenesis and supports vessel morphogenesis and integrity. Evidence was provided that SPARCL1-mediated stabilization of vessel integrity counteracts vessel permeability and inflammation in acute and chronic dextran sodium sulfate colitis models. Structure-function analyses of purified SPARCL1 identified the acidic domain of the protein necessary for its anti-angiogenic activity. Conclusions Our findings inaugurate SPARCL1 as a blood vessel–derived anti-angiogenic molecule required for vessel morphogenesis and integrity. SPARCL1 opens new perspectives as a vascular marker of susceptibility to colitis and as a therapeutic molecule to support blood vessel stability in this disease.

Aim: To analyze the efficacy of checkpoint inhibitors in soft tissue sarcoma. Materials & methods: We retrospectively reviewed patients with advanced soft tissue sarcoma treated with ipilimumab and nivolumab. All patients who received at least one cycle were included. Results: One patient had a complete response and five had a partial response, for an objective response rate of 15%. Clinical benefit rate was 34% with a median duration of 12.0 months (range: 4.5 to 28.9+ months [mo]). Median overall survival was 12.0 months (95% CI: 4.5–23.7+ mo). Median progression-free survival was 2.7 months (95% CI: 2.3–4.5+ mo) by Response Evaluation Criteria in Solid Tumors 1.1 and 2.9 months (2.5–6.0+ mo) by immune-related Response Evaluation Criteria in Solid Tumors. Adverse events of any grade were seen in 58% of patients, the most common being fatigue (21%) and cough (10%), 5% of patients experienced a grade 3 adverse event (AE) (hyperglycemia) or grade 4 AE (myocarditis). Conclusion: Ipilimumab/nivolumab combination showed efficacy and was well tolerated in advanced soft tissue sarcoma.

Objectives Prior research found the gut microbiota-dependent and pro-atherogenic molecule trimethylamine-N-oxide (TMAO) to be associated with cardiovascular events as well as all-cause mortality in different patient populations with cardiovascular disease. Our aim was to investigate the prognostic value of TMAO regarding clinical outcomes in patients after out-of-hospital cardiac arrest (OHCA). Methods We included consecutive OHCA patients upon intensive care unit admission into this prospective observational study between October 2012 and May 2016. We studied associations of admission serum TMAO with in-hospital mortality (primary endpoint), 90-day mortality and neurological outcome defined by the Cerebral Performance Category (CPC) scale. Results We included 258 OHCA patients of which 44.6% died during hospitalization. Hospital non-survivors showed significantly higher admission TMAO levels (μmol L−1) compared to hospital survivors (median interquartile range (IQR) 13.2 (6.6–34.9) vs. 6.4 (2.9–15.9), p Conclusions In patients after OHCA, TMAO levels were independently associated with in-hospital mortality and other adverse clinical outcomes and may help to improve prognostication for these patients in the future. Whether TMAO levels can be influenced by nutritional interventions should be addressed in future studies.

The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. As the transit-amplifying progenitors of the intestinal epithelium generate ~300 cells per crypt every day, regulated cell death and sloughing at the apical surface keeps the overall cell number in check. An aberrant increase in the rate of intestinal epithelial cell (IEC) death underlies instances of extensive epithelial erosion, which is characteristic of several intestinal diseases such as inflammatory bowel disease and infectious colitis. Emerging evidence points to a crucial role of necroptosis, autophagy and pyroptosis as important modes of programmed cell death in the intestine in addition to apoptosis. The mode of cell death affects tissue restitution responses and ultimately the long-term risks of intestinal fibrosis and colorectal cancer. A vicious cycle of intestinal barrier breach, misregulated cell death and subsequent inflammation is at the heart of chronic inflammatory and infectious gastrointestinal diseases. This Review discusses the underlying molecular and cellular underpinnings that control programmed cell death in IECs, which emerge during intestinal diseases. Translational aspects of cell death modulation for the development of novel therapeutic alternatives for inflammatory bowel diseases and colorectal cancer are also discussed.

To evaluate the variability of quantitative measurements of metastatic liver lesions by using a multi-radiation-dose-level and multi-reader comparison. Twenty-three study subjects (mean age, 60 years) with 39 liver lesions who underwent a single-energy dual-source contrast-enhanced staging CT between June 2015 and December 2015 were included. CT data were reconstructed with seven different radiation dose levels (ranging from 25 to 100%) on the basis of a single CT acquisition. Four radiologists independently performed manual tumor measurements and two radiologists performed semi-automated tumor measurements. Interobserver, intraobserver, and interdose sources of variability for longest diameter and volumetric measurements were estimated and compared using Wilcoxon rank-sum tests and intraclass correlation coefficients. Inter- and intraobserver variabilities for manual measurements of the longest diameter were higher compared to semi-automated measurements (p

The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn’s disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD., Dietary lipids are linked to the development of inflammatory bowel diseases through unclear mechanisms. Here, the authors report that dietary polyunsaturated fatty acids trigger intestinal inflammation resembling aspects of Crohn’s disease, which is restricted by glutathione peroxidase 4 in the intestinal epithelium.

The design of software systems inevitably enacts normative boundaries around the site of intervention. These boundaries are, in part, a reflection of the values, ethics, power, and politics of the situation and the process of design itself. This paper argues that Requirements Engineering (RE) require more robust frameworks and techniques to navigate the values implicit in systems design work. To this end, we present the findings from a case of action research where we employed Critical Systems Heuristics (CSH), a framework from Critical Systems Thinking (CST) during requirements gathering for Homesound, a system to safeguard elderly people living alone while protecting their autonomy. We use categories from CSH to inform expert interviews and reflection, showing how CSH can be simply combined with RE techniques (such as the Volere template) to explore and reveal the value-judgements underlying requirements., 1 figure, submitted to and accepted for publication in IEEESW

Alzheimer's disease (AD) is the most commonly diagnosed dementia but its underlying pathological mechanisms still unclear. Neuroinflammation and secretion of cytokines such as interleukin-6 (IL-6) accompany the main hallmarks of the disease: amyloid plaques and neurofibrillary tangles. In this study, we analyzed the role of IL-6 trans-signaling in two mouse models of AD, Tg2576 and 3xTg-AD mice. The inhibition of IL-6 trans-signaling partially rescued the AD-induced mortality in females of both models. Before amyloid plaques deposition, it reversed AD-induced changes in exploration and anxiety (but did not affect locomotion) in Tg2576 female mice. However, after plaque deposition the only behavioral trait affected by the inhibition of IL-6 trans-signaling was locomotion. Results in the Morris water maze suggest that cognitive flexibility was reduced by the blocking of the IL-6 trans-signaling in young and old Tg2576 female mice. The inhibition of IL-6 trans-signaling also decreased amyloid plaque burden in cortex and hippocampus, and Aβ40 and Aβ42 levels in the cortex, of Tg2576 female mice. The aforementioned changes might be correlated with changes in blood vessels and matrix structure and organization rather than changes in neuroinflammation. 3xTgAD mice showed a very mild phenotype regarding amyloid cascade, but results were in accordance with those of Tg2576 mice. These results strongly suggest that the inhibition of the IL-6 trans-signaling could represent a powerful therapeutic target in AD.

Epidemiological studies have shown an increased risk of cardiovascular events in migraineurs. The pathophysiological mechanisms of this observation remain largely unknown. Recent genetic and epidemiologic studies suggest, that atherosclerosis might be the overlapping pathophysiological mechanism in migraine and coronary heart disease. The aim of the present study was to evaluate if the increased cardiovascular risk in migraineurs is attributed to an increased coronary artery calcification. For this the coronary artery calcium score was assessed by computed tomography of the heart in 1.437 patients of which 337 were migraineurs. All patients had a similar cardiovascular risk profile, so that the risk for coronary calcifications could be considered similar between migraineurs and non-migraineurs. The results showed no significant differences in the amount of coronary calcifications in patients with or without migraine. This suggests that a more pronounced coronary artery calcification, as a surrogate marker of coronary atherosclerosis, does not underlie the increased cardiovascular risk in migraineurs. A distinct common pathophysiological mechanism in migraine and coronary heart disease such as endothelial dysfunction or vasospasm should be discussed instead. However, it has to be considered, that the coronary artery calcification score does not indicate the total risk of atherosclerotic changes in the coronary arteries.

Simple Summary Autophagy is the capability of cells to dismantle and recycle parts of themselves. This process is closely intertwined with other crucial cell functions, such as growth and control of metabolism. Autophagy is oftentimes dysregulated in cancer and offers established and advanced tumors protection against a lack of nutrients and an advantage regarding proliferation. This review will present an overview of the basics of human autophagy, its dysregulation in cancer, and approaches to target autophagy in cancer treatment in recent and current clinical trials as well as new findings of preclinical research. Abstract Autophagy is a crucial general survival tactic of mammalian cells. It describes the capability of cells to disassemble and partially recycle cellular components (e.g., mitochondria) in case they are damaged and pose a risk to cell survival or simply if their resources are urgently needed elsewhere at the time. Autophagy-associated pathomechanisms have been increasingly recognized as important disease mechanisms in non-malignant (neurodegeneration, diffuse parenchymal lung disease) and malignant conditions alike. However, the overall consequences of autophagy for the organism depend particularly on the greater context in which autophagy occurs, such as the cell type or whether the cell is proliferating. In cancer, autophagy sustains cancer cell survival under challenging, i.e., resource-depleted, conditions. However, this leads to situations in which cancer cells are completely dependent on autophagy. Accordingly, autophagy represents a promising yet complex target in cancer treatment with therapeutically induced increase and decrease of autophagic flux as important therapeutic principles.

AIMS OF THE STUDY: There is increasing interest in better understanding of long COVID, a condition characterised by long-term sequelae — appearing or persisting after the typical convalescence period — of coronavirus disease 2019 (COVID-19). Herein, we describe long-term outcomes regarding residual symptoms and psychological distress in hospitalised patients 1 year after COVID-19. METHODS: This prospective cohort study included consecutive adult patients hospitalised for confirmed COVID-19 in two Swiss tertiary-care hospitals between March and June 2020. The primary endpoint was evidence of long COVID 1 year after discharge, defined as ≥1 persisting or new symptom related to COVID-19, from a predefined list of symptoms. Secondary endpoints included psychological distress and symptoms of post-traumatic stress disorder (PTSD). RESULTS: Among 90 patients included in the study, 63 (70%) had symptoms of long COVID 1 year after hospitalisation, particularly fatigue (46%), concentration difficulties (31%), shortness of breath (21%) and post-exertion malaise (20%). Three predictors, namely duration of hospitalisation (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.00–1.22; p = 0.041), severity of illness (OR 1.19, 95% CI 1.04–1.37; p = 0.013), and self-perceived overall health status 30 days after hospitalisation (OR 0.97, 95% CI 0.94–1.00; p = 0.027) were associated with long COVID. Regarding secondary endpoints, 16 (18%) experienced psychological distress and 3 (3.3%) patients had symptoms of PTSD. CONCLUSION: A high proportion of COVID-19 patients report symptoms of long COVID 1 year after hospitalisation, which negatively affects their quality of life. The most important risk factors were severe initial presentation of COVID-19 with long hospital stays.

Systemic inflammatory disorders (SIDs) comprise a broad range of diseases characterized by dysregulated excessive innate immune responses. Severe forms of SIDs can lead to organ failure and death, and their increasing incidence represents a major issue for the health care system. Protease-mediated ectodomain shedding of cytokines and their receptors represents a central mechanism in the regulation of inflammatory responses. The metalloprotease A Disintegrin And Metalloproteinase (ADAM) 17 is the best-characterized ectodomain sheddase capable of releasing TNF-α and soluble IL-6 receptor, which are decisive factors of systemic inflammation. Recently, meprin metalloproteases were also identified as IL-6 receptor sheddases and activators of the pro-inflammatory cytokines IL-1β and IL-18. In different mouse models of SID, particularly those mimicking a sepsis-like phenotype, ADAM17 and meprins have been found to promote disease progression. In this review, we summarize the role of ADAM10, ADAM17 and meprins in the onset and progression of sepsis and discuss their potential as therapeutic targets.

Inflammatory bowel diseases (IBD) are characterized by chronic dysregulation of immune homeostasis, epithelial demise, immune cell activation, and microbial translocation. Each of these processes leads to proinflammatory changes via the release of cytokines, damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs), respectively. The impact of these noxious agents on the survival and function of the enteric nervous system (ENS) is poorly understood. Here, we show that in contrast to an expected decrease, experimental as well as clinical colitis causes an increase in the transcript levels of enteric neuronal and glial genes. Immunostaining revealed an elevated neuronal innervation of the inflamed regions of the gut mucosa. The increase was seen in models with overt damage to epithelial cells and models of T cell-induced colitis. Transcriptomic data from treatment naïve pediatric IBD patients also confirmed the increase in the neuroglial genes and were replicated on an independent adult IBD dataset. This induction in the neuroglial genes was transient as levels returned to normal upon the induction of remission in both mouse models as well as colitis patients. Our data highlight the dynamic and robust nature of the enteric nervous system in colitis and open novel questions on its regulation.

Key Points Question Are communication interventions at hospital discharge associated with rates of hospital readmission? Findings In this systematic review and meta-analysis including a pooled analysis of 19 randomized clinical trials involving 3953 patients for the primary end point, communication interventions at discharge were significantly associated with lower readmission rates, higher medication adherence, and higher patient satisfaction. Meaning These findings suggest that communication interventions at discharge have the potential to decrease hospital readmissions and improve treatment adherence and patient satisfaction., This systematic review and meta-analysis examines the associations of communication interventions at hospital discharge with readmission rates and other patient-relevant outcomes., Importance Shortcomings in the education of patients at hospital discharge are associated with higher risks for treatment failure and hospital readmission. Whether improving communication at discharge through specific interventions has an association with patient-relevant outcomes remains unclear. Objective To conduct a systematic review and meta-analysis on the association of communication interventions at hospital discharge with readmission rates and other patient-relevant outcomes. Data Sources PubMed, EMBASE, PsycINFO, and CINAHL were systematically searched from the inception of each database to February 28, 2021. Study Selection Randomized clinical trials that randomized patients to receiving a discharge communication intervention or a control group were included. Data Extraction and Synthesis Two independent reviewers extracted data on outcomes and trial and patient characteristics. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Data were pooled using a random-effects model, and risk ratios (RRs) with corresponding 95% CIs are reported. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures The primary outcome was hospital readmission, and secondary outcomes included adherence to treatment regimen, patient satisfaction, mortality, and emergency department reattendance 30 days after hospital discharge. Results We included 60 randomized clinical trials with a total of 16 070 patients for the qualitative synthesis and 19 trials with a total of 3953 patients for the quantitative synthesis of the primary outcome. Of these, 11 trials had low risk of bias, 6 trials had high risk of bias, and 2 trials had unclear risk of bias. Communication interventions at discharge were significantly associated with lower readmission rates (179 of 1959 patients [9.1%] in intervention groups vs 270 of 1994 patients [13.5%] in control groups; RR, 0.69; 95% CI, 0.56-0.84), higher adherence to treatment regimen (1729 of 2009 patients [86.1%] in intervention groups vs 1599 of 2024 patients [79.0%] in control groups; RR, 1.24; 95% CI, 1.13-1.37), and higher patient satisfaction (1187 of 1949 patients [60.9%] in intervention groups vs 991 of 2002 patients [49.5%] in control groups; RR, 1.41; 95% CI, 1.20-1.66). Conclusions and Relevance These findings suggest that communication interventions at discharge are significantly associated with fewer hospital readmissions, higher treatment adherence, and higher patient satisfaction and thus are important to facilitate the transition of care.

OBJECTIVES Recent research suggests that the gender of health care providers may affect their medical performance. This trial investigated (1) the effects of the gender composition of resuscitation teams on leadership behaviour of first responders and (2) the effects of a brief gender-specific instruction on leadership behaviour of female first responders. METHODS This prospective randomised single-blinded trial, carried out between 2008 and 2016, included 364 fourth-year medical students of two Swiss universities. One hundred and eighty-two teams of two students each were confronted with a simulated cardiac arrest, occurring in the presence of a first responder while a second responder is summoned to help. The effect of gender composition was assessed by comparing all possible gender-combinations of first and second responders. The gender-specific instruction focused on the importance of leadership, gender differences in self-esteem and leadership, acknowledgement of unease while leading, professional role, and mission statement to lead was delivered orally for 10 min by a staff physician and tested by randomising female first responders to the intervention group or the control group. The primary outcome, based on ratings of video-recorded performance, was the first responders' percentage contribution to their teams' leadership statements and critical treatment decision making. RESULTS Female first responders contributed significantly less to leadership statements (53% vs. 76%; P = 0.001) and critical decisions (57% vs. 76%; P = 0.018) than male first responders. For critical treatment decisions, this effect was more pronounced (P = 0.007) when the second responder was male. The gender-specific intervention significantly increased female first responder's contribution to leadership statements (P = 0.024) and critical treatment decisions (P = 0.034). CONCLUSIONS Female first responders contributed less to their rescue teams' leadership and critical decision making than their male colleagues. A brief gender-specific leadership instruction was effective in improving female medical students' leadership behaviours.

We describe a 40-year-old man with severe COVID-19 requiring mechanical ventilation who developed aorto-bi-iliac arterial, right lower extremity arterial, intracardiac, pulmonary arterial and ilio-caval venous thromboses and required right lower extremity amputation for acute limb ischemia. This unique case illustrates COVID-19-associated thrombotic complications occurring at multiple, different sites in the cardiovascular system of a single infected patient., Highlights • COVID-19 related thrombosis may have various cardiovascular manifestations in the same patient. • Imaging has an important role in detection of COVID-19 related complications. • Knowledge of imaging and increased thromboembolism risk can lead to early detection and treatment.

Background Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort. Objective To compare bedside versus outside the room patient case presentation regarding patients' knowledge about their medical care. Design Randomized, controlled, parallel-group trial. (ClinicalTrials.gov: NCT03210987). Setting 3 Swiss teaching hospitals. Patients Adult medical patients who were hospitalized. Intervention Patients were randomly assigned to bedside or outside the room case presentation. Measurements The primary endpoint was patients' average knowledge of 3 dimensions of their medical care (each rated on a visual analogue scale from 0 to 100): understanding their disease, the therapeutic approach being used, and further plans for care. Results Compared with patients in the outside the room group (n = 443), those in the bedside presentation group (n = 476) reported similar knowledge about their medical care (mean, 79.5 points [SD, 21.6] vs. 79.4 points [SD, 19.8]; adjusted difference, 0.09 points [95% CI, -2.58 to 2.76 points]; P = 0.95). Also, an objective rating of patient knowledge by the study team was similar for the 2 groups, but the bedside presentation group had higher ratings of confusion about medical jargon and uncertainty caused by team discussions. Bedside ward rounds were more efficient (mean, 11.89 minutes per patient [SD, 4.92] vs. 14.14 minutes per patient [SD, 5.65]; adjusted difference, -2.31 minutes [CI, -2.98 to -1.63 minutes]; P Limitation Only Swiss hospitals and medical patients were included. Conclusion Compared with outside the room case presentation, bedside case presentation was shorter and resulted in similar patient knowledge, but sensitive topics were more often avoided and patient confusion was higher. Physicians presenting at the bedside need to be skilled in the use of medical language to avoid confusion and misunderstandings. Primary funding source Swiss National Foundation (10531C_ 182422).

Inflammatory cytokines initiate and sustain the perpetuation of processes leading to chronic inflammatory conditions such as inflammatory bowel diseases (IBD). The nature of the trigger causing an inflammatory reaction decides whether type 1, type 17, or type 2 immune responses, typically characterized by the respective T- helper cell subsets, come into effect. In the intestine, Type 2 responses have been linked with mucosal healing and resolution upon an immune challenge involving parasitic infections. However, type 2 cytokines are frequently elevated in certain types of IBD in particular ulcerative colitis (UC) leading to the assumption that Th2 cells might critically support the pathogenesis of UC raising the question of whether such elevated type 2 responses in IBD are beneficial or detrimental. In line with this, previous studies showed that suppression of IL-13 and other type 2 related molecules in murine models could improve the outcomes of intestinal inflammation. However, therapeutic attempts of neutralizing IL-13 in ulcerative colitis patients have yielded no benefits. Thus, a better understanding of the role of type 2 cytokines in regulating intestinal inflammation is required. Here, we took a comparative transcriptomic approach to address how Th2 responses evolve in different mouse models of colitis and human IBD datasets. Our data show that type 2 immune-related transcripts are induced in the inflamed gut of IBD patients in both Crohn's disease and UC and across widely used mouse models of IBD. Collectively our data implicate that the presence of a type 2 signature rather defines a distinct state of intestinal inflammation than a disease-specific pathomechanism.

BackgroundDue to the dramatic measures accompanying isolation and the general uncertainty and fear associated with COVID-19, patients and relatives may be at high risk for adverse psychological outcomes. Until now there has been limited research focusing on the prevalence of psychological distress and associated factors in COVID-19 patients and their relatives. The objective of our study was to assess psychological distress in COVID-19 patients and their relatives 30 days after hospital discharge.MethodsIn this prospective observational cohort study at two Swiss tertiary-care hospitals we included consecutive adult patients hospitalized between March and June 2020 for a proven COVID-19 and their relatives. Psychological distress was defined as symptoms of anxiety and/or depression measured with the Hospital Anxiety and Depression Scale (HADS), i.e., a score of ≥8 on the depression and/or anxiety subscale. We further evaluated symptoms of post-traumatic stress disorder (PTSD), defined as a score of ≥1.5 on the Impact of Event Scale-Revised (IES-R).ResultsAmong 126 included patients, 24 (19.1%) had psychological distress and 10 (8.7%) had symptoms of PTSD 30 days after hospital discharge. In multivariate logistic regression analyses three factors were independently associated with psychological distress in patients: resilience (OR 0.82; 95%CI 0.71 to 0.94; p = 0.005), high levels of perceived stress (OR 1.21; 95%CI 1.06 to 1.38; p = 0.006) and low frequency of contact with relatives (OR 7.67; 95%CI 1.42 to 41.58; p = 0.018). The model showed good discrimination, with an area under the receiver-operating characteristic curve (AUC) of 0.92. Among 153 relatives, 35 (22.9%) showed symptoms of psychological distress, and 3 (2%) of PTSD. For relatives, resilience was negatively associated (OR 0.85; 95%CI 0.75 to 0.96; p = 0.007), whereas perceived overall burden caused by COVID-19 was positively associated with psychological distress (OR 1.72; 95%CI 1.31 to 2.25; pConclusionA relevant number of COVID-19 patients as well as their relatives exhibited psychological distress 30 days after hospital discharge. These results might aid in development of strategies to prevent psychological distress in COVID-19 patients and their relatives.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with rising incidence. Diseased tissues are heavily vascularized. Surprisingly, the pathogenic impact of the vasculature in IBD and the underlying regulatory mechanisms remain largely unknown. IFN-γ is a major cytokine in IBD pathogenesis, but in the context of the disease, it is almost exclusively its immune-modulatory and epithelial cell-directed functions that have been considered. Recent studies by our group demonstrated that IFN-γ also exerts potent effects on blood vessels. Based on these considerations, we analyzed the vessel-directed pathogenic functions of IFN-γ and found that it drives IBD pathogenesis through vascular barrier disruption. Specifically, we show that inhibition of the IFN-γ response in vessels by endothelial-specific knockout of IFN-γ receptor 2 ameliorates experimentally induced colitis in mice. IFN-γ acts pathogenic by causing a breakdown of the vascular barrier through disruption of the adherens junction protein VE-cadherin. Notably, intestinal vascular barrier dysfunction was also confirmed in human IBD patients, supporting the clinical relevance of our findings. Treatment with imatinib restored VE-cadherin/adherens junctions, inhibited vascular permeability, and significantly reduced colonic inflammation in experimental colitis. Our findings inaugurate the pathogenic impact of IFN-γ-mediated intestinal vessel activation in IBD and open new avenues for vascular-directed treatment of this disease.

Zusammenfassung. Die Kommunikation im Arzt-Patienten-Gespräch gehört zum Fundament einer guten Behandlung und wird heute als eine der Kernkompetenzen in der Medizin angesehen. Kommunikation hat Einfluss auf Behandlungsqualität und Patienten-Outcomes, schafft Vertrauen und hilft, Behandlungsfehler zu vermeiden. Sowohl Arzt-zentrierte als auch Patienten-zentrierte Techniken ermöglichen, in bis zu 80 % aller medizinischen Fälle eine Diagnosefindung alleine durch die Anamnese zu finden. Neben Informationsgewinnung ist auch die Übermittlung komplexer sowie schlechter Nachrichten ein wichtiger Bereich der medizinischen Kommunikation. Eine gute Kommunikation trägt nicht nur zu mehr Zufriedenheit von Patienten und Angehörigen bei sondern kann auch deren Outcome massgeblich verbessern.

The use of finite element analysis (FEA) to predict material flow and die deflection is well implemented in the scientific community but it is still new in the extrusion industry or for die makers. This paper deals with the advantages and limitations of FE-analysis to predict material flow and to optimize die design from an industrial point of view. For this study two software packages, HyperXtrude® and PF-Extrude®, have been used to predict the material flow in two applications, the optimization of a heat sink profile and the filling process of a porthole die

Objective During cardiopulmonary resuscitation (CPR), it remains unclear whether designating an individual person as team leader compared with emergent leadership results in better team performance. Also, the effect of CPR team size on team performance remains understudied. Methods This randomized-controlled trial compared designated versus emergent leadership and size of rescue team (3 vs 6 rescuers) on resuscitation performance. Results We included 90 teams with a total of 408 students. No difference in mean (±SD) hands-on time (seconds) were observed between emergent leadership (106 ± 30) compared to designated leadership (103 ± 27) groups (adjusted difference − 2.97 (95%CI -15.75 to 9.80, p = 0.645), or between smaller (103 ± 30) and larger teams (106 ± 26, adjusted difference 3.53, 95%CI -8.47 to 15.53, p = 0.56). Emergent leadership groups had a shorter time to circulation check and first defibrillation, but the quality of CPR based on arm and shoulder position was lower. No differences in CPR quality measures were observed between smaller and larger teams. Conclusions Within this international US/Swiss trial, leadership designation and larger team size did not improve hands-on time, but emergent leadership teams initiated defibrillation earlier. Improvements in performance may be more likely to be achieved by optimization of emergent leadership than increasing the size of cardiac arrest teams.

ObjectiveBleeding ulcers and erosions are hallmarks of active ulcerative colitis (UC). However, the mechanisms controlling bleeding and mucosal haemostasis remain elusive.DesignWe used high-resolution endoscopy and colon tissue samples of active UC (n = 36) as well as experimental models of physical and chemical mucosal damage in mice deficient for peptidyl-arginine deiminase-4 (PAD4), gnotobiotic mice and controls. We employed endoscopy, histochemistry, live-cell microscopy and flow cytometry to study eroded mucosal surfaces during mucosal haemostasis.ResultsErosions and ulcerations in UC were covered by fresh blood, haematin or fibrin visible by endoscopy. Fibrin layers rather than fresh blood or haematin on erosions were inversely correlated with rectal bleeding in UC. Fibrin layers contained ample amounts of neutrophils coaggregated with neutrophil extracellular traps (NETs) with detectable activity of PAD. Transcriptome analyses showed significantly elevatedPAD4expression in active UC. In experimentally inflicted wounds, we found that neutrophils underwent NET formation in a PAD4-dependent manner hours after formation of primary blood clots, and remodelled clots to immunothrombi containing citrullinated histones, even in the absence of microbiota. PAD4-deficient mice experienced an exacerbated course of dextrane sodium sulfate-induced colitis with markedly increased rectal bleeding (96 % vs 10 %) as compared with controls. PAD4-deficient mice failed to remodel blood clots on mucosal wounds eliciting impaired healing. Thus, NET-associated immunothrombi are protective in acute colitis, while insufficient immunothrombosis is associated with rectal bleeding.ConclusionOur findings uncover that neutrophils induce secondary immunothrombosis by PAD4-dependent mechanisms. Insufficient immunothrombosis may favour rectal bleeding in UC.

Chronic idiopathic inflammatory bowel disease (IBD) cases are on the rise, with approximately 6.8 million people diagnosed in 2017 [1]. Diagnosing the two main forms of IBD, ulcerative colitis (UC) and Crohn’s disease (CD), involves a combination of clinical history, laboratory findings, imaging, endoscopy and histology [2]. The histopathological diagnosis of IBD is based on a combination of microscopic findings, with consideration of clinical data that include the patient’s age, symptoms, duration of symptoms and endoscopic results [3–17]. CD is a chronic, progressively destructive disease with an intermittent course in most cases. UC is most often described as relapsing and remitting, with symptoms of active disease that alternate with periods of clinical quiescence called remission [18, 19]. Until recently, therapeutic strategies in both diseases aimed to achieve adequate control of gastrointestinal inflammation. In recent years, however, mucosal healing has become the key treatment goal in IBD. It is associated with improved clinical outcomes, prolonged remission, fewer hospitalizations and decreased probability for surgery [20–36]. Patients with mucosal healing have lower rates of clinical relapse compared to those with evidence of active or quiescent disease. Endoscopic evaluation without histology, however, may be insufficient to deem treated IBD mucosa as completely healed [34, 36]. Furthermore, histologic identification of active disease has also been shown to better predict the development of neoplasia in patients with UC compared to endoscopic assessment of activity [30–32, 34, 37]. The fact that concordance between endoscopic and histological remission is moderate only—with histological remission being superior—underscores the necessity of incorporating histologic methods of activity scoring into clinical trials [34]. In fact, in 2016, the Food and Drug Administration (FDA) of the United States Department of Health and Human Services recommended that histologic assessment be used in conjunction with endoscopy [38]. A number of histologic indices for assessing activity in UC and CD exist. Nevertheless, they all have limitations, including lack of full validation, difficulty of usage and heterogeneity in their standards for distinguishing between quiescent disease and histologic normalization [39, 40]. Moreover, there is also a need for standardization of biopsy procedures in UC and CD on the endoscopic end. Recommendations for biopsy procedures and IBD scoring exist from many internationally recognized organizations, such as the European Crohn’s and Colitis Organisation (ECCO), the World Gastroenterology Organisation (WGO), the British Society of Gastroenterology (BSG), the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD), the American College of Gastroenterology (ACG) and the American Society for Gastrointestinal Endoscopy (ASGE). Some of them have recently been updated [17, 19, 28, 41–51]. However, in practice, these existing recommendations are not widely adhered to and there is still a need for standardizing the number of IBD biopsies, the locations they are taken from and an accepted validated IBD histologic assessment tool for daily practice. For these reasons, the objectives of the 2020 International Consensus Conference on IBD Activity Scoring were (i) to review existing recommendations and to agree upon ten recommendations with the highest impact to maximize diagnostic information from biopsies for UC and CD and (ii) to agree on a simple, histologic scoring system for both types of IBD that is able to distinguish between quiescent disease and mucosal healing and has potential for use in daily routine practice as well as for clinical trials.

Background and Aims Histological scoring plays a key role in the assessment of disease activity in ulcerative colitis [UC] and is also important in Crohn´s disease [CD]. Currently, there is no common scoring available for UC and CD. We aimed to validate the Inflammatory Bowel Disease [IBD]—Distribution [D], Chronicity [C], Activity [A] score [IBD-DCA score] for histological disease activity assessment in IBD. Methods Inter- and intra-rater reliability were assessed by 16 observers on biopsy specimens from 59 patients with UC and 25 patients with CD. Construct validity and responsiveness to treatment were retrospectively evaluated in a second cohort of 30 patients. Results Inter-rater reliability was moderate to good for the UC cohort (intraclass correlation coefficients [ICCs] = 0.645, 0.623, 0.767 for D, C, and A, respectively) and at best moderate for the CD cohort [ICC = 0.690, 0.303, 0.733 for D, C, and A, respectively]. Intra-rater agreement ranged from good to excellent in both cohorts. Correlation with the Nancy Histological Index [NHI] was moderate and strong with the Simplified Geboes Score [SGS] and a Visual Analogue Scale [VAS], respectively. Large effect sizes were obtained for all three parameters. External responsiveness analysis revealed correlated changes between IBD-DCA score and NHI, SGS and VAS. Conclusions The IBD-DCA score is a simple histological activity score for UC and CD, agreed and validated by a large group of IBD specialists. It provides reliable information on treatment response. Therefore, it has potential value for use in routine diagnostics as well as clinical studies.

The gut is among the most complex organs of the human body. It has to exert several functions including food and water absorption while setting up an efficient barrier to the outside world. Dysfunction of the gut can be life-threatening. Diseases of the gastrointestinal tract such as inflammatory bowel disease, infections, or colorectal cancer, therefore, pose substantial challenges to clinical care. The intestinal epithelium plays an important role in intestinal disease development. It not only establishes an important barrier against the gut lumen but also constantly signals information about the gut lumen and its composition to immune cells in the bowel wall. Such signaling across the epithelial barrier also occurs in the other direction. Intestinal epithelial cells respond to cytokines and other mediators of immune cells in the lamina propria and shape the microbial community within the gut by producing various antimicrobial peptides. Thus, the epithelium can be considered as an interpreter between the microbiota and the mucosal immune system, safeguarding and moderating communication to the benefit of the host. Type 2 immune responses play important roles in immune-epithelial communication. They contribute to gut tissue homeostasis and protect the host against infections with helminths. However, they are also involved in pathogenic pathways in inflammatory bowel disease and colorectal cancer. The current review provides an overview of current concepts regarding type 2 immune responses in intestinal physiology and pathophysiology.

(1) Background: In patients with shock, the L-arginine nitric oxide pathway is activated, causing an elevation of nitric oxide, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels. Whether these metabolites provide prognostic information in patients after out-of-hospital cardiac arrest (OHCA) remains unclear. (2) Methods: We prospectively included OHCA patients, recorded clinical parameters and measured plasma ADMA, SDMA and Arginine levels by liquid chromatography tandem mass spectrometry (LC-MS). The primary endpoint was 90-day mortality. (3) Results: Of 263 patients, 130 (49.4%) died within 90 days after OHCA. Compared to survivors, non-survivors had significantly higher levels of ADMA and lower Arginine and Arginine/ADMA ratios in univariable regression analyses. Arginine levels and Arginine/ADMA ratio were significantly associated with 90-day mortality (OR 0.51 (95%CI 0.34 to 0.76), p &lt, 0.01 and OR 0.40 (95%CI 0.26 to 0.61), p &lt, 0.001, respectively). These associations remained significant in several multivariable models. Arginine/ADMA ratio had the highest predictive value with an area under the curve (AUC) of 0.67 for 90-day mortality. Results for secondary outcomes were similar with significant associations with in-hospital mortality and neurological outcome. (4) Conclusion: Arginine and Arginine/ADMA ratio were independently associated with 90-day mortality and other adverse outcomes in patients after OHCA. Whether therapeutic modification of the L-arginine-nitric oxide pathway has the potential to improve outcome should be evaluated.

With the progress in healthcare over recent decades and a growing life expectancy, discussions and decisions regarding end-of-life issues have become increasingly important. Especially in intensive care and emergency medicine there is a growing need of decision making for optimised end-of-life care. Prolonging life and preventing death is considered to be the highest principle of healthcare professionals; however, in some cases alleviation of suffering is a more appropriate goal. This article discusses communication challenges in end-of-life decision making and outlines strategies from an area of growing interest and research.

Guidelines recommend a ‘do-not-resuscitate’ (DNR) code status for inpatients in which cardiopulmonary resuscitation (CPR) attempts are considered futile because of low probability of survival with good neurological outcome. We retrospectively assessed the prevalence of DNR code status and its association with presumed CPR futility defined by the Good Outcome Following Attempted Resuscitation score and the Clinical Frailty Scale in patients hospitalised in the Divisions of Internal Medicine and Traumatology/Orthopedics at the University Hospital of Basel between September 2018 and June 2019. The definition of presumed CPR futility was met in 467 (16.2%) of 2889 patients. 866 (30.0%) patients had a DNR code status. In a regression model adjusted for age, gender, main diagnosis, nationality, language and religion, presumed CPR futility was associated with a higher likelihood of a DNR code status (37.3% vs 7.1%, adjusted OR 2.99, 95% CI 2.31 to 3.88, p

Macrophages are part of the innate immunity and are key players for the maintenance of intestinal homeostasis. They belong to the group of mononuclear phagocytes, which exert bactericidal functions and help to clear apoptotic cells. Moreover, they play essential roles for the maintenance of epithelial integrity and tissue remodeling during wound healing processes and might be implicated in intestinal tumor development. Macrophages are antigen-presenting cells and secrete immune-modulatory factors, like chemokines and cytokines, which are necessary to activate other intestinal immune cells and therefore to shape immune responses in the gut. However, overwhelming activation or increased secretion of pro-inflammatory cytokines might also contribute to the pathogenesis of inflammatory bowel disease. Presently, intestinal macrophages are in the center of intense studies, which might help to develop new therapeutic strategies to counteract the development or treat already existing inflammatory diseases in the gut. In this review, we focus on the origin of intestinal macrophages and, based on current knowledge, discuss their role in the gut during homeostasis and inflammation, as well as during intestinal wound healing and tumor development.

Screening colonoscopy is crucial in reducing the mortality of colorectal cancer. However, detecting adenomas against the backdrop of an inflamed mucosa (e.g. in ulcerative colitis) remains exceedingly difficult. Therefore, we aimed to improve neoplastic lesion detection by employing a fluorescence-based endoscopic approach. We used the well-established murine AOM/DSS model to induce inflammation-driven carcinogenesis in the colon. In our diagnostic approach, we evaluated Chlorin e6 polyvinylpyrrolidone (Ce6-PVP)-based fluorescence endoscopy in comparison to standard white-light endoscopy. A specialized pathologist then analyzed the histology of the detected lesions. Complementary in vitro studies were performed using human cell lines and a murine organoid system. Ce6-PVP-based fluorescence endoscopy had an improved detection rate of 100% (8/8) in detecting high-grade dysplasias and carcinomas over white-light detection alone with 75% (6/8). Trade-off for this superior detection rate was an increased rate of false positive lesions with an increase in the false discovery rate from 45% for white-light endoscopy to 81% for fluorescence endoscopy. We demonstrate in a proof-of-concept study that Ce6-PVP-based fluorescence endoscopy is a highly sensitive red flag technology to identify biopsy-worthy lesions in the colon.

Participation is key to building an equitable, realistic and democratic future. Yet a lack of agency in decision making and agenda-setting is a growing phenomenon in the design of digital public services. We call this pseudo-participation by and in design. The configuration of digital artifacts and/or processes can provide an illusion of participation but lack supportive processes and affordances to allow meaningful participation to happen. This exploratory paper examines the realm of pseudo-participation in the design of public digital services through two concepts: 1) pseudo-participation by design, digital interfaces, and tools that provide the illusion of participation to the people, 2) pseudo-participation in design, processes in which those affected by the design decisions are marginalized and not given any agency. We contribute to the re-imagination of participatory design in modern societies where the role of politics has become ubiquitous and is yet to be critically scrutinized by designers.

Values play a central role in technology design. But beyond acknowledging the politics of technology, questions remain around where those values are coming from, which values we need, and how they play out and shape the socio-technical systems we create. New challenges such as the climate crisis and societal polarization call for technologists to become part of the public and political arena. This results in a new sense of responsibility, but the closing of CPSR, the Computing Professionals for Social Responsibility, has left a gap. Today, across tech workers, academics and computing professionals, there is a renewed sense of urgency for engaging the public and politics to change course in how computing shapes society. What should a CPSR for the 21st century look like? This interactive workshop aims to re-invigorate the debate around values and social responsibility in Participatory Design with special attention to the Latin American context.

Background: Studies have suggested that taurine may have neuro- and cardio-protective functions, but there is little research looking at taurine levels in patients after out-of-hospital cardiac arrest (OHCA). Our aim was to evaluate the association of taurine with mortality and neurological deficits in a well-defined cohort of OHCA patients. Methods: We prospectively measured serum taurine concentration in OHCA patients upon admission to the intensive care unit (ICU) of the University Hospital Basel (Switzerland). We analyzed the association of taurine levels and in-hospital mortality (primary endpoint). We further evaluated neurological outcomes assessed by the cerebral performance category scale. We calculated logistic regression analyses and report odds ratios (OR) and 95% confidence intervals (CI). We calculated different predefined multivariable regression models including demographic variables, comorbidities, initial vital signs, initial blood markers and resuscitation measures. We assessed discrimination by means of area under the receiver operating curve (ROC). Results: Of 240 included patients, 130 (54.2%) survived until hospital discharge and 110 (45.8%) had a favorable neurological outcome. Taurine levels were significantly associated with higher in-hospital mortality (adjusted OR 4.12 (95%CI 1.22 to 13.91), p = 0.02). In addition, a significant association between taurine concentration and a poor neurological outcome was observed (adjusted OR of 3.71 (95%CI 1.13 to 12.25), p = 0.03). Area under the curve (AUC) suggested only low discrimination for both endpoints (0.57 and 0.57, respectively). Conclusion: Admission taurine levels are associated with mortality and neurological outcomes in OHCA patients and may help in the risk assessment of this vulnerable population. Further studies are needed to assess whether therapeutic modulation of taurine may improve clinical outcomes after cardiac arrest.

Introduction Code status discussions are useful for understanding patientsr preferences in the case of a cardiac/pulmonary arrest. These discussions can also provide patients with a basis for informed decision-making regarding life-sustaining treatment. We conducted a survey to understand current practices and perceptions of code status discussions in a tertiary-care Swiss hospital. Methods We performed systematic interviews across different departments of the University Hospital of Basel. We interviewed 258 physicians and 145 patients who were hospitalised between May and July 2018 using a questionnaire designed to assess the use of code status discussions and to gauge patientsr individual experiences and opinions. Results A total of 61.4% of patients did not recall having had a code status discussion during the hospital stay. However, a higher proportion of medical patients compared to surgical patients recalled having had a discussion (43.6 vs 22.4%, p = 0.03). For 9 out of 38 (23.7%) patients who did recall the discussion, there was a lack of agreement between the preference given in the interview regarding resuscitation measures and the documented code status in the medical electronic chart. Furthermore, a majority of physicians (72.4%) recalled defining a do-not-resuscitate (DNR) status for a patient without prior discussion with the patient. Physicians who recalled determining the DNR status without patient consultation reported conflicts with patients and relatives regarding code status at a higher rate compared to physicians who did not define DNR status without consultation (62.4 vs 39.4%, p l0.001). Conclusion A majority of patients do not report having discussed code status during their hospital stay and physicians frequently omit such discussions, thereby potentially failing to attend to patientsr preferences for care. Physician training regarding code status discussions may improve the quality of informed decision-making and patient-centred care.

There is interest in novel blood markers to improve risk stratification in patients presenting with cardiac arrest. We assessed associations of different plasma sphingomyelin concentrations and neurological outcome in patients with cardiac arrest. In this prospective observational study, adult patients with cardiac arrest were included upon admission to the intensive care unit (ICU). We studied associations of admission plasma levels of 15 different sphingomyelin species with neurological outcome at hospital discharge (primary endpoint) defined by the modified Rankin Scale by the calculation of univariable and multivariable logistic regression models adjusted for age, gender, and clinical shock markers. We included 290 patients (72% males, median age 65 years) with 162 (56%) having poor neurological outcome at hospital discharge. The three sphingomyelin species SM C24:0, SM(OH) C22:1, and SM(OH) C24:1 were significantly lower in patients with poor neurological outcome compared to patients with favorable outcome with areas under the curve (AUC) of 0.58, 0.59, and 0.59. SM(OH) C24:1 was independently associated with poor neurological outcome in a fully-adjusted regression model (adjusted odds ratio per log-transformed unit increase in SM(OH) C24:1 blood level 0.18, 95% CI 0.04 to 0.87, p = 0.033). Results were similar for 1-year mortality. Low admission sphingomyelin levels showed a weak association with poor neurological outcome in patients after cardiac arrest. If validated in future studies, a better understanding of biological sphingomyelin function during cardiac arrest may help to further advance the therapeutic approach and risk stratification in this vulnerable patient group.

Cardiopulmonary resuscitation represents a major physical and psychological challenge for all involved health care workers because survival of the patients is closely related to the timely and accurate actions of rescuers. Consequently, rescuers may experience high levels of acute mental stress. Stress, in turn, may influence attentional resources and distractibility, which may affect the quality of resuscitation. This narrative review summarizes the current state of research concerning the influence of stress on resuscitation performance. Peer-reviewed studies retrieved in scientific databases were eligible. We found that rescuers experience high levels of stress and some associations of higher levels of stress with lower resuscitation performance. Finally, few interventional studies assessed whether interventions aiming at reducing levels of stress may have a beneficial effect on resuscitation performance, but results are variable. Although the mechanisms linking stress to performance of emergency teams are still not fully understood, factors such as individual experience and self-confidence of rescuers, gender composition and hierarchy within resuscitation teams may play an important role. This review provides a targeted overview of how stress can be defined and measured, how it may influence emergency situations such as a cardiopulmonary resuscitation, and which interventions have the potential to reduce overwhelming stress.

International audience; Sustainability has emerged as a concern of central relevance. As a wicked problem, it poses challenges to business-as-usual in many areas, including that of modeling. This article addresses a question at the intersection of model-driven engineering and sustainability research: "How can we better support sustainability by bringing together model-driven engineering, data, visualization and self-adaptive systems, to facilitate engagement, exploration, and understanding of the effects that individual and organizational choices have on sustainability?" We explore this question via an idealized vision of an evaluation environment that facilitates integration and mapping of models from multiple diverse sources, visual exploration, and evaluation of what-if scenarios, for stakeholders with divergent perspectives. The article identifies research challenges to be addressed to enable decision making to support sustainability and provides a map of sustainability modeling issues across disciplines.

Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality, yet the prediction of its outcome remains challenging. Serum Acyl Carnitines (ACs), a biomarker of beta-oxidation, have been associated with cardiovascular events. We evaluated the association of different AC species with mortality and neurological outcome in a cohort of OHCA patients.We consecutively included OHCA patients in this prospective observational study upon admission to the intensive care unit. We studied the association of thirty-nine different ACs measured at admission and 30-day mortality (primary endpoint), as well as neurological outcome at hospital discharge (secondary endpoint) using the Cerebral Performance Category scale. Multivariate models were adjusted for age, gender, comorbidities and shock markers.Of 281 included patients, 137 (48.8%) died within 30 days and of the 144 survivors (51.2%), 15 (10.4%) had poor neurological outcome. While several ACs were associated with mortality, AC C2 had the highest prognostic value for mortality (fully-adjusted odds ratio 4.85 (95%CI 1.8 to 13.06, p .01), area under curve (AUC) 0.65) and neurological outcome (fully-adjusted odds ratio 3.96 (95%CI 1.47 to 10.66, p .01), AUC 0.63).ACs are interesting surrogate biomarkers that are associated with mortality and poor neurological outcome in patients after OHCA and may help to improve the understanding of pathophysiological mechanisms and risk stratification.

The CSCW community has long discussed the ethics and politics of sociotechnical systems and how they become embedded in society and public policy. In light of the Black Lives Matter protests and Hong Kong protests, technologies such as facial recognition and contact tracing have re-invigorated conversations about the ethical and social responsibility of tech corporations, tech workers, and academics in science and technology. The goal of this workshop is to move beyond a call for the usual suspects of participatory design and human-centered design by committing to concrete steps to transform society through advocacy and activism.

Crohn's disease (CD) patients can be grouped into patients suffering from ileitis, ileocolitis, jejunoileitis, and colitis. The pathophysiological mechanism underlying this regional inflammation is still unknown. Although most murine models of inflammatory bowel disease (IBD) develop inflammation in the colon, there is an unmet need for novel models that recapitulate the spontaneous and fluctuating nature of inflammation as seen in CD. Recently, mice with an intestinal epithelial cell-specific deletion for Caspase-8 (Casp8ΔIEC mice), which are characterized by cell death-driven ileitis and disrupted Paneth cell homeostasis, have been identified as a novel model of CD-like ileitis. Here we uncovered that genetic susceptibility alone is sufficient to drive ileitis in Casp8ΔIEC mice. In sharp contrast, environmental factors, such as a disease-relevant microbial flora, determine colonic inflammation. Accordingly, depending on the microbial environment, isogenic Casp8ΔIEC mice either exclusively developed ileitis or suffered from pathologies in several parts of the gastrointestinal tract. Colitis in these mice was characterized by massive epithelial cell death, leading to spread of commensal gut microbes to the extra-intestinal space and hence an aberrant activation of the systemic immunity. We further uncovered that Casp8ΔIEC mice show qualitative and quantitative changes in the intestinal microbiome associated with an altered mucosal and systemic immune response. In summary, we identified that inflammation in this murine model of CD-like inflammation is characterized by an immune reaction, presumably directed against a disease-relevant microbiota in a genetically susceptible host, with impaired mucosal barrier function and bacterial clearance at the epithelial interface.

Background: We investigated whether Neuron-specific enolase (NSE) serum concentration predicts long-term mortality and poor neurological outcome in adult cardiac arrest patients. Methods: Within this prospective observational study, we included consecutive adult patients admitted to the intensive care unit (ICU) after cardiac arrest. NSE was measured upon ICU admission and on days 1, 2, 3, 5 and 7. Results: Of 403 patients, 176 (43.7%) survived. Median follow-up duration was 43.7 months (IQR 14.3 to 63.0 months). NSE levels on day 3 were increased more than threefold in non-survivors compared to survivors (median NSE (ng/mL) 19.8 (IQR 15.7 to 27.8) vs. 72.6 (IQR 26 to 194)) and showed the highest prognostic performance for mortality compared to other days of measurement, with an AUC of 0.81 and an adjusted hazard ratio of 1.55 (95% CI 1.41 to 1.71, p &lt, 0.001). Subgroup analysis showed an excellent sensitivity and negative predictive value of 100% of NSE in patients &lt, 54 years of age. Conclusion: NSE measured three days after cardiac arrest is associated with long-term mortality and neurological outcome and may provide prognostic information that improves clinical decision making. Particularly in the subgroup of younger patients (&lt, 54 years), NSE showed excellent negative predictive value.

OBJECTIVE: COVID-19 causes psychological distress for patients and their relatives at short term. However, little research addressed the longer-term psychological outcomes in this population. Therefore, we aimed to prospectively assess clinically relevant psychological distress in hospitalized patients with COVID-19 and their relatives 90 days after hospital discharge. METHODS: This exploratory, prospective, observational cohort study included consecutive adult patients hospitalized in two Swiss tertiary-care hospitals between March and June 2020 for confirmed COVID-19 and their relatives. The primary outcome was psychological distress defined as clinically relevant symptoms of anxiety and/or depression measured with the Hospital Anxiety and Depression Scale (HADS) 90 days after discharge. RESULTS: Clinically relevant psychological distress 90 days after hospital discharge was present in 23/108 patients (21.3%) and 22/120 relatives (18.3%). For patients, risk and protective factors associated with clinically relevant psychological distress included sociodemographic, illness-related, psychosocial, and hospital-related factors. A model including these factors showed good discrimination, with an area under the receiver-operating characteristic curve (AUC) of 0.84. For relatives, relevant risk factors were illness-related, psychosocial, and hospital-related factors. Resilience was negatively associated with anxiety and depression in both patients and relatives and regarding PTSD in relatives only. CONCLUSION: COVID-19 is linked to clinically relevant psychological distress in a subgroup of patients and their relatives 90 days after hospitalization. If confirmed in an independent and larger patient cohort, knowledge about these potential risk and protective factors might help to develop preventive strategies.