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Robotics is widely seen as a key enabling technology for the society of tomorrow. This work examines the role of robotics and intelligent medical devices in Intensive Care Medicine. Demographics predict that more elderly patients will need to be treated with fewer healthcare personnel, calling for innovations in ICU management. Robotics is a key enabling technology for the 21st century and may help to smooth the foreseeable workload/manpower disparity in medicine. Studying the application of robotics in the ICU in a manner beneficial for patients and accepted by intensive care team is desirable. Financial sustainability is essential for the introduction of these new technologies to the ICU. This study therefore assesses the state of the art in robotics in intensive care medicine and identifies opportunities for progress, using an observational approach in a teaching hospital ICU in combination with an in-depth review of the literature and a survey of the market. Tasks amenable to robotics are identified, their acceptability to patients and caregivers are examined and their quantitative contribution to future management of an intensive care unit is assessed.

Background ICU risk assessment tools, routinely used for predicting population outcomes, are not recommended for evaluating individual risk. The state of health of single patients is mostly subjectively assessed to inform relatives and presumably to decide on treatment decisions. However, little is known how subjective and objective survival estimates compare. Methods We performed a prospective cohort study in mechanically ventilated critically ill patients across five European centres, assessed 62 objective markers and asked the clinical staff to subjectively estimate the probability of surviving 28 days. Results Within the 961 included patients, we identified 27 single objective predictors for 28-day survival (73.8%) and pooled them into predictive groups. While patient characteristics and treatment models performed poorly, the disease and biomarker models had a moderate discriminative performance for predicting 28-day survival, which improved for predicting 1-year survival. Subjective estimates of nurses (c-statistic [95% CI] 0.74 [0.70–0.78]), junior physicians (0.78 [0.74–0.81]) and attending physicians (0.75 [0.72–0.79]) discriminated survivors from non-survivors at least as good as the combination of all objective predictors (c-statistic: 0.67–0.72). Unexpectedly, subjective estimates were insufficiently calibrated, overestimating death in high-risk patients by about 20% in absolute terms. Combining subjective and objective measures refined discrimination and reduced the overestimation of death. Conclusions Subjective survival estimates are simple, cheap and similarly discriminative as objective models; however, they overestimate death risking that live-saving therapies are withheld. Therefore, subjective survival estimates of individual patients should be compared with objective tools and interpreted with caution if not agreeing. Trial registration ISRCTN ISRCTN59376582, retrospectively registered October 31st 2013.

New-onset atrial fibrillation (NOAF) is the most common complication after cardiac surgery, occurring in 25-50% of patients. It is associated with post-operative stroke, increased mortality, prolonged hospital length of stay, and higher treatment costs. Previous small observational studies have identified the left atrium as a source of the electrical rotors and foci maintaining NOAF, but confirmation by a large prospective clinical study is still missing. The aim of the proposed study is to investigate whether the source of NOAF lies in the left atrium. The correct identification of NOAF-maintaining structures in cardiac surgical patients might offer potential therapeutic targets for prophylactic perioperative ablation strategies.; This is a prospective single-centre observational study of patients developing NOAF after cardiac surgery. The primary outcome is the description of NOAF-maintaining structures within the atria. Key secondary outcomes include overall mortality, intensive care unit length of stay, hospital-ventilator-free days, and proportion of persistent NOAF. In NOAF patients, the non-invasive electrophysiological mapping will be conducted using a 252-electrode electrocardiogram vest. After mapping, a low-dose computed tomography scan of the chest will be performed to integrate the electrophysiological mapping results into a 3D picture of the heart. The study will include approximately 570 patients, of whom 30% (n = 170) are expected to develop NOAF. Sample size calculation revealed that 157 NOAF patients are necessary to assess the primary outcome. Patients will be tracked for a total of 5 years.; This is the largest prospective study to date describing the electrophysiological mechanisms of NOAF using non-invasive mapping.

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.

AIMS: To assess the do-not-resuscitate preferences of the general Swiss population and to identify predictors influencing decision-making. METHODS: A nationwide web-based survey was conducted in Switzerland on a representative sample of the adult population. The primary endpoint was the preference for a “Do Not Resuscitate” order (DNR Code Status) vs. cardiopulmonary resuscitation (CPR Code Status) in a clinical case vignette of an out-of-hospital cardiac arrest. Secondary endpoint were participants’ own personal preferences for DNR. RESULTS: 1138 subjects participated in the web-based survey, 1044 were included in the final analysis. Preference for DNR code status was found in 40.5% (n = 423) in the case vignette and in 20.3% (n = 209) when making a personal decision for themselves. Independent predictors for DNR Code Status for the case vignette were: Personal preferences for their own DNR Code Status (adjusted OR 2.44, 95%CI 1.67 to 3.55; p

Efficacy of donated COVID-19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics.In a single-center hypothesis-generating prospective case-control study with 1:2 matched dCCP recipients to controls according to disease severity at day 1, hospitalized adults with COVID-19 pneumonia received 2 × 200 ml pathogen-reduced treated dCCP from 2 different donors. We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 convalescent plasma donors and recipients using multiple antibody assays including a Coronavirus antigen microarray (COVAM), and binding and neutralizing antibody assays. Outcomes were dCCP characteristics, antibody responses, 28-day mortality, and dCCP -related adverse events in recipients.Eleven of 13 dCCPs (85%) contained neutralizing antibodies (nAb). PRT did not affect dCCP antibody activity. Fifteen CCP recipients and 30 controls (median age 64 and 65 years, respectively) were enrolled. dCCP recipients received 2 dCCPs from 2 different donors after a median of one hospital day and 11 days after symptom onset. One dCCP recipient (6.7%) and 6 controls (20%) died (p = 0.233). We observed no dCCP-related adverse events. Transfusion of unselected dCCP led to heterogeneous SARS CoV-2 antibody responses. COVAM clustered dCCPs in 4 distinct groups and showed endogenous immune responses to SARS-CoV-2 antigens over 14-21 days post dCCP in all except 4 immunosuppressed recipients.PRT did not impact dCCP anti-virus neutralizing activity. Transfusion of unselected dCCP did not impact survival and had no adverse effects. Variable dCCP antibodies and post-transfusion antibody responses indicate the need for controlled trials using well-characterized dCCP with informative assays.

OBJECTIVES: Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to the clinical and epidemiological assessment of CoVID-19. We cross-validated manual and automated high-throughput testing for SARS-CoV-2-RNA, evaluated SARS-CoV-2 loads in nasopharyngeal-oropharyngeal swabs (NOPS), lower respiratory fluids, and plasma, and analyzed detection rates after lockdown and relaxation measures. METHODS: Basel-S-gene, Roche-E-gene, and Roche-cobas®6800-Target1 and Target2 were prospectively validated in 1344 NOPS submitted during the first pandemic peak (Week 13). Follow-up cohort (FUP) 1, 2, and 3 comprised 10,999, 10,147, and 19,389 NOPS submitted during a 10-week period until Weeks 23, 33, and 43, respectively. RESULTS: Concordant results were obtained in 1308 cases (97%), including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman's r > .95; p < .001) for all assays and high precision by Bland-Altman analysis. Discordant samples (N = 36, 3%) had significantly lower SARS-CoV-2 loads (p < .001). Following lockdown, detection rates declined to

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

ImportanceGrowing evidence suggests that coronavirus disease 2019 (COVID-19) is associated with neurological sequelae. However, the underlying pathophysiological mechanisms resulting in central nervous system (CNS) derogation remain unclear.ObjectiveTo identify severity-dependent immune mechanisms in the cerebrospinal fluid (CSF) and plasma of COVID-19 patients and their association with brain imaging alterations.DesignProspective cross-sectional cohort study.SettingThis study was performed from August 2020 to April 2021. Participants were enrolled in the outpatient clinics, hospital wards and intensive care units (ICU) of two clinical sites in Basel and Zurich, Switzerland.ParticipantsAge >18 years and a positive SARS-CoV-2 test result were inclusion criteria. Potentially matching individuals were identified (n=310), of which 269 declined to participate and 1 did not match inclusion criteria. Paired CSF and plasma samples, as well as brain images, were acquired. The COVID-19 cohort (n=40; mean [SD] age, 54 [20] years; 17 women (42%)) was prospectively assorted by neurological symptom severity (classes I, II and III). Age/sex-matched inflammatory (n=25) and healthy (n=25) CSF and plasma control samples were obtained. For volumetric brain analysis, a healthy age/sex-matched control cohort (n=36) was established.ExposuresLumbar puncture, blood sampling and cranial MRI and/or CT.Main outcomes and measuresProteomics, standard parameters and antibody profiling of paired CSF and plasma samples in COVID-19 patients and controls. Brain imaging and gray matter volumetric analysis in association with biomarker profiles. Follow-up after 10-months.ResultsCOVID-19 patients displayed a plasma cytokine storm but a non-inflammatory CSF profile. Class III patients displayed signs of blood-brain barrier (BBB) impairment and a polyclonal B cell response targeting self- and non-self antigens. Decreased regional brain volumes were present in COVID-19 patients and associated with specific CSF and plasma parameters.Conclusion and relevanceNeuro-COVID class III patients had a strong, peripheral immune response resulting in (1) BBB impairment (2) ingress of (auto-)antibodies, (3) microglia activation and neuronal damage signatures. Our data point towards several potentially actionable targets that may be addressed to prevent COVID-19-related neurological sequelae.Trial registrationThe trial (NCT04472013) was registered on clinicaltrials.gov.Key pointsQuestionDoes a severity-dependent pattern of immune mechanisms exist in the cerebrospinal fluid (CSF) and plasma of COVID-19 patients and are these associated with clinical and brain imaging findings?FindingsNeuro-COVID patients display a robust class III-specific peripheral immune response resulting in (1) blood-brain barrier (BBB) impairment, (2) ingress of (auto-)antibodies, (3) microglia activation and neuronal damage signatures. Integration of MRIs, brain volumetry and proteomics identified biomarkers associated with regional brain volume loss in severe Neuro-COVID.MeaningWe provide a multidimensional framework of mechanisms associated with severe Neuro-COVID and present possible targets to prevent COVID-19-related neurological sequelae.

Commercially available SARS-CoV-2-directed antibody assays may assist in diagnosing past exposure to SARS-CoV-2 antigens. We cross-compared the following eight immunoassays detecting antibodies against SARS-CoV-2 nucleocapsid (N) or spike (S) antigens in three cohorts consisting of 859 samples from 622 patients: (#1) EDI novel coronavirus COVID-19 (Epitope), (#2) RecomWell SARS-CoV-2 (Mikrogen), (#3) COVID-19 ELISA (VirCell), (#4) Elecsys anti-SARS-CoV-2 N (Roche), (#5) Liaison SARS-CoV-2 S1/S2 (DiaSorin), (#6) anti-SARS-CoV-2 ELISA (EuroImmun), (#7) Elecsys anti-SARS-CoV-2 S (Roche), and (#8) Liaison SARS-CoV-2 TrimericS (DiaSorin). In cross-sectional cohort 1 (68 sera from 38 patients with documented SARS-CoV-2 infection), agreement between assays #1 to #6 ranged from 75% to 93%, whereby discordance mostly resulted from N-based assays #1 to #4. In cross-sectional cohort 2 (510 sera from 510 patients; 56 documented, 454 unknown SARS-CoV-2 infection), assays #4 to #6 were analyzed further together with assays #7 and #8, revealing 94% concordance (44 [9%] positives and 485 [85%] negatives). Discordance was highest within 2 weeks after SARS-CoV-2/COVID-19 diagnosis and confirmed in the longitudinal cohort 3 (281 sera from 74 COVID-19 patients), using assays #4, #6, #7, and #8. Subanalysis of 20 (27%) initially seronegative cohort 3 patients revealed assay-dependent 50% and 90% seroconversion rates after 8 to 11 days and 14 to 18 days, respectively. Increasing SARS-CoV-2 antibodies were significantly associated with declining levels of viral loads, lactate dehydrogenase, interleukin-6, and C-reactive protein and preceded clearance of SARS-CoV-2 detection in the upper respiratory tract by approximately 1 week. SARS-CoV-2-specific antibody assays show substantial agreement, but interpretation of qualitative and semiquantitative results depends on the time elapsed postdiagnosis and the choice of viral antigen. Mounting of systemic SARS-CoV-2-specific antibodies may predict recovery from viral injury and clearance of mucosal replication.

BackgroundEvidence to date indicates that mortality of acute coronavirus disease (COVID-19) is higher in men than in women. Conversely, women seem more likely to suffer from long-term consequences of the disease and pronounced negative social and economic impacts. Sex- and gender specific risk factors of COVID-19-related long-term effects are unknown. MethodsWe conducted a multicentre prospective observational cohort study of 5838 (44.6% women) individuals in Switzerland who were tested positive for SARS-CoV-2 RNA between February and December 2020. Of all surviving individuals who met the inclusion criteria, 2799 (1285 [45.9%] women) completed a follow-up questionnaire. FindingsAfter a mean follow-up time of 197{+/-}77 days, women more often reported at least one persistent symptom (43.0% vs 31.5%, p

Objective:To determine whether colonization with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) predicts the risk for subsequent infection and impacts carbapenem-consumption and outcome in intensive care unit (ICU) patients.Design:Prospective cohort study.Setting:The 2 ICUs in the University Hospital Basel in Switzerland.Patients:All patients admitted to the 2 ICUs providing mechanical ventilation and an expected ICU stay >48 hours.Methods:Patients were routinely screened for ESBL-PE carriage by rectal swab on admission. Competing risk regression analyses were applied to calculate hazard ratios (HRs) for infection with ESBL-PE and mortality. Length of hospital stay, length of ICU stay, and duration of carbapenem exposure were compared using the Mann-Whitney U test.Results:Among 302 patients, 24 (8.0%) were colonized with ESBL-PE on ICU admission. Infections with ESBL-PE occurred in 4 patients, of whom 3 (75%) were identified as ESBL-PE colonized on admission. ESBL-PE colonization on admission was associated with subsequent ESBL-PE infection (hazard ratio [HR], 25.52; 95% confidence interval [CI], 2.40–271.41; P = .007) and exposure to carbapenems (HR, 2.42; 95% CI, 1.01–5.79; P = .047), whereas duration of carbapenem exposure did not differ in relation to ESBL-PE colonization (median, 7 days [IQR, 3–8 days] vs median, 6 days [IQR 3–9 days]; P = 0.983). Patients colonized with ESBL-PE were not at increased risk for death overall (HR, 1.00; 95% CI, 0.44–2.30; P = .993) or death attributable to infection (HR, 1.20; 95% CI, 0.28–5.11; P = .808).Conclusions:Screening strategies for detection of ESBL-PE colonization on ICU admission may allow the identification of patients at highest risk for ESBL-PE infection and the correct allocation of empiric carbapenem treatment.

The morbidity and mortality of patients requiring mechanical ventilation for coronavirus disease 2019 (COVID-19) pneumonia is considerable. We studied the use of whole-lung low dose radiation therapy (LDRT) in this patient cohort.Patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation for COVID-19 pneumonia were included in this randomized double-blind study. Patients were randomized to 1 Gy whole-lung LDRT or sham irradiation (sham-RT). Treatment group allocation was concealed from patients and ICU clinicians, who treated patients according to the current standard of care. Patients were followed for the primary endpoint of ventilator-free days (VFDs) at day 15 post-intervention. Secondary endpoints included overall survival, as well as changes in oxygenation and inflammatory markers.Twenty-two patients were randomized to either whole-lung LDRT or sham-RT between November and December 2020. Patients were generally elderly and comorbid, with a median age of 75 years in both arms. No difference in 15-day VFDs was observed between groups (p = 1.00), with a median of 0 days (range, 0-9) in the LDRT arm, and 0 days (range, 0-13) in the sham-RT arm. Overall survival at 28 days was identical at 63.6% (95%CI, 40.7-99.5%) in both arms (p = 0.69). Apart from a more pronounced reduction in lymphocyte counts following LDRT (p0.01), analyses of secondary endpoints revealed no significant differences between the groups.Whole-lung LDRT failed to improve clinical outcomes in critically ill patients requiring mechanical ventilation for COVID-19 pneumonia.

The proportion of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive and the potential benefit of systematic screening during the SARS-CoV-2-pandemic is controversial. We investigated the proportion of asymptomatic inpatients who were identified by systematic screening for SARS-CoV-2 upon hospital admission. Our analysis revealed that systematic screening of asymptomatic inpatients detects a low total number of SARS-CoV-2 infections (0.1%), questioning the cost–benefit ratio of this intervention. Even when the population-wide prevalence was low, the proportion of asymptomatic carriers remained stable, supporting the need for universal infection prevention and control strategies to avoid onward transmission by undetected SARS-CoV-2-carriers during the pandemic.

PURPOSE: The morbidity and mortality of patients requiring mechanical ventilation for coronavirus disease 2019 (COVID-19) pneumonia is considerable. We studied the use of whole-lung low-dose radiation therapy (LDRT) in this patient cohort. METHODS AND MATERIALS: Patients admitted to the intensive care unit and requiring mechanical ventilation for COVID-19 pneumonia were included in this randomized double-blind study. Patients were randomized to 1 Gy whole-lung LDRT or sham irradiation (sham-RT). Treatment group allocation was concealed from patients and intensive care unit clinicians, who treated patients according to the current standard of care. Patients were followed for the primary endpoint of ventilator-free days at day 15 postintervention. Secondary endpoints included overall survival, as well as changes in oxygenation and inflammatory markers. RESULTS: Twenty-two patients were randomized to either whole-lung LDRT or sham-RT between November and December 2020. Patients were generally elderly and comorbid, with a median age of 75 years in both arms. No difference in 15-day ventilator-free days was observed between groups (P = 1.00), with a median of 0 days (range, 0-9) in the LDRT arm and 0 days (range, 0-13) in the sham-RT arm. Overall survival at 28 days was identical at 63.6% (95% confidence interval, 40.7%-99.5%) in both arms (P = .69). Apart from a more pronounced reduction in lymphocyte counts after LDRT (P < .01), analyses of secondary endpoints revealed no significant differences between the groups. CONCLUSIONS: Whole-lung LDRT failed to improve clinical outcomes in critically ill patients requiring mechanical ventilation for COVID-19 pneumonia.

Antiviral treatments for COVID-19 have involved many repurposed drugs. Currently, SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded bynsp12-nsp7-nsp8) has been targeted by numerous inhibitors with debated clinical impact. Among these, remdesivir has been conditionally approved for the treatment of COVID-19 patients. Although the emergence of antiviral resistance, an indirect proxy for antiviral efficacy, poses a considerable healthcare threat, an evolutionary perspective on emerging resistant mutants is still lacking.Here we show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare, and unlikely to lead to viral fitness loss.In more than 56,000 viral genomes from 105 countries dating from December 2019 to July 2020 we found negative selective pressure affectingnsp12(Tajima’s D = −2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Those affected known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations found globally,in silicostructural models show that this rarely implies loss of stability in RdRp. No potential escape mutation were found in our local cohort of remdesivir treated patients from the first wave (n=8). Our results indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. Our study could be the starting point of a larger monitoring effort of drug resistance throughout the COVID-19 pandemic. We recommend the application of repetitive genome sequencing of SARS-CoV-2 from patients treated with antivirals to provide early insights into the evolution or antiviral resistance.

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T (‘Basel cluster’), including 157 identical sequences at the root of the ‘Basel cluster’, some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503., Author summary COVID-19 was first reported in December 2019 in Wuhan, China, and has spread around the globe since. The most common tool for tracking and containing the spread of the disease-causing virus–SARS-CoV-2 –are classical epidemiology and contact tracing, which collapse under too high case burdens as seen in this pandemic. However, whole-genome sequencing and phylogenetic analyses of the viral genomes will be crucial to understand the virus evolution and outbreak dynamics to ultimately stop the spread of the disease. Here we combined epidemiological data and whole-genome sequences originating from the time of the arrival of the virus in early 2020 in a typical medium-sized European city, namely Basel-City, Switzerland. On one hand, we identified limited community spread of very distinct viral variants originating from travel returners, which is possibly due to the heightened attention and restrictions imposed on international travellers. On the other hand, we find evidence for large cryptic community spread of a single virus variant in the city, which we infer to have originated around mid-February 2020 in the larger tri-national area around Basel, and which has epidemiological links to a mass gathering event in the region of Alsace, France.

BackgroundTransmission chains within small urban areas (accommodating∼30% of the European population) greatly contribute to case burden and economic impact during the ongoing COVID-19 pandemic, and should be a focus for preventive measures to achieve containment. Here, at very high spatio-temporal resolution, we analysed determinants of SARS-CoV-2 transmission in a European urban area, Basel-City (Switzerland). Methodology. We combined detailed epidemiological, intra-city mobility, and socioeconomic data-sets with whole-genome-sequencing during the first SARS-CoV-2 wave. For this, we succeeded in sequencing 44% of all reported cases from Basel-City and performed phylogenetic clustering and compartmental modelling based on the dominating viral variant (B.1-C15324T; 60% of cases) to identify drivers and patterns of transmission. Based on these results we simulated vaccination scenarios and corresponding healthcare-system burden (intensive-care-unit occupancy). Principal Findings. Transmissions were driven by socioeconomically weaker and highly mobile population groups with mostly cryptic transmissions, whereas amongst more senior population transmission was clustered. Simulated vaccination scenarios assuming 60-90% transmission reduction, and 70-90% reduction of severe cases showed that prioritizing mobile, socioeconomically weaker populations for vaccination would effectively reduce case numbers. However, long-term intensive-care-unit occupation would also be effectively reduced if senior population groups were prioritized, provided there were no changes in testing and prevention strategies. Conclusions. Reducing SARS-CoV-2 transmission through vaccination strongly depends on the efficacy of the deployed vaccine. A combined strategy of protecting risk groups by extensive testing coupled with vaccination of the drivers of transmission (i.e. highly mobile groups) would be most effective at reducing the spread of SARS-CoV-2 within an urban area.Author summaryWe examined SARS-CoV-2 transmission patterns within a European city (Basel, Switzerland) to infer drivers of the transmission during the first wave in spring 2020. The combination of diverse data (serological, genomic, transportation, socioeconomic) allowed us to combine phylogenetic analysis with mathematical modelling on related cases that were mapped to a residential address. As a result we could evaluate population groups driving SARS-CoV-2 transmission and quantify their effect on the transmission dynamics. We found traceable transmission chains in wealthier or more senior population groups and cryptic transmissions in the mobile, young or socioeconomic weaker population groups - these were identified as transmission drivers of the first wave. Based on this insight, we simulated vaccination scenarios for various vaccine efficacies to reflect different approaches undertaken to handle the epidemic. We conclude that vaccination of the mobile inherently younger population group would be most effective to handle following waves.

AIMS OF THE STUDY: Long-term intensive care treatment confers a substantial physical, psychological and social burden on patients, their relatives and the treatment team. It is essential to know the outcome of patients with long-term treatment and to establish factors that possibly can predict mortality. Only few Swiss studies have previously addressed this issue. METHODS: This retrospective observational study at a Swiss tertiary academic medical care centre included patients who were treated for ≥7 consecutive days at the surgical intensive care unit (ICU) between 1 January 2011 and 31 December 2012. Follow-up ended on 30 September 2018. RESULTS: Two-hundred and fifty patients were included, and three were lost to follow-up. Fifty-two patients (21.1%) died in the ICU, 25 (10.1%) after transfer to the normal ward. Thirty-one patients (12.5%) died within one year after the beginning of intensive care treatment. Altogether, the one-year mortality was 43.7% (108 patients). At the end of follow-up, 99 patients (40.1%) were still alive. Polytrauma patients represent a special group with a survival of more than 90%. Median patient age was 66 years (interquartile range 56–75); two thirds were men. Patients who died within one year of beginning treatment in the ICU were significantly older (median 71 vs 63 years, p

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China as the cause of coronavirus disease 2019 in December 2019 and reached Europe by late January 2020, when community-acquired respiratory viruses (CARVs) are at their annual peak. We validated the World Health Organization (WHO)–recommended SARS-CoV-2 assay and analyzed the epidemiology of SARS-CoV-2 and CARVs. Methods Nasopharyngeal/oropharyngeal swabs (NOPS) from 7663 patients were prospectively tested by the Basel S-gene and WHO-based E-gene (Roche) assays in parallel using the Basel N-gene assay for confirmation. CARVs were prospectively tested in 2394 NOPS by multiplex nucleic acid testing, including 1816 (75%) simultaneously for SARS-CoV-2. Results The Basel S-gene and Roche E-gene assays were concordant in 7475 cases (97.5%) including 825 (11%) SARS-CoV-2 positives. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 (1.4%). Adults were more frequently SARS-CoV-2 positive, whereas children tested more frequently CARV positive. CARV coinfections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced CARVs within 3 weeks, reaching 48% of all detected respiratory viruses followed by rhinovirus/enterovirus (13%), influenza virus (12%), coronavirus (9%), respiratory syncytial virus (6%), and metapneumovirus (6%). Conclusions Winter CARVs were dominant during the early SARS-CoV-2 pandemic, impacting infection control and treatment decisions, but were rapidly replaced, suggesting competitive infection. We hypothesize that preexisting immune memory and innate immune interference contribute to the different SARS-CoV-2 epidemiology among adults and children., Community-acquired respiratory viruses were dominant during the early severe acute respiratory syndrome coronavirus 2 pandemic in winter 2020, but were rapidly replaced, suggesting competitive infection. Preexisting immune memory and innate immune interference may contribute to the different epidemiology among adults and children.

Background In Switzerland, long-term circulatory support programs have been limited to heart transplant centers. In 2014, to improve the management of patients with end-stage heart failure not eligible for transplantation, we implemented a left ventricular assist device (LVAD) program for destination therapy at the University Hospital of Basel. Methods We described the program set-up with practical aspects. Patients aged 65 and above with therapy refractory end-stage heart failure without major contraindication for LVAD implantation were included. Younger patients with bridge-to-candidacy profile were also considered. Using the Kaplan-Meier estimate, we retrospectively analyzed the overall survival and freedom from major adverse events after LVAD implantation. We compared our results to internationally reported data. Results Between October 2014 and September 2019, 16 patients received an LVAD in our center. The mean age at implantation was 67.1 years. The mean EuroSCORE II was 24.4% and the median INTERMACS level was 4. Thirteen patients received an LVAD as destination therapy and three patients as bridge-to-candidacy. The overall survival was 87.5 and 70% at 1 and 2 years, respectively. Freedom from stroke was 81.3% at 1 and 2 years. Freedom from device infection was 67.7 and 58.7% at 1 and 2 years, respectively. Freedom from gastrointestinal bleeding was 75 and 56.3% at 1 and 2 years, respectively. Freedom from readmission was 50 and 31.3% and at 6 months and 1 year, respectively. Conclusions The Basel experience demonstrated the possible implementation of an LVAD program for destination therapy or bridge-to-candidacy in a non-transplant comprehensive heart-failure center with midterm survival results and freedom from major adverse events comparable to international registries. Patient selection remains crucial. Trial registration This study was registered on the ClinicalTrials.gov database (NCT04263012).

IntroductionSARS-CoV-2-detection is critical for clinical and epidemiological assessment of the ongoing CoVID-19 pandemic.AimTo cross-validate manual and automated high-throughput (Roche-cobas®6800-Target1/Target2) testing for SARS-CoV-2-RNA, to describe detection rates following lockdown and relaxation, and to evaluate SARS-CoV-2-loads in different specimens.MethodThe validation cohort prospectively compared Basel-S-gene, Roche-E-gene, and Roche-cobas®6800-Target1/Target2 in 1344 naso-oropharyngeal swabs (NOPS) taken in calendar week 13 using Basel-ORF8-gene-assay for confirmation. Follow-up-cohort-1 and -2 comprised 12363 and 10207 NOPS taken over 10 weeks until calendar week 24 and 34, respectively. SARS-CoV-2-loads were compared in follow-up NOPS, lower respiratory fluids, and plasma.ResultsConcordant results were obtained in 1308 cases (97%) including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman r>0.95; pConclusionEvaluated manual and automated assays are highly concordant and correlate quantitatively. Following successful lockdown, declining positive predictive values require dual-target-assays for clinical and epidemiologic assessment. Confirmatory and quantitative follow-up testing should be considered within

BackgroundThe first case of SARS-CoV-2 in Basel, Switzerland, was detected on February 26th2020. We present a phylogenetic longitudinal study and explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26thuntil March 23rd.MethodsWe sequenced SARS-CoV-2 from naso-oropharyngeal swabs, generated 468 high quality genomes, and called variants with our COVID-19 Pipeline (COVGAP). We analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny.FindingsThe early outbreak in Basel was dominated by lineage B.1 (83·6%), detected from March 2nd, although the first lineage identified was B.1.1. Within B.1, a clade containing 68·2% of our samples, defined by the SNP C15324T, suggests local spreading events. We infer the geographic origin of this mutation to our tri-national region. The remaining genomes map broadly over the global phylogenetic tree, evidencing several events of introduction from and/or dissemination to other regions of the world. We also observe family transmission events.InterpretationA single lineage dominated the outbreak in the City of Basel while other lineages such as the first (B1.1) did not propagate. Thus spreading events seem to have contributed most to viral spread, while travel returners and family transmissions were better controlled by the recommended measures. This phylogenetic analysis enriches epidemiological and contact tracing data, allowing connection of seemingly unconnected events, and can inform public health interventions.FundingNo dedicated funding was used for this work.

BackgroundSARS-CoV-2 emerged in China in December 2019 as new cause of severe viral pneumonia (CoVID-19) reaching Europe by late January 2020. We validated the WHO-recommended assay and describe the epidemiology of SARS-CoV-2 and community-acquired respiratory viruses (CARVs).MethodsNaso-oropharyngeal swabs (NOPS) from 7663 individuals were prospectively tested by the Basel-S-gene and the WHO-based E-gene-assay (Roche) using Basel-N-gene-assay for confirmation. CARVs were tested in 2394 NOPS by multiplex-NAT, including 1816 together with SARS-CoV-2.ResultsBasel-S-gene and Roche-E-gene-assays were concordant in 7475 cases (97.5%) including 825 (11%) positive samples. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 NOPS. Adults were more likely to test positive for SARS-CoV-2, while children were more likely to test CARV-positive. CARV co-infections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced other CARVs within 3 weeks reaching 48% of all detected respiratory viruses followed by rhino/enterovirus (13%), influenzavirus (12%), coronavirus (9%), respiratory syncytial (6%) and metapneumovirus (6%).ConclusionsThe differential diagnosis for respiratory infections was broad during the early pandemic, affecting infection control and treatment decisions. We discuss the role of pre-existing immunity and competitive CARV replication for the epidemiology of SARS-CoV-2 infection among adults and children.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China as the cause of coronavirus disease 2019 in December 2019 and reached Europe by late January 2020, when community-acquired respiratory viruses (CARVs) are at their annual peak. We validated the World Health Organization (WHO)–recommended SARS-CoV-2 assay and analyzed the epidemiology of SARS-CoV-2 and CARVs. Methods Nasopharyngeal/oropharyngeal swabs (NOPS) from 7663 patients were prospectively tested by the Basel S-gene and WHO-based E-gene (Roche) assays in parallel using the Basel N-gene assay for confirmation. CARVs were prospectively tested in 2394 NOPS by multiplex nucleic acid testing, including 1816 (75%) simultaneously for SARS-CoV-2. Results The Basel S-gene and Roche E-gene assays were concordant in 7475 cases (97.5%) including 825 (11%) SARS-CoV-2 positives. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 (1.4%). Adults were more frequently SARS-CoV-2 positive, whereas children tested more frequently CARV positive. CARV coinfections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced CARVs within 3 weeks, reaching 48% of all detected respiratory viruses followed by rhinovirus/enterovirus (13%), influenza virus (12%), coronavirus (9%), respiratory syncytial virus (6%), and metapneumovirus (6%). Conclusions Winter CARVs were dominant during the early SARS-CoV-2 pandemic, impacting infection control and treatment decisions, but were rapidly replaced, suggesting competitive infection. We hypothesize that preexisting immune memory and innate immune interference contribute to the different SARS-CoV-2 epidemiology among adults and children.

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.

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.

OBJECTIVES Patients with severe COVID-19 may be at risk of longer term sequelae. Long-term clinical, immunological, pulmonary and radiological outcomes of patients treated with anti-inflammatory drugs are lacking. METHODS In this single-centre prospective cohort study, we assessed 90-day clinical, immunological, pulmonary and radiological outcomes of hospitalised patients with severe COVID-19 treated with tocilizumab from March 2020 to May 2020. Criteria for tocilizumab administration were oxygen saturation 30/min, C-reactive protein levels >75 mg/l, extensive area of ground-glass opacities or progression on computed tomography (CT). Descriptive analyses were performed using StataIC 16. RESULTS Between March 2020 and May 2020, 50 (27%) of 186 hospitalised patients had severe COVID-19 and were treated with tocilizumab. Of these, 52% were hospitalised on the intensive care unit (ICU) and 12% died. Eleven (22%) patients developed at least one microbiologically confirmed super-infection, of which 91% occurred on ICU. Median duration of hospitalisation was 15 days (interquartile range [IQR] 10–24) with 24 days (IQR 14–32) in ICU patients and 10 days (IQR 7–15) in non-ICU patients. At day 90, 41 of 44 survivors (93%) were outpatients. No long-term adverse events or late-onset infections were identified after acute hospital care. High SARS-CoV-2 antibody titres were found in all but one patient, who was pretreated with rituximab. Pulmonary function tests showed no obstructive patterns, but restrictive patterns in two (5.7%) and impaired diffusion capacities for carbon monoxide in 11 (31%) of 35 patients, which predominated in prior ICU patients. Twenty-one of 35 (60%) CT-scans at day 90 showed residual abnormalities, with similar distributions between prior ICU and non-ICU patients. CONCLUSIONS In this cohort of severe COVID-19 patients, no tocilizumab-related long-term adverse events or late-onset infections were identified. Although chest CT abnormalities were highly prevalent at day 90, the majority of patients showed normal lung function. Trial registration ClinicalTrials.gov NCT04351503

AIMS The aim of this study was to analyse the demographics, risk factors and in-hospital mortality rates of patients admitted with coronavirus disease 2019 (COVID-19) to a tertiary care hospital in Switzerland. METHODS In this single-centre retrospective cohort study at the University Hospital Basel, we included all patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection hospitalised from 27 February 2020 to 10 May 2021. Patients’ characteristics were extracted from the electronic medical record system. The primary outcome of this study was temporal trends of COVID-19-related in-hospital mortality. Secondary outcomes were COVID-19-related mortality in patients hospitalised on the intensive care unit (ICU), admission to ICU, renal replacement therapy and length of hospital stay, as well as a descriptive analysis of risk factors for in-hospital mortality. RESULTS During the study period we included 943 hospitalisations of 930 patients. The median age was 65 years (interquartile range [IQR] 53–76) and 63% were men. The numbers of elderly patients, patients with multiple comorbidities and need for renal replacement therapy decreased from the first and second to the third wave. The median length of stay and need for ICU admission were similar in all waves. Throughout the study period 88 patients (9.3%) died during the hospital stay. Crude in-hospital mortality was similar over the course of the first two waves (9.5% and 10.2%, respectively), whereas it decreased in the third wave (5.4%). Overall mortality in patients without comorbidities was low at 1.6%, but it increased in patients with any comorbidity to 12.6%. Predictors of all-cause mortality over the whole period were age (adjusted odds ratio [aOR] per 10-year increase 1.81, 95% confidence interval [CI] 1.45–2.26; p

n BACKGROUND: Chronically critical illness is highly relevant in intensive care units, but the definitions in literature vary greatly. The timely detection of prolonged intensive care unit length of stay could support care planning for chronically critical ill patients. Aim To develop and validate a risk score for predicting prolonged length of stay in the surgical intensive care unit. Methods This single centre cohort study formed part of a nursing-led project in one surgical intensive care unit. We examined the performance of seven predefined predictive factors of prolonged (g20 days) intensive care unit length of stay in adults on the seventh day of stay in intensive care to develop (n = 304) and validate (n = 101) a risk score. Candidate variables (Charlson Comorbidity Index, Simplified Acute Physiology Score II, minimum plasma albumin, need for anti-infective drugs, time of mechanical ventilation, main feeding method and score on the Sedation-Agitation Scale) were analysed using multiple logistical regression analysis. Results Our risk score assigned different points to the following conditions: Charlson Comorbidity Index g2, minimum albumin l20 g/l between days 1 and 7, mechanical ventilation g14 hr on day 7 and the need for parenteral nutrition on day 7. For a validation data set (n = 101), the area under the receiver operating characteristic curve was 0.89 (95% confidence interval 0.77s0.87). At a cut-off value of 100 points, the degree of sensitivity was 88%, the specificity 75%, the positive predictive value 53%, the negative predictive value 95%, and the model fit R2 0.40. Conclusions Our model allowed the timely detection of prolonged intensive care unit length of stay with four candidate predictive factors. The timely identification of patients with prolonged intensive care unit length of stay is possible and could influence the person-centred prevention of chronically critical illness and adequate resource allocation. (Trial registration no DRKS 00017073) &nbsp.

Background Existential questions concerning the limitation of treatment must be answered when a major complication occurs after an elective operation. In these situations, the patient himself/herself cannot be asked about his/her will. Therefore, medical professionals must attempt to determine the patient's presumed will either through an existing advance directive (AD) or by consulting with the patient's relatives. Only one-fifth of all patients create an AD in advance, and the relatives cannot always reliably reproduce the patient's presumed will. Thus, it is important to talk about issues such as do-not-resuscitate before a patient undergoes elective major surgery. However, such discussions may unsettle and frighten the patient. This study aimed to determine if patients are willing to talk about difficult questions such as resuscitation before major surgery. How many patients create an AD? Who should decide when patients themselves are no longer capable? Objectives Between March 1 and October 30, 2014, patients who attended the preoperative anaesthesia consultation service received a one-page questionnaire. In addition to a few personal questions (e.g. sex, age, surgery, health status), the questionnaire included four questions that could be answered according to a four-point Likert scale, with a yes or no response, or a with a selection of answers. Results 272 men (45.5%) and 321 women (53.7%) with a mean age of 52.9 years (standard deviation: 17.8 years) completed a questionnaire. 312 patients (52.2%) claimed to be healthy, while 116 patients (19.4%) observed a minimal health restriction. 125 patients (19.4%) suffered from a chronic illness that markedly (n = 108) or strongly (n = 17) limited daily life. More than three-fourths of the respondents were very ready (377/63.0%) or ready (79 patients/13.2%) to talk about the treatment of severe complications after an elective operation. 12.7% of the patients would rather not to talk about this topic (n = 47) or refused (n = 37). 58 patients (9.7%) checked the box "I do not know" or gave no answer. There was no significant difference between men and women (p = 0.58). The patient's state of health did not significantly affect the patient's willingness to talk (p = 0.61). 110 patients (18.4%) had already completed an AD. The probability of having an AD is highly dependent on the age and state of health. The likelihood of having one increases by 4% for each year of life, and in health-impaired patients it is 73% higher than in healthy ones. If the patient could no longer decide for himself/herself, the following options were selected from multiple possible answers: a relative decides (n = 272), discussing this with a physician prior to surgery (n = 212), previously created AD (n = 198), the treatment team decides (n = 28), I do not know/not (n = 48). Conclusions Although the majority of the respondents were willing to talk about difficult issues before an operation, it remains unclear to what extent these results can be generalized. However, the results justify efforts to carefully inquire about and document the will of sick patients prior to major surgery. Both the treatment team and the relatives are relieved if the patient's will is known when difficult decisions have to be made.

Summary Background & aims Cardiac surgery is accompanied by oxidative stress and systemic inflammatory response, which may be associated with organ dysfunction and increased mortality. Selenium and selenoenzymes are important constituents of anti-oxidative defense. We hypothesized that high-dose sodium selenite supplementation can attenuate the postoperative inflammation and might, therefore, improve clinical outcome. Methods Randomized, placebo-controlled, double-blinded, bi-center study on 411 adult patients undergoing elective cardiac surgery. Patients received an intravenous bolus of 4000 μg selenium (in the form of sodium selenite) or placebo after induction of anesthesia and 1000 μg/d selenium or placebo during their intensive care unit (ICU) stay. Primary outcome measure was the Sequential Organ Failure Assessment (SOFA) score on the second postoperative day. Secondary endpoints included the change in perioperative selenium levels, change of inflammatory and cardiac markers, use of vasoactive medication, incidence of acute kidney injury, ICU and hospital length of stay, and mortality. Results The perioperative administration of high-dose sodium selenite prevented the postoperative drop of blood and serum selenium levels, reduced the number of patients depending on postoperative vasoactive support but failed to reduce the postoperative SOFA score and its related organ-specific scores compared to placebo. Except for an increase of postoperative procalcitonin and bilirubin levels in the sodium selenite group, other inflammatory markers, organ function variables and clinical endpoints remained unchanged. Conclusions The perioperative administration of high-dose sodium selenite in cardiac surgery patients prevented the postoperative fall of blood selenium levels and reduced the need for postoperative vasoactive support by a yet unknown mechanism. Trial registration Registered under ClinicalTrials.gov Identifier no. NCT01141556 .

Zusammenfassung: Hintergrund: Der Berufsalltag vieler Mitarbeitender im Gesundheitswesen ist in den letzten Jahren anspruchsvoller geworden, und die Anforderungen werden immer größer. Häufig stellen sich neben rein fachlichen auch ethische Fragen, z.B. nach der Sinnhaftigkeit einer Therapie am Lebensende. So genannte "medical futility", eine nutzlose, aussichtslose Therapie, wird von Pflegenden und Ärzten auf Intensivstationen häufig wahrgenommen. Das medizinethische Modell METAP (Akronym aus Module, Ethik, Therapieentscheidung, Allokation und Prozess) stellt Verfahren und Kriterien zur Verfügung, die es dem Behandlungsteam ermöglichen, diese Fragen gemeinsam, eigenständig und lösungsorientiert zu bearbeiten. Material und Methode: Alle Protokolle der 44 ethischen Fallbesprechungen (eFB), die zwischen Januar 2011 und Juni 2012 auf einer chirurgischen Intensivstation stattfanden, wurden zusammengefasst. Ein kurzer Fragebogen an alle Teilnehmenden erfasste deren Beurteilung des Nutzens für den Patienten und das Team sowie die Wahrnehmung der Reduktion persönlicher Belastung. Ergebnisse: Interprofessionelle eFB finden regelmäßig statt (ca. 2/Monat). Von den 41 in der eFB behandelten Patienten verstarben im Verlauf 23. Die Befragten (Rücklaufquote 52 %) schätzen den Nutzen für Patienten und Team als hoch ein (Ärzte etwas höher als Pflegende). Mehr als zwei Drittel der Pflegenden und die Hälfte der Ärzte nehmen eine Reduktion der Belastung durch die eFB wahr. Schlussfolgerungen: Eine methodisch strukturierte ethische Entscheidungsfindung kann in die klinische Routine integriert werden, wenn sie einen festen Platz im Alltag erhält, die ärztliche und die pflegerische Leitung die Implementierung unterstützen sowie die Verantwortung für die Organisation und Durchführung festgelegt ist.

Data regarding immunomodulatory effects of parenteral n-3 fatty acids in sepsis are conflicting. In this study, the effect of administration of parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients was investigated.; Fifty patients with sepsis were randomized to receive either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to the intensive care unit or standard treatment. Markers of brain injury and inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis-associated delirium was performed daily. The primary outcome was the difference in S-100β from baseline to peak level between both the intervention and the control group, compared by t-test. Changes of all markers over time were explored in both groups, fitting a generalized estimating equations model.; Mean difference in change of S-100β from baseline to peak level was 0.34 (95% CI: -0.18-0.85) between the intervention and control group, respectively (P = 0.19). We found no difference in plasma levels of S-100β, neuron-specific enolase, interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time. Incidence of sepsis-associated delirium was 75% in the intervention and 71% in the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796).; Administration of n-3 fatty acids did not affect markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients.

Hintergrund Hochleistungsmedizin und Kostenrationierung konnen zu moralischem Disstress und Burn-out-Syndromen fuhren – mit z. T. schwerwiegenden Konsequenzen fur die direkt Betroffenen, die Qualitat der Patientenversorgung und die Institutionen. Das multimodale Modell METAP (Modul, Ethik, Therapieentscheide, Allokation, Prozess) wurde als masgeschneiderte klinische Alltagsethik entwickelt und unterstutzt die interprofessionelle ethische Entscheidungsfindung. Die Besonderheit des Modells liegt in der Ausbildung einer Ethikkompetenz im Umgang mit schwierigen Therapieentscheiden. METAP wurde zur Qualitatsprufung evaluiert.

Background To investigate the long-term outcome in polytrauma victims with traumatic brain injury (TBI) and without traumatic brain injury (NTBI). Methods Cohort study based on prospectively collected data. Evaluation of functional outcome and quality of life at least 2 years (median 2.5) following trauma in 111 survivors [39.5 ± 20.9 years; injury severity score (ISS) 27.9 ± 8.2; TBI: n = 45; NTBI: n = 66] out of a total of 211 consecutive multiply-injured patients with an ISS > 16, all primarily admitted to the intensive care unit. Results Significantly fewer TBI patients lived independently compared with NTBI patients (71% vs. 95%; P

The stressful work environment of ICUs can lead to burnout. Burnout can impact on the welfare and performance of caregivers, and may lead them to resign their job. The shortage of ICU caregivers is becoming a real threat for health care leaders.To investigate the factors associated with burnout on a national level in order to determine potential important factors.Prospective, multicenter, observational survey of all caregivers from 74 of the 92 Swiss ICUs, measuring the prevalence of burnout among the caregivers and the pre-specified center-, patient- and caregiver-related factors influencing its prevalence.Out of the 4322 questionnaires distributed from March 2006 to April 2007, 3052 (71%) were returned, with a response rate of 72% by center, 69% from nurse-assistants, 73% from nurses and 69% from physicians. A high proportion of female nurses among the team was associated with a decreased individual risk of high burnout (OR 0.98, 95% CI:0.97-0.99 for every %). The caregiver-related factors associated with a high risk of burnout were being a nurse-assistant, being a male, having no children and being under 40 years old.The findings of this study seem to open a new frontier concerning burnout in ICUs, highlighting the importance of team composition. Our results should be confirmed in a prospective multicenter, multinational study. Whether our results can be exported to other medical settings where team-working is pivotal remains to be investigated.

Background Ventilator-associated pneumonia (VAP) is the most common hospital-acquired, life-threatening infection. Poor outcome and health-care costs of nosocomial pneumonia remain a global burden. Currently, physicians rely on their experience to discriminate patients with good and poor outcome. However, standardized prognostic measures might guide medical decisions in the future. Pancreatic stone protein (PSP)/regenerating protein (reg) is associated with inflammation, infection, and other disease-related stimuli. The prognostic value of PSP/reg among critically ill patients is unknown. The aim of this pilot study was to evaluate PSP/reg in VAP. Methods One hundred one patients with clinically diagnosed VAP were assessed. PSP/reg was retrospectively analyzed using deep-frozen serum samples from VAP onset up to day 7. The main end point was death within 28 days after VAP onset. Results Serum PSP/reg was associated with the sequential organ failure assessment score from VAP onset (Spearman rank correlation coefficient 0.49 P Conclusions Serum PSP/reg is a biomarker related to organ failure and outcome in patients with VAP. Trial registry ISRCTN.org; No.: ISRCTN61015974; URL: www.isrctn.org.

Zusammenfassung: Ethische Leitlinien für die klinische Praxis erfreuen sich zunehmender Beliebtheit. Damit klinisch-ethische Leitlinien aber überhaupt erfolgreich wirksam werden können, ist noch Pionierarbeit zu leisten. Solche Leitlinien müssen wissenschaftlich stärker fundiert und ihre praktische Anwendbarkeit muss verbessert werden. In dieser Arbeit werden die ersten Schritte des Projekts METAP zur methodischen Entwicklung und praktischen Implementierung einer Leitlinie für eine patientengerechte Versorgung am Krankenbett beschrieben und zur Diskussion gestellt. Das Projekt orientiert sich methodisch an der Entwicklung medizinischer Leitlinien und generiert damit eine forschungs- und konsensgestützte Leitlinie, die systematischer Evaluation und Modifikation unterliegt und Rechenschaft über ihre wissenschaftliche Fundierung gibt. Zusätzlich zur Leitlinie bietet das Projekt in der Form eines Handbuchs ein Entscheidungsfindungsverfahren an, welches unter anderem deliberative Aspekte unterstützt. Das Handbuch konzentriert sich auf ethische Fragen der Mikroallokation und liefert darüber hinaus Informationen über empirische, ethische und rechtliche Grundlagen für Therapieentscheidungen. Anhand eines Eskalationsmodells können unterschiedliche Instrumente nach Bedarf als ethische Lösungsstrategien eingesetzt werden, von der Kurzfassung im Kitteltaschenformat ("Leporello") mit den wichtigsten Fakten, weiterführenden Texten und Empfehlungen mit normativen und prozeduralen Hinweisen, über stationsinterne Lösungsversuche bis hin zum Ethikkonsil. Klinische Partner sind von Beginn an aktiv in den Entwicklungsprozess eingebunden und verbessern so die Praxistauglichkeit und Akzeptanz sowie die Ausrichtung des Instrumentariums an den tatsächlichen Bedürfnissen. Dieses partnerschaftliche, partizipative Vorgehen scheint eine wichtige Voraussetzung dafür zu sein, dass METAP in der Klinik Fuß fassen konnte

Healthcare-associated infections affect 1.4 million patients at any time worldwide, as estimated by the World Health Organization. In intensive care units, the burden of healthcare-associated infections is greatly increased, causing additional morbidity and mortality. Multidrug-resistant pathogens are commonly involved in such infections and render effective treatment challenging. Proper hand hygiene is the single most important, simplest, and least expensive means of preventing healthcare-associated infections. In addition, it is equally important to stop transmission of multidrug-resistant pathogens. According to the Centers for Disease Control and Prevention and World Health Organization guidelines on hand hygiene in health care, alcohol-based handrub should be used as the preferred means for routine hand antisepsis. Alcohols have excellent in vitro activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, Mycobacterium tuberculosis, a variety of fungi, and most viruses. Some pathogens, however, such as Clostridium difficile, Bacillus anthracis, and noroviruses, may require special hand hygiene measures. Failure to provide user friendliness of hand hygiene equipment and shortage of staff are predictors for noncompliance, especially in the intensive care unit setting. Therefore, practical approaches to promote hand hygiene in the intensive care unit include provision of a minimal number of handrub dispensers per bed, monitoring of compliance, and choice of the most attractive product. Lack of knowledge of guidelines for hand hygiene, lack of recognition of hand hygiene opportunities during patient care, and lack of awareness of the risk of cross-transmission of pathogens are barriers to good hand hygiene practices. Multidisciplinary programs to promote increased use of alcoholic handrub lead to an increased compliance of healthcare workers with the recommended hand hygiene practices and a reduced prevalence of nosocomial infections.

Prospective data regarding the prognostic value of the Sequential Organ Failure Assessment (SOFA) score in comparison with the Simplified Acute Physiology Score (SAPS II) and trauma scores on the outcome of multiple-trauma patients are lacking.Single-center evaluation (n = 237, Injury Severity Score [ISS]16; mean ISS = 29). Uni- and multivariate analysis of SAPS II, SOFA, revised trauma, polytrauma, and trauma and ISS scores (TRISS) was performed.The 30-day mortality was 22.8% (n = 54). SOFA day 1 was significantly higher in nonsurvivors compared with survivors (P.001) and correlated well with the length of intensive care unit stay (r = .50, P.001). Logistic regression revealed SAPS II to have the best predictive value of 30-day mortality (area under the receiver operating characteristic = .86 +/- .03). The SOFA score significantly added prognostic information with regard to mortality to both SAPS II and TRISS.The combination of critically ill and trauma scores may increase the accuracy of mortality prediction in multiple-trauma patients.

In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy. In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis. Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2-21) days versus 9.5 (1.5-17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02-2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar. Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia.

Das Thema Therapiebegrenzung wird seit mehr als zehn Jahren stark diskutiert. In verschiedenen Landern wurden Studien durchgefuhrt, die die Haufigkeit von Therapieunterlassung und Therapieabbruch bestimmten. Noch kaum untersucht ist aber die Fragestellung: Wie wird eine Therapiebegrenzung auf einer Intensivstation praktisch umgesetzt und erfolgt diese Umsetzung in wiederkehrenden Schritten? Auf einer chirurgischen Intensivstation wurden zehn Falle dokumentiert, bei denen eine Therapie nicht begonnen (Therapieunterlassung) oder eine bereits begonnene Therapie abgebrochen (Therapieabbruch) wurde. Alle medizinisch und ethisch relevanten Informationen wurden in einem eigens dafur entwickelten dreiteiligen Dokumentationsbogen erfasst. Zusatzlich wurden alle Krankengeschichten dahingehend untersucht, in welcher Reihenfolge und zu welchem Zeitpunkt eine neue Therapie begonnen und wann welche Therapie begrenzt wurde. Die Auswahl der Patienten erfolgte nach dem Zufallsprinzip. Es zeigte sich ein Muster im Ablauf der Therapiebegrenzung. In funf Fallen erfolgte die Therapiebegrenzung sehr schnell. Mehrere Therapien wurden fast gleichzeitig abgebrochen. In allen Fallen war die Prognose infaust. Bei sicher schlechter Prognose wurden also verschiedene Therapien gleichzeitig gestoppt. Anders war es bei noch unklarer Prognose. Hier erfolgte die Therapiebegrenzung sehr viel weniger schnell. Zuerst beschrankte man sich darauf, Therapien gar nicht erst zu beginnen. Erst in einem spateren Schritt wurden dann Therapien abgebrochen. Dieser Abbruch erfolgte schrittweise in folgender Reihenfolge: Keine Reanimation mehr, Vasoaktiva und Antibiotika nur eingeschrankt, kein Ausbau der mechanischen Beatmung, Stopp einzelner Medikamente, Einstellung der Ernahrung bei Aufrechterhaltung der Flussigkeitszufuhr. Trotz bereits stattgefundener Therapiebegrenzung wurden auch neue Therapien begonnen. Beim Ablauf der Therapiebegrenzung lies sich in den untersuchten Fallen ein „Muster“ erkennen, das abhangig ist von der Prognose des betreffenden Patienten. Nicht auszuschliesen ist deshalb, dass sich auf Stationen, die regelmasig mit solchen Situationen konfrontiert sind, einer Art „Ritual“ herausbildet, das fast automatisch ablauft. Es ist wichtig, sich dessen bewusst zu werden und diese Ablaufe immer wieder zu hinterfragen. Bei jedem Patienten sollte individuell entschieden werden, welche Therapien sinnvoll sind und welche nur zusatzliches Leiden verursachen. Dabei sollte man sich, wenn immer moglich, am Patientenwillen bzw. am mutmaslichen Patientenwillen orientieren.

The aim of the study was to compare the adrenal response, the course of the ACTH/cortisol ratio, as well as the variance and the diagnostic performance of different cutoffs after 1 and 250 microg ACTH stimulation in different stress situations.We investigated three groups with increasing stress levels: ambulatory controls (group A; n = 20), hospitalized medical patients (group B; n = 25), and patients undergoing coronary artery bypass grafting (group C; n = 29). All subjects underwent four consecutive ACTH stimulation tests and were randomized to either a 1- or 250-microg dose.Stimulated cortisol levels in group A were similar to basal cortisol levels under maximal stress (C3; P = 0.8). Peak cortisol concentrations were higher after 250 microg compared with 1 microg ACTH in group B (P = 0.006) and under maximal stress after extubation (group C3; P = 0.027), whereas there were no differences in group A. The ACTH/cortisol ratio was lower in surgical patients after extubation compared with unstressed conditions (Por = 0.03) The within-subject variance was similar in ambulatory controls and medical patients and after both ACTH doses (all 17-36% of total variance). Cutoff dependent, the diagnosis of relative adrenal insufficiency would have been made in 0-58.3%, respectively.In moderate and major stress situations, cortisol concentrations in patients without hypothalamic-pituitary-adrenal disease were higher after stimulation with 250 microg compared with 1 mug ACTH. Data from our study give insight into the physiological adaptations of the hypothalamic-pituitary-adrenal axis to stress.