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BACKGROUND & AIMS: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. METHODS: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. RESULTS: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). CONCLUSIONS: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. IMPACT AND IMPLICATIONS: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies. ispartof: JOURNAL OF HEPATOLOGY vol:78 issue:4 pages:783-793 ispartof: location:Netherlands status: published

To assess the incidence and severity of changes in hearing threshold in patients undergoing high-dose pencil-beam-scanning proton therapy (PBS-PT). This retrospective cohort study included fifty-one patients (median 50 years (range, 13–68)) treated with PBS-PT for skull base tumors. No chemotherapy was delivered. Pure tone averages (PTAs)were determined before (baseline) and after PBS-PT as the average hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz. Hearing changes were calculated as PTA differences between pre-and post-PBS-PT. A linear mixed-effects model was used to assess the relationship between the PTA at the follow-up and the baseline, the cochlea radiation dose intensity, the increased age, and the years after PBS-PT. Included patients were treated for chordoma (n = 24), chondrosarcoma (n = 9), head and neck tumors (n = 9), or meningioma (n = 3), with a mean tumor dose of 71.1 Gy (RBE) (range, 52.0–77.8), and a mean dose of 37 Gy (RBE) (range, 0.0–72.7) was delivered to the cochleas. The median time to the first follow-up was 11 months (IQR, 5.5–33.7). The PTA increased from a median of 15 dB (IQR 10.0–25) at the baseline to 23.8 (IQR 11.3–46.3) at the first follow-up. In the linear mixed-effect model, the baseline PTA (estimate 0.80, 95%CI 0.64 to 0.96, p ≤ 0.001), patient’s age (0.30, 0.03 to 0.57, p = 0.029), follow-up time (2.07, 0.92 to 3.23, p ≤ 0.001), and mean cochlear dose in Gy (RBE) (0.34, 0.21 to 0.46, p ≤ 0.001) were all significantly associated with an increase in PTA at follow-up. The applied cochlear dose and baseline PTA, age, and time after treatment were significantly associated with hearing loss after proton therapy.

To assess the incidence and severity of changes in hearing threshold in patients undergoing high-dose pencil-beam-scanning proton therapy (PBS-PT). This retrospective cohort study included fifty-one patients (median 50 years (range, 13-68)) treated with PBS-PT for skull base tumors. No chemotherapy was delivered. Pure tone averages (PTAs)were determined before (baseline) and after PBS-PT as the average hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz. Hearing changes were calculated as PTA differences between pre-and post-PBS-PT. A linear mixed-effects model was used to assess the relationship between the PTA at the follow-up and the baseline, the cochlea radiation dose intensity, the increased age, and the years after PBS-PT. Included patients were treated for chordoma (n = 24), chondrosarcoma (n = 9), head and neck tumors (n = 9), or meningioma (n = 3), with a mean tumor dose of 71.1 Gy (RBE) (range, 52.0-77.8), and a mean dose of 37 Gy (RBE) (range, 0.0-72.7) was delivered to the cochleas. The median time to the first follow-up was 11 months (IQR, 5.5-33.7). The PTA increased from a median of 15 dB (IQR 10.0-25) at the baseline to 23.8 (IQR 11.3-46.3) at the first follow-up. In the linear mixed-effect model, the baseline PTA (estimate 0.80, 95%CI 0.64 to 0.96

PurposeSimplified first-trimester abortion protocols are well established as they facilitate access to services and improve patient satisfaction without compromising safety. However, data on abortion protocols across Switzerland by facility type are lacking. Therefore, the first aim of this study was to analyse hospital-derived abortion protocols, as opposed to office-based protocols, across Switzerland in terms of their acceptance among women. The second aim was to assess abortion protocols and outcomes of specialised general practitioners (GPs) following simplified protocols.MethodsThis study consists of two parts. (i) A nationwide questionnaire was distributed among hospitals and private practices covering details of abortion protocols and numbers between April and July, 2019. The primary endpoint was the proportion of women undergoing an abortion after the first consultation at the chosen facility (adherence), regarding the complexity of abortion protocols in each setting. (ii) A retrospective study was conducted to analyse the outcomes of office-based institutions with simplified abortion procedures over a period of 10 years from January, 2008, to December, 2018. (BASEC-No. Req-2018-01031).Results (i) Office-based facilities showed less complex abortion protocols, resulting in a significantly higher probability of undergoing an abortion after the first consultation than hospitals. Their protocols allowed for a higher gestational age by medical means, and they offered mifepristone intake within the first consultation along with fewer staff members involved and a lower number of overall consultations. (ii) From 5,495 women, a total of 5,274 patients were included, of which the incidence of complications requiring surgery was at a low of 2.5%. ConclusionThis study highlights that simplified abortion protocols are crucial to ease access to abortion services, as represented by higher adherence in office-based facilities. Simplified protocols in abortion services are safe, and repetitive counselling and in-person visits should only be reserved for selected cases.

Background Hospital acquired pneumonia (HAP) is divided in two distinct groups, ventilator-associated pneumonia (VAP) and non-ventilator-associated HAP (nvHAP). Although nvHAP occurs more frequently than VAP and results in similar mortality and costs, prevention guidelines and prevention focus almost exclusively on VAP. Scientific evidence about nvHAP prevention and its implementation is scarce. Therefore, we designed a mixed-methods hybrid type 2 effectiveness-implementation study to investigate both the effectiveness and implementation of a newly developed nvHAP prevention bundle. Methods This single-centre project at the 950-bed University Hospital Zurich (UHZ) will engage the wards of nine departments with substantial nvHAP rates. The nvHAP bundle consists of five primary prevention measures: 1) oral care, 2) prevention of dysphagia-related aspiration, 3) mobilization, 4) stopping unnecessary proton pump inhibitors, and, 5) respiratory therapy. Implementation includes the engagement of department-level implementation teams, who sustain the ‘core’ intervention components of education, training, and environmental restructuring and tailor the implementation strategy to local needs. Both effectiveness and implementation outcomes will be assessed using mixed-methods. As a primary outcome, nvHAP incidence rates will be analysed by Poisson regression models to compare incidence rates before, during, and after the implementation phases (on the hospital and department level). Additionally, the association between process indicators and nvHAP incidence rates will be analysed using longitudinal Poisson regression models. A longitudinal, qualitative study and formative evaluation based on interviews, focus groups, and observations identifies supporting or hindering factors for implementation success in participating departments dynamically over time. This accumulating implementation experience will be constantly fed back to the implementation teams and thus, represents an active implementation element. Discussion This comprehensive hybrid mixed-methods study is designed to both, measure the effectiveness of a new nvHAP prevention bundle and multifaceted implementation strategy, while also providing insights into how and why it worked or failed. The results of this study may contribute substantially to advancing knowledge and patient safety in the area of a rediscovered healthcare-associated infection - nvHAP. Trial registration ClinicalTrials.gov: NCT03361085. Registered December 2017.

Portal hypertensive polyps (PHPs) are incompletely characterized lesions that can be found in the distal stomach of patients with portal hypertension. We aimed to delineate clinical factors associated with the appearance of these rare polyps. We conducted a cross-sectional study of a cohort with 513 cirrhotic patients comparing patients with and without PHP using descriptive analyses and multivariable logistic regression. To address the problem of missing values, in particular for HVPG and liver stiffness, we used multiple imputation of missing values. The prevalence of macroscopically diagnosed PHP was 3.3% (95% confidence interval 2.0 − 5.4%). In 53% of cases, the correct classification was missed on index gastroscopy. Patients with PHP were older at gastroscopy (65 years vs. 59), had higher hepatic venous pressure gradients (HVPG, 28 mmHg vs. 19 mmHg), higher transient elastography (TE) measurements (50.7 kPa vs. 21.8 kPa) and more often had previous rubber band ligations (RBL, 64.7% vs. 25.8%). The multivariable logistic regression on the outcome macroscopically diagnosed PHP estimated an odds ratio (OR) for HPVG of 1.13 (CI 0.95–1.34), increased liver stiffness of 1.03 (1.00 − 1.07) and previous RBL of 3.84 (1.24 − 11.88), respectively. The prevalence of PHPs in the stomach was higher than assumed in previous studies and misclassification was commonly observed. The appearance of these rare polyps is associated with previous RBL and may correlate with severity of PH. Thus, PHPs may be regarded as marker for relevant PH, but clinical significance of these polyps is still uncertain.

ImportanceIntraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date.ObjectiveTo assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH.Design, Setting, and ParticipantsBetween April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age InterventionsInfants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life.Main Outcomes and MeasuresSecondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023).ResultsSixty infants (48% male [n = 29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [n = 37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9–28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; P = .15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores.Conclusions and RelevanceThis preliminary report of a randomized clinical trial found no evidence that high-dose erythropoietin in preterm infants with IVH affects brain injury scores on conventional magnetic resonance imaging at TEA. Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials.Trial RegistrationClinicalTrials.gov Identifier: NCT02076373

Background Measures of the sonorheometry based Quantra® viscoelastic hemostatic analyzer (HemoSonics, LCC, Charlottesville, VA, USA) were compared with corresponding results of the ROTEM® sigma device (Instrumentation Laboratory, Bedford, MA, USA). Methods In thirty-eight patients scheduled for elective cardiac surgery between December 2018 and October 2019, blood samples were taken after induction of anesthesia (sample 1) and after heparin neutralization (sample 2) and measured on Quantra (QPlus® Cartridge) and ROTEM sigma (ROTEM® sigma complete + hep Cartridge). Clot times and clot stiffness values were recorded. Clot stiffness values of ROTEM amplitudes (A in mm) were converted to shear modulus (G) in hectoPascal (hPa): G (hPa) = (5 x A)/(100-A). Additionally, time-to-results was recorded. Spearman rank test correlation and Bland Altman analysis were performed. Results Clot stiffness parameters of the Quantra correlated strongly with corresponding measurements of the ROTEM with r = 0.93 and 0.94 for EXTEM A10 vs CS and r = 0.94 and 0.96 for FIBTEM A10 vs FCS for sample 1 and 2, respectively. Quantra clot time correlated strongly with ROTEM INTEM CT with r = 0.71 for sample 1 and r = 0.75 for sample 2. However, Bland Altman analysis showed no agreement in all compared assays of both methods. The median time to delivery of first and complete results was significantly shorter for Quantra (412 and 658 s) compared to ROTEM sigma (839 and 1290 s). Conclusions The Quantra showed a strong correlation with the ROTEM sigma for determining clot times and clot stiffness and the parameters assess similar aspects of clot development. However, these parameters are not directly interchangeable and implicate that separate cut-off values need to be established for users of the Quantra device. Word count: 278. Trial registration The study was retrospectively registered with ClinicalTrials.gov (ID: NCT04210830) at December 20th 2019.

Background With the goal of reducing the prevalence of early childhood caries, the city of Zurich, Switzerland, started a specific prevention programme in 2010. All 2-year-olds are invited to a free dental check-up at a local public dental health service before the first legally mandated yearly dental check-up for school children between 4 and 5 years of age (at kindergarten). However, for the success of this prevention programme, it is of particular importance that children at high risk of caries are reached. The objective of our study was to assess the effectiveness of the prevention programme in (1) reaching the children who needed it the most and (2) improving subsequent oral health. Methods This retrospective cohort study included all children born between July 1, 2013 and July 15, 2014 who had lived in Zurich between the ages of 23 and 36 months. Socio-economic data were extracted from official school records, and dental health data from public dental clinic records. Binomial and quasi-binomial generalised linear models were used to identify the socio-economic factors associated with toddler check-up attendance and to assess the associations between attendance and caries experience (dmft $$\ge$$ ≥ 1) as well as degree of treatment (proportion m+f out of dmft) at the kindergarten check-up, adjusting for socio-economic factors. Results From a total of 4376 children, 2360 (54%) attended the toddler check-up (mean age 2.4 years) and 3452 (79%) had a dental examination at kindergarten (mean age 5.3 years). Non-Swiss origin of the primary caretaker, presence of older siblings, low amount of savings and allocation to certain public dental clinics were associated with a lower odds of attendance. Factors associated with a higher odds of caries experience were similar to those associated with a lower odds of attendance at the toddler check-up, but additionally included low income. Attendance at the toddler check-up was non-significantly associated with a lower odds of caries experience at kindergarten (adjusted OR 0.84, 95% CI from 0.70 to 1.01), but was significantly associated with a higher degree of treatment at this stage (adjusted OR 2.41, 95% CI from 1.79 to 3.24). Conclusions Our study suggests that children with a high caries risk are less likely to attend the toddler check-up. Greater effort should be put into reaching these children.

Background Families of critically ill persons face uncertainty and experience distress during and after their close other's stay in an intensive care unit (ICU). Proactive nurse engagement and support is recommended to meet families' needs in the ICU, but little is known about its impact on quality of family care. We introduced a family support intervention that consisted of an interprofessional family support pathway and a new role of an advanced practice family nurse. Objectives The aim of the study was to examine the effect of an advanced practice nurse–led family support intervention on family members' satisfaction, wellbeing, and psychological distress. Methods We conducted a quasi-experimental before-and-after study with embedded qualitative interviews in a Swiss University Hospital from March 2018 to July 2019 using a questionnaire (Family Satisfaction in the ICU-24 Survey, Hospital Anxiety and Depression Scale, and Impact of Event Scale-Revised-6) and qualitative interviews (n = 19) after patient discharge. Results Families in the intervention group (n = 75) showed a trend for increased overall satisfaction (difference of 5.544, 95% confidence interval [CI]: −0.11 to 11.20), a statistically significant increase in satisfaction with decision-making (7.258, 95% CI: 0.89 to 13.63), and a nonsignificant increase in satisfaction with care (4.178, 95% CI: −1.53 to 9.89). Psychological distress was higher in the intervention group, with depression reaching statistical significance (difference of 1.706, 95% CI: 0.16 to 3.25), which may be explained by longer ICU stays and higher proportion of deaths in the intervention group. Families receiving the intervention reported to be feeling cared for, well informed, and better able to cope. Data integration suggests that early onset, fit to need, and quality of intervention were the most important intervention characteristics impacting family wellbeing. Conclusions Our study found that family members experience a nurse-led support intervention as beneficial for their wellbeing. It increased their satisfaction, but was unable to demonstrate a favourable impact on psychological distress.

Background Neonatal mortality in Guinea accounts for about 30% of all fatalities in children younger than five years. Countrywide, specialized neonatal intensive care is provided in one single clinic with markedly limited resources. To implement targeted measures, prospective data on patient characteristics and factors of neonatal death are needed. Objective To determine the rates of morbidity and mortality, to describe clinical characteristics of admitted newborns requiring intensive care, to assess the quality of disease management, and to identify factors contributing to neonatal mortality. Methods Prospective observational cohort study of newborns admitted to the hospital between mid-February and mid-March 2019 after birth in other institutions. Data were collected on maternal/prenatal history, delivery, and in-hospital care via convenience sampling. Associations of patient characteristics with in-hospital death were assessed using cause-specific Cox proportional-hazards models. Results Half of the 168 admitted newborns underwent postnatal cardiopulmonary resuscitation. Reasons for admission included respiratory distress (49.4%), poor postnatal adaptation (45.8%), prematurity (46.2%), and infections (37.1%). 101 newborns (61.2%) arrived in serious/critical general condition; 90 children (53.9%) showed clinical signs of neurological damage. Quality of care was poor: Only 59.4% of the 64 newborns admitted with hypothermia were externally heated; likewise, 57.1% of 45 jaundiced infants did not receive phototherapy. Death occurred in 56 children (33.3%) due to birth asphyxia (42.9%), prematurity (33.9%), and sepsis (12.5%). Newborns in serious/critical general condition at admission had about a fivefold higher hazard to die than those admitted in good condition (HR 5.21 95%-CI 2.42–11.25, p = Conclusion Neonatal mortality was strikingly high. Birth asphyxia, prematurity, and infection accounted for 89.3% of death, aggravated by poor quality of in-hospital care. Children with serious general condition at admission had poor chances of survival. The whole concept of perinatal care in Guinea requires reconsideration.

Background Klebsiella spp. are opportunistic pathogens which can cause severe infections, are often multi-drug resistant and are a common cause of hospital-acquired infections. Multiple new Klebsiella species have recently been described, yet their clinical impact and antibiotic resistance profiles are largely unknown. We aimed to explore Klebsiella group- and species-specific clinical impact, antimicrobial resistance (AMR) and virulence. Methods We analysed whole-genome sequence data of a diverse selection of Klebsiella spp. isolates and identified resistance and virulence factors. Using the genomes of 3594 Klebsiella isolates, we predicted the masses of 56 ribosomal subunit proteins and identified species-specific marker masses. We then re-analysed over 22,000 Matrix-Assisted Laser Desorption Ionization - Time Of Flight (MALDI-TOF) mass spectra routinely acquired at eight healthcare institutions in four countries looking for these species-specific markers. Analyses of clinical and microbiological endpoints from a subset of 957 patients with infections from Klebsiella species were performed using generalized linear mixed-effects models. Results Our comparative genomic analysis shows group- and species-specific trends in accessory genome composition. With the identified species-specific marker masses, eight Klebsiella species can be distinguished using MALDI-TOF MS. We identified K. pneumoniae (71.2%; n = 12,523), K. quasipneumoniae (3.3%; n = 575), K. variicola (9.8%; n = 1717), “K. quasivariicola” (0.3%; n = 52), K. oxytoca (8.2%; n = 1445), K. michiganensis (4.8%; n = 836), K. grimontii (2.4%; n = 425) and K. huaxensis (0.1%; n = 12). Isolates belonging to the K. oxytoca group, which includes the species K. oxytoca, K. michiganensis and K. grimontii, were less often resistant to 4th-generation cephalosporins than isolates of the K. pneumoniae group, which includes the species K. pneumoniae, K. quasipneumoniae, K. variicola and “K. quasivariicola” (odds ratio = 0.17, p < 0.001, 95% confidence interval [0.09,0.28]). Within the K. pneumoniae group, isolates identified as K. pneumoniae were more often resistant to 4th-generation cephalosporins than K. variicola isolates (odds ratio = 2.61, p = 0.003, 95% confidence interval [1.38,5.06]). K. oxytoca group isolates were found to be more likely associated with invasive infection to primary sterile sites than K. pneumoniae group isolates (odds ratio = 2.39, p = 0.0044, 95% confidence interval [1.05,5.53]). Conclusions Currently misdiagnosed Klebsiella spp. can be distinguished using a ribosomal marker-based approach for MALDI-TOF MS. Klebsiella groups and species differed in AMR profiles, and in their association with invasive infection, highlighting the importance for species identification to enable effective treatment options.

Fatih Karbeyaz,1 Seraphina Kissling,2 Paul Julius Jaklin,1 Jaqueline Bachofner,1 Barbara Brunner,1 Beat Müllhaupt,1 Thomas Winder,3 Joachim C Mertens,1 Benjamin Misselwitz,1,4 Stefanie von Felten,5 Alexander R Siebenhüner6,7 1Division of Gastroenterology and Hepatology, University Hospital Zurich and Zurich University, Zurich, Switzerland; 2Master Program in Biostatistics, University of Zurich, Zurich, Switzerland; 3Division of Oncology, Landeskrankenhaus Feldkirch, Feldkirch, Austria; 4Department of Visceral Surgery and Medicine, Inselspital Bern and Bern University, Bern, Switzerland; 5Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; 6Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland; 7Department of Medical Oncology, Cantonal Hospital Schaffhausen, Schaffhausen, SwitzerlandCorrespondence: Alexander R SiebenhünerKlinik für Medizinische Onkologie und Hämatologie, Universitätsspital Zürich, Rämistrasse 100, Zürich, CH-8091, SwitzerlandEmail alexander.siebenhuener@usz.chBackground: Direct-acting antivirals (DAA) have revolutionized the therapy of chronic hepatitis C (CHC) and have replaced previous PEG-interferon/ribavirin (PEG-IFN/RBV) treatment. Patients with CHC and advanced liver disease are at increased risk for hepatocellular carcinoma (HCC). However, the effects of DAA-based CHC treatment on subsequent HCC incidence remain poorly understood.Patients and Methods: This retrospective single-institution cohort study included 243 consecutive patients after PEG-IFN/RBV and 263 patients after DAA treatment. Multivariable cause-specific Cox proportional hazards models were used to compare time to HCC between treatment types, censoring patients who died or had an orthotopic liver transplantation (OLT) at the time of the competing event. Age, gender, BMI, viral load, cirrhosis, fibrosis stage, diabetes, virus genotype and previous PEG-IFN/RBV (before DAA) were used as covariates. In addition, we performed a propensity score-matched analysis.Results: Nineteen HCC cases were observed after DAA therapy compared to 18 cases after PEG-IFN/RBV treatment. Patients were followed for a median of 4.1 years (IQR: 3.5– 4.7) for DAA and 9.3 years (IQR: 6.6– 12.4) for the PEG-IFN/RBV group. In an unadjusted Cox model, a hazard ratio (HR) of 6.40 (CI: 2.20– 18.61, p=0.006) for HCC following DAA vs PEG-IFN/RBV was estimated. In multivariable Cox proportional hazard models, age and liver cirrhosis were identified as further HCC risk factors but the HR estimates for DAA vs PEG-IFN/RBV still indicate a considerably increased hazard associated with DAA treatment (HR between 7.23 and 11.52, p≤ 0.001, depending on covariates). A HR of 6.62 (CI: 2.01– 21.84, p=0.002) for DAA vs PEG-IFN/RBV was estimated in the propensity score-matched analysis. The secondary outcomes death and OLT did not differ between treatment groups.Conclusion: In a cohort study from a tertiary care hospital rates of HCC after the start of DAA treatment were higher compared to PEG-IFN/RBV treatment. Our data reinforce the recommendation that surveillance should be continued after successful CHC treatment.Keywords: hepatocellular carcinoma, chronic hepatitis C, direct-acting antivirals, PEG-interferon and ribavirin, viral load, liver transplantation, sustained virological response

Objective Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed. Methods The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. Results A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 – 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ2 = 6.58, p = .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 – 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 – 0.88, p = .019). Conclusion Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable.

The reporting quality in medical research has recently been critically discussed. While reporting guidelines intend to maximize the value from funded research, and initiatives such as the EQUATOR network have been introduced to advance high quality reporting, the uptake of the guidelines by researchers could be improved. The aim of this study was to assess the contribution of a biostatistician to the reporting and methodological quality of health research, and to identify methodological knowledge gaps.In a retrospective, single center, observational cohort study, two groups of publications were compared. The group of exposed publications had an academic biostatistician on the author list, whereas the group of non-exposed publications did not include a biostatistician of the evaluated group. Rating of reporting quality was done in blinded fashion and in duplicate. The primary outcome was a sum score based on six dimensions, ranging between 0 (worst) and 11 (best). The study protocol was reviewed and approved as a registered report.There were 131 publications in the exposed group published between 2017 and 2018. Of these, 95 were either RCTs, observational, or prediction / prognostic studies. Corresponding matches in the group of non-exposed publications were identified in a reproducible manner. Comparison of reporting quality overall revealed a 1.60 (95%CI from 0.92 to 2.28, p0.0001) units higher reporting quality for exposed publications. A subgroup analysis within study types showed higher reporting quality across all three study types.Our study is the first to report an association of a higher reporting quality and methodological strength in health research publications with a biostatistician on the author list. The higher reporting quality persisted through subgroups of study types and dimensions. Methodological knowledge gaps were identified for prediction / prognostic studies, and for reporting on statistical methods in general and missing values, specifically.

BackgroundAdverse responses to critical illness, such as symptoms of depression, anxiety or posttraumatic stress, are relatively common among family members. The role of risk factors, however, remains insufficiently understood, but may be important to target those family members most in need for support. We therefore examined the association of patient-, family member- and care-related factors with post-ICU psychological distress in family members in a general population of critical ill patients.MethodsWe conducted a prospective, single-centre observational study in a twelve-bed surgical ICU in a 900-bed University Hospital in Switzerland. Participants were family members of patients treated in ICU who completed the Family Satisfaction in ICU-24 Survey, the Hospital Anxiety Depression Scale, Impact of Event Scale-Revised-6, and a demographic form within the first 3 months after their close other’s ICU stay. Data were analysed using linear mixed-effects models, with depression, anxiety, and posttraumatic stress as outcome measures.ResultsA total of 214 family members (53% return rate) returned a completed questionnaire. We found that higher levels of satisfaction were significantly associated with lower levels of depression, anxiety and posttraumatic stress. There was no statistically significant association between family member characteristics and any measure of psychological distress. Among the included patient characteristics, younger patient age was associated with higher levels of depression, and patient death was associated with higher levels of depression and posttraumatic stress.ConclusionsOur results suggest that satisfaction with ICU care is strongly associated with family well-being post-ICU. Family members of younger patients and of those who die seem to be most at risk for psychological distress, requiring specific support, whereas family member characteristics may have less relevance.

IntroductionDelirium is frequently observed in the intensive care unit (ICU) population, in particular. Until today, there is no evidence for any reliable pharmacological intervention to treat delirium. The Basel BOMP-AID (BetterOutcome withMelatonin compared toPlaceboAdministered to normalize sleep-wake cycle and treat hypoactiveICUDelirium) randomised trial targets improvement of hypoactive delirium therapy in critically ill patients and will be conducted as a counterpart to the Basel ProDex Study (Study Protocol, BMJ Open, July 2017) on hyperactive and mixed delirium. The aim of the BOMP-AID trial is to assess the superiority of melatonin to placebo for the treatment of hypoactive delirium in the ICU. The study hypothesis is based on the assumption that melatonin administered at night restores a normal circadian rhythm, and that restoration of a normal circadian rhythm will cure delirium.Methods and analysisThe Basel BOMP-AID study is an investigator-initiated, single-centre, randomised controlled clinical trial for the treatment of hypoactive delirium with the once daily oral administration of melatonin 4 mg versus placebo in 190 critically ill patients. The primary outcome measure is delirium duration in 8-hour shifts. Secondary outcome measures include delirium-free days and death at 28 days after study inclusion, number of ventilator days, length of ICU and hospital stay, and sleep quality. Patients will be followed after 3 and 12 months for activities of daily living and mortality assessment. Sample size was calculated to demonstrate superiority of melatonin compared with placebo regarding the duration of delirium. Results will be presented using an intention-to-treat approach.Ethics and disseminationThis study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the International Conference on Harmonisation (ICH) of technical requirements for registration of pharmaceuticals for human use; Good Clinical Practice (GCP) or ISO EN 14155 (as far as applicable), as well as all national legal and regulatory requirements. Study results will be presented in international conferences and published in a peer-reviewed journal.Trial registration numberNCT03438526.Protocol versionClinical Study Protocol Version 3, 10.03.2019.

The success of habitat enhancements is typically assessed by subsequent monitoring of the focal taxonomic group. However, enhancement actions are likely to affect other, non-targeted species. On a south-facing slope in the Swiss Jura mountains, a mixed-forest stand was thinned out by irregular removal cuttings to improve the habitat conditions for reptiles. We used this enhancement action as a case study to monitor changes in the macrofungal community that came along with it. During 3 years before and after forest thinning, the site was visited between six and twelve times per year. Thereby, all apparent fungal species were recorded along a ringlike transect, split into 32 transect sections. We used site-occupancy models to estimate fungal species richness and abundance. These models allow to separately estimate occurrence probability and detection probability of species, and to account for differences in detection probability, depending on habitat and season. After the forest thinning, the occurrence probabilities of ectomycorrhizal and saprobic fungi were significantly higher than before. As a result, we estimated a mean increase in overall species richness by 4.4% (median 4.3%, CI 2.1–6.8%) and an increase in abundance by 20.0% (median 19.9%, CI 14.8–25.7%). The two major habitat changes associated with forest thinning, the decrease in living wood and the increase in dead wood on most transect sections, could not explain the whole extent of the estimated increase in species richness and abundance. We believe that forest thinning may have fostered fungal species richness by creating a larger density and diversity of suitable microhabitats. With some caution, we conclude that the small-scale habitat enhancement for reptiles at the Bolberg, creating islands of open forest, did not negatively affect species richness and abundance of macrofungi, a non-targeted species group.

Contains fulltext : 217065.pdf (Publisher’s version ) (Open Access) Abstract Locally, plant species richness supports many ecosystem functions. Yet, the mechanisms driving these often-positive biodiversity?ecosystem functioning relationships are not well understood. Spatial resource partitioning across vertical resource gradients is one of the main hypothesized causes for enhanced ecosystem functioning in more biodiverse grasslands. Spatial resource partitioning occurs if species differ in where they acquire resources and can happen both above- and belowground. However, studies investigating spatial resource partitioning in grasslands provide inconsistent evidence. We present the results of a meta-analysis of 21 data sets from experimental species-richness gradients in grasslands. We test the hypothesis that increasing spatial resource partitioning along vertical resource gradients enhances ecosystem functioning in diverse grassland plant communities above- and belowground. To test this hypothesis, we asked three questions. (1) Does species richness enhance biomass production or community resource uptake across sites? (2) Is there evidence of spatial resource partitioning as indicated by resource tracer uptake and biomass allocation above- and belowground? (3) Is evidence of spatial resource partitioning correlated with increased biomass production or community resource uptake? Although plant species richness enhanced community nitrogen and potassium uptake and biomass production above- and belowground, we found that plant communities did not meet our criteria for spatial resource partitioning, though they did invest in significantly more aboveground biomass in higher canopy layers in mixture relative to monoculture. Furthermore, the extent of spatial resource partitioning across studies was not positively correlated with either biomass production or community resource uptake. Our results suggest that spatial resource partitioning across vertical resource gradients alone does not offer a general explanation for enhanced ecosystem functioning in more diverse temperate grasslands.

Aggressive behavior and violence in psychiatric patients have often been quoted to justify more restrictive settings in psychiatric facilities. However, the effects of open vs. locked door policies on aggressive incidents remain unclear. This study had a naturalistic observational design and analyzed the occurrence of aggressive behavior as well as the use of seclusion or restraint in 21 German hospitals. The analysis included data from 1998 to 2012 and contained a total of n = 314,330 cases, either treated in one of 17 hospitals with (n = 68,135) or in one of 4 hospitals without an open door policy (n = 246,195). We also analyzed the data according to participants' stay on open, partially open, or locked wards. To compare hospital and ward types, we used generalized linear mixed-effects models on a propensity score matched subset (n = 126,268) and on the total dataset. The effect of open vs. locked door policy was non-significant in all analyses of aggressive behavior during treatment. Restraint or seclusion during treatment was less likely in hospitals with an open door policy. On open wards, any aggressive behavior and restraint or seclusion were less likely, whereas bodily harm was more likely than on closed wards. Hospitals with open door policies did not differ from hospitals with locked wards regarding different forms of aggression. Other restrictive interventions used to control aggression were significantly reduced in open settings. Open wards seem to have a positive effect on reducing aggression. Future research should focus on mental health care policies targeted at empowering treatment approaches, respecting the patient's autonomy and promoting reductions of institutional coercion.

Background: Over the past decades, stroke risk associated with carotid disease has decreased, reflecting improvements in medical therapy and a more rigorous control of vascular risk factors. It is less clear whether the procedural risk of carotid revascularization has declined over time. Methods: We analyzed temporal changes in procedural risks among 4597 patients with symptomatic carotid stenosis treated with carotid artery stenting (n=2326) or carotid endarterectomy (n=2271) in 4 randomized trials between 2000 and 2008, using generalized linear mixed-effects models with a random intercept for each source trial. Models were additionally adjusted for age and other baseline characteristics predicting treatment risk. The primary outcome event was any procedural stroke or death, occurring during or within 30 days after revascularization. Results: The procedural stroke or death risk decreased significantly over time in all patients (unadjusted odds ratio per year, 0.91; 95% CI, 0.85–0.97; P =0.006). This effect was driven by a decrease in the carotid endarterectomy group (unadjusted odds ratio per year, 0.82; 95% CI, 0.73–0.92; P =0.003), whereas no significant decrease was found after carotid artery stenting (unadjusted odds ratio, 0.96; 95% CI, 0.88–1.04; P =0.33). Carotid endarterectomy patients had a lower procedural stroke or death risk compared with carotid artery stenting patients, and the difference significantly increased over time (interaction P =0.031). After adjustment for baseline characteristics, the results remained essentially the same. Conclusions: The risk of stroke or death associated with carotid endarterectomy for symptomatic carotid stenosis decreased over an 8-year period, independent of clinical predictors of procedural risk. No corresponding reduction in procedural risk was seen in patients treated with stenting. Clinical Trial Registration: URL: https://www.clinicaltrials.gov ; http://www.isrctn.com . Unique identifier: NCT00190398 (EVA-3S), NCT00004732 (CREST), ISRCTN57874028 (SPACE), and ISRCTN25337470 (ICSS).

Importance: Therapeutic options for patients with secondary progressive multiple sclerosis (SPMS) are limited. Objective: To analyze disability progression in patients with SPMS treated with rituximab compared with matched control patients never treated with rituximab. Design, Setting, and Participants: This retrospective cohort study analyzed data obtained from patients with SPMS at 3 multiple sclerosis centers located in Basel and Lugano, Switzerland, and Amsterdam, the Netherlands, from 2004 to 2017. Patients were included for analysis if they had received a diagnosis of SPMS, were treated (57 eligible; 54 included) or never treated (504 eligible; 59 included) with rituximab, and had at least 1 follow-up visit. The variables used for propensity score matching were sex, age, Expanded Disability Status Scale (EDSS) score, and disease duration. Follow-up duration was up to 10 years, with a mean (SD) of 3.5 (2.6) years for rituximab-treated patients and 5.4 (2.4) years for controls in the total cohort and a mean (SD) of 3.5 (2.7) years for rituximab-treated patients and 4.8 (2.2) years for controls in the matched cohort. Exposures: Comparing EDSS score progression in patients with SPMS (treated with rituximab vs not treated with rituximab) using propensity score matching. Main Outcomes and Measures: The primary end point was progression of EDSS score after baseline, and the secondary end point was time to confirmed disability progression. Results: After 1:1 propensity score matching, 44 matched pairs (88 patients) were included in the analysis. At baseline, patients treated with rituximab had a mean (SD) age of 49.7 (10.0) years, mean (SD) disease duration of 18.2 (9.4) years, and mean (SD) EDSS score of 5.9 (1.4), and 26 (59%) were women, whereas controls had a mean (SD) age of 51.3 (7.4) years, mean (SD) disease duration of 19.4 (8.7) years, and mean (SD) EDSS score of 5.70 (1.29), and 27 (61%) were women. In the covariate-adjusted analysis of the matched set, patients with SPMS who were treated with rituximab had a significantly lower EDSS score during a mean (SD) follow-up of 3.5 (2.7) years (mean difference, -0.52; 95% CI, -0.79 to -0.26; P

Inpatient suicide and absconding of inpatients at risk of self-endangering behaviour are important challenges for all medical disciplines, particularly psychiatry. Patients at risk are often admitted to locked wards in psychiatric hospitals to prevent absconding, suicide attempts, and death by suicide. However, there is insufficient evidence that treatment on locked wards can effectively prevent these outcomes. We did this study to compare hospitals without locked wards and hospitals with locked wards and to establish whether hospital type has an effect on these outcomes.In this 15 year, naturalistic observational study, we examined 349 574 admissions to 21 German psychiatric inpatient hospitals from Jan 1, 1998, to Dec 31, 2012. We used propensity score matching to select 145 738 cases for an analysis, which allowed for causal inference on the effect of ward type (ie, locked, partly locked, open, and day clinic wards) and hospital type (ie, hospitals with and without locked wards) on suicide, suicide attempts, and absconding (with and without return), despite the absence of an experimental design. We used generalised linear mixed-effects models to analyse the data.In the 145 738 propensity score-matched cases, suicide (OR 1·326, 95% CI 0·803-2·113; p=0·24), suicide attempts (1·057, 0·787-1·412; p=0·71), and absconding with return (1·288, 0·874-1·929; p=0·21) and without return (1·090, 0·722-1·659; p=0·69) were not increased in hospitals with an open door policy. Compared with treatment on locked wards, treatment on open wards was associated with a decreased probability of suicide attempts (OR 0·658, 95% CI 0·504-0·864; p=0·003), absconding with return (0·629, 0·524-0·764; p0·0001), and absconding without return (0·707, 0·546-0·925; p=0·01), but not completed suicide (0·823, 0·376-1·766; p=0·63).Locked doors might not be able to prevent suicide and absconding.None.

Persistent black holes (PBH) are associated with axonal loss and disability progression in multiple sclerosis (MS). The objective of this work was to determine if BHT-3009, a DNA plasmid-encoding myelin basic protein (MBP), reduces the risk of new lesions becoming PBH, compared to placebo, and to test if pre-treatment serum anti-MBP antibody levels impact on the effect of BHT-3009 treatment. In this retrospective, blinded MRI study, we reviewed MRI scans of 155 MS patients from a double-blind, randomized, phase II trial with three treatment arms (placebo, 0.5 and 1.5 mg BHT-3009). New lesions at weeks 8 and 16 were tracked at week 48 and those appearing as T1-hypointense were classified as PBH. A subset of 46 patients with available pre-treatment serum anti-MBP IgM levels were analyzed separately. Overall, there was no impact of treatment on the risk for PBH. However, there was a significant interaction between anti-MBP antibodies and treatment effect: patients receiving 0.5 mg BHT-3009 showed a reduced risk of PBH with higher antibody levels compared to placebo (p

The nervous system plays a key role in controlling the dynamic functions of multicellular complex organisms. Although peripheral nerves are supposed to play a pivotal role in tumor growth and dissemination, little experimental evidence exists to date. We assessed the effect of denervation on breast cancer growth by magnetic resonance imaging (MRI) in rats. Human breast cancer cells were implanted into adipofascial flaps with intact or surgically excised supplying nerve. Tumor volumes were measured 2 and 8 weeks after implantation by in vivo MRI. Results were validated by histology. Postoperative tumor volumes at 2 and 8 weeks were reduced by 76% (95% CI: 22-93%) in the denervated groups. Tumor area as determined histologically was reduced by 70% (95% CI: 60-78%). Thus, peripheral denervation may be an effective surgical approach for the palliative treatment of locally progressing or uncontrollable breast cancer.

Background Chronic hyponatremia is common and associated with increased morbidity and mortality. However, whether treatment improves outcome in patients without significant symptoms is unclear. We here assessed the therapeutic outcome on clinical symptoms, neurocognitive and neuromuscular function in patients with chronic non profound hyponatremia. Material and methods Prospective case-control study in 19 patients from the University Hospital Wurzburg with chronic non profound hyponatremia without clinically apparent symptoms. At baseline and after a 14-day treatment period of hyponatremia, patients were assessed by specific clinical symptoms questionnaire, neurocognitive and neuromuscular function was analysed by five attention tests and a gait test consisting of 3 steps "in tandem." The results were compared to a control group of healthy volunteers. Results Compared to healthy volunteers, patients with mild (n = 10, mean serum sodium 132 ± 1.2 mmol/L) and moderate hyponatremia (n = 9, mean 126 ± 3.3 mmol/L) performed significantly worse in the neurocognitive subtests alertness (P = 0.018), divided attention (P = 0.017) and go/no-go (P = 0.026). Performance in the neuromuscular subtests was also lower in the patient group without reaching significance. The extent of hyponatremia had no impact on the specific test and questionnaire results. Fourteen-day treatment of hyponatremia improved clinical symptoms in all patients (P = 0.003) and neurocognitive function in sodium-normalised patients (go/no-go test, P = 0.029). Conclusion Chronic hyponatremia is symptomatic and impairs neurocognitive and neuromuscular function. Short-time therapeutic intervention led to improved clinical symptoms and neurocognitive function, but had no effect on neuromuscular function. Larger trials with long-term treatment are needed to specify the therapeutic need in chronic hyponatremia.

Background/objectives Delirium is a neurobehavioural disturbance that frequently develops particularly in the intensive care unit (ICU) population. It was first described more than half a century ago, where it was already discovered as a state that might come along with serious complications such as prolonged ICU and hospital stay, reduced quality of life and increased mortality. However, in most cases, there is still lack of proof for causal relationship. Its presence frequently remains unrecognised due to suggested predominance of the hypoactive form. Furthermore, in the general ICU population, it has been shown that the duration of delirium is associated with worse long-term cognitive function. Due to the multifactorial origin of delirium, we have several but no incontestable treatment options. Nonetheless, delirium bears a high burden for patient, family members and the medical care team.The Basel ProDex Study targets improvement of hyperactive and mixed delirium therapy in critically ill patients. We will focus on reducing the duration and severity of delirium by implementing dexmedetomidine into the treatment plan. Dexmedetomidine compared with other sedatives shows fewer side effects representing a better risk profile for delirium treatment in general. This could further contribute to higher patient safety.The aim of the BaProDex Trial is to assess the superiority of dexmedetomidine to propofol for treatment of hyperactive and mixed delirium in the ICU. We hypothesise that dexmedetomidine, compared with propofol administered at night, shortens both the duration and severity of delirium. Methods/design The Basel ProDex Study is an investigator-initiated, one-institutional, two-centre randomised controlled clinical trial for the treatment of delirium with dexmedetomidine versus propofol in 316 critically ill patients suffering from hyperactive and mixed delirium. The primary outcome measure is delirium duration in hours. Secondary outcomes include delirium-free days at day 28, death at day 28, delirium severity, amount of ventilator days, amount of rescue sedation with haloperidol, length of ICU and hospital stay, and pharmaceutical economic analysis of the treatments. Sample size was estimated to be able to show the superiority of dexmedetomidine compared with propofol regarding the duration of delirium in hours. The trial will be externally monitored according to good clinical practice (GCP) requirements. There are no interim analyses planned for this trial. Ethics and dissemination This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the International Conference on Harmonization- Good Clinical Practice (ICH-GCP) or Europaische Norm International Organization for Standardization (ISO EN 14155; as far as applicable) as well as all national legal and regulatory requirements. Only the study team will have access to trial specific data. Anonymisation will be achieved by a unique patient identification code. Trial data will be archived for a minimum of 10 years after study termination. We plan to publish the data in a major peer-reviewed clinical journal. Trials registration ClinicalTrials.gov Identifier: NCT02807467 PROTOCOL VERSION: Clinical Study Protocol Version 2, 16.08.2016.

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 .