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

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

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

Objective To characterize a critically ill cohort with status epilepticus (SE) by the illness severity scoring systems SAPS II (Simplified Acute Physiology Score II), APACHE II (Acute Physiology and Chronic Health Evaluation II), and SOFA (Sequential Organ Failure Assessment), and to compare their performance with the STESS (Status Epilepticus Severity Score) for outcome prediction. Methods The prospective cohort study was carried out at the University Hospital Basel, a Swiss tertiary academic medical care center. Consecutive adult SE patients hospitalized in the intensive care units from 2011 to 2016 were included. Illness severity scores and additional clinical data were recorded. Logistic regression models using automated variable selection were applied to identify scores associated with no return to functional and neurological baseline and death. Measures of discrimination and calibration were assessed. Results Among 184 patients, 33% returned to baseline. Median scores of the illness severity scores were within the lowest third of the possible scoring ranges, and all differed significantly between patients with and without return to baseline. The areas under the receiver operating curves for the prediction of no return to baseline and death ranged from 0.64 to 0.73, with the highest value for the STESS predicting no return to baseline. Measures of calibration revealed adequate model fit for all analyses. Among integral components of the scoring systems, only the Glasgow Coma Scale (GCS) differed significantly between patients with and without return to baseline. In multivariable analyses, decreasing GCS and increasing STESS had the strongest associations (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.77-0.93 and OR = 1.34, 95% CI = 1.05-1.68, respectively) with no return to baseline independent of all other scoring systems, whereas the APACHE II revealed the strongest association with death (OR = 1.15, 95% CI = 1.06-1.25). Significance Although complex illness severity scoring systems in SE patients facilitate benchmarking and comparisons with other severely ill patient cohorts, they offer no advantages over the STESS and GCS regarding prediction of no return to baseline.

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

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

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

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

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.

Aim Neuron-specific enolase (NSE) increases in response to brain injury and is recommended for outcome prediction in cardiac arrest patients. Our aim was to investigate whether NSE measured at different days after a cardiac arrest and its kinetics would improve the prognostic ability of two cardiac arrest specific risk scores. Methods Within this prospective observational study, we included consecutive adult patients after cardiac arrest. We calculated the Out-of-hospital cardiac arrest (OHCA) score and the Cardiac Arrest Hospital Prognosis (CAHP) score upon ICU admission and measured serum NSE upon admission and days 1, 2, 3, 5 and 7. We calculated logistic regression models to study associations of scores and NSE levels with neurological outcome defined by Cerebral Performance Category (CPC) scale and in-hospital death. Results From 336 included patients, 180 (54%) survived until hospital discharge, of which 150 (45%) had a good neurological outcome. NSE at day 3 showed the highest prognostic accuracy (discrimination) for neurological outcome (area under the curve (AUC) 0.89) and in-hospital mortality (AUC 0.88). These results were robust in reclassification statistics and across different subgroups. NSE kinetics with admission levels serving as a baseline did not further improve prognostication. NSE on day 3 significantly improved discrimination of both clinical risk scores (CAHP from AUC 0.81 to 0.91; OHCA from AUC 0.79 to 0.89). Conclusion NSE measured at day 3 significantly improves clinical risk scores for outcome prediction in cardiac arrest patients and may thus add to clinical decision making about escalation or withdrawal of therapy in this vulnerable patient population.

Aim Several scores are available to predict mortality and neurological outcome in cardiac arrest patients admitted to the intensive care unit (ICU). The aim of the study was to externally validate the prognostic value of four previously published risk scores. Methods For this observational, single-center study, we prospectively included 349 consecutive adult cardiac arrest patients upon ICU admission. We calculated two cardiac arrest specific risk scores (OHCA and CAHP) and two general severity of illness scores (APACHE II and SAPS II). The primary endpoint was in-hospital mortality. Secondary endpoints were neurological outcome at hospital discharge and 30-day mortality. Results 170 patients (49%) died until hospital discharge. All scores were independently associated with outcomes in logistic regression analysis and showed acceptable discrimination for in-hospital mortality with highest AUCs of the cardiac arrest specific risk scores (OHCA: 0.80 (95%CI 0.75–0.85) and CAHP: 0.84 (95%CI 0.79–0.88) compared to the severity of illness scores (APACHE II: 0.78 (95%CI 0.73–0.83) and SAPS II: 0.77 (95%CI 0.72–0.82). Results were robust in subgroup analysis except for worse performance in elderly patients (>75 years) and patients with respiratory cause of cardiac arrest. Results were similar for 30-days mortality and slightly higher for neurological outcome. Conclusions This study confirms the good prognostic performance of cardiac arrest specific scores to predict mortality and neurological outcomes in cardiac arrest patients. Routine use of OHCA or CAHP score helps to objectively risk stratify these vulnerable patients and thereby may improve therapeutic decisions.

Prognostication of cardiac arrest patients admitted to the intensive care unit (ICU) may influence treatment decision, but remains challenging. We evaluated the incremental usefulness of routine blood markers from different biological pathways for predicting fatal outcome and neurological deficits in cardiac arrest patients.We prospectively included consecutive, adult cardiac arrest patients upon ICU admission. We recorded initial clinical parameters and measured blood markers of cardiac injury/stress (troponin, BNP, CK), inflammation/infection (WBC, CRP, procalcitonin) and shock (lactate, creatinine, urea). The primary and secondary endpoints were all-cause in-hospital mortality and bad neurological outcome defined by the Cerebral Performance Category (CPC) score.Mortality in the 321 included patients was 49% (n = 156). Procalcitonin (adjusted odds ratio 1.84, 95%CI 1.34 to 2.53, p 0.001; AUC 0.73) and lactate (adjusted odds ratio 7.29, 95%CI 3.05 to 17.42, p 0.001; AUC 0.70) were identified as independent prognostic factors for mortality and significantly improved discrimination of a parsimonious clinical model including resuscitation measures (no-flow time, shockable rhythm) and initial vital signs (Glasgow coma scale, respiratory rate) from an AUC of 0.79 to 0.84 (p 0.001). Cardiac markers did not further improve the model. Results for neurological outcome were similar with model improvements by procalcitonin and lactate from AUC 0.83 to 0.87 (p = 0.004).Assessment of routine markers of inflammation/infection and shock provide significant improvements for prognostication of cardiac arrest patients, while cardiac markers did not further improve statistical models. Combination of blood markers and clinical parameters may help to improve initial management decisions in this vulnerable patient population.

Background and purpose The aim was to determine differences of clinical, treatment and outcome characteristics between patients with in-hospital and out-of-hospital status epilepticus (SE). Methods From 2005 to 2014, clinical data were assessed in adults with SE treated in an academic medical care centre. Clinical characteristics, treatment and outcomes were compared between patients with in-hospital and out-of-hospital SE. Results Amongst 352 patients, 213 were admitted with SE and 139 developed in-hospital SE. Patients with in-hospital SE had more acute/fatal aetiologies (60% vs. 35%, P < 0.001), fewer previous seizures (33% vs. 50%, P = 0.002), a higher median Charlson Comorbidity Index (3 vs. 2, P < 0.001), longer median SE duration (1 vs. 0.5 days, P = 0.001), more refractory SE (52% vs. 39%, P = 0.022), less return to functional baseline (38% vs. 54%, P = 0.006) and increased mortality (29% vs. 19%, P = 0.001). Whilst in multivariable analyses an increasing Status Epilepticus Severity Score (STESS) was an independent predictor for death in both groups, increased Charlson Comorbidity Index and treatment refractory SE were associated with death only in patients with in-hospital SE. Continuous anaesthesia for refractory SE was associated with increased mortality only in patients with out-of-hospital SE. The area under the receiver operating curve was 0.717 for prediction of death by STESS in patients with in-hospital SE and 0.811 in patients with out-of-hospital SE. Conclusions Patients with in-hospital SE had more fatal aetiologies and comorbidities, refractory SE, less return to functional baseline, and increased mortality compared to patients with out-of-hospital SE. Whilst the STESS was a robust predictor for death in both groups, the association between continuous anaesthesia and death was limited to out-of-hospital SE.