K63-Ubiquitylation and TRAF6 Pathways Regulate Mammalian P-Body Formation and mRNA Decapping.

Signals and posttranslational modifications regulating the decapping step in mRNA degradation pathways are poorly defined. In this study we reveal the importance of K63-linked ubiquitylation for the assembly of decapping factors, P-body formation, and constitutive decay of instable mRNAs encoding mediators of inflammation by various experimental approaches. K63-branched ubiquitin chains also regulate IL-1-inducible phosphorylation of the P-body component DCP1a. The E3 ligase TRAF6 binds to DCP1a and indirectly regulates DCP1a phosphorylation, expression of decapping factors, and gene-specific mRNA decay. Mutation of six C-terminal lysines of DCP1a suppresses decapping activity and impairs the interaction with the mRNA decay factors DCP2, EDC4, and XRN1, but not EDC3, thus remodeling P-body architecture. The usage of ubiquitin chains for the proper assembly and function of the decay-competent mammalian decapping complex suggests an additional layer of control to allow a coordinated function of decapping activities and mRNA metabolism in higher eukaryotes.

The difference between arterial pCO2 and etCO2 after cardiac arrest - Outcome predictor or marker of unfavorable resuscitation circumstances?

INTRODUCTION: In former studies, the arterio-alveolar carbon dioxide gradient (ΔCO2) predicted in-hospital mortality after initially survived cardiac arrest. As early outcome predictors are urgently needed, we evaluated ΔCO2 as predictor for good neurological outcome in our cohort. METHODS: We retrospectively analyzed all patients ≥18 years of age after non-traumatic in- and out of hospital cardiac arrest in the year 2018 from our resuscitation database. Patients without advanced airway management, incomplete datasets or without return of spontaneous circulation were excluded. The first arterial pCO2 after admission and the etCO2 in mmHg at the time of blood sampling were recorded from patient's charts. We then calculated ΔCO2 (pCO2 - etCO2). For baseline analyses, ΔCO2 was dichotomized into a low and high group with separation at the median. Good neurological outcome on day 30, expressed as Cerebral Performance Category 1-2, defined our primary endpoint. Survival to 30 days was used as secondary endpoint. RESULTS: Out of 302 screened patients, 128 remained eligible for analyses. ΔCO2 was lower in 30-day survivors with good neurological outcome (12.2 mmHg vs. 18.8 mmHg, p = 0.009) and in 30-day survivors (12.5 mmHg vs. 20.0 mmHg, p = 0.001). In patients with high ΔCO2, a cardiac etiology of arrest was found less often. They had a higher body mass index, longer duration of resuscitation, higher amounts of epinephrine, lower pO2 levels but both higher pCO2 and blood lactate levels, resulting in lower blood pH and HCO3- levels at admission. In a crude binary logistic regression analysis, ΔCO2 was associated with 30-day neurological outcome (OR = 1.041 per mmHg of ΔCO2, 95% CI 1.008-1.074, p = 0.014). This association persisted after the adjustment for age, sex, witnessed arrest and shockable first rhythm. However, after addition of the duration of resuscitation or the cumulative epinephrine dosage to the model, ΔCO2 lost its association. CONCLUSION: ΔCO2 at admission after a successfully resuscitated cardiac arrest is associated with 30 days survival with good neurological outcome. However, a higher ΔCO2 may rather be a surrogate for unfavorable resuscitation circumstances than an independent outcome predictor.

Extracorporeal cardiopulmonary resuscitation at the emergency department: A retrospective patient selection evaluation.

BACKGROUND: There is an increasing use of extracorporeal life support in refractory cardiac arrest. Recent studies highlighted the importance of an early and accurate patient selection for this invasive procedure. OBJECTIVES: The aim of this study was to retrospectively validate a six-criteria-screening-checklist (witnessed collapse, bystander-cardiopulmonary resuscitation/first medical contact <5 min, shockable, age <70 years, end tidal carbon dioxide >14 mmHg and pupils not anisocoric/distorted/mydriatic) as an early screening tool in patients treated with extracorporeal cardiopulmonary resuscitation (eCPR) at the emergency department. DESIGN: Retrospective observational study. SETTING/PATIENTS: All patients at least 18 years of age with nontraumatic cardiac arrest and without return of spontaneous circulation before eCPR treatment at our department between January 2013 and December 2018 were included in this retrospective observational study. INTERVENTION: No specific intervention was set in this observational study. MAIN OUTCOME MEASURES: Primary outcome was the rate of patients who fulfilled all criteria, secondary outcome was 30-day and 6-month survival in accordance with the criteria. RESULTS: Overall, data from a total of 92 patients were eligible for analyses. Out of these, 27 patients (29%) met all criteria. Patients, who fulfilled all criteria, showed significantly higher odds for 30-day survival [OR 6.0 (95% CI 1.78 to 20.19)] P = 0.004. Patients, who did not fulfil all criteria, showed significantly higher rates of early mortality after eCPR initiation [OR 4.57 (95% CI 1.69 to 12.37)] P = 0.003. CONCLUSION: Patients fulfilling all inclusion criteria showed higher rates of survival after eCPR. Our results affirm that there is a possibility and even an obvious necessity for early patient selection based on standardised criteria before eCPR treatment. Large randomised trials are urgently needed to answer this question accurately.

The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells.

Coronavirus replication takes place in the host cell cytoplasm and triggers inflammatory gene expression by poorly characterized mechanisms. To obtain more insight into the signals and molecular events that coordinate global host responses in the nucleus of coronavirus-infected cells, first, transcriptome dynamics was studied in human coronavirus 229E (HCoV-229E)-infected A549 and HuH7 cells, respectively, revealing a core signature of upregulated genes in these cells. Compared to treatment with the prototypical inflammatory cytokine interleukin(IL)-1, HCoV-229E replication was found to attenuate the inducible activity of the transcription factor (TF) NF-κB and to restrict the nuclear concentration of NF-κB subunits by (i) an unusual mechanism involving partial degradation of IKKß, NEMO and IκBα and (ii) upregulation of TNFAIP3 (A20), although constitutive IKK activity and basal TNFAIP3 expression levels were shown to be required for efficient virus replication. Second, we characterized actively transcribed genomic regions and enhancers in HCoV-229E-infected cells and systematically correlated the genome-wide gene expression changes with the recruitment of Ser5-phosphorylated RNA polymerase II and prototypical histone modifications (H3K9ac, H3K36ac, H4K5ac, H3K27ac, H3K4me1). The data revealed that, in HCoV-infected (but not IL-1-treated) cells, an extensive set of genes was activated without inducible p65 NF-κB being recruited. Furthermore, both HCoV-229E replication and IL-1 were shown to upregulate a small set of genes encoding immunomodulatory factors that bind p65 at promoters and require IKKß activity and p65 for expression. Also, HCoV-229E and IL-1 activated a common set of 440 p65-bound enhancers that differed from another 992 HCoV-229E-specific enhancer regions by distinct TF-binding motif combinations. Taken together, the study shows that cytoplasmic RNA viruses fine-tune NF-κB signaling at multiple levels and profoundly reprogram the host cellular chromatin landscape, thereby orchestrating the timely coordinated expression of genes involved in multiple signaling, immunoregulatory and metabolic processes.

Initial end-tidal carbon dioxide as a predictive factor for return of spontaneous circulation in nonshockable out-of-hospital cardiac arrest patients: A retrospective observational study.

BACKGROUND: Early outcome prediction in out-of-hospital cardiac arrest is still a challenge. End-tidal carbon dioxide (ETCO2) has been shown to be a reliable parameter to reflect the quality of cardiopulmonary resuscitation and the chance of return of spontaneous circulation (ROSC). OBJECTIVES: This study assessed the validity of early capnography as a predictive factor for ROSC and survival in out-of-hospital cardiac arrest victims with an underlying nonshockable rhythm. DESIGN: Retrospective observational study. SETTING/PATIENTS: During a 2-year observational period, data from 2223 out-of-hospital cardiac arrest victims within the city of Vienna were analysed. The focus was on the following patients: age more than 18 years, an underlying nonshockable rhythm, and advanced airway management within the first 15 min of advanced life support with subsequent capnography. INTERVENTION: No specific intervention was set in this observational study. MAIN OUTCOME MEASURES: The first measured ETCO2, assessed immediately after placement of an advanced airway, was used for further analysis. The primary outcome was defined as sustained ROSC, and the secondary outcome was 30-day survival. RESULTS: A total of 526 patients met the inclusion criteria. These were stratified into three groups according to initial ETCO2 values (<20, 20 to 45, >45 mmHg). Baseline data and resuscitation factors were similar among all groups. The odds of sustained ROSC and survival were significantly higher for patients presenting with higher values of initial ETCO2 (>45 mmHg): 3.59 [95% CI, 2.19 to 5.85] P = 0.001 and 5.02 [95% CI, 2.25 to 11.23] P = 0.001, respectively. On the contrary ETCO2 levels less than 20 mmHg were associated with significantly poorer outcomes. CONCLUSION: Patients with a nonshockable out-of-hospital cardiac arrest who presented with higher values of initial ETCO2 had an increased chance of sustained ROSC and survival. This finding could help decision making as regards continuation of resuscitation efforts.

Histrelin for central precocious puberty-a single surgeon experience.

BACKGROUND: The most common cause of precocious puberty is idiopathic central precocious puberty (CPP), which is usually treated with monthly injections. An alternative treatment of precious puberty is a subcutaneous implant that contains histrelin acetate, which is continuously released for more than 1 y and then removed or replaced with a new implant. METHODS: The aim of this study was to conduct a retrospective review of one surgeon's experience with the histrelin implant and to examine patient satisfaction. After obtaining institutional review board approval, the charts of all children who had undergone at least one implant were reviewed. RESULTS: Fifty-eight children, average age 8.4 y old (range 7-14), underwent at least one histrelin implant insertion for treatment of CPP. Parents of 44 patients were able to be reached by telephone for this study and rated the histrelin implant treatment highly. All implants were placed, replaced, or removed without significant difficulty, and there were no complications. CONCLUSIONS: This study suggests that the use of a histrelin subcutaneous implant for control of CPP is a safe and effective method for the treatment of this condition.

Feasibility of resuscitative transesophageal echocardiography at out-of-hospital emergency scenes of cardiac arrest.

Guidelines recommend the use of ultrasound in cardiac arrest. Transthoracic echocardiography, has issues with image quality and by increasing hands-off times during resuscitation. We assessed the feasibility of transesophageal echocardiography (TEE), which does not have both problems, at out-of-hospital cardiac arrest (OHCA) emergency scenes. Included were 10 adults with non-traumatic OHCA in Vienna, Austria. An expert in emergency ultrasound was dispatched to the scenes in addition to the resuscitation team. Feasibility was defined as the ability to collect specific items of information by TEE within 10 min. Descriptive statistics were compiled and hands-off times were compared to a historical control group. TEE examinations were feasible in 9 of 10 cases and prompted changes in clinical management in 2 cases (cardiac tamponade: n = 1; right ventricular dilatation: n = 1). Their mean time requirement was 5.1 ± 1.7 (2.8-8.0) min, and image quality was invariably rated as excellent or good during both compressions and pauses. No TEE-related complications, or interferences with activities of advanced life support were observed. The hands-off times during resuscitation were comparable to a historical control group not involving ultrasound (P = 0.24). Given these feasibility results, we expect that TEE can be used routinely at OHCA emergency scenes.

Resuscitative transoesophageal echocardiography performed by emergency physicians in the emergency department: insights from a 1-year period.

AIMS: Transoesophageal echocardiography (TOE) has increasingly been described as a possible complementary and point-of-care approach for patients with cardiac arrest (CA). It provides information about potentially reversible causes and prognosis and allows monitoring of resuscitation efforts without affecting ongoing chest compressions. The aim of this study was to assess the feasibility of TOE performed by emergency physicians (EPs) during CA in an emergency department (ED). METHODS AND RESULTS: This prospective study was performed at the Department of Emergency Medicine at the Medical University of Vienna from February 2020 to February 2021. All patients of ≥18 years old presenting with ongoing resuscitation efforts were screened. After exclusion of potential contraindications, a TOE examination was performed and documented by EPs according to a standardized four-view imaging protocol. The primary endpoint represents feasibility defined as successful probe insertion and acquisition of interpretable images. Of 99 patients with ongoing non-traumatic CA treated in the ED, a total of 62 patients were considered to be examined by TOE. The examination was feasible in 57 patients (92%) [females, 14 (25%), mean age 53 ± 13, and witnessed collapse 48 (84%)]. Within these, the examiners observed 51 major findings in 32 different patients (66%). In 21 patients (37%), these findings led to a direct change of therapy. In 18 patients (32%), the examiner found ventricular contractions without detectable pulse. No TOE-related complications were found. CONCLUSION: Our findings suggest that EPs may be able to acquire and interpret TOE images in the majority of patients during CA using a standardized four-view imaging protocol.

[Extracorporeal resuscitation-criteria, prerequisites, outcome : A reality check]. / Extrakorporale Reanimation ­ Kriterien, Bedingungen, Outcome : Ein Reality-Check.

In select patients, in whom conventional cardiopulmonary resuscitation (cCPR) fails to re-establish circulation, the 2021 European Resuscitation Council guidelines suggest considering extracorporeal resuscitation (eCPR) as a rescue therapy in settings in which it can be implemented. eCPR is becoming established during refractory cardiac arrest as a bridge-to-therapy for diagnosis and treatment of reversible causes of cardiac arrest, such as myocardial infarction, pulmonary embolism, accidental hypothermia, overdose with cardiotoxic substances, and acute hypoxia. Patient selection criteria comprise prognostic characteristics of cardiac arrest such as witnessed status, resuscitation efforts within 5 min, shockable initial rhythm, and characteristics of effective cCPR such as signs of life during resuscitation, persistent ventricular fibrillation, intermittent episodes of spontaneous circulation or end-tidal CO2 levels constantly > 10 mm Hg, patient age and health status. The timeframe from cardiac arrest to eCPR is a major contributor for neurologically favourable survival and should not exceed 60 min according to current guidelines. This may be achieved with an efficient "load & go" strategy, including early patient selection and rapid transport with ongoing mechanical cCPR to the eCPR centre, or with a prehospital eCPR strategy. Two randomized controlled eCPR trials demonstrated survival rates of 43% and 31.5% in patients with refractory ventricular fibrillation and cardiac-origin cardiac arrest, respectively. Whether these results are generalizable outside such highly specialized centres, and which prehospital and in-hospital strategy is best for which patients, remains to be determined in future studies.

Out-of-Sample Validity of the PROLOGUE Score to Predict Neurologic Function after Cardiac Arrest.

BACKGROUND: The clinical value of a prognostic score depends on its out-of-sample validity because inaccurate outcome prediction can be not only useless but potentially fatal. We aimed to evaluate the out-of-sample validity of a recently developed and highly accurate Korean prognostic score for predicting neurologic outcome after cardiac arrest in an independent, plausibly related sample of European cardiac arrest survivors. METHODS: Analysis of data from a European cardiac arrest center, certified in compliance with the specifications of the German Council for Resuscitation. The study sample included adults with nontraumatic out-of-hospital cardiac arrest admitted between 2013 and 2018. Exposure was the PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages (PROLOGUE) score, including 12 clinical variables readily available at hospital admission. The outcome was poor 30-day neurologic function, as assessed using the cerebral performance category scale. The risk of a poor outcome was calculated using the PROLOGUE score regression equation. Predicted risk deciles were compared to observed outcome estimates in a complete-case analysis, a best-case analysis, and a multiple-data-imputation analysis using the Markov chain Monte Carlo method. RESULTS: A total of 1051 patients (median 61 years, IQR 50-71; 29% female) were analyzed. A total of 808 patients (77%) were included in the complete-case analysis. The PROLOGUE score overestimated the risk of poor neurologic outcomes in the range of 40% to 100% predicted risk, involving 63% of patients. The model fit did not improve after missing data imputation. CONCLUSIONS: In a plausibly related sample of European cardiac arrest survivors, risk prediction by the PROLOGUE score was largely too pessimistic and failed to replicate the high accuracy found in the original study. Using the PROLOGUE score as an example, this study highlights the compelling need for independent validation of a proposed prognostic score to prevent potentially fatal mispredictions.

Targeted temperature management after cardiac arrest is associated with reduced metabolism of pantoprazole - A probe drug of CYP2C19 metabolism.

OBJECTIVE: Targeted temperature management (TTM) is part of standard post-resuscitation care. TTM may downregulate cytochrome enzyme activity and thus impact drug metabolism. This study compared the pharmacokinetics (PK) of pantoprazole, a probe drug of CYP2C19-dependent metabolism, at different stages of TTM following cardiac arrest. METHODS: This prospective controlled study was performed at the Medical University of Vienna and enrolled 16 patients following cardiac arrest. The patients completed up to three study periods (each lasting 24 h) in which plasma concentrations of pantoprazole were quantified: (P1) hypothermia (33 °C) after admission, (P2) normothermia after rewarming (36 °C, intensive care), and (P3) normothermia during recovery (normal ward, control group). PK was analysed using non-compartmental analysis and nonlinear mixed-effects modelling. RESULTS: 16 patients completed periods P1 and P2; ten completed P3. The median half-life of pantoprazole was 2.4 h (quartiles: 1.8-4.8 h) in P1, 2.8 h (2.1-6.8 h, p = 0.046 vs. P1, p = 0.005 vs. P3) in P2 and 1.2 h (0.9 - 2.3 h, p = 0.007 vs. P1) in P3. A two-compartment model described the PK data best. Typical values for clearance were estimated separately for each study period, indicating 40% and 29% reductions during P1 and P2, respectively, compared to P3. The central volume of distribution was estimated separately for P2, indicating a 64% increase compared to P1 and P3. CONCLUSION: CYP2C19-dependent drug metabolism is downregulated during TTM following cardiac arrest. These results may influence drug choice and dosing of similarly metabolized drugs and may be helpful for designing studies in similar clinical situations.

Comparing micellar, hemolytic, and antibacterial properties of di- and tricarboxyl dendritic amphiphiles.

Homologous dicarboxyl dendritic amphiphiles-RCONHC(CH(3))(CH(2)CH(2)COOH)(2), 4(n); and ROCONHC(CH(3))(CH(2)CH(2)COOH)(2), 5(n), where R=n-C(n)H(2)(n)(+1) and n=13-22 carbon atoms-were synthesized. Critical micelle concentrations (CMCs) in aqueous triethanolamine solutions and at pH 7.4 were measured along with hemolytic activity (effective concentrations, EC(10)) in phosphate-buffered saline (PBS). LogCMC showed a linear dependence on chain length (n); the longest chain in each series had the lowest CMC-in triethanolamine: 4(21), 180µM and 5(22), 74µM and at pH 7.4: 4(21), 78µM and 5(22), 33µM. These two series, 4(n) and 5(n), and three series of homologous tricarboxyl dendritic amphiphiles-RCONHC(CH(2)CH(2)COOH)(3), 1(n); ROCONHC(CH(2)CH(2)COOH)(3), 2(n); RNHCONHC(CH(2)CH(2)COOH)(3), 3(n), where R=n-C(n)H(2)(n)(+1) and n=13-22 carbon atoms-were tested for growth inhibition of Staphylococcus aureus strain ATCC 6358 and methicillin-resistant S. aureus (MRSA) strain ATCC 43330 by microdilution in 0.1-strength brain heart infusion broth (BHIB). Amphiphiles 4(19), 4(21), 5(18), and 5(20) showed the strongest antibacterial activity (2.2-3.4µg/mL) against S. aureus (vancomycin, MIC=0.25µg/mL). These four plus 1(21), 2(20), 2(22), and 3(20) exhibited the strongest antibacterial activity (1.7-6.8µg/mL) against MRSA (vancomycin, MIC=0.25µg/mL). The MICs of these amphiphiles against six clinical MRSA were similar to those against the ATCC strain. In PBS, EC(10)s of the most active homologues ranged from 7 to 18µg/mL and 18 to 220µg/mL for di- and tricarboxyl dendritic amphiphiles, respectively. To assess the potential safety of using dendritic amphiphiles as drugs, measurements of micellar and hemolytic properties were conducted in the same medium (full-strength BHIB) that was used for antibacterial activity. The CMCs (9-36µg/mL, ∼18-72µM) of ten amphiphiles were measured by microdilution (log2 progression) with dye-covered beads. The EC(10)s were similar to those in PBS. The MICs of most amphiphiles (14-72µg/mL) and vancomycin (1.1-2.2µg/mL) against both S. aureus and MRSA increased significantly compared to the MICs measured in 0.1-strength BHIB. The one exception, 5(18), had an MIC against S. aureus of 1.1µg/mL compared to vancomycin (2.2µg/mL). With CMC (9-18µg/mL) and EC(10) (16µg/mL) values higher than the MIC, 5(18) was discovered as a lead for further development.

Thrombolysis of a massive intracardiac thrombus during resuscitation: documentation by transoesophageal echocardiography.

Acute pulmonary embolism is a frequent potentially reversible cause of sudden cardiac arrest. The early diagnosis is challenging but essential for further treatment. New therapeutic options in resuscitation, such as extracorporeal resuscitation, are leading to frequent transports of patients to emergency rooms with ongoing resuscitation. A transoesophageal echo performed during resuscitation can give hints for reversible causes for the cardiac arrest. We present a case of a 40-year-old female patient who was transferred to our department with ongoing resuscitation and received a transoesophageal echo immediately on arrival. The examination showed a massive intracardiac thrombus. The subsequent thrombolysis and following resuscitation were observed and documented via transoesophageal echo.

Initial Blood pH, Lactate and Base Deficit Add No Value to Peri-Arrest Factors in Prognostication of Neurological Outcome After Out-of-Hospital Cardiac Arrest.

Background: In cardiac arrest survivors, metabolic parameters [pH value, lactate concentration, and base deficit (BD)] are routinely added to peri-arrest factors (including age, sex, bystander cardiopulmonary resuscitation, shockable first rhythm, resuscitation duration, adrenaline dose) to enhance early outcome prediction. However, the additional value of this strategy remains unclear. Methods: We used our resuscitation database to screen all patients ≥18 years who had suffered in- or out-of-hospital cardiac arrest (IHCA, OHCA) between January 1st, 2005 and May 1st, 2019. Patients with incomplete data, without return of spontaneous circulation or treatment with sodium bicarbonate were excluded. To analyse the added value of metabolic parameters to prognosticate neurological function, we built three models using logistic regression. These models included: (1) Peri-arrest factors only, (2) peri-arrest factors plus metabolic parameters and (3) metabolic parameters only. Receiver operating characteristics curves regarding 30-day good neurological function (Cerebral Performance Category 1-2) were analysed. Results: A total of 2,317 patients (OHCA: n = 1842) were included. In patients with OHCA, model 1 and 2 had comparable predictive value. Model 3 was inferior compared to model 1. In IHCA patients, model 2 performed best, whereas both metabolic (model 3) and peri-arrest factors (model 1) demonstrated similar power. PH, lactate and BD had interchangeable areas under the curve in both IHCA and OHCA. Conclusion: Although metabolic parameters may play a role in IHCA, no additional value in the prediction of good neurological outcome could be found in patients with OHCA. This highlights the importance of accurate anamnesis especially in patients with OHCA.

Coronary angiography in patients after cardiac arrest without ST-elevation myocardial infarction : A retrospective cohort analysis.

BACKGROUND: Coronary artery disease (CAD) is the most common cause of sudden cardiac arrest (SCA). Although coronary angiography (CAG) should be performed also in the absence of ST-elevation (STE) after sustained return of spontaneous circulation (ROSC), this recommendation is not well implemented in daily routine. METHODS: A retrospective database analysis was conducted in a tertiary care center between January 2005 and December 2014. We included all SCA patients aged ≥ 18 years with presumed cardiac cause and sustained ROSC in the absence of STE at hospital admission. The rate and timing of CAG were defined as the primary endpoints. As secondary endpoints, the reasons pro and contra CAG were analyzed. Furthermore, we observed if the signs and symptoms used for decision making occurred more often in patients with treatable CAD. RESULTS: We included 645 (53.6%) of the 1203 screened patients, CAG was performed in 343 (53.2%) patients with a diagnosis of occlusive CAD in 214 (62.4%) patients. Of these, 151 (71.0%) patients had occlusive CAD treated with coronary intervention, thrombus aspiration, or coronary artery bypass grafting. In an adjusted binomial logistic regression analysis, age ≥ 70 years, female sex, non-shockable rhythms, and cardiomyopathy were associated with withholding of CAG. In patients diagnosed and treated with occlusive CAD, initially shockable rhythms, previously diagnosed CAD, hypertension, and smoking were found more often. CONCLUSION: Although selection bias is unavoidable due to the retrospective design of this study, a high proportion of the examined patients had occlusive CAD. The criteria used for patient selection may be suboptimal.

Copeptin Levels Are Independent from Mild Therapeutic Hypothermia but Do Not Predict Infarct Size in Patients Presenting with ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Mild therapeutic hypothermia (MTH) is a treatment adjunct in ST-segment elevation myocardial infarction (STEMI) that deserves investigation. Copeptin-a surrogate marker for vasopressin-is an early biomarker in STEMI. Data from cardiac arrest patients suggest a reduction of copeptin levels through MTH; however, copeptin levels have not been investigated in MTH during STEMI. METHODS: We analyzed patients treated with MTH during STEMI in a sub-study of the STATIM trial (Testori, Heart 2019). Patients were randomized to normothermia or MTH with out-of-hospital initiation. Seven copeptin samples were collected from each patient. Primary endpoint was the difference in copeptin levels between the groups. As secondary endpoints, we defined differences in the kinetics between the sampling timepoints and the correlation between copeptin and the infarct size in relation to left ventricular myocardium. RESULTS: We included 99 patients (MTH n = 47, control n = 52) in our intention to treat analysis. No differences in copeptin values at first medical contact between the MTH and normothermia groups were found. MTH showed no effect on copeptin levels, neither during cooling phase nor through the course. Copeptin peaked at first medical contact and hospital admission in both groups. No differences in kinetics between the timepoints were found. Copeptin showed no correlation with infarct size, neither at first medical contact nor hospital admission. CONCLUSIONS: Copeptin levels were not influenced by MTH in STEMI, suggesting the use of this biomarker also during temperature management. Furthermore, copeptin levels were not usable as a surrogate marker for infarct size at any timepoint.

Change of Hemoglobin Levels in the Early Post-cardiac Arrest Phase Is Associated With Outcome.

Background: The post-cardiac arrest (CA) phase is characterized by high fluid requirements, endothelial activation and increased vascular permeability. Erythrocytes are large cells and may not leave circulation despite massive capillary leak. We hypothesized that dynamic changes in hemoglobin concentrations may reflect the degree of vascular permeability and may be associated with neurologic function after CA. Methods: We included patients ≥18 years, who suffered a non-traumatic CA between 2013 and 2018 from the prospective Vienna Clinical Cardiac Arrest Registry. Patients without return of spontaneous circulation (ROSC), with extracorporeal life support, with any form of bleeding, undergoing surgery, receiving transfusions, without targeted temperature management or with incomplete datasets for multivariable analysis were excluded. The primary outcome was neurologic function at day 30 assessed by the Cerebral Performance Category scale. Differences of hemoglobin concentrations at admission and 12 h after ROSC were calculated and associations with neurologic function were investigated by uni- and multivariable logistic regression. Results: Two hundred and seventy-five patients were eligible for analysis of which 143 (52%) had poor neurologic function. For every g/dl increase in hemoglobin from admission to 12 h the odds of poor neurologic function increased by 26% (crude OR 1.26, 1.07-1.49, p = 0.006). The effect remained unchanged after adjustment for fluid balance and traditional prognostication markers (adjusted OR 1.27, 1.05-1.54, p = 0.014). Conclusion: Increasing hemoglobin levels in spite of a positive fluid balance may serve as a surrogate parameter of vascular permeability and are associated with poor neurologic function in the early post-cardiac arrest period.

The association of early diarrhea after successful resuscitation following out-of-hospital cardiac arrest with neurological outcome: A retrospective observational study.

ABSTRACT: Gastrointestinal ischemia with reperfusion tissue injury contributes to post-cardiac arrest syndrome. We hypothesized that diarrhea is a symptom of intestinal ischemia/reperfusion injury and investigated whether the occurrence of early diarrhea (≤12 hours) after successful cardiopulmonary resuscitation is associated with an unfavorable neurological outcome.We analyzed data from the Vienna Clinical Cardiac Arrest Registry. Inclusion criteria comprised ≥18 years of age, a witnessed, non-traumatic out-of-hospital cardiac arrest, return of spontaneous circulation (ROSC), initial shockable rhythm, and ST-segment elevation in electrocardiogram after ROSC with consecutive coronary angiography. Patients with diarrhea caused by other factors (e.g., infections, antibiotic treatment, or chronic diseases) were excluded. The primary endpoint was neurological function between patients with or without "early diarrhea" (≤12 hours after ROSC) according to cerebral performance categories.We included 156 patients between 2005 and 2012. The rate of unfavorable neurologic outcome was higher in patients with early diarrhea (67% vs 37%). In univariate analysis, the crude odds ratio for unfavorable neurologic outcome was 3.42 (95% confidence interval, 1.11-10.56, P = .03) for early diarrhea. After multivariate adjustment for traditional prognostication markers the odds ratio of early diarrhea was 5.90 (95% confidence interval, 1.28-27.06, P = .02).In conclusion, early diarrhea within 12 hours after successful cardiopulmonary resuscitation was associated with an unfavorable neurological outcome.