Alteration of mechanical stresses in the murine brain by age and hemorrhagic stroke.

Residual mechanical stresses, also known as solid stresses, emerge during rapid differential growth or remodeling of tissues, as observed in morphogenesis and tumor growth. While residual stresses typically dissipate in most healthy adult organs, as the growth rate decreases, high residual stresses have been reported in mature, healthy brains. However, the origins and consequences of residual mechanical stresses in the brain across health, aging, and disease remain poorly understood. Here, we utilized and validated a previously developed method to map residual mechanical stresses in the brains of mice across three age groups: 5-7 days, 8-12 weeks, and 22 months. We found that residual solid stress rapidly increases from 5-7 days to 8-12 weeks and remains high in mature 22 months mice brains. Three-dimensional mapping revealed unevenly distributed residual stresses from the anterior to posterior coronal brain sections. Since the brain is rich in negatively charged hyaluronic acid, we evaluated the contribution of charged extracellular matrix (ECM) constituents in maintaining solid stress levels. We found that lower ionic strength leads to elevated solid stresses, consistent with its unshielding effect and the subsequent expansion of charged ECM components. Lastly, we demonstrated that hemorrhagic stroke, accompanied by loss of cellular density, resulted in decreased residual stress in the murine brain. Our findings contribute to a better understanding of spatiotemporal alterations of residual solid stresses in healthy and diseased brains, a crucial step toward uncovering the biological and immunological consequences of this understudied mechanical phenotype in the brain.

Distribution of infectious and parasitic agents among three sentinel bee species across European agricultural landscapes.

Infectious and parasitic agents (IPAs) and their associated diseases are major environmental stressors that jeopardize bee health, both alone and in interaction with other stressors. Their impact on pollinator communities can be assessed by studying multiple sentinel bee species. Here, we analysed the field exposure of three sentinel managed bee species (Apis mellifera, Bombus terrestris and Osmia bicornis) to 11 IPAs (six RNA viruses, two bacteria, three microsporidia). The sentinel bees were deployed at 128 sites in eight European countries adjacent to either oilseed rape fields or apple orchards during crop bloom. Adult bees of each species were sampled before their placement and after crop bloom. The IPAs were detected and quantified using a harmonised, high-throughput and semi-automatized qPCR workflow. We describe differences among bee species in IPA profiles (richness, diversity, detection frequencies, loads and their change upon field exposure, and exposure risk), with no clear patterns related to the country or focal crop. Our results suggest that the most frequent IPAs in adult bees are more appropriate for assessing the bees' IPA exposure risk. We also report positive correlations of IPA loads supporting the potential IPA transmission among sentinels, suggesting careful consideration should be taken when introducing managed pollinators in ecologically sensitive environments.

Graphene oxide nanosheets augment silk fibroin aerogels for enhanced water stability and oil adsorption.

Nanocomposite aerogels exhibit high porosity and large interfacial surface areas, enabling enhanced chemical transport and reactivity. Such mesoporous architectures can be prepared by freeze-casting naturally-derived biopolymers such as silk fibroin, but often form mechanically weak structures that degrade in water, which limits their performance under ambient conditions. Adding 2D material fillers such as graphene oxide (GO) or transition metal carbides (e.g. MXene) could potentially reinforce these aerogels via stronger intermolecular interactions with the polymeric binder. Here, we show that freeze-casting of GO nanosheets with silk fibroin results in a highly water-stable, mechanically robust aerogel, with considerably enhanced properties relative to silk-only or silk-MXene aerogels. These silk-GO aerogels exhibit high contact angles with water and are highly water stable. Moreover, aerogels can adsorb up 25-35 times their mass in oil, and can be used robustly for selective oil separation from water. This increased stability may occur due to strengthened intermolecular interactions such as hydrogen bonding, despite the random coil and α-helix conformation of silk fibroin, which is typically more soluble in water. Finally, we show these aerogels can be prepared at scale by freeze-casting on a copper mesh. Ultimately, we envision that these multicomponent aerogels could be widely utilized for molecular separations and environmental sensing, as well as for thermal insulation and electrical conductivity.

Characteristics, Treatment Strategies and Outcome in Cardiogenic Shock Complicating Acute Myocardial Infarction: A Contemporary Dutch Cohort.

Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) is associated with high morbidity and mortality. Our study aimed to gain insights into patient characteristics, outcomes and treatment strategies in CS patients. Patients with CS who underwent percutaneous coronary intervention (PCI) between 2017 and 2021 were identified in a nationwide registry. Data on medical history, laboratory values, angiographic features and outcomes were retrospectively assessed. A total of 2328 patients with a mean age of 66 years and of whom 73% were male, were included. Mortality at 30 days was 39% for the entire cohort. Non-survivors presented with a lower mean blood pressure and increased heart rate, blood lactate and blood glucose levels (p-value for all <0.001). Also, an increased prevalence of diabetes, multivessel coronary artery disease and a prior coronary event were found. Of all patients, 24% received mechanical circulatory support, of which the majority was via intra-aortic balloon pumps (IABPs). Furthermore, 79% of patients were treated with at least one vasoactive agent, and multivessel PCI was performed in 28%. In conclusion, a large set of hemodynamic, biochemical and patient-related characteristics was identified to be associated with mortality. Interestingly, multivessel PCI and IABPs were frequently applied despite a lack of evidence.

Viral Co-Infections and Antiviral Immunity in Honey Bees.

Over the past few decades, honey bees have been facing an increasing number of stressors. Beyond individual stress factors, the synergies between them have been identified as a key factor in the observed increase in colony mortality. However, these interactions are numerous and complex and call for further research. Here, in line with our need for a systemic understanding of the threats that they pose to bee health, we review the interactions between honey bee viruses. As viruses are obligate parasites, the interactions between them not only depend on the viruses themselves but also on the immune responses of honey bees. Thus, we first summarise our current knowledge of the antiviral immunity of honey bees. We then review the interactions between specific pathogenic viruses and their interactions with their host. Finally, we draw hypotheses from the current literature and suggest directions for future research.

Trehalose-Guanosine Glycopolymer Hydrogels Direct Adaptive Glia Responses in CNS Injury.

Neural tissue damaged after central nervous system (CNS) injury does not naturally regenerate but is instead replaced by non-neural fibrotic scar tissue that serves no neurological function. Scar-free repair to create a more permissive environment for regeneration requires altering the natural injury responses of glial cells. In this work, glycopolymer-based supramolecular hydrogels are synthesized to direct adaptive glia repair after CNS injury. Combining poly(trehalose-co-guanosine) (pTreGuo) glycopolymers with free guanosine (fGuo) generates shear-thinning hydrogels through stabilized formation of long-range G-quadruplex secondary structures. Hydrogels with smooth or granular microstructures and mechanical properties spanning three orders of magnitude are produced through facile control of pTreGuo hydrogel composition. Injection of pTreGuo hydrogels into healthy mouse brains elicits minimal stromal cell infiltration and peripherally derived inflammation that is comparable to a bioinert methyl cellulose benchmarking material. pTreGuo hydrogels alter astrocyte borders and recruit microglia to infiltrate and resorb the hydrogel bulk over 7 d. Injections of pTreGuo hydrogels into ischemic stroke alter the natural responses of glial cells after injury to reduce the size of lesions and increase axon regrowth into lesion core environments. These results support the use of pTreGuo hydrogels as part of neural regeneration strategies to activate endogenous glia repair mechanisms.

Buffered Lidocaine as an Endotracheal Tube Cuff Media In Immediate Postoperative Cardiac Surgery Patients And Its Effect On Sedation Requirements: A Prospective Feasibility Study.

Tracheal mucosal inflammation and irritation caused by the endotracheal tube (ETT) may exacerbate symptoms of pain and discomfort which create challenges including ETT tolerance and postintubation emergence phenomena. Various sedative and analgesic agents are used to mitigate these symptoms, however, there is concern that such medications may contribute to prolonged duration of intubation, length of intensive care unit (ICU) stay, as well as increased morbidity. This randomized control pilot study explored the feasibility and potential efficacy of instillation of a buffered lidocaine solution as an ETT cuff medium in adult rapid recovery eligible cardiac surgical patients. Thirty-two patients were randomized to the intervention (1.8% lidocaine/0.76% sodium bicarbonate) or control (air) group. Data were analyzed using median, standard deviation (SD), Wilcoxon rank sum, mean ± SD, two-sample t-test, and Fisher's exact test. The intervention arm demonstrated a trend toward a reduction in the incidence of cough at ICU arrival (0 versus 22%), incidence of pharyngitis at all time intervals, and propofol requirement (345 ± 248 mg versus 1,158 ± 1,426 mg) with no difference in adverse events between groups. These results support the development of larger studies to confirm the efficacy and feasibility of buffered lidocaine as an ETT cuff medium in this population.

The Predictive Power of the 14-51 Ng/L High Sensitive Troponin T (hsTnT) Values for Predicting Cardiac Revascularization in a Clinical Setting.

Background: high sensitive Troponin T (hsTnT) values between 14−50 ng/L represent a challenge in diagnosing acute coronary syndrome (ACS) at the Emergency Department (ED). The European Society for Cardiology (ESC) recommends a second hsTnT measurement 3 h later to distinguish between ACS and other causes depending on the Δ hsTnT. Our study aims to evaluate the predictive power this approach in a clinical setting by following patients presenting at the ED with hsTnT values 14−51 ng/L. Materials and methods: patients presenting with chest pain or dyspnea and a hsTnT value between 14 and 50 ng/L at the Erasmus MC ED in 2012−2013 were included and retrospectively monitored for 90 days after initial presentation for the occurrence of a cardiac revascularization. Patient records were reviewed according to the standing protocol, which depended on the Δ hsTnT. The "event-group" consists of patients receiving cardiac revascularization within 90 days after the ED visit, whereas the "no event-group" consisted of patients without revascularization. Results: a total of 889 patients patient records were reviewed. After excluding out-of-hospital-cardia-arrests (60), non-cardiological chest pain (373) and incomplete follow-up (100), 356 patients remained for final analysis. In 207 patients, a second hsTnT was actually performed (58%). From these 207 patients, 68 (33%) had a Δ hsTnT ≥7 ng/L. In these patients, 37 (54%) experienced an event within 90 days. In the 139 patients with a Δ hsTnT < 7 ng/L, 23 (17%) presented with an event within 90 days. Conclusion: our study demonstrated a sensitivity of 62%, a specificity of 79%, a positive predicted value (PPV) of 54% and a negative predictive value (NPV) of 83% for using a 3-h Δ hsTnT ≥7 ng/L cut-off, related to risk of an event in 90 days following ED presentation.

Specific detection and quantification of three microsporidia infecting bees, Nosema apis, Nosema ceranae, and Nosema bombi, using probe-based real-time PCR.

Among stressors affecting bee health, Nosema microsporidia are prevalent intracellular parasites. Nosema apis and Nosema ceranae have been described in honey bees (Apis spp.), while Nosema bombi has been described in bumble bees (Bombus spp.). Although available molecular methods serve as a complement to microscopic diagnosis of nosemosis, they do not enable accurate quantification of these three Nosema species. We developed three quantitative real-time PCRs (qPCRs) starting from in silico design of specific primers, probes, and recombinant plasmids, to target the RNA polymerase II subunit B1 (RPB1) gene in the three species. The complete methods, including bee grinding, DNA purification, and qPCR, were validated in honey bee (Apis mellifera) homogenate. Specificity was assessed in silico and in vitro with several types of bee samples. The limit of detection was estimated at 4 log10 copies/honey bee. A small, systematic method bias was corrected for accurate quantification up to 10 log10 copies/honey bee. Method accuracy was also verified in bumble bee (Bombus terrestris) and mason bee (Osmia bicornis) homogenates in the range of 5 to 10 log10 copies/bee. These validated qPCR methods open perspectives in nosemosis diagnosis and in the study of the parasite's eco-dynamics in managed and wild bees.

Transmission of deformed wing virus between Varroa destructor foundresses, mite offspring and infested honey bees.

BACKGROUND: Varroa destructor is the major ectoparasite of the western honey bee (Apis mellifera). Through both its parasitic life-cycle and its role as a vector of viral pathogens, it can cause major damage to honey bee colonies. The deformed wing virus (DWV) is the most common virus transmitted by this ectoparasite, and the mite is correlated to increased viral prevalence and viral loads in infested colonies. DWV variants A and B (DWV-A and DWV-B, respectively) are the two major DWV variants, and they differ both in their virulence and transmission dynamics. METHODS: We studied the transmission of DWV between bees, parasitic mites and their offspring by quantifying DWV loads in bees and mites collected in in vitro and in situ environments. In vitro, we artificially transmitted DWV-A to mites and quantified both DWV-A and DWV-B in mites and bees. In situ, we measured the natural presence of DWV-B in bees, mites and mites' offspring. RESULTS: Bee and mite viral loads were correlated, and mites carrying both variants were associated with higher mortality of the infected host. Mite infestation increased the DWV-B loads and decreased the DWV-A loads in our laboratory conditions. In situ, viral quantification in the mite offspring showed that, after an initially non-infected egg stage, the DWV-B loads were more closely correlated with the foundress (mother) mites than with the bee hosts. CONCLUSIONS: The association between mites and DWV-B was highlighted in this study. The parasitic history of a mite directly impacts its DWV infection potential during the rest of its life-cycle (in terms of variant and viral loads). Regarding the mite's progeny, we hypothesize that the route of contamination is likely through the feeding site rather than by vertical transmission, although further studies are needed to confirm this hypothesis.

Ischaemic electrocardiogram patterns and its association with survival in out-of-hospital cardiac arrest patients without ST-segment elevation myocardial infarction: a COACT trials' post-hoc subgroup analysis.

AIMS: ST-depression and T-wave inversion are frequently present on the post-resuscitation electrocardiogram (ECG). However, the prognostic value of ischaemic ECG patterns is unknown. METHODS AND RESULTS: In this post-hoc subgroup analysis of the Coronary Angiography after Cardiac arrest (COACT) trial, the first in-hospital post-resuscitation ECG in out-of-hospital cardiac arrest patients with a shockable rhythm was analysed for ischaemic ECG patterns. Ischaemia was defined as ST-depression of ≥0.1 mV, T-wave inversion in ≥2 contiguous leads, or both. The primary endpoint was 90-day survival. Secondary endpoints were rate of acute unstable lesions, levels of serum troponin-T, and left ventricular function. Of the 510 out-of-hospital cardiac arrest patients, 340 (66.7%) patients had ischaemic ECG patterns. Patients with ischaemic ECG patterns had a worse 90-day survival compared with those without [hazard ratio 1.51; 95% confidence interval (CI) 1.08-2.12; P = 0.02]. A higher sum of ST-depression was associated with lower survival (log-rank = 0.01). The rate of acute unstable lesions (14.5 vs. 15.8%; odds ratio 0.90; 95% CI 0.51-1.59) did not differ between the groups. In patients with ischaemic ECG patterns, maximum levels of serum troponin-T (µg/L) were higher [0.595 (interquartile range 0.243-1.430) vs. 0.359 (0.159-0.845); ratio of geometric means 1.58; 1.13-2.20] and left ventricular function (%) was worse (44.7 ± 12.5 vs. 49.9 ± 13.3; mean difference -5.13; 95% CI -8.84 to -1.42). Adjusted for age and time to return of spontaneous circulation, ischaemic ECG patterns were no longer associated with survival. CONCLUSION: Post-arrest ischaemic ECG patterns were associated with worse 90-day survival. A higher sum of ST-depression was associated with lower survival. Adjusted for age and time to return of spontaneous circulation, ischaemic ECG patterns were no longer associated with survival.

Adult patients with congenital heart disease in the intensive care unit.

OBJECTIVE: Current data on intensive care unit (ICU) admissions in patients with adult congenital heart disease (ACHD) are limited and focus on admissions after elective cardiac surgery. This study describes non-elective ICU admissions in patients with ACHD. METHODS: A retrospective matched cohort study was performed from January 2000 until December 2015 in a tertiary care centre ICU (there was no cardiac care unit). Primary outcomes were short-term (during hospital stay or <30 days after discharge) and long-term (>30 days after discharge until end of follow-up) mortality. Outcomes were compared with non-ACHD non-elective ICU admissions, matched 1:1 on age, sex and admission diagnosis. RESULTS: A total of 138 admissions in 104 patients with ACHD (65.9% male, median age 30 years) were included, during 8.6 years of follow-up. The majority had a moderate-to-severe heart defect. Arrhythmia was the most common admission diagnosis (44.2%), followed by haemorrhage (10.9%), heart failure (8.7%) and pulmonary disease (8.7%). Short-term mortality and total mortality were lower in the ACHD admissions than in the non-ACHD admissions (4.8% vs 16.3%, p=0.005 and 17.3% vs 28.9%, p=0.030), whereas long-term (12.5% vs 12.6%, p=0.700) did not differ. Severe CHD (HR 3.1, 95% CI 1.1 to 8.6) at baseline, and mechanical circulatory support device use (8.3, 1.4 to 47.4) and emergency intervention (0.2, 0.1 to 0.7) during the ICU stay were independently associated with mortality in the ACHD group. CONCLUSIONS: Non-elective ICU admissions in patients with ACHD are most often for arrhythmia and in patients with moderate-to-severe CHD. Reassuringly, short-term and total mortality are lower compared with patients without ACHD, however, long-term mortality is higher than expected for patients with ACHD.

Development and Internal Validation of a Practical Model to Identify Observe Patients of the European Society of Cardiology 0/1-h Algorithm at Low Risk of a Coronary Diagnosis.

BACKGROUND: Patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) assigned to the "observe" zone of the European Society of Cardiology (ESC) 0/1-h algorithm form a heterogeneous group known to have an unfavourable prognosis. We aim to elucidate the clinical characteristics and management of these patients and generate a model that is predictive of a coronary diagnosis at index visit to the emergency department (ED). METHODS: A retrospective observational cohort study, including adult patients presenting to the ED with suspected NSTE-ACS assigned to the "observe" zone of the ESC 0/1-h algorithm. Multivariable logistic regression analysis was performed for the prediction of a coronary diagnosis. Internal validation was performed using bootstrap resampling. RESULTS: A total of 750 patients were included; mean age 66 ± 13 years, 35% women, 50% with prior history of coronary artery disease (CAD). In 372 (50%) patients a diagnosis was established within 30 days of index presentation, of whom 169 (45%) patients had a coronary-related event. Multivariable logistic regression analysis generated a 12-point risk score incorporating 5 variables for the prediction of such event, including type of angina, chest pain occurring during inspiration, prior history of CAD, ST-segment deviation on electrocardiogram, and estimated glomerular filtration rate <60. The final model had an optimism-corrected c-statistic of 0.78 (95% confidence interval [CI]: 0.74-0.82). A score <6 ruled out a coronary event in 276 (37%) patients, with a sensitivity and negative predictive value of 90% (95% CI: 84-94) and 94% (91-96), respectively. CONCLUSION: A score <6 identifies patients at low risk of a coronary diagnosis and can guide clinical decision-making in choosing the appropriate diagnostic test.

Cost Analysis From a Randomized Comparison of Immediate Versus Delayed Angiography After Cardiac Arrest.

Background In patients with out-of-hospital cardiac arrest without ST-segment elevation, immediate coronary angiography did not improve clinical outcomes when compared with delayed angiography in the COACT (Coronary Angiography After Cardiac Arrest) trial. Whether 1 of the 2 strategies has benefits in terms of health care resource use and costs is currently unknown. We assess the health care resource use and costs in patients with out-of-hospital cardiac arrest. Methods and Results A total of 538 patients were randomly assigned to a strategy of either immediate or delayed coronary angiography. Detailed health care resource use and cost-prices were collected from the initial hospital episode. A generalized linear model and a gamma distribution were performed. Generic quality of life was measured with the RAND-36 and collected at 12-month follow-up. Overall total mean costs were similar between both groups (EUR 33 575±19 612 versus EUR 33 880±21 044; P=0.86). Generalized linear model: (ß, 0.991; 95% CI, 0.894-1.099; P=0.86). Mean procedural costs (coronary angiography and percutaneous coronary intervention, coronary artery bypass graft) were higher in the immediate angiography group (EUR 4384±3447 versus EUR 3028±4220; P<0.001). Costs concerning intensive care unit and ward stay did not show any significant difference. The RAND-36 questionnaire did not differ between both groups. Conclusions The mean total costs between patients with out-of-hospital cardiac arrest randomly assigned to an immediate angiography or a delayed invasive strategy were similar during the initial hospital stay. With respect to the higher invasive procedure costs in the immediate group, a strategy awaiting neurological recovery followed by coronary angiography and planned revascularization may be considered. Registration URL: https://trialregister.nl; Unique identifier: NL4857.

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

OBJECTIVES: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm. DESIGN: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial. SETTING: Nineteen hospitals in The Netherlands. PATIENTS: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups. CONCLUSIONS: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.

Coronary CT angiography for improved assessment of patients with acute chest pain and low-range positive high-sensitivity troponins: study protocol for a prospective, observational, multicentre study (COURSE trial).

INTRODUCTION: Current evaluation of patients suspected of a non-ST-elevation acute coronary syndrome (NSTE-ACS) involves the use of algorithms that incorporate clinical information, electrocardiogram (ECG) and high-sensitivity cardiac troponins (hs-troponins). While primarily designed to rule out NSTE-ACS safely, these algorithms can also be used for rule in of NSTE-ACS in some patients. Still, in a substantial number of patients, these algorithms do not provide a conclusive work-up. These patients often present with an atypical clinical profile and low-range positive hs-troponin values without a characteristic rise or fall pattern. They represent a heterogeneous group of patients with various underlying conditions; only a fraction (30%-40%) will eventually be diagnosed with a myocardial infarction. Uncertainty exists about the optimal diagnostic strategy and their management depends on the clinical perspective of the treating physician ranging from direct discharge to admission for invasive coronary angiography. Coronary CT angiography (CCTA) is a non-invasive test that has been shown to be safe, fast and reliable in the evaluation of coronary artery disease. In this study, we will determine the usefulness of CCTA in patients with acute chest pain and low-range positive hs-troponin values. METHODS AND ANALYSIS: A prospective, double-blind, observational, multicentre study conducted in the Netherlands. Patients aged 30-80 years presenting to the emergency department with acute chest pain and a suspicion of NSTE-ACS, a normal or non-diagnostic ECG and low-range positive hs-troponins will be scheduled to undergo CCTA. The primary outcome is the diagnostic accuracy of CCTA for the diagnosis of NSTE-ACS at discharge, in terms of sensitivity and negative predictive value. ETHICS AND DISSEMINATION: This study was approved by the Medical Research Ethics Committee of Erasmus Medical Center in Rotterdam, the Netherlands (registration number MEC-2017-506). Written informed consent to participate will be obtained from all participants. This study's findings will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03129659).

Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial.

BACKGROUND: High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients. METHODS: This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations. DISCUSSION: Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest. TRIAL REGISTRATION: ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662 European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL.

Undetectable High-Sensitivity Troponin T as a Gatekeeper for Coronary Computed Tomography Angiography in Patients Suspected of Acute Coronary Syndrome.

OBJECTIVES: The aim of this study was to characterize the safety and efficiency of a strategy employing the limit of detection (LoD) of high-sensitivity troponin T (hs-TnT) as a gatekeeper for coronary computed tomography angiography (CCTA) in suspected acute coronary syndrome (ACS) patients in the emergency department (ED). METHODS: We included suspected ACS patients who underwent CCTA and were evaluated with hs-TnT. Patients were categorized as below the LoD and at or above the LoD. The primary outcome was 30-day major adverse cardiac events (MACEs), defined as all-cause mortality, ACS, or coronary revascularization. RESULTS: The study population consisted of 177 patients (mean age 55 ± 10 years, 50.3% women), and 16 (9.0%) patients reached the primary outcome. None of the patients died, while 13 had an adjudicated diagnosis of ACS, and 3 underwent elective coronary revascularization. There were 77 patients (44%) with an hs-TnT value below the LoD (MACEs; n = 1 [1.3%]) and 100 (56%) with at or above the LoD levels (MACEs; n = 15 [15%]). None of 67 patients with an hs-TnT value below the LoD and <50% stenosis on CCTA experienced MACEs. Out of the 10 patients with an hs-TnT value below the LoD and ≥50% stenosis on CCTA, 1 patient underwent elective percutaneous coronary revascularization. In patients with an hs-TnT value at or above the LoD, 74 patients had <50% stenosis on CCTA, and 2 patients (3%) were diagnosed with myocardial infarction without obstructive coronary artery disease confirmed on invasive angiography. Thirteen (50%) patients with an hs-TnT value at or above the LoD and ≥50% stenosis on CCTA experienced MACEs (11 ACS and 2 elective percutaneous coronary revascularizations). CONCLUSION: Our findings support that implementing the LoD of hs-TnT as a gatekeeper may reduce the need for CCTA in suspected ACS patients in the ED.

The effect of immediate coronary angiography after cardiac arrest without ST-segment elevation on left ventricular function. A sub-study of the COACT randomised trial.

BACKGROUND: The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients who are successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) on left ventricular function is currently unknown. METHODS: This prespecified sub-study of a multicentre trial evaluated 552 patients, successfully resuscitated from out-of-hospital cardiac arrest without signs of STEMI. Patients were randomized to either undergo immediate coronary angiography or delayed coronary angiography, after neurologic recovery. All patients underwent PCI if indicated. The main outcomes of this analysis were left ventricular ejection fraction and end-diastolic and systolic volumes assessed by cardiac magnetic resonance imaging or echocardiography. RESULTS: Data on left ventricular function was available for 397 patients. The mean (± standard deviation) left ventricular ejection fraction was 45.2% (±12.8) in the immediate angiography group and 48.4% (±13.2) in the delayed angiography group (mean difference: -3.19; 95% confidence interval [CI], -6.75 to 0.37). Median left ventricular end-diastolic volume was 177 ml in the immediate angiography group compared to 169 ml in the delayed angiography group (ratio of geometric means: 1.06; 95% CI, 0.95-1.19). In addition, mean left ventricular end-systolic volume was 90 ml in the immediate angiography group compared to 78 ml in the delayed angiography group (ratio of geometric means: 1.13; 95% CI 0.97-1.32). CONCLUSION: In patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, immediate coronary angiography was not found to improve left ventricular dimensions or function compared with a delayed angiography strategy. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register number, NTR4973.

Diagnostic approach for myocardial contusion: a retrospective evaluation of patient data and review of the literature.

PURPOSE: Myocardial contusion can be a life-threatening condition in patients who sustained blunt thoracic trauma. The diagnostic approach remains a subject of debate. The aim of this study was to determine the sensitivity and specificity of echocardiography, electrocardiography, troponins T and I (TnT and TnI), and creatine kinase muscle/brain (CK-MB) for identifying patients with a myocardial contusion following blunt thoracic trauma. METHODS: Sensitivity and specificity were first determined in a 10-year retrospective cohort study and second by a systematic literature review with meta-analysis. RESULTS: Of the 117 patients in the retrospective study, 44 (38%) were considered positive for myocardial contusion. Chest X-ray, chest CT scan, electrocardiograph, and echocardiography had poor sensitivity (< 15%) but good specificity (≥ 90%). Sensitivity to cardiac biomarkers measured at presentation ranged from 59% for TnT to 77% for hs-TnT, specificity ranged from 63% for CK-MB to 100% for TnT. The systematic literature review yielded 28 studies, with 14.5% out of 7242 patients reported as positive for myocardial contusion. The pooled sensitivity of electrocardiography, troponin I, and CK-MB was between 62 and 71%, versus only 45% for echocardiography and 38% for troponin T. The pooled specificity ranged from 63% for CK-MB to 85% for troponin T and 88% for echocardiography. CONCLUSION: The best diagnostic approach for myocardial contusion is a combination of electrocardiography and measurement of cardiac biomarkers. If abnormalities are found, telemonitoring is necessary for the early detection of life-threatening arrhythmias. Chest X-ray and CT scan may show other thoracic injuries but provide no information on myocardial contusion.