Epidemiological studies link COVID-19 to increased cardiac arrest (CA) risk, but causality remains unclear due to potential confounding factors in observational studies . We conducted a Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data, employing COVID-19-associated single nucleotide polymorphisms (SNPs) with significance values smaller than 5 × 10⁻⁸. We calculated inverse-variance weighted (IVW) MR estimates and performed sensitivity analyses using MR methods robust to horizontal pleiotropy. Additionally, a reverse MR analysis was conducted using CA-associated SNPs with significance values smaller than 1 × 10⁻⁵. Results indicated that infected COVID-19 (OR = 1.12, 95% CI = 0.47-2.67, p = 0.79), hospitalized COVID-19 (OR = 1.02, 95% CI = 0.70-1.49, p = 0.920), and severe respiratory COVID-19 (OR = 0.99, 95% CI = 0.81-1.21, p = 0.945) did not causally influence CA risk. Reverse MR analysis also did not support a causal effect of CA on COVID-19. Thus, associations in observational studies may stem from shared biological factors or environmental confounding.

UNASSIGNED: This study investigates the association between the mean arterial blood pressure (MAP), vasopressor requirement, and severity of hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA).
UNASSIGNED: Between 2008 and 2017, we retrospectively analyzed the MAP 200 h after CA and quantified the vasopressor requirements using the cumulative vasopressor index (CVI). Through a postmortem brain autopsy in non-survivors, the severity of the HIE was histopathologically dichotomized into no/mild and severe HIE. In survivors, we dichotomized the severity of HIE into no/mild cerebral performance category (CPC) 1 and severe HIE (CPC 4). We investigated the regain of consciousness, causes of death, and 5-day survival as hemodynamic confounders.
UNASSIGNED: Among the 350 non-survivors, 117 had histopathologically severe HIE while 233 had no/mild HIE, without differences observed in the MAP (73.1 vs. 72.0 mmHg, pgroup = 0.639). Compared to the non-survivors, 211 patients with CPC 1 and 57 patients with CPC 4 had higher MAP values that showed significant, but clinically non-relevant, MAP differences (81.2 vs. 82.3 mmHg, pgroup < 0.001). The no/mild HIE non-survivors (n = 54), who regained consciousness before death, had higher MAP values compared to those with no/mild HIE (n = 179), who remained persistently comatose (74.7 vs. 69.3 mmHg, pgroup < 0.001). The no/mild HIE non-survivors, who regained consciousness, required fewer vasopressors (CVI 2.1 vs. 3.6, pgroup < 0.001). Independent of the severity of HIE, the survivors were weaned faster from vasopressors (CVI 1.0).
UNASSIGNED: Although a higher MAP was associated with survival in CA patients treated with a vasopressor-supported MAP target above 65 mmHg, the severity of HIE was not. Awakening from coma was associated with less vasopressor requirements. Our results provide no evidence for a MAP target above the current guideline recommendations that can decrease the severity of HIE.

UNASSIGNED: Early prediction of outcomes in comatose patients after out-of-hospital cardiac arrest is challenging. Prognostication tools include clinical examination, biomarkers, and neuroradiological and neurophysiological tests. We studied the association between transcranial Doppler (TCD) and the outcome.
UNASSIGNED: This was a pre-defined sub-study of the prospective observational Norwegian Cardiorespiratory Arrest Study. Patients underwent standardized post-resuscitation care, including target temperature management (TTM) to 33°C for 24 h. TCD was performed at days 1, 3, and 5-7. The primary endpoint was cerebral performance category (CPC) at 6 months, dichotomized into good (CPC 1-2) and poor (CPC 3-5) outcomes. We used linear mixed modeling time-series analysis.
UNASSIGNED: Of 139 TCD-examined patients, 81 (58%) had good outcomes. Peak systolic velocity in the middle cerebral artery (PSV) was low during TTM (Day 1) and elevated after rewarming (Day 3). Thereafter, it continued to rise in patients with poor, but normalized in patients with good, outcomes. At days 5-7, PSV was 1.0 m/s (95% CI 0.9; 1.0) in patients with good outcomes and 1.3 m/s (95% CI 1.1; 1.4) in patients with poor outcomes (p < 0.001).
UNASSIGNED: Elevated PSV at days 5-7 indicated poor outcomes. Our findings suggest that serial TCD examinations during the first week after cardiorespiratory arrest may improve our understanding of serious brain injury.

UNASSIGNED: Head computed tomography (CT) is used to predict neurological outcome after cardiac arrest (CA). The current reference standard includes quantitative image analysis by a neuroradiologist to determine the Gray-White-Matter Ratio (GWR) which is calculated via the manual measurement of radiodensity in different brain regions. Recently, automated analysis methods have been introduced. There is limited data on the Inter-rater agreement of both methods.
UNASSIGNED: Three blinded human raters (neuroradiologist, neurologist, student) with different levels of clinical experience retrospectively assessed the Gray-White-Matter Ratio (GWR) in head CTs of 95 CA patients. GWR was also quantified by a recently published computer algorithm that uses coregistration with standardized brain spaces to identify regions of interest (ROIs). We calculated intraclass correlation (ICC) for inter-rater agreement between human and computer raters as well as area under the curve (AUC) and sensitivity/specificity for poor outcome prognostication.
UNASSIGNED: Inter-rater agreement on GWR was very good (ICC 0.82-0.84) between all three human raters across different levels of expertise and between the computer algorithm and neuroradiologist (ICC 0.83; 95% CI 0.78-0.88). Despite high overall agreement, we observed considerable, clinically relevant deviations of GWR measurements (up to 0.24) in individual patients. In our cohort, at a GWR threshold of 1.10, this did not lead to any false poor neurological outcome prediction.
UNASSIGNED: Human and computer raters demonstrated high overall agreement in GWR determination in head CTs after CA. The clinically relevant deviations of GWR measurement in individual patients underscore the necessity of additional qualitative evaluation and integration of head CT findings into a multimodal approach to prognostication of neurological outcome after CA.

Loss of gray-white matter discrimination is the primary early imaging finding within of cranial computed tomography in cardiac arrest survivors, and this has been also regarded as a novel predictor for evaluating neurologic outcome. As displayed clearly on computed tomography and based on sensitivity to hypoxia, the gray-white matter ratio at basal ganglia (GWR-BG) region was frequently detected to assess the neurologic outcome by several studies. The specificity of GWR-BG is 72.4 to 100%, while the sensitivity is significantly different. Herein we review the mechanisms mediating cerebral edema following cardiac arrest, demonstrate the determination procedures with respect to GWR-BG, summarize the related researches regarding GWR-BG in predicting neurologic outcomes within cardiac arrest survivors, and discuss factors associated with predicting the accuracy of this methodology. Finally, we describe the effective measurements to increase the sensitivity of GWR-BG in predicting neurologic outcome.

We discuss the achievements of the ACNS critical care EEG nomenclature proposed in 2013 and, from a clinical angle, outline some limitations regarding translation into treatment implications. While the recently proposed updated 2021 version of the nomenclature will probable improve some uncertainty areas, a refined understanding of the mechanisms at the origin of the EEG patterns, and a multimodal integration of the nomenclature to the clinical context may help improving the rationale supporting therapeutic procedures. We illustrate these aspects on prognostication after cardiac arrest.

UNASSIGNED: Current guidelines recommend a 50 mm or greater compression depth for manual chest compression in adults. However, whether this uniform compression depth is a suitable requirement for mechanical CPR remains to be determined. We hypothesized that a relatively shallow compression depth (30 mm) would have similar hemodynamic efficacy but fewer complications versus the standard compression depth (50 mm) during mechanical cardiopulmonary resuscitation (CPR) with the miniaturized chest compressor (MCC) in a porcine model.
UNASSIGNED: In the current study, we used a total of 16 domestic male pigs (38±2 kg). All pigs were exposed to 7 min of ventricular fibrillation (VF) followed by 5 min of CPR. Then the animals were randomly assigned to the shallow (30 mm) group and the standard (50 mm) group. At the second min of CPR, every pig was given epinephrine (20 µg/kg) through the femoral vein and repeated every 3 min. First defibrillation was delivered with a single 120 J shock at 5 min of CPR. Hemodynamics, carotid blood flow (CBF), end-tidal carbon dioxide (ETCO2), coronary perfusion pressure (CPP), intrathoracic pressure (ITP) and arterial blood gas were measured. Rib fractures and lung injuries, as indicated by ground-glass opacification (GGO), as well as intense parenchymal opacification (IPO), were assessed and calculated by quantitative computed tomography (QCT) scan.
UNASSIGNED: We found no significant differences in CPP, CBF, or ETCO2 between the both groups throughout the CPR period. After administration of epinephrine, the CPP of all animals increased while ETCO2 and CBF decreased during CPR. A significantly lower intrathoracic positive pressure (ITPP) and systolic artery pressure (SAP) were measured in the shallow group at the first min of CPR. However, we didn\'t find remarkable differences in these values between the both groups for the next 4 min of CPR. All animals were successfully resuscitated. The shallow group had significantly lower IPO QCT scores compared with the standard group. We found no significant differences in GGO QCT scores after resuscitation between both groups.
UNASSIGNED: Relatively shallow compression depth has similar hemodynamic efficacy but fewer complications versus the standard compression depth.

UNASSIGNED: Cardiac arrest (CA), a common disease with a high mortality rate, is a leading cause of ischemia/reperfusion (I/R)-induced dysfunction of the intestinal barrier. Long non-coding RNAs (lncRNAs) play crucial roles in multiple pathological processes. However, the effect of the lncRNA maternally expressed 3 (MEG3) on intestinal I/R injury and the intestinal barrier has not been fully determined. Therefore, this study aimed to investigate the function of MEG3 in CA-induced intestinal barrier dysfunction.
UNASSIGNED: The oxygen and glucose deprivation (OGD) model in the human colorectal adenocarcinoma Caco-2 cells and in vivo cardiac arrest-induced intestinal barrier dysfunction model in Sprague-Dawley (SD) rats were established. The effect and underlying mechanism of MEG3 on the intestinal barrier from cardiac arrest-induced ischemia/reperfusion injury were analyzed by methyl thiazolyl tetrazolium (MTT) assays, Annexin V-FITC/PI apoptosis detection kit, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining, quantitative polymerase chain reaction (qPCR) assays, Western blot analysis, luciferase reporter gene assays, transepithelial electrical resistance (TEER) measurements, immunofluorescence analysis, and enzyme-linked immunosorbent assay (ELISA) assays.
UNASSIGNED: Interestingly, we found that MEG3 could protect Caco-2 cells from oxygen-glucose deprivation (OGD)/reoxygenation-induced I/R injury by modulating cell proliferation and apoptosis. Moreover, MEG3 relieved OGD-induced intestinal barrier dysfunction in vitro, as demonstrated by its significant rescue effect on transepithelial electrical resistance and the expression of tight junction proteins such as occludin and claudin-1 (CLDN1), which were impaired in OGD-treated Caco-2 cells. Mechanistically, MEG3 inhibited the expression of inflammatory factors including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon-gamma (IFN)-γ, inflammatory factors including interleukin (IL)-10, and transforming growth factor beta (TGFb)-1, as well as nuclear factor-kappa B (NF-κB) signaling. In response to OGD treatment in vitro, MEG3 also activated the expression of sirtuin 1 (SIRT1) by Caco-2 cells via sponging miR-34a-3p. Furthermore, MEG3 relieved CA-induced intestinal barrier dysfunction through NF-κB signaling in vivo.
UNASSIGNED: LncRNA MEG3 can protect the intestinal barrier from cardiac arrest-induced I/R injury via miR-34a-3p/SIRT1/NF-κB signaling. This finding provides new insight into the mechanism by which MEG3 restores intestinal barrier function following I/R injury, presenting it as a potential therapeutic candidate or strategy in intestinal injury.

UNASSIGNED: Dietary restriction (DR) is a well-known intervention that increases lifespan and resistance to multiple forms of acute stress, including ischemia reperfusion injury. However, the effect of DR on neurological injury after cardiac arrest (CA) remains unknown.
UNASSIGNED: The effect of short-term DR (one week of 70% reduced daily diet) on neurological injury was investigated in rats using an asphyxial CA model. The survival curve was obtained using Kaplan-Meier survival analysis. Serum S-100β levels were detected by enzyme linked immunosorbent assay. Cellular apoptosis and neuronal damage were assessed by terminal deoxyribonucleotide transferase dUTP nick end labeling assay and Nissl staining. The oxidative stress was evaluated by immunohistochemical staining of 8-hydroxy-2\'-deoxyguanosine (8-OHdG). Mitochondrial biogenesis was examined by electron microscopy and mitochondrial DNA copy number determination. The protein expression was detected by western blot. The reactive oxygen species (ROS) and metabolite levels were measured by corresponding test kits.
UNASSIGNED: Short-term DR significantly improved 3-day survival, neurologic deficit scores (NDS) and decreased serum S-100β levels after CA. Short-term DR also significantly attenuated cellular apoptosis, neuronal damage and oxidative stress in the brain after CA. In addition, short-term DR increased mitochondrial biogenesis as well as brain PGC-1α and SIRT1 protein expression after CA. Moreover, short-term DR increased adenosine triphosphate, β-hydroxybutyrate, acetyl-CoA levels and nicotinamide adenine dinucleotide (NAD+)/reduced form of NAD+ (NADH) ratios as well as decreased serum lactate levels.
UNASSIGNED: Reduction of oxidative stress, upregulation of mitochondrial biogenesis and increase of ketone body metabolism may play a crucial role in preserving neuronal function after CA under short-term DR.

Automated electrical defibrillator (AED) is critical in saving children who develop unexpected cardiac arrest (CA), but its diagnostic capacity is not fully acknowledged. Retrospective cohort study of patients with aborted sudden cardiac death (SCD) was performed. Twenty-five patients (14 males) aged 1.3 to 17.5 years who presented with CA survived with prompt cardiopulmonary resuscitation. Eighteen patients had no prior cardiac diagnosis. Cardiac arrest occurred in 10 patients with more than moderate exercise, in 7 with light exercise, and in 8 at rest (including one during sleep). Twenty-two patients were resuscitated with AED, all of which were recognized as a shockable cardiac rhythm. Thorough investigations revealed 6 ion channelopathies (4 catecholaminergic polymorphic ventricular tachycardia, one long QT syndrome, and one Brugada syndrome), 5 congenital heart disease (including 2 with coronary artery obstruction), 6 cardiomyopathies, 2 myocarditis, and 2 miscellaneous. Four patients had no identifiable heart disease. In 5 patients, the downloaded AED-recorded rhythm strip delineated the underlying arrhythmias and their responses to electrical shocks. Four patients who presented with generalized seizure at rest were initially managed for seizure disorder until AED recording identified lethal ventricular arrhythmias.Conclusions: AED reliably identifies the underlying lethal ventricular arrhythmias in addition to aborting SCD. What is Known: • Although infrequent in children, sudden cardiac death (SCD) is often an unexpected and tragic event. The etiology is diverse and sometimes remains unknown despite extensive investigations. • Automated external defibrillator (AED) is both therapeutic in aborting SCD and diagnostic in identifying the underlying lethal ventricular arrhythmias. However, the diagnostic aspect of AED is under-acknowledged by most medical providers. What is New: • Four of 25 patients (16%) were initially managed for possible seizure disorders until AED recording identified lethal ventricular arrhythmia. • The AED recording of the lethal arrhythmia during cardiopulmonary resuscitation (CPR) should always be obtained as it plays a crucial role in the decision-making process before ICD implantation. All medical providers should become familiar with downloading cardiac rhythm strips from AED when requested.