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Objective: We aimed to determine if machine learning can predict acute brain injury and to identify modifiable risk factors for acute brain injury in patients receiving venoarterial extracorporeal membrane oxygenation. Methods: We included adults (age ≥18 years) receiving venoarterial extracorporeal membrane oxygenation or extracorporeal cardiopulmonary resuscitation in the Extracorporeal Life Support Organization Registry (2009-2021). Our primary outcome was acute brain injury: central nervous system ischemia, intracranial hemorrhage, brain death, and seizures. We used Random Forest, CatBoost, LightGBM, and XGBoost machine learning algorithms (10-fold leave-1-out cross-validation) to predict and identify features most important for acute brain injury. We extracted 65 total features: demographics, pre-extracorporeal membrane oxygenation/on-extracorporeal membrane oxygenation laboratory values, and pre-extracorporeal membrane oxygenation/on-extracorporeal membrane oxygenation settings. Results: Of 35,855 patients receiving venoarterial extracorporeal membrane oxygenation (nonextracorporeal cardiopulmonary resuscitation) (median age of 57.8 years, 66% were male), 7.7% (n = 2769) experienced acute brain injury. In venoarterial extracorporeal membrane oxygenation (nonextracorporeal cardiopulmonary resuscitation), the area under the receiver operator characteristic curves to predict acute brain injury, central nervous system ischemia, and intracranial hemorrhage were 0.67, 0.67, and 0.62, respectively. The true-positive, true-negative, false-positive, false-negative, positive, and negative predictive values were 33%, 88%, 12%, 67%, 18%, and 94%, respectively, for acute brain injury. Longer extracorporeal membrane oxygenation duration, higher 24-hour extracorporeal membrane oxygenation pump flow, and higher on-extracorporeal membrane oxygenation partial pressure of oxygen were associated with acute brain injury. Of 10,775 patients receiving extracorporeal cardiopulmonary resuscitation (median age of 57.1 years, 68% were male), 16.5% (n = 1787) experienced acute brain injury. The area under the receiver operator characteristic curves for acute brain injury, central nervous system ischemia, and intracranial hemorrhage were 0.72, 0.73, and 0.69, respectively. Longer extracorporeal membrane oxygenation duration, older age, and higher 24-hour extracorporeal membrane oxygenation pump flow were associated with acute brain injury. Conclusions: In the largest study predicting neurological complications with machine learning in extracorporeal membrane oxygenation, longer extracorporeal membrane oxygenation duration and higher 24-hour pump flow were associated with acute brain injury in nonextracorporeal cardiopulmonary resuscitation and extracorporeal cardiopulmonary resuscitation venoarterial extracorporeal membrane oxygenation.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Abstract Background Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. Methods This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. Discussion In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. Trial registration ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

Abstract Background Extracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse. Methods Using the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders. Results Among 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28–1.99, p

ObjectivesThe study of autonomic responses to cardiac arrest (CA) resuscitation deserves attention due to the impact of autonomic function on survival and arousal. Orexins are known to modulate autonomic function, but the role of endogenous orexin in hyperacute recovery of autonomic function post-resuscitation is not well understood. We hypothesized that endogenous orexin facilitates hyperacute cardiovascular sympathetic activity post-resuscitation, and this response could be attenuated by suvorexant, a dual orexin receptor antagonist.MethodsA well-established 7-min asphyxial CA rat model was studied. Heart rate (HR) and blood pressure were monitored from baseline to 90-min post-resuscitation. Autonomic function was evaluated by spectral analysis of HR variability, whereby the ratio of low- and high-frequency components (LF/HF ratio) represents the balance between sympathetic/parasympathetic activities. Plasma orexin-A levels and orexin receptors immunoreactivity in the rostral ventrolateral medulla (RVLM), the key central region for regulating sympathetic output, were measured post-resuscitation. Neurological outcome was assessed via neurologic-deficit score at 4-h post-resuscitation.Key resultsA significant increase in HR was found over 25–40 min post-resuscitation (p

Objectives: Although many studies have addressed such disparities caused by COVID-19, to our knowledge, no study has focused on the association of race on outcomes for patients with COVID-19 requiring venovenous extracorporeal membrane oxygenation support. The goal of this study was to assess association of race on death and duration on venovenous extracorporeal membrane oxygenation in both the pre–COVID-19 and COVID-19 eras. Methods: We retrospectively reviewed the Extracorporeal Life Support Organization registry and included adults (≥18 years) who required venovenous extracorporeal membrane oxygenation between January 2019 and April 2021. We performed descriptive statistics and multivariable logistic regression. Our primary outcomes were death and extracorporeal membrane oxygenation duration. Results: A total of 7477 patients were included after excluding 340 patients (4.3%) who were missing race data. In the COVID-19 era, 1474 of 2777 COVID-19–positive patients (53.1%) died. Our regression model suggested somewhat of a protective effect on death for Black and multiple race patients. Additionally, a diagnosis of COVID-19 and patients in the COVID-19 era in general, irrespective of COVID-19 diagnosis, had higher odds of death. Hispanic patients had the longest average venovenous extracorporeal membrane oxygenation run times. Conclusions: Our study using data from the international Extracorporeal Life Support Organization Registry provides updated data on patients supported with venovenous extracorporeal membrane oxygenation in the pre–COVID-19 and COVID-19 eras between 2019 and 2021 with a focus on race. Patients in the COVID-19 era group also had higher mortality compared with those in the pre–COVID-19 era even after being adjusted for COVID-19 diagnosis. Black and multiple races appeared somewhat protective in terms of death. Hispanic race was associated with longer venovenous extracorporeal membrane oxygenation duration.

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Abstract Objective There is a complex interaction between nervous and cardiovascular systems, but sparse data exist on brain–heart electrophysiological responses to cardiac arrest resuscitation. Our aim was to investigate dynamic changes in autonomic and cortical function during hyperacute stage post‐resuscitation. Methods Ten rats were resuscitated from 7‐min cardiac arrest, as indicators of autonomic response, heart rate (HR), and its variability (HRV) were measured. HR was monitored through continuous electrocardiography, while HRV was assessed via spectral analysis, whereby the ratio of low−/high‐frequency (LF/HF) power indicates the balance between sympathetic/parasympathetic activities. Cortical response was evaluated by continuous electroencephalography and quantitative analysis. Parameters were quantified at 5‐min intervals over the first‐hour post‐resuscitation. Neurological outcome was assessed by Neurological Deficit Score (NDS, range 0–80, higher = better outcomes) at 4‐h post‐resuscitation. Results A significant increase in HR was noted over 15–30 min post‐resuscitation (p

Abstract Background Improving access to healthcare for ethnic minorities is a public health priority in many countries, yet little is known about how to incorporate information on race, ethnicity, and related social determinants of health into large international studies. Most studies of differences in treatments and outcomes of COVID-19 associated with race and ethnicity are from single cities or countries. Methods We present the breadth of race and ethnicity reported for patients in the COVID-19 Critical Care Consortium, an international observational cohort study from 380 sites across 32 countries. Patients from the United States, Australia, and South Africa were the focus of an analysis of treatments and in-hospital mortality stratified by race and ethnicity. Inclusion criteria were admission to intensive care for acute COVID-19 between January 14th, 2020, and February 15, 2022. Measurements included demographics, comorbidities, disease severity scores, treatments for organ failure, and in-hospital mortality. Results Seven thousand three hundred ninety-four adults met the inclusion criteria. There was a wide variety of race and ethnicity designations. In the US, American Indian or Alaska Natives frequently received dialysis and mechanical ventilation and had the highest mortality. In Australia, organ failure scores were highest for Aboriginal/First Nations persons. The South Africa cohort ethnicities were predominantly Black African (50%) and Coloured* (28%). All patients in the South Africa cohort required mechanical ventilation. Mortality was highest for South Africa (68%), lowest for Australia (15%), and 30% in the US. Conclusions Disease severity was higher for Indigenous ethnicity groups in the US and Australia than for other ethnicities. Race and ethnicity groups with longstanding healthcare disparities were found to have high acuity from COVID-19 and high mortality. Because there is no global system of race and ethnicity classification, researchers designing case report forms for international studies should consider including related information, such as socioeconomic status or migration background. *Note: “Coloured” is an official, contemporary government census category of South Africa and is a term of self-identification of race and ethnicity of many citizens of South Africa.

Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with refractory cardiorespiratory failure. Despite its benefits, ECMO carries a significant risk of neurological complications, including acute brain injury (ABI). Although standardized neuromonitoring and neurological care have been shown to improve early detection of ABI, the inability to perform neuroimaging in a timely manner is a major limitation in the accurate diagnosis of neurological complications. Therefore, blood-based biomarkers capable of detecting ongoing brain injury at the bedside are of great clinical significance. This review aims to provide a concise review of the current literature on plasma biomarkers for ABI in patients on ECMO support.

Abstract We aimed to investigate whether mitochondrial dysfunction in extracellular cerebrospinal fluid (CSF), which is associated with autophagy and mitophagy, might be involved in neurological outcomes in adult patients with hemorrhagic moyamoya disease (MMD) whose pathogenesis related to poor outcomes is not well-known. CSF samples were collected from 43 adult MMD patients and analyzed according to outcomes at 3 months. Fluorescence-activated cell sorter analysis (FACS) and the JC-1 red/green ratio were used to assess mitochondrial cells and intact mitochondrial membrane potential (MMP). We performed quantitative real-time polymerase chain reaction and Western blotting analyses of autophagy and mitophagy-related markers, including HIF1α, ATG5, pBECN1, BECN1, BAX, BNIP3L, DAPK1, and PINK1. Finally, FACS analysis with specific fluorescence-conjugated antibodies was performed to evaluate the potential cellular origin of CSF mitochondrial cells. Twenty-seven females (62.8%) with a mean age of 47.4 ± 9.7 years were included in the study. Among 43 patients with hemorrhagic MMD, 23 (53.5%) had poor outcomes. The difference in MMP was evident between the two groups (2.4 ± 0.2 in patients with poor outcome vs. 3.5 ± 0.4 in patients with good outcome; p = 0.02). A significantly higher expression (2–ΔCt) of HIF1α, ATG5, DAPK1 followed by BAX and BNIP3L mRNA and protein was also observed in poor-outcome patients compared to those with good outcomes. Higher percentage of vWF-positive mitochondria, suggesting endothelial cell origins, was observed in patients with good outcome compared with those with poor outcome (25.0 ± 1.4% in patients with good outcome vs. 17.5 ± 1.5% in those with poor outcome; p

Abstract A simple sidewall patterning process for organic–inorganic multilayer thin-film encapsulation (TFE) has been proposed and demonstrated. An Al2O3 thin film grown by atomic layer deposition (ALD) was patterned by adhesion lithography using the difference in interfacial adhesion strength. The difference in interfacial adhesion strength was provided by the vapor-deposited fluoro-octyl-trichloro-silane self-assembled monolayer (SAM) patterns formed by a shadow mask. The sidewall patterning of multilayer TFE was shown possible by repeating the adhesion lithography and the vapor deposition of organic polymer and SAM patterns using shadow masks. The proposed process has the advantage of being able to pattern the blanket ALD-grown Al2O3 thin films by adhesion lithography using a SAM pattern that can be more accurately predefined with a shadow mask.

Objective: To determine whether there is racial/ethnical discrepancy between pulse oximetry (SpO2) and oxygen saturation (SaO2) in patients receiving extracorporeal membrane oxygenation (ECMO). Methods: This was a retrospective observational study at a tertiary academic ECMO center with adults (>18 years) on venoarterial (VA) or venovenous (VV) ECMO. Datapoints were excluded if oxygen saturation ≤70% or SpO2–SaO2 pairs were not measured within 10 minutes. The primary outcome was the presence of a SpO2–SaO2 discrepancy between different races/ethnicities. Bland–Altman analyses and linear mixed-effects modeling, adjusting for prespecified covariates, were used to assess the SpO2–SaO2 discrepancy between races/ethnicities. Occult hypoxemia was defined as SaO2

Acute brain injury (ABI) and neuroinflammation is reported in COVID-19 and acute respiratory distress syndrome (ARDS). It remains unclear if COVID-19 plays an independent role in development of ABI compared to those with non-COVID-19 ARDS. We aimed to evaluate if COVID-19 ARDS is associated with higher risk and specific patterns of ABI compared to non-COVID-19 ARDS. We conducted an age and sex matched case-control autopsy study at a tertiary academic center. Ten patients with COVID-19 ARDS were matched to 20 non-COVID-19 ARDS patients. Baseline demographics were comparable between the two groups including severity of ARDS (p = 0.3). The frequency of overall ABI (70 vs. 60%), infratentorial ABI (40 vs. 25%), ischemic infarct (40 vs. 25%), intracranial hemorrhage (30 vs. 35%), and hypoxic-ischemic brain injury (30 vs. 35%) was similar between COVID-19 and non-COVID-19 ARDS patients, respectively (p > 0.05). Intracapillary megakaryocytes were exclusively seen in 30% of COVID-19 patients. Overall, frequency and pattern of ABI in COVID-19 ARDS was comparable to non-COVID-19.

Abstract Background Stroke patients requiring mechanical ventilation often have a poor prognosis. The optimal timing of tracheostomy and its impact on mortality in stroke patients remains uncertain. We performed a systematic review and meta-analysis of tracheostomy timing and its association with reported all-cause overall mortality. Secondary outcomes were the effect of tracheostomy timing on neurological outcome (modified Rankin Scale, mRS), hospital length of stay (LOS), and intensive care unit (ICU) LOS. Methods We searched 5 databases for entries related to acute stroke and tracheostomy from inception to 25 November 2022. We adhered to PRISMA guidance for reporting systematic reviews and meta-analyses. Selected studies included (1) ICU-admitted patients who had stroke (either acute ischaemic stroke, AIS or intracerebral haemorrhage, ICH) and received a tracheostomy (with known timing) during their stay and (2) > 20 tracheotomised. Studies primarily reporting sub-arachnoid haemorrhage (SAH) were excluded. Where this was not possible, adjusted meta-analysis and meta-regression with study-level moderators were performed. Tracheostomy timing was analysed continuously and categorically, where early ( 10 days) timing was defined per the protocol of SETPOINT2, the largest and most recent randomised controlled trial on tracheostomy timing in stroke patients. Results Thirteen studies involving 17,346 patients (mean age = 59.8 years, female 44%) met the inclusion criteria. ICH, AIS, and SAH comprised 83%, 12%, and 5% of known strokes, respectively. The mean time to tracheostomy was 9.7 days. Overall reported all-cause mortality (adjusted for follow-up) was 15.7%. One in five patients had good neurological outcome (mRS 0–3; median follow-up duration was 180 days). Overall, patients were ventilated for approximately 12 days and had an ICU LOS of 16 days and a hospital LOS of 28 days. A meta-regression analysis using tracheostomy time as a continuous variable showed no statistically significant association between tracheostomy timing and mortality (β = − 0.3, 95% CI = − 2.3 to 1.74, p = 0.8). Early tracheostomy conferred no mortality benefit when compared to late tracheostomy (7.8% vs. 16.4%, p = 0.7). Tracheostomy timing was not associated with secondary outcomes (good neurological outcome, ICU LOS and hospital LOS). Conclusions In this meta-analysis of over 17,000 critically ill stroke patients, the timing of tracheostomy was not associated with mortality, neurological outcomes, or ICU/hospital LOS. Trial registration: PROSPERO—CRD42022351732 registered on 17th of August 2022.

Early detection of acute brain injury (ABI) is critical to intensive care unit (ICU) patient management and intervention to decrease major complications. Head CT (HCT) is the standard of care for the assessment of ABI in ICU patients; however, it has limited sensitivity compared to MRI. We retrospectively compared the ability of ultra-low-field portable MR (ULF-pMR) and head HCT, acquired within 24 h of each other, to detect ABI in ICU patients supported on extracorporeal membrane oxygenation (ECMO). A total of 17 adult patients (median age 55 years; 47% male) were included in the analysis. Of the 17 patients assessed, ABI was not observed on either ULF-pMR or HCT in eight patients (47%). ABI was observed in the remaining nine patients with a total of 10 events (8 ischemic, 2 hemorrhagic). Of the eight ischemic events, ULF-pMR observed all eight, while HCT only observed four events. Regarding hemorrhagic stroke, ULF-pMR observed only one of them, while HCT observed both. ULF-pMR outperformed HCT for the detection of ABI, especially ischemic injury, and may offer diagnostic advantages for ICU patients. The lack of sensitivity to hemorrhage may improve with modification of the imaging acquisition program.

Background: Despite the high prevalence of neurological complications and mortality associated with extracorporeal cardiopulmonary resuscitation (ECPR), neurologically-focused animal models are scarce. Our objective is to review current ECPR models investigating neurological outcomes and identify key elements for a recommended model. Methods: We searched PubMed and four other engines for animal ECPR studies examining neurological outcomes. Inclusion criteria were: animals experiencing cardiac arrest, ECPR/ECMO interventions, comparisons of short versus long cardiac arrest times, and neurological outcomes. Results: Among 20 identified ECPR animal studies (n = 442), 13 pigs, 4 dogs, and 3 rats were used. Only 10% (2/20) included both sexes. Significant heterogeneity was observed in experimental protocols. 90% (18/20) employed peripheral VA-ECMO cannulation and 55% (11/20) were survival models (median survival = 168 hours; ECMO duration = 60 minutes). Ventricular fibrillation (18/20, 90%) was the most common method for inducing cardiac arrest with a median duration of 15 minutes (IQR = 6–20). In two studies, cardiac arrests exceeding 15 minutes led to considerable mortality and neurological impairment. Among seven studies utilizing neuromonitoring tools, only four employed multimodal devices to evaluate cerebral blood flow using Transcranial Doppler ultrasound and near-infrared spectroscopy, brain tissue oxygenation, and intracranial pressure. None examined cerebral autoregulation or neurovascular coupling. Conclusions: The substantial heterogeneity in ECPR preclinical model protocols leads to limited reproducibility and multiple challenges. The recommended model includes large animals with both sexes, standardized pre-operative protocols, a cardiac arrest time between 10–15 minutes, use of multimodal methods to evaluate neurological outcomes, and the ability to survive animals after conducting experiments.

Abstract A rational regulation of the solar water splitting reaction pathway by adjusting the surface composition and phase structure of catalysts is a substantial approach to ameliorate the sluggish reaction kinetics and improve the energy conversion efficiency. In this study, we demonstrate a nanocrystalline iron pyrophosphate (Fe4(P2O7)3, FePy)-regulated hybrid overlayer with amorphous iron phosphate (FePO4, FePi) on the surface of metal oxide nanostructure with boosted photoelectrochemical (PEC) water oxidation. By manipulating the facile electrochemical surface treatment followed by the phosphating process, nanocrystalline FePy is localized in the FePi amorphous overlayer to form a heterogeneous hybrid structure. The FePy-regulated hybrid overlayer (FePy@FePi) results in significantly enhanced PEC performance with long-term durability. Compared with the homogeneous FePi amorphous overlayer, FePy@FePi can improve the charge transfer efficiency more significantly, from 60% of FePi to 79% of FePy@FePi. Our density-functional theory calculations reveal that the coexistence of FePi and FePy phases on the surface of metal oxide results in much better oxygen evolution reaction kinetics, where the FePi was found to have a typical down-hill reaction for the conversion from OH* to O2, while FePy has a low free energy for the formation of OH*. Graphical abstract

BackgroundVeno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used in patients with COVID-19 acute respiratory distress syndrome (ARDS). We aim to assess the characteristics of delirium and describe its association with sedation and in-hospital mortality.MethodsWe retrospectively reviewed adult patients on VV-ECMO for severe COVID-19 ARDS in the Johns Hopkins Hospital ECMO registry in 2020–2021. Delirium was assessed by the Confusion Assessment Method for the ICU (CAM-ICU) when patients scored−3 or above on the Richmond Agitation-Sedation Scale (RASS). Primary outcomes were delirium prevalence and duration in the proportion of days on VV-ECMO.ResultsOf 47 patients (median age = 51), 6 were in a persistent coma and 40 of the remaining 41 patients (98%) had ICU delirium. Delirium in the survivors (n = 21) and non-survivors (n = 26) was first detected at a similar time point (VV-ECMO day 9.5(5,14) vs. 8.5(5,21), p = 0.56) with similar total delirium days on VV-ECMO (9.5[3.3, 16.8] vs. 9.0[4.3, 28.3] days, p = 0.43). Non-survivors had numerically lower RASS scores on VV-ECMO days (−3.72[−4.42, −2.96] vs. −3.10[−3.91, −2.21], p = 0.06) and significantly prolonged delirium-unassessable days on VV-ECMO with a RASS of −4/−5 (23.0[16.3, 38.3] vs. 17.0(6,23), p = 0.03), and total VV-ECMO days (44.5[20.5, 74.3] vs. 27.0[21, 38], p = 0.04). The proportion of delirium-present days correlated with RASS (r = 0.64, p < 0.001), the proportions of days on VV-ECMO with a neuromuscular blocker (r = −0.59, p = 0.001), and with delirium-unassessable exams (r = −0.69, p < 0.001) but not with overall ECMO duration (r = 0.01, p = 0.96). The average daily dosage of delirium-related medications on ECMO days did not differ significantly. On an exploratory multivariable logistic regression, the proportion of delirium days was not associated with mortality.ConclusionLonger duration of delirium was associated with lighter sedation and shorter paralysis, but it did not discern in-hospital mortality. Future studies should evaluate analgosedation and paralytic strategies to optimize delirium, sedation level, and outcomes.

Post-acute COVID-19 syndrome (PCS) is highly prevalent. Critically ill patients requiring intensive care unit (ICU) admission are at a higher risk of developing PCS. The mechanisms underlying PCS are still under investigation and may involve microvascular damage in the brain. Cerebral misery perfusion, characterized by reduced cerebral blood flow (CBF) and elevated oxygen extraction fraction (OEF) in affected brain areas, has been demonstrated in cerebrovascular diseases such as carotid occlusion and stroke. This pilot study aimed to examine whether COVID-19 ICU survivors exhibited regional misery perfusion, indicating cerebral microvascular damage. In total, 7 COVID-19 ICU survivors (4 female, 20–77 years old) and 19 age- and sex-matched healthy controls (12 female, 22–77 years old) were studied. The average interval between ICU admission and the MRI scan was 118.6 ± 30.3 days. The regional OEF was measured using a recently developed technique, accelerated T2-relaxation-under-phase-contrast MRI, while the regional CBF was assessed using pseudo-continuous arterial spin labeling. COVID-19 ICU survivors exhibited elevated OEF (β = 5.21 ± 2.48%, p = 0.047) and reduced relative CBF (β = −0.083 ± 0.025, p = 0.003) in the frontal lobe compared to healthy controls. In conclusion, misery perfusion was observed in the frontal lobe of COVID-19 ICU survivors, suggesting microvascular damage in this critical brain area for high-level cognitive functions that are known to manifest deficits in PCS. Physiological biomarkers such as OEF and CBF may provide new tools to improve the understanding and treatment of PCS.

Background In this study, we aimed to investigate the prevalence, timing, risk factors, and outcomes of acute respiratory distress syndrome (ARDS) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods PubMed and four other databases were searched for randomized controlled trials (RCTs) and observational studies of patients 18 years or older through October 20, 2021. Study quality was assessed, using the Cochrane Risk of Bias tool for RCTs and the Newcastle-Ottawa scale for cohort and case-control studies. High-grade aSAH was defined as a Hunt-Hess grade ≥3 and/or a modified Fisher score ≥3. A good neurological outcome was defined as a Glasgow outcome scale score ≥4. Random-effects meta-analyses were conducted to estimate the pooled outcome prevalence and 95% confidence interval (CI). Results Eleven observational studies (n=6,107) met the inclusion criteria. Overall, 15% of the patients (95% CI, 10.5–20.0; I2=97.8%) developed ARDS after aSAH, with a mean time of 3 days (95% CI, 1.9–3.7; I2=54%). Overall survival at discharge was 80% (95% CI, 75–86; I2=96%), and 67% of aSAH patients (95% CI, 54.9–78.9; I2=94%) had a good neurological outcome at any time. The aSAH cohort without ARDS had a higher rate of survival than those with ARDS (79% vs. 49%, P=0.028). Male sex, patients with a high-grade aSAH, patients who developed pneumonia, and systemic inflammatory response syndrome during hospital admission were at a higher risk of developing ARDS. Conclusion In this meta-analysis, approximately one in six patients developed ARDS after aSAH, with a mean time of 3 days from the initial presentation, and ARDS was associated with increased mortality.

Abstract Background To assess the safety and feasibility of imaging of the brain with a point-of-care (POC) magnetic resonance imaging (MRI) system in patients on extracorporeal membrane oxygenation (ECMO). Early detection of acute brain injury (ABI) is critical in improving survival for patients with ECMO support. Methods Patients from a single tertiary academic ECMO center who underwent head CT (HCT), followed by POC brain MRI examinations within 24 h following HCT while on ECMO. Primary outcomes were safety and feasibility, defined as completion of MRI examination without serious adverse events (SAEs). Secondary outcome was the quality of MR images in assessing ABIs. Results We report 3 consecutive adult patients (median age 47 years; 67% male) with veno-arterial (n = 1) and veno-venous ECMO (n = 2) (VA- and VV-ECMO) support. All patients were imaged successfully without SAEs. Times to complete POC brain MRI examinations were 34, 40, and 43 min. Two patients had ECMO suction events, resolved with fluid and repositioning. Two patients were found to have an unsuspected acute stroke, well visualized with MRI. Conclusions Adult patients with VA- or VV-ECMO support can be safely imaged with low-field POC brain MRI in the intensive care unit, allowing for the assessment of presence and timing of ABI.

Background: Despite the high vaccination coverage rate, in-hospital transmission of measles continues to occur in South Korea. We present a measles outbreak in which two healthcare workers (HCWs) with presumptive evidence of measles immunity were infected by a patient with typical measles at a single hospital in South Korea. This facilitated the evaluation of measles seroprevalence in all HCWs. Methods: In 2018, suspected patients and contacts exposed during a measles outbreak were investigated based on their medical histories and vaccination status. Cases were confirmed by the detection of measles-specific immunoglobulin M or RNA. After the measles outbreak in 2018, measles IgG testing was conducted on a total of 972 HCWs for point-prevalence, including those exposed to the measles. In addition, we have routinely performed measles IgG tests on newly employed HCWs within one week of their hire date since 2019. The measles vaccine was administered to HCWs who tested negative or equivocally negative for IgG antibodies. Results: An index patient who returned from China with fever and rash was diagnosed with measles at a hospital in Korea. Two additional HCWs were revealed as measles cases: one was vaccinated with the two-dose measles–mumps–rubella (MMR) vaccine, and the other, who was born in 1967, was presumed to have immunity from natural infection in South Korea. All three patients harbored the same D8 genotype. No additional measles cases were identified among the 964 contacts of secondary patients. A total of 2310 HCWs, including those tested during the 2018 outbreak, underwent measles IgG tests. The average age at the time of the test was 32.6 years, and 74.3% were female. The overall seropositivity of measles was 88.9% (95% confidence interval, 87.5–90.1). Although the birth cohorts between 1985 and 1994 were presumed to have received the measles–rubella (MR) catch-up vaccination in 2001, 175 (89.3%) HCWs were born after 1985 among the 195 seronegative cases. Conclusion: Despite high population immunity, imported measles transmission occurred among HCWs with presumed immunity. This report underscores the importance of understanding the prevalence of measles susceptibility among newly employed HCWs. This is important for policymaking regarding hospital-wide vaccinations to prevent the spread of vaccine-preventable diseases.

The addition of extracorporeal membrane oxygenation (ECMO) to conventional cardiopulmonary resuscitation (CPR), termed extracorporeal cardiopulmonary resuscitation (ECPR), has significantly improved survival in selected patient populations. Despite this advancement, significant neurological impairment persists in approximately half of survivors. ECPR represents a potential advancement for patients who experience refractory cardiac arrest (CA) due to a reversible etiology and do not regain spontaneous circulation. Important risk factors for acute brain injury (ABI) in ECPR include lack of perfusion, reperfusion, and altered cerebral autoregulation. The initial hypoxic-ischemic injury caused by no-flow and low-flow states after CA and during CPR is compounded by reperfusion, hyperoxia during ECMO support, and nonpulsatile blood flow. Additionally, ECPR patients are at risk for Harlequin syndrome with peripheral cannulation, which can lead to preferential perfusion of cerebral vessels with deoxygenated blood. Lastly, the oxygenator membrane is prothrombotic and requires systemic anticoagulation. The two competing phenomena result in thrombus formation, hemolysis, and thrombocytopenia, increasing the risk of ischemic and hemorrhagic ABI. In addition to clinical studies, we assessed available ECPR animal models to identify the mechanisms underlying ABI at the cellular level. Standardized multimodal neurological monitoring may facilitate early detection of and intervention for ABI. With the increasing use of ECPR, it is critical to understand the pathophysiology of ABI, its prevention, and the management strategies for improving the outcomes of ECPR. Translational and clinical research focusing on acute ABI immediately after ECMO cannulation and its short- and long-term neurological outcomes are warranted.

Abstract Objective Although COVID-19 is a respiratory disease, all organs can be affected including the brain. To date, specific investigations of brain injury markers (BIM) and endothelial injury markers (EIM) have been limited. Additionally, a male bias in disease severity and mortality after COVID-19 is evident globally. Sex differences in the immune response to COVID-19 may mediate this disparity. We investigated BIM, EIM and inflammatory cytokine/chemokine (CC) levels after COVID-19 and in across sexes. Methods Plasma samples from 57 subjects at

Acute respiratory distress syndrome (ARDS) is commonly seen in patients with acute brain injury (ABI), with prevalence being as high as 35%. These patients often have additional risk factors for ARDS compared to general critical care patients. Lung injury in ABI occurs secondary to catecholamine surge and neuro-inflammatory processes. ARDS patients benefit from lung protective ventilation using low tidal volumes, permissive hypercapnia, high PEEP, and lower PO2 goals. These strategies can often be detrimental in ABI given the risk of brain hypoxia and elevation of intracranial pressure (ICP). While lung protective ventilation is not contraindicated in ABI, special consideration is warranted to make sure it does not interfere with neurological recovery. Permissive hypercapnia with low lung volumes can be utilized in patients without any ICP issues but those with ICP elevations can benefit from continuous ICP monitoring to personalize PCO2 goals. Hypoxia leads to poor outcomes in ABI, hence the ARDSnet protocol of lower PO2 target (55–80 mmHg) might not be the best practice in patients with concomitant ARDS and ABI. High-normal PO2 levels are reasonable in target in severe ABI with ARDS. Studies have shown that PEEP up to 12 mmHg does not cause significant elevations in ICP and is safe to use in ABI though mean arterial pressure, respiratory system compliance, and cerebral perfusion pressure should be closely monitored. Given most trials investigating therapeutics in ARDS have excluded ABI patients, focused research is needed in the field to advance the care of these patients using evidence-based medicine.

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors, such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and ischemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients in order to prevent and minimize the morbidity of HIBI. Further studies aimed at standardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.

OBJECTIVES:. The objectives of this study were to 1) in patients without pulmonary function, determine resting energy expenditure (REE) in venovenous extracorporeal membrane oxygenation (ECMO) acute respiratory distress syndrome (ARDS) patients by paralysis status and 2) determine the threshold tidal volume (TV) associated with meaningful gas exchange as determined by measurable end-tidal carbon dioxide elimination (etV̇co2). DESIGN:. Retrospective observational study. SETTING:. A tertiary high ECMO volume academic institution. PATIENTS/SUBJECTS:. Ten adult ARDS patients on venovenous ECMO. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The modified Weir equation, Fick principle, Henderson-Hasselbalch equation, ECMO flow, hemoglobin, and pre and post oxygenator blood gases were used to determine ECMO carbon dioxide production (V̇co2), ECMO oxygen consumption, and REE. REE values were matched to patients’ paralysis status based on medication flowsheets and compared using a paired t test. Linear regression was performed to determine the threshold TV normalized to ideal body weight (IBW) associated with measurable ventilator etV̇co2, above which meaningful ventilation occurs. When lungs were not functioning, patients had significantly lower mean REE when paralyzed (23.4 ± 2.8 kcal/kg/d) than when not paralyzed (29.2 ± 5.8 kcal/kg/d) (p = 0.02). Furthermore, mean REE was not similar between patients and varied as much as 1.7 times between patients when paralyzed and as much as 1.4 times when not paralyzed. Linear regression showed that ventilator V̇co2 was measurable and increased linearly when TV was greater than or equal to 0.7 mL/kg. CONCLUSIONS:. REE is patient-specific and varies significantly with and without patient paralysis. When TV exceeds 0.7 mL/kg IBW, ventilator V̇co2 increases measurably and must be considered in determining total REE.

IntroductionNeurological manifestations and complications in coronavirus disease-2019 (COVID-19) patients are frequent. Prior studies suggested a possible association between neurological complications and fatal outcome, as well as the existence of potential modifiable risk factors associated to their occurrence. Therefore, more information is needed regarding the incidence and type of neurological complications, risk factors, and associated outcomes in COVID-19.MethodsThis is a pre-planned secondary analysis of the international multicenter observational study of the COVID-19 Critical Care Consortium (which collected data both retrospectively and prospectively from the beginning of COVID-19 pandemic) with the aim to describe neurological complications in critically ill COVID-19 patients and to assess the associated risk factors, and outcomes. Adult patients with confirmed COVID-19, admitted to Intensive Care Unit (ICU) will be considered for this analysis. Data collected in the COVID-19 Critical Care Consortium study includes patients' pre-admission characteristics, comorbidities, severity status, and type and severity of neurological complications. In-hospital mortality and neurological outcome were collected at discharge from ICU, and at 28-days.Ethics and DisseminationThe COVID-19 Critical Care Consortium main study and its amendments have been approved by the Regional Ethics Committee of participating sites. No further approval is required for this secondary analysis.Trial Registration NumberACTRN12620000421932.

The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed “long COVID” or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, “brain fog”, headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood–brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.

Abstract Background Persistent apnea despite an adequate rise in arterial pressure of CO2 is an essential component of the criteria for brain death (BD) determination. Current guidelines vary regarding the utility of arterial pH changes during the apnea test (AT). We aimed to study the effect of incorporating an arterial pH target < 7.30 during the AT (in addition to the existing PaCO2 threshold) on brain death declarations. Methods We performed retrospective analysis of consecutive adult patients who were diagnosed with BD and underwent AT at the Cleveland Clinic over the last 10 years. Data regarding baseline and post-AT blood gas analyses were collected and analyzed. Results Ninety-eight patients underwent AT in the study period, which was positive in 89 (91%) and inconclusive in 9 (9%) patients. The mean age was 50 years old (standard deviation [SD] 16) and 54 (55%) were female. The most common etiology BD was hypoxic ischemic brain injury (HIBI) due to cardiac arrest (42%). Compared to those with positive AT, patients with inconclusive AT had a higher post-AT pH (7.24 vs 7.17, p = 0.01), lower PaO2 (47 vs 145, p < 0.01), and a lower PaCO2 (55 vs 73, p = 0.01). Among patients with a positive AT using PaCO2 threshold alone, the frequency of patients with post-AT pH < 7.30 was 95% (83/87). Conclusion Implementing a BD criteria requiring both arterial pH and PaCO2 thresholds reduced the total number of positive ATs; these inconclusive cases would have required longer duration of AT to reach both targets, repeated ATs, or ancillary studies to confirm BD. The impact of this on the overall number BD declarations requires further research.

IntroductionNeurological complications are frequent in patients with coronavirus disease-2019 (COVID-19). The use of non-invasive neuromonitoring in subjects without primary brain injury but with potential neurological derangement is gaining attention outside the intensive care unit (ICU). This systematic review and meta-analysis investigates the use of non-invasive multimodal neuromonitoring of the brain in non-critically ill patients with COVID-19 outside the ICU and quantifies the prevalence of abnormal neuromonitoring findings in this population.MethodsA structured literature search was performed in MEDLINE/PubMed, Scopus, Cochrane, and EMBASE to investigate the use of non-invasive neuromonitoring tools, including transcranial doppler (TCD); optic nerve sheath diameter (ONSD); near-infrared spectroscopy (NIRS); pupillometry; and electroencephalography (EEG) inpatients with COVID-19 outside the ICU. The proportion of non-ICU patients with CVOID-19 and a particular neurological feature at neuromonitoring at the study time was defined as prevalence.ResultsA total of 6,593 records were identified through literature searching. Twenty-one studies were finally selected, comprising 368 non-ICU patients, of whom 97 were considered for the prevalence of meta-analysis. The pooled prevalence of electroencephalographic seizures, periodic and rhythmic patterns, slow background abnormalities, and abnormal background on EEG was.17 (95% CI 0.04–0.29), 0.42 (95% CI 0.01–0.82), 0.92 (95% CI 0.83–1.01), and.95 (95% CI 0.088–1.09), respectively. No studies investigating NIRS and ONSD outside the ICU were found. The pooled prevalence for abnormal neuromonitoring findings detected using the TCD and pupillometry were incomputable due to insufficient data.ConclusionsNeuromonitoring tools are non-invasive, less expensive, safe, and bedside available tools with a great potential for both diagnosis and monitoring of patients with COVID-19 at risk of brain derangements. However, extensive literature searching reveals that they are rarely used outside critical care settings.Systematic Review Registration:www.crd.york.ac.uk/prospero/display_record.php?RecordID=265617, identifier: CRD42021265617.

Since the 1960s, EEG has been used to assess the neurologic function of patients in the hours and days after cardiac arrest. Accurate and reliable prognostication after cardiac arrest is vital for tailoring aggressive patient care for those with a high likelihood of recovery and setting appropriate goals of care for those who have a high likelihood of a poor outcome. Attempts to define EEG’s role in this process has evolved over the years.In this review, we provide important historical context about EEG’s use, it’s perceived unreliability in the post-cardiac arrest patient in the past and provide a detailed analysis of how this role has changed recently. A review of the 71 most recent and highest quality studies demonstrates that the introduction of a uniform classification and a timed approach to EEG analysis have positioned EEG as a complementary tool in the multimodal approach for prognostication.The review was created and intended for medical staff in the intensive care units and emphasizes EEG patterns and timing which portend both favorable and poor prognoses. Also, the review addresses the overall quality of the existing studies and discusses future directions to address the knowledge gaps in this field.

Objectives Demand for hand sanitizers has surged since the coronavirus broke out and spread around the world. Hand sanitizers are usually applied by squirting the sanitizer liquid when one presses a pump with one’s hand. This causes many people to come into contact with the pump handle, which increases the risk of viral transmission. Some hand sanitizers on the market are automatically pumped. However, because sanitizer containers and pump devices are designed to be compatible only between products produced by the same manufacturer, consumers must also repurchase the container for the liquid if they replace the hand sanitizer. Therefore, this paper suggests the design of an automatic hand sanitizer system compatible with various sanitizer containers. Methods An automatic hand sanitizer system was designed, which will be presented in two stages describing the instrument structure and control parts. This work focused on using the elasticity of pumps and improving people’s access to devices. Results We have designed an automatic hand sanitizer system that is compatible with various containers. When one moves one’s hand close to the device sensor, the hand sanitizer container is pumped once. Conclusions The automatic hand sanitizer device proposed in this paper is ultimately expected to contribute to contactless hand disinfection in public places and virus infection prevention. Additionally, it is economical and eco-friendly by decreasing waste emissions.

Abstract Background Posterior lumbar fusion is a widely accepted surgical technique; however, it has been related to the possibility of paraspinal muscle atrophy after surgery. We investigated 1-year postoperative changes in paraspinal muscle volume using a simple formula applicable to magnetic resonance imaging (MRI) or computed tomography (CT) images. Methods Patients with degenerative lumbar spinal stenosis who underwent posterior interbody fusion (PLIF) at the L4/5 level in the period from May 2010 to June 2017 were enrolled in this study. Radiologic parameters were measured using MRI or CT images which were taken before surgery and at 1 year after surgery. The volume of the paraspinal muscles was calculated using a simple formula which was derived from the formula for calculating the volume of truncated elliptic cones. Results A total of 40 patients were included; 24 were analyzed using MRI and 16 were analyzed using CT. The mean age of the patients was 59.6 ± 12.1 years and 32 (80.5%) were female. When comparing the preoperative and 1-year-postoperative images, multifidus muscle (MF) reduction was consistently observed in the MRI and CT groups, right and left (p = 0.003, p

This paper proposes an adaptive protection method using sensitivity analysis that examines the effect of changed network topologies (CNTs) on the operation time of protective devices (PDs) for a base network topology (BNT) in a distribution network. In this study, BNT refers to the topological structure of the distribution network maintained over the long-term, whereas CNT is the changed structure maintained for a relatively short term for field workings, fault restoration, or real-time reconfiguration. The main purpose is to consider the PD's operating speed and the number of controls for changing the settings and to calculate the optimal setting values for two terms while including the CNT in the BNT over a long duration. For this purpose, we used two approaches: First, a sensitivity index, defined as the increase in the operation time of the PD for the BNT when each CNT is included in the BNT, is used to determine the CNT's inclusion priority. Second, an objective function (OF) is used to evaluate the maximum acceptable number of CNTs based on the priorities derived from the sensitivity analysis. This OF aims to minimize the weighted sum of the average operation time and the number of setting changes for the PDs. Case studies on the test systems were conducted, and the effectiveness of the proposed method was verified by comparing it with existing adaptive protection methods.

Advanced collision-based single trace attacks which can be applied on simple power analysis resistant scalar multiplications become virtual threat on elliptic curve cryptosystems recently as their practical experimental results are increasingly reported in the literature. Since such attacks are based on detecting collisions of data dependent leakage caused by underlying long integer multiplications, so-called global shuffling countermeasure which breaks such collision correlation by independently randomizing the execution order of unit operations such as single precision multiplication and carry propagation, is considered as promising countermeasure if theoretical randomness of shuffling order is guaranteed. In this paper, we firstly analyze the practical security of the global shuffling long integer multiplications by exhibiting a combined single trace attack on software implementations on an ARM Cortex-M4 microcontroller. Our combined attack consists of a simple power analysis for revealing random permutation vectors which enables later collision-based single trace attack. First we demonstrate how to reveal random permutation vectors for carry propagation process of whole global shuffling long integer multiplications within a single power trace by simple power analysis accompanied with straightforward substitution of power consumption samples. Then we perform collision-based single trace attacks after rearranging the order of subtraces for unit carry propagations based on revealed permutation vectors. Since the vulnerability to simple power analysis is originated from the if-statement for selection of proper entries of the permutation vectors, we propose a novel countermeasure which eliminates such selection with simple addition and modulus operation and also demonstrate practical result achieving regularity in power trace patterns.

We propose an algorithm to set the parameters of volt-var curves to improve the performance of distributed generation. Specifically, we optimally set the volt-var curves of the smart inverter for proper control of the distributed generation output. To improve the overall distribution system performance, we consider the minimization of voltage deviation, system loss, and peak of reactive power in an objective function, thereby providing optimal volt-var curve parameters. The proposed algorithm overcomes various limitations of existing studies. First, we use distribution system factors in a multiobjective optimization function to adjust volt-var curve parameters that deviate from the default settings. Second, we consider the service transformers that affect the system voltage according to the photovoltaic generation output in the test model during optimization. Third, we analyze the system improvement according to the number of parameters to be optimized. Fourth, we analyze the implementation of the optimized volt-var curve according to the practical periods when the smart inverter settings can be updated. Fifth, we evaluate different suitable volt-var curves for multiple photovoltaic generators grouped using clustering. Using the proposed algorithm, the distribution system operator can set the optimal volt-var curve according to the system conditions and requirements. We conducted simulations of the proposed method using OpenDSS, a quasistatic time-series simulation, on a test model reflecting the characteristics of a South Korean distribution system. The simulation results confirm that the overall system performance increases when the optimal volt-var curve settings obtained from the proposed algorithm are used.

Abstract Light‐based therapy such as photobiomodulation (PBM) reportedly produces beneficial physiological effects in cells and tissues. However, most reports have focused on the immediate and instant effects of light. Considering the physiological effects of natural light exposure in living organisms, the latent reaction period after irradiation should be deliberated. In contrast to previous reports, we examined the latent reaction period after light exposure with optimized irradiating parameters and validated novel therapeutic molecular mechanisms for the first time. we demonstrated an organic light‐emitting diode (OLED)‐based PBM (OPBM) strategy that enhances the angiogenic efficacy of human adipose‐derived stem cells (hADSCs) via direct irradiation with red OLEDs of optimized wavelength, voltage, current, luminance, and duration, and investigated the underlying molecular mechanisms. Our results revealed that the angiogenic paracrine effect, viability, and adhesion of hADSCs were significantly intensified by our OPBM strategy. Following OPBM treatment, significant changes were observed in HIF‐1α expression, intracellular reactive oxygen species levels, activation of the receptor tyrosine kinase, and glycolytic pathways in hADSCs. In addition, transplantation of OLED‐irradiated hADSCs resulted in significantly enhanced limb salvage ratio in a mouse model of hindlimb ischemia. Our OPBM might serve as a new paradigm for stem cell culture systems to develop cell‐based therapies in the future.

In recent years, reports of diabetes mellitus (DM) cases that do not fit the traditional classification system have increased in prevalence. While insulin deficiency appears as type 1 DM (T1DM), the new type also has the clinical features of type 2 DM (T2DM); as such, this new type of DM is called ketosis-prone diabetes (KPD) and is correlated with findings of severe hyperglycemia and ketoacidosis. To provide a clear, clinical classification of DM, new classification systems are being studied. Among these, the Aβ system demonstrates the highest sensitivity and specificity in predicting clinical features and prognosis. We report 2 cases of KPD in Korean pediatric patients. The first patient was referred while in a state of diabetic ketoacidosis (DKA) and was considered to have T1DM. However, their blood glucose was well-controlled even with small doses of insulin, and the treatment was able to be changed to metformin therapy. The second patient seemed to be a typical case of T2DM because of his obesity and strong family history. However, blood glucose was not well-controlled with a regular diet, and ketosis occurred. After performing a glucagon stimulation test, both patients showed different clinical features that were finally diagnosed as type A-β+ KPD. The rapid and accurate diagnosis of KPD can reduce the duration of inappropriate insulin use and improve patients' quality of life. Further, the treatment of KPD children should be individualized according to each patient’s lifestyle to preventing recurrent DKA.

Comprehensive research has led to significant preclinical outcomes in modified human adipose-derived mesenchymal stem cells (hADSCs). Photobiomodulation (PBM), a technique to enhance the cellular capacity of stem cells, has attracted considerable attention owing to its effectiveness and safety. Here, we suggest a red organic light-emitting diode (OLED)-based PBM strategy to augment the therapeutic efficacy of hADSCs. In vitro assessments revealed that hADSCs basked in red OLED light exhibited enhanced angiogenesis, cell adhesion, and migration compared to naïve hADSCs. We demonstrated that the enhancement of cellular capacity was due to an increased level of intracellular reactive oxygen species. Furthermore, accelerated healing and regulated inflammatory response was observed in mice transplanted with red light-basked hADSCs. Overall, our findings suggest that OLED-based PBM may be an easily accessible and attractive approach for tissue regeneration that can be applied to various clinical stem cell therapies.

COVID-19 is an ongoing pandemic with a devastating impact on public health. Acute neurological symptoms have been reported after a COVID-19 diagnosis, however, the long-term neurological symptoms including pain is not well established. Using a prospective registry of hospitalized COVID-19 patients, we assessed pain and neurological function (including functional, cognitive and psychiatric assessments) of several hospitalized patients at 3 months. Our main finding is that 60% of the patients report pain symptoms. 71% of the patients still experienced neurological symptoms at 3 months and the most common symptoms being fatigue (42%) and PTSD (25%). Cognitive symptoms were found in 12%. Our preliminary findings suggests the importance of investigating long-term outcomes and rationalizes the need for further studies investigating the neurologic outcomes and symptoms of pain after COVID-19.

IMPORTANCE:. Factors associated with mortality in coronavirus disease 2019 patients on invasive mechanical ventilation are still not fully elucidated. OBJECTIVES:. To identify patient-level parameters, readily available at the bedside, associated with the risk of in-hospital mortality within 28 days from commencement of invasive mechanical ventilation or coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS:. Prospective observational cohort study by the global Coronavirus Disease 2019 Critical Care Consortium. Patients with laboratory-confirmed coronavirus disease 2019 requiring invasive mechanical ventilation from February 2, 2020, to May 15, 2021. MAIN OUTCOMES AND MEASURES:. Patient characteristics and clinical data were assessed upon ICU admission, the commencement of invasive mechanical ventilation and for 28 days thereafter. We primarily aimed to identify time-independent and time-dependent risk factors for 28-day invasive mechanical ventilation mortality. RESULTS:. One-thousand five-hundred eighty-seven patients were included in the survival analysis; 588 patients died in hospital within 28 days of commencing invasive mechanical ventilation (37%). Cox-regression analysis identified associations between the hazard of 28-day invasive mechanical ventilation mortality with age (hazard ratio, 1.26 per 10-yr increase in age; 95% CI, 1.16–1.37; p < 0.001), positive end-expiratory pressure upon commencement of invasive mechanical ventilation (hazard ratio, 0.81 per 5 cm H2O increase; 95% CI, 0.67–0.97; p = 0.02). Time-dependent parameters associated with 28-day invasive mechanical ventilation mortality were serum creatinine (hazard ratio, 1.28 per doubling; 95% CI, 1.15–1.41; p < 0.001), lactate (hazard ratio, 1.22 per doubling; 95% CI, 1.11–1.34; p < 0.001), Paco2 (hazard ratio, 1.63 per doubling; 95% CI, 1.19–2.25; p < 0.001), pH (hazard ratio, 0.89 per 0.1 increase; 95% CI, 0.8–14; p = 0.041), Pao2/Fio2 (hazard ratio, 0.58 per doubling; 95% CI, 0.52–0.66; p < 0.001), and mean arterial pressure (hazard ratio, 0.92 per 10 mm Hg increase; 95% CI, 0.88–0.97; p = 0.003). CONCLUSIONS AND RELEVANCE:. This international study suggests that in patients with coronavirus disease 2019 on invasive mechanical ventilation, older age and clinically relevant variables monitored at baseline or sequentially during the course of invasive mechanical ventilation are associated with 28-day invasive mechanical ventilation mortality hazard. Further investigation is warranted to validate any causative roles these parameters might play in influencing clinical outcomes.

(1) Background: Fifty percent of patients supported on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are concurrently supported with an intra-aortic balloon pump (IABP). Acute brain injury (ABI) is a devastating complication related to ECMO and IABP use. The standard of care for ABI diagnosis requires transport to a head CT (HCT) scanner. Recent data suggest that point-of-care (POC) magnetic resonance imaging (MRI) is safe and may be effective in diagnosing ABI in ECMO patients; however, no data exist in patients supported on ECMO with an IABP. We report pre-clinical safety data and a case series to evaluate the safety and feasibility of POC brain MRI in ECMO patients supported with IABP. (2) Methods: Prior to patient use, ex vivo testing with an IABP catheter within the Swoop® Portable MRI (0.064 T) System™ was conducted. After IRB approval, clinical testing was performed for the safety and feasibility of early ABI detection. (3) Results: No deflection force was measured with a 7.5 French Maquet Linear IABP within the 0.064 T field. Three adult ECMO patients (average age: 40 years; 67% female) supported with IABP completed four POC brain MRI exams (median exam time: 30 min). Multiple signal abnormalities were detected on the POC brain MRI, corresponding to HCT results. (4) Conclusions: Our preliminary results suggest that adult VA-ECMO patients with IABP support can be safely imaged with low-field POC brain MRI in the intensive care unit, allowing for the early and bedside imaging of patients.

Background: In a disease that has only existed for 18 months, it is difficult to be fully informed of the long-term sequelae of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Evidence is growing that most organ systems can be affected by the virus, causing severe disabilities in survivors. The extent of the aftermath will declare itself over the next 5–10 years, but it is likely to be substantial with profound socio-economic impact on society.Methods: This is an international multi-center, prospective long-term follow-up study of patients who developed severe coronavirus disease-2019 (COVID-19) and were admitted to Intensive Care Units (ICUs). The study will be conducted at international tertiary hospitals. Patients will be monitored from time of ICU discharge up to 24 months. Information will be collected on demographics, co-existing illnesses before ICU admission, severity of illness during ICU admission and post-ICU quality of life as well as organ dysfunction and recovery. Statistical analysis will consist of patient trajectories over time for the key variables of quality of life and organ function. Using latent class analysis, we will determine if there are distinct patterns of patients in terms of recovery. Multivariable regression analyses will be used to examine associations between baseline characteristics and severity variables upon admission and discharge in the ICU, and how these impact outcomes at all follow-up time points up to 2 years.Ethics and Dissemination: The core study team and local principal investigators will ensure that the study adheres to all relevant national and local regulations, and that the necessary approvals are in place before a site may enroll patients.Clinical Trial Registration:anzctr.org.au: ACTRN12620000799954.

In this paper, we propose a novel key recovery attack against secure ECDSA signature generation employing regular table-based scalar multiplication. Our attack exploits novel leakage, denoted by collision information, which can be constructed by iteratively determining whether two entries loaded from the table are the same or not through side-channel collision analysis. Without knowing the actual value of the table entries, an adversary can recover the private key of ECDSA by finding the condition for which several nonces are linearly dependent by exploiting only the collision information. We show that this condition can be satisfied practically with a reasonable number of digital signatures and corresponding traces. Furthermore, we also show that all entries in the pre-computation table can be recovered using the recovered private key and a sufficient number of digital signatures based on the collision information. As case studies, we find that fixed-base comb and T_SM scalar multiplication are vulnerable to our attack. Finally, we verify that our attack is a real threat by conducting an experiment with power consumption traces acquired during T_SM scalar multiplication operations on an ARM Cortex-M based microcontroller. We also provide the details for validation process.

Background: There is growing evidence that SARS-Cov-2 infection is associated with severe neurological complications. Understanding the nature and prevalence of these neurologic manifestations is essential for identifying higher-risk patients and projecting demand for ongoing resource utilisation. This review and meta-analysis report the neurologic manifestations identified in hospitalised COVID-19 patients and provide a preliminary estimate of disease prevalence.Methods: MEDLINE, Embase and Scopus were searched for studies reporting the occurrence of neurological complications in hospitalised COVID-19 patients.Results: A total of 2,207 unique entries were identified and screened, among which 14 cohort studies and 53 case reports were included, reporting on a total of 8,577 patients. Central nervous system manifestations included ischemic stroke (n = 226), delirium (n = 79), intracranial haemorrhage (ICH, n = 57), meningoencephalitis (n = 13), seizures (n = 3), and acute demyelinating encephalitis (n = 2). Peripheral nervous system manifestations included Guillain-Barrè Syndrome (n = 21) and other peripheral neuropathies (n = 3). The pooled period prevalence of ischemic stroke from identified studies was 1.3% [95%CI: 0.9–1.8%, 102/7,715] in all hospitalised COVID-19 patients, and 2.8% [95%CI: 1.0–4.6%, 9/318] among COVID-19 patients admitted to ICU. The pooled prevalence of ICH was estimated at 0.4% [95%CI: 0–0.8%, 6/1,006].Conclusions: The COVID-19 pandemic exerts a substantial neurologic burden which may have residual effects on patients and healthcare systems for years. Low quality evidence impedes the ability to accurately predict the magnitude of this burden. Robust studies with standardised screening and case definitions are required to improve understanding of this disease and optimise treatment of individuals at higher risk for neurologic sequelae.