The Role of Phospholipid Alterations in Mitochondrial and Brain Dysfunction after Cardiac Arrest.

The human brain possesses three predominate phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS), which account for approximately 35-40%, 35-40%, and 20% of the brain's phospholipids, respectively. Mitochondrial membranes are relatively diverse, containing the aforementioned PC, PE, and PS, as well as phosphatidylinositol (PI) and phosphatidic acid (PA); however, cardiolipin (CL) and phosphatidylglycerol (PG) are exclusively present in mitochondrial membranes. These phospholipid interactions play an essential role in mitochondrial fusion and fission dynamics, leading to the maintenance of mitochondrial structural and signaling pathways. The essential nature of these phospholipids is demonstrated through the inability of mitochondria to tolerate alteration in these specific phospholipids, with changes leading to mitochondrial damage resulting in neural degeneration. This review will emphasize how the structure of phospholipids relates to their physiologic function, how their metabolism facilitates signaling, and the role of organ- and mitochondria-specific phospholipid compositions. Finally, we will discuss the effects of global ischemia and reperfusion on organ- and mitochondria-specific phospholipids alongside the novel therapeutics that may protect against injury.

The Current Discussion Regarding End-of-Life Care for Patients with Out-of-Hospital Cardiac Arrest with Initial Non-Shockable Rhythm: A Narrative Review.

Despite recent advances in resuscitation science, outcomes in patients with out-of-hospital cardiac arrest (OHCA) with initial non-shockable rhythm remains poor. Those with initial non-shockable rhythm have some epidemiological features, including the proportion of patients with a witnessed arrest, bystander cardiopulmonary resuscitation (CPR), age, and presumed etiology of cardiac arrest have been reported, which differ from those with initial shockable rhythm. The discussion regarding better end-of-life care for patients with OHCA is a major concern among citizens. As one of the efforts to avoid unwanted resuscitation, advance directive is recognized as a key intervention, safeguarding patient autonomy. However, several difficulties remain in enhancing the effective use of advance directives for patients with OHCA, including local regulation of their use, insufficient utilization of advance directives by emergency medical services at the scene, and a lack of established tools for discussing futility of resuscitation in advance care planning. In addition, prehospital termination of resuscitation is a common practice in many emergency medical service systems to assist clinicians in deciding whether to discontinue resuscitation. However, there are also several unresolved problems, including the feasibility of implementing the rules for several regions and potential missed survivors among candidates for prehospital termination of resuscitation. Further investigation to address these difficulties is warranted for better end-of-life care of patients with OHCA.

Should Transport Ventilators Be Used in Times of Crisis? The Use of Emergency Authorized Nonconventional Ventilators Is Associated With Mortality Among Patients With COVID-19 Acute Respiratory Distress Syndrome.

OBJECTIVES: Nonconventional ventilators (NCVs), defined here as transport ventilators and certain noninvasive positive pressure devices, were used extensively as crisis-time ventilators for intubated patients with COVID-19. We assessed whether there was an association between the use of NCV and higher mortality, independent of other factors. DESIGN: This is a multicenter retrospective observational study. SETTING: The sample was recruited from a single healthcare system in New York. The recruitment period spanned from March 1, 2020, to April 30, 2020. PATIENTS: The sample includes patients who were intubated for COVID-19 acute respiratory distress syndrome (ARDS). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 28-day in-hospital mortality. Multivariable logistic regression was used to derive the odds of mortality among patients managed exclusively with NCV throughout their ventilation period compared with the remainder of the sample while adjusting for other factors. A secondary analysis was also done, in which the mortality of a subset of the sample exclusively ventilated with NCV was compared with that of a propensity score-matched subset of the control group. Exclusive use of NCV was associated with a higher 28-day in-hospital mortality while adjusting for confounders in the regression analysis (odds ratio, 1.41; 95% CI [1.07-1.86]). In the propensity score matching analysis, the mortality of patients exclusively ventilated with NCV was 68.9%, and that of the control was 60.7% (p = 0.02). CONCLUSIONS: Use of NCV was associated with increased mortality among patients with COVID-19 ARDS. More lives may be saved during future ventilator shortages if more full-feature ICU ventilators, rather than NCVs, are reserved in national and local stockpiles.

External validation of the rCAST for patients after in-hospital cardiac arrest: a multicenter retrospective observational study.

No established predictive or risk classification tool exists for the neurological outcomes of post-cardiac arrest syndrome (PCAS) in patients with in-hospital cardiac arrest (IHCA). This study aimed to investigate whether the revised post-cardiac arrest syndrome for therapeutic hypothermia score (rCAST), which was developed to estimate the prognosis of PCAS patients with out-of-hospital cardiac arrest (OHCA), was applicable to patients with IHCA. A retrospective, multicenter observational study of 140 consecutive adult IHCA patients admitted to three intensive care units. The area under the receiver operating characteristic curves (AUCs) of the rCAST for poor neurological outcome and mortality at 30 days were 0.88 (0.82-0.93) and 0.83 (0.76-0.89), respectively. The sensitivity and specificity of the risk classification according to rCAST for poor neurological outcomes were 0.90 (0.83-0.96) and 0.67 (0.55-0.79) for the low, 0.63 (0.54-0.74) and 0.67 (0.55-0.79) for the moderate, and 0.27 (0.17-0.37) and 1.00 (1.00-1.00) for the high-severity grades. All 22 patients classified with a high-severity grade showed poor neurological outcomes. The rCAST showed excellent predictive accuracy for neurological prognosis in patients with PCAS after IHCA. The rCAST may be useful as a risk classification tool for PCAS after IHCA.

Chest CT findings in severe acute respiratory distress syndrome requiring V-V ECMO: J-CARVE registry.

BACKGROUND: Chest computed tomography findings are helpful for understanding the pathophysiology of severe acute respiratory distress syndrome (ARDS). However, there is no large, multicenter, chest computed tomography registry for patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). The aim of this study was to describe chest computed tomography findings at V-V ECMO initiation and to evaluate the association between the findings and outcomes in severe ARDS. METHODS: This multicenter, retrospective cohort study enrolled patients with severe ARDS on V-V ECMO, who were admitted to the intensive care units of 24 hospitals in Japan between January 1, 2012, and December 31, 2022. RESULTS: The primary outcome was 90-day in-hospital mortality. The secondary outcomes were the successful liberation from V-V ECMO and the values of static lung compliance. Among the 697 registry patients, of the 582 patients who underwent chest computed tomography at V-V ECMO initiation, 394 survived and 188 died. Multivariate Cox regression showed that traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality (hazard ratio [95% confidence interval] 1.77 [1.19-2.63], p = 0.005 and 1.97 [1.02-3.79], p = 0.044, respectively). The presence of traction bronchiectasis was also associated with decreased successful liberation from V-V ECMO (odds ratio: 0.27 [0.14-0.52], p < 0.001). Lower static lung compliance was associated with some chest computed tomography findings related to changes outside of pulmonary opacity, but not with the findings related to pulmonary opacity. CONCLUSIONS: Traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality in patients with severe ARDS who required V-V ECMO.

Association between regional critical care capacity and the incidence of invasive mechanical ventilation for coronavirus disease 2019: a population-based cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has exposed critical care supply shortages worldwide. This study aimed to investigate the association between regional critical care capacity and the incidence of invasive mechanical ventilation following novel COVID-19 during the pandemic in Japan, a country with a limited intensive care unit (ICU) bed capacity of a median of 5.1 ICU beds per 100,000 individuals. METHODS: This population-based cohort study used data from the CRoss Icu Searchable Information System database and publicly available databases provided by the Japanese government and Japanese Society of Intensive Care Medicine. We identified patients recently diagnosed with COVID-19, those who received invasive mechanical ventilation, and those who received extracorporeal membrane oxygenation (ECMO) between February 2020 and March 2023. We analyzed the association between regional critical care capacity (ICU beds, high-dependency care unit (HDU) beds, resource-rich ICU beds, and intensivists) and the incidence of invasive mechanical ventilation, ECMO, and risk-adjusted mortality across 47 Japanese prefectures. RESULTS: Among the approximately 127 million individuals residing in Japan, 33,189,809 were recently diagnosed with COVID-19, with 12,203 and 1,426 COVID-19 patients on invasive mechanical ventilation and ECMO, respectively, during the study period. Prefecture-level linear regression analysis revealed that the addition of ICU beds, resource-rich ICU beds, and intensivists per 100,000 individuals increased the incidence of IMV by 5.37 (95% confidence interval, 1.99-8.76), 7.27 (1.61-12.9), and 13.12 (3.48-22.76), respectively. However, the number of HDU beds per 100,000 individuals was not statistically significantly associated with the incidence of invasive mechanical ventilation. None of the four indicators of regional critical care capacity was statistically significantly associated with the incidence of ECMO and risk-adjusted mortality. CONCLUSIONS: The results of prefecture-level analyses demonstrate that increased numbers of ICU beds, resource-rich ICU beds, and intensivists are associated with the incidence of invasive mechanical ventilation among patients recently diagnosed with COVID-19 during the pandemic. These findings have important implications for healthcare policymakers, aiding in efficiently allocating critical care resources during crises, particularly in regions with limited ICU bed capacities. Registry and the registration no. of the study/trial The approval date of the registry was August 20, 2020, and the registration no. of the study was lUMIN000041450.

Association between hospital volume and in-hospital mortality in pediatric severe traumatic brain injury: a nationwide retrospective observational study in Japan.

OBJECTIVE: The objective of this study was to investigate the association between hospital volume and in-hospital mortality in pediatric patients with severe traumatic brain injury (TBI). METHODS: This retrospective cohort study used data from the Japan Trauma Data Bank between 2010 and 2018, specifically those of pediatric patients with severe TBI (Glasgow Coma Scale [GCS] score < 9 and head Abbreviated Injury Scale score > 2). Hospital volume was defined as the number of pediatric patients with severe TBI throughout the study period. Hospital volume was categorized as low (reference category: 1-9 patients), middle (10-17 patients), or high (> 18 patients) volume. Multivariate mixed-effects logistic regression analysis was performed to determine the association between hospital volume categories and in-hospital mortality. Subgroup analyses were performed using data on craniotomy and the presence of severe torso injuries. In the sensitivity analyses, patients with a GCS score of 3, interhospital transfer, and major intensive care unit complications were excluded. RESULTS: A total of 1148 pediatric patients with severe TBI, with a median age of 12 years (IQR 7-16 years), treated at 141 hospitals were included. In total, 236 patients (20.6%) died in the hospital. Multivariate analysis showed no significant association between hospital volume and in-hospital mortality (high volume: OR 1.15, 95% CI 0.80-1.64; middle volume: OR 0.89, 95% CI 0.62-1.26). Subgroup and sensitivity analyses showed similar results. CONCLUSIONS: Hospital volume may not be associated with in-hospital mortality in pediatric patients with severe TBI.

Prediction of the neurological outcomes post-cardiac arrest: A prospective validation of the CAST and rCAST.

INTRODUCTION: The neurologic prognosis of out-of-hospital cardiac arrest (OHCA) patients in whom return of spontaneous circulation (ROSC) is achieved remains poor. The aim of this study was to externally and prospectively validate two scoring systems developed by us: the CAST score, a scoring system to predict the neurological prognosis of OHCA patients undergoing targeted temperature management (TTM), and a simplified version of the same score developed for improved ease of use in clinical settings, the revised CAST (rCAST) score. METHODS: This study was a prospective, multicenter, observational study conducted using the SOS KANTO 2017 registry, an OHCA registry involving hospitals in the Kanto region (including Tokyo) of Japan. The primary outcome was favorable neurological outcome (defined as Cerebral Performance Category score of 1 or 2) at 30 days and the secondary outcomes were favorable neurological outcome at 90 days and survival at 30 and 90 days. The predictive accuracies of the original CAST (oCAST) and rCAST scores were evaluated by using area under the receiver operating characteristic curve (AUC). RESULTS: Of 9909 OHCA patients, 565 showed ROSC and received TTM. Of these, we analyzed the data of 259 patients in this study. The areas under the receiver operating characteristic curve (AUCs) of the oCAST and rCAST scores for predicting a favorable neurological outcome at 30 days were 0.86 and 0.87, respectively, and those for predicting a favorable neurological outcome at 90 days were 0.87 and 0.88, respectively. The rCAST showed a higher predictive accuracy for the neurological outcome as compared with the NULL-PLEASE score. The patients with a favorable neurological outcome who had been classified into the high severity group based on the rCAST tended to have hypothermia at hospital arrival and to not show any signs of loss of gray-white matter differentiation on brain CT. Neurological function at 90 days was correlated with the rCAST (r = 0.63, p < 0.001). CONCLUSIONS: rCAST showed high predictive accuracy for the neurological prognosis of OHCA patients managed by TTM, comparable to that of the oCAST score. The scores on the rCAST were strongly correlated with the neurological functions at 90 days, implying that the rCAST is a useful scale for assessing the severity of brain injury after cardiac arrest.

Wolf Creek XVII part 9: Wolf Creek Innovator in Cardiac Arrest and Resuscitation Science Award.

The Wolf Creek Conferences on Cardiac Arrest Resuscitation began in 1975, and have served as an important forum for thought leaders and scientists from industry and academia to come together with the common goal of advancing the field of cardiac arrest resuscitation. The Wolf Creek XVII Conference was hosted by the Max Harry Weil Institute of Critical Care Research and Innovation in Ann Arbor, Michigan on June 14-17, 2023. A new component of the conference was the Wolf Creek Innovator in Cardiac Arrest and Resuscitation Science Award competition. The competition was designed to recognize early career investigators from around the world who's science is challenging the current paradigms in the field. Finalists were selected by a panel of international experts and invited to present in-person at the conference. The winner was chosen by electronic vote of conference participants and awarded a $10,0000 cash prize. Finalists included Carolina Barbosa Maciel from the University of Florida, Adam Gottula from the University of Michigan, Rajat Kalra from the University of Minnesota, Ryan Morgan from the Children's Hospital of Philadelphia, Mitsuaki Nishikimi form Hiroshima University, and Jacob Sunshine from the University of Washington. Ryan Morgan from the Children's Hospital of Philadelphia was selected as the 2023 Wolf Creek Innovator Awardee. This manuscript provides a summary of the work presented by each of the finalists and provides a preview of the future of resuscitation science.

Neurological Improvement via Lysophosphatidic Acid Administration in a Rodent Model of Cardiac Arrest-Induced Brain Injury.

Lysophosphatidic acid (LPA) serves as a fundamental constituent of phospholipids. While prior studies have shown detrimental effects of LPA in a range of pathological conditions, including brain ischemia, no studies have explored the impact of LPA in the context of cardiac arrest (CA). The aim of this study is to evaluate the effects of the intravenous administration of an LPA species containing oleic acid, LPA (18:1) on the neurological function of rats (male, Sprague Dawley) following 8 min of asphyxial CA. Baseline characteristics, including body weight, surgical procedure time, and vital signs before cardiac arrest, were similar between LPA (18:1)-treated (n = 10) and vehicle-treated (n = 10) groups. There was no statistically significant difference in 24 h survival between the two groups. However, LPA (18:1)-treated rats exhibited significantly improved neurological function at 24 h examination (LPA (18:1), 85.4% ± 3.1 vs. vehicle, 74.0% ± 3.3, p = 0.045). This difference was most apparent in the retention of coordination ability in the LPA (18:1) group (LPA (18:1), 71.9% ± 7.4 vs. vehicle, 25.0% ± 9.1, p < 0.001). Overall, LPA (18:1) administration in post-cardiac arrest rats significantly improved neurological function, especially coordination ability at 24 h after cardiac arrest. LPA (18:1) has the potential to serve as a novel therapeutic in cardiac arrest.

Instruments to assess post-intensive care syndrome assessment: a scoping review and modified Delphi method study.

BACKGROUND: The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors. METHODS: We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1-3), important, but not critical (4-6), and critical (7-9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important. RESULTS: In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R. CONCLUSION: Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families.

COVID-19-Associated Portal Vein Thrombosis Post-Cholecystitis.

This case study describes a 45-year-old Caucasian male with a past medical history of obesity, hypertension, and non-insulin-dependent diabetes mellitus, who in the setting of coronavirus disease 2019 (COVID-19) pneumonia, developed portal vein thrombosis (PVT) presenting as an acute abdomen after hospital discharge from a cholecystitis episode. PVT is a very infrequent thromboembolic condition, classically occurring in patients with systemic conditions such as cirrhosis, malignancy, pancreatitis, diverticulitis, autoimmunity, and thrombophilia. PVT can cause serious complications, such as intestinal infarction, or even death, if not promptly treated. Due to the limited number of reports in the literature describing PVT in the COVID-19 setting, its prevalence, natural history, mechanism, and precise clinical features remain unknown. Therefore, clinical suspicion should be high for PVT, in any COVID-19 patient who presents with abdominal pain or associated signs and symptoms. To the best of our knowledge, this is the first report of COVID-19-associated PVT causing extensive thrombosis in the portal vein and its right branch, occurring in the setting of early-stage cirrhosis after a preceding episode of cholecystitis.

High versus low positive end-expiratory pressure setting in patients receiving veno-venous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome: study protocol for the multicentre, randomised ExPress SAVER Trial.

INTRODUCTION: While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay. ETHICS AND DISSEMINATION: Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals. TRIAL REGISTRATION NUMBER: The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022. PROTOCOL VERSION: 28 March 2023, version 4.0.

Continuously increased generation of ROS in human plasma after cardiac arrest as determined by Amplex Red oxidation.

Oxidative stress is believed to be a major cause of injury after cardiac arrest (CA). While the effects of ROS generated within tissues have been extensively investigated, the potential of plasma-generated ROS in contributing to CA pathology has not been examined. We utilized Amplex Red (AR) to measure the real time-generation of ROS in isolated plasma from human CA patients. We first used post-CA rat plasma to identify interfering factors for AR oxidation, and then applied this knowledge to analyze human plasma samples, accounting for the identified confounders. We found significantly increased AR oxidation rates lasting for 4 h in post-CA rat plasma compared to baseline. AR oxidation was unchanged with removal of horseradish peroxidase or addition of catalase. However, adding carboxylesterase inhibitors significantly decreased AR oxidation in rat plasma, which implicated increased carboxylesterase activity, not ROS leading to increased AR oxidation. AR oxidation rates were also significantly increased in human CA patient plasma compared to control and this increase persisted even with carboxylesterase inhibition, suggesting continuously increased ROS-generation within plasma post-CA in humans. The increased ROS generation may be one major source of injury post-CA that may be mitigated with antioxidative therapeutic strategies that can manage the ROS systemically generated in plasma over time.KEY POLICY HIGHLIGHTSWe examined the potential of plasma as a source of ROS generation post-cardiac arrestRat cardiac arrest was used to guide the application of Amplex Red in human plasmaROS generation in plasma is significantly increased after cardiac arrest in humansScavenging excessive ROS in post-resuscitation plasma may improve outcomes of patients.

Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents.

BACKGROUND: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct the multiple dysregulated metabolic pathways elicited following cardiac arrest have failed to demonstrate clear benefit. Many scientists have opined on the need for novel, multidimensional approaches to the multiple metabolic disturbances after cardiac arrest. In the current study, we have developed a therapeutic cocktail that includes ten drugs capable of targeting multiple pathways of ischemia-reperfusion injury after CA. We then evaluated its effectiveness in improving neurologically favorable survival through a randomized, blind, and placebo-controlled study in rats subjected to 12 min of asphyxial CA, a severe injury model. RESULTS: 14 rats were given the cocktail and 14 received the vehicle after resuscitation. At 72 h post-resuscitation, the survival rate was 78.6% among cocktail-treated rats, which was significantly higher than the 28.6% survival rate among vehicle-treated rats (log-rank test; p = 0.006). Moreover, in cocktail-treated rats, neurological deficit scores were also improved. These survival and neurological function data suggest that our multi-drug cocktail may be a potential post-CA therapy that deserves clinical translation. CONCLUSIONS: Our findings demonstrate that, with its ability to target multiple damaging pathways, a multi-drug therapeutic cocktail offers promise both as a conceptual advance and as a specific multi-drug formulation capable of combatting neuronal degeneration and death following cardiac arrest. Clinical implementation of this therapy may improve neurologically favorable survival rates and neurological deficits in patients suffering from cardiac arrest.

Characteristics of the pulmonary opacities on chest CT associated with difficulty in short-term liberation from veno-venous ECMO in patients with severe ARDS.

BACKGROUND: It is clinically important to predict difficulty in short-term liberation from veno-venous extracorporeal membrane oxygenation (V-V ECMO) in patients with severe acute respiratory distress syndrome (ARDS) at the time of initiation of the support. The aim of this study was to identify the characteristics of pulmonary opacities on chest CT that is associated with difficulty in short-term liberation from V-V ECMO (< 14 days). METHODS: This multicenter retrospective study was conducted in adult patients initiated on V-V ECMO for severe ARDS between January 2014 and June 2022. The pulmonary opacities on CT at the time of initiation of the ECMO support were evaluated in a blinded manner, focusing on the following three characteristics of the opacities: (1) their distribution (focal/diffuse on the dorso-ventral axis or unilateral/bilateral on the left-right axis); (2) their intensity (pure ground glass/pure consolidation/mixed pattern); and (3) the degree of fibroproliferation (signs of traction bronchiectasis or reticular opacities). RESULTS: Among the 153 patients, 72 (47%) were successfully liberated from ECMO in the short term, while short-term liberation failed in the remaining 81 (53%) patients. Multivariate logistic regression analysis showed that the presence of mixed-pattern pulmonary opacities and signs of traction bronchiectasis, but not the distribution of the opacities, were independently associated with difficulty in short-term liberation (OR [95% CI]; 4.8 [1.4-16.5] and 3.9 [1.4-11.2], respectively). CONCLUSIONS: The presence of a mixed pattern of the pulmonary opacities and signs of traction bronchiectasis on the chest CT were independently associated with difficulty in short-term liberation from V-V ECMO in severe ARDS patients.

Predictive Accuracy of the ROX Index for Re-Intubation in Mechanically Ventilated Patients With COVID-19.

BACKGROUND: Several studies have suggested that high-flow nasal cannula (HFNC) is useful for respiratory support after extubation in subjects with COVID-19 pneumonia, whereas 18% subsequently needed to undergo re-intubation. This study aimed to evaluate whether the breathing frequency (f)-ratio of oxygen saturation (ROX) index, which has been shown to be useful for predicting future intubation, is also useful for re-intubation in subjects with COVID-19. METHODS: We retrospectively analyzed mechanically ventilated subjects with COVID-19 who underwent HFNC therapy after extubation at 4 participating hospitals between January 2020-May 2022. We evaluated the predictive accuracy of ROX at 0, 1, and 2 h for re-intubation until ICU discharge and compared the area under the receiver operating characteristic (ROC) curve of the ROX index with those of f and SpO2 /FIO2 . RESULTS: Among the 248 subjects with COVID-19 pneumonia, 44 who underwent HFNC therapy after extubation were included. A total of 32 subjects without re-intubation were classified into the HFNC success group, and 12 with re-intubation were classified into the failure group. The overall trend that the area under the ROC curve of the ROX index was greater than that of the f and SaO2 /FIO2 was observed, although there was no statistical significance at any time point. The ROX index at 0 h, at the cutoff point of < 7.44, showed a sensitivity and specificity of 0.42 and 0.97, respectively. A trend of positive correlation between the time until re-intubation and ROX index at each time point was observed. CONCLUSIONS: The ROX index in the early phase of HFNC therapy after extubation was useful for predicting re-intubation with high accuracy in mechanically ventilated subjects with COVID-19. Close observation for patients with < 7.44 ROX index just after extubation may be warranted because of their high risk for re-intubation.

Lung Abscess and Pyothorax in Critically Ill COVID-19 Patients: A Single-Center Retrospective Study.

The mortality rate of patients with COVID-19 pneumonia requiring mechanical ventilation remains high. This study determined the percentage and characteristics of patients who developed lung abscesses or pyothorax and their mortality rates among adult patients with COVID-19 admitted to the ICU who required mechanical ventilation. Of the 64 patients with COVID-19 assessed, 30 (47%) developed ventilator-associated pneumonia (VAP), of whom 6 (20%) developed pyothorax or lung abscess. There were no statistically significant differences in patient characteristics, treatment after ICU admission, or outcomes between those with and without these complications, except for age. VAP complicated by Lung abscess or pyothorax was caused by a single organism, with Staphylococcus aureus (n = 4) and Klebsiella species (n = 2) being the primary causative agents. Occur infrequently in patients with COVID-19 requiring mechanical ventilation. Large-scale studies are required to elucidate their effects on clinical outcomes.

Exogenous mitochondrial transplantation improves survival and neurological outcomes after resuscitation from cardiac arrest.

BACKGROUND: Mitochondrial transplantation (MTx) is an emerging but poorly understood technology with the potential to mitigate severe ischemia-reperfusion injuries after cardiac arrest (CA). To address critical gaps in the current knowledge, we test the hypothesis that MTx can improve outcomes after CA resuscitation. METHODS: This study consists of both in vitro and in vivo studies. We initially examined the migration of exogenous mitochondria into primary neural cell culture in vitro. Exogenous mitochondria extracted from the brain and muscle tissues of donor rats and endogenous mitochondria in the neural cells were separately labeled before co-culture. After a period of 24 h following co-culture, mitochondrial transfer was observed using microscopy. In vitro adenosine triphosphate (ATP) contents were assessed between freshly isolated and frozen-thawed mitochondria to compare their effects on survival. Our main study was an in vivo rat model of CA in which rats were subjected to 10 min of asphyxial CA followed by resuscitation. At the time of achieving successful resuscitation, rats were randomly assigned into one of three groups of intravenous injections: vehicle, frozen-thawed, or fresh viable mitochondria. During 72 h post-CA, the therapeutic efficacy of MTx was assessed by comparison of survival rates. The persistence of labeled donor mitochondria within critical organs of recipient animals 24 h post-CA was visualized via microscopy. RESULTS: The donated mitochondria were successfully taken up into cultured neural cells. Transferred exogenous mitochondria co-localized with endogenous mitochondria inside neural cells. ATP content in fresh mitochondria was approximately four times higher than in frozen-thawed mitochondria. In the in vivo survival study, freshly isolated functional mitochondria, but not frozen-thawed mitochondria, significantly increased 72-h survival from 55 to 91% (P = 0.048 vs. vehicle). The beneficial effects on survival were associated with improvements in rapid recovery of arterial lactate and glucose levels, cerebral microcirculation, lung edema, and neurological function. Labeled mitochondria were observed inside the vital organs of the surviving rats 24 h post-CA. CONCLUSIONS: MTx performed immediately after resuscitation improved survival and neurological recovery in post-CA rats. These results provide a foundation for future studies to promote the development of MTx as a novel therapeutic strategy to save lives currently lost after CA.

Quantification of respiratory sounds by a continuous monitoring system can be used to predict complications after extubation: a pilot study.

To show that quantification of abnormal respiratory sounds by our developed device is useful for predicting respiratory failure and airway problems after extubation. A respiratory sound monitoring system was used to collect respiratory sounds in patients undergoing extubation. The recorded respiratory sounds were subsequently analyzed. We defined the composite poor outcome as requiring any of following medical interventions within 48 h as defined below. This composite outcome includes reintubation, surgical airway management, insertion of airway devices, unscheduled use of noninvasive ventilation or high-flow nasal cannula, unscheduled use of inhaled medications, suctioning of sputum by bronchoscopy and unscheduled imaging studies. The quantitative values (QV) for each abnormal respiratory sound and inspiratory sound volume were compared between composite outcome groups and non-outcome groups. Fifty-seven patients were included in this study. The composite outcome occurred in 18 patients. For neck sounds, the QVs of stridor and rhonchi were significantly higher in the outcome group vs the non-outcome group. For anterior thoracic sounds, the QVs of wheezes, rhonchi, and coarse crackles were significantly higher in the outcome group vs the non-outcome group. For bilateral lateral thoracic sounds, the QV of fine crackles was significantly higher in the outcome group vs the non-outcome group. Cervical inspiratory sounds volume (average of five breaths) immediately after extubation was significantly louder in the outcome group vs non-outcome group (63.3 dB vs 54.3 dB, respectively; p < 0.001). Quantification of abnormal respiratory sounds and respiratory volume may predict respiratory failure and airway problems after extubation.