Multi-omics Study of Hypoxic-Ischemic Brain Injury After Cardiopulmonary Resuscitation in Swine.

BACKGROUND: Hypoxic-ischemic brain injury is a common cause of mortality after cardiac arrest (CA) and cardiopulmonary resuscitation; however, the specific underlying mechanisms are unclear. This study aimed to explore postresuscitation changes based on multi-omics profiling. METHODS: A CA swine model was established, and the neurological function was assessed at 24 h after resuscitation, followed by euthanizing animals. Their fecal, blood, and hippocampus samples were collected to analyze gut microbiota, metabolomics, and transcriptomics. RESULTS: The 16S ribosomal DNA sequencing showed that the microbiota composition and diversity changed after resuscitation, in which the abundance of Akkermansia and Muribaculaceae_unclassified increased while the abundance of Bifidobacterium and Romboutsia decreased. A relationship was observed between CA-related microbes and metabolites via integrated analysis of gut microbiota and metabolomics, in which Escherichia-Shigella was positively correlated with glycine. Combined metabolomics and transcriptomics analysis showed that glycine was positively correlated with genes involved in apoptosis, interleukin-17, mitogen-activated protein kinases, nuclear factor kappa B, and Toll-like receptor signal pathways. CONCLUSIONS: Our results provided novel insight into the mechanism of hypoxic-ischemic brain injury after resuscitation, which is envisaged to help identify potential diagnostic and therapeutic markers.

Alda-1, an Activator of ALDH2, Improves Postresuscitation Cardiac and Neurological Outcomes by Inhibiting Pyroptosis in Swine.

Aldehyde dehydrogenase 2 (ALDH2) has been proven to protect the heart and brain against regional ischemia/reperfusion injury, in which the protective role is related to the inhibition of pyroptosis. In the present study, we investigated whether an ALDH2 activator N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichloro-benzamide (Alda-1) would improve postresuscitation cardiac and neurological outcomes in a clinically relevant swine model of cardiac arrest (CA) and resuscitation. The animal model was established by 8 min of untreated ventricular fibrillation and then 8 min of cardiopulmonary resuscitation (CPR). After restoring spontaneous circulation, the animals were randomly divided to receive either Alda-1 (0.88 mg/kg, n = 6) or saline (n = 5). Postresuscitation hemodynamic parameters, cardiac function, and cardiac and cerebral injuries were periodically measured for a total of 24 h. At 24 h postresuscitation, neurological function was evaluated, and then the animals were sacrificed, and cardiac and cerebral tissue samples were obtained for the measurements of oxidative stress, inflammation and pyroptosis. Consequently, postresuscitation cardiac and neurological dysfunction were significantly improved accompanied with significantly milder cardiac and cerebral injuries in the Alda-1 group compared with the CPR group. In addition, the increase in NLR family pyrin domain-containing 3 inflammasome expression and proinflammatory cytokine production, which indicated the occurrence of inflammatory response, were significantly less in the Alda1 group than in the CPR group. The expression level of gasdermin D used as a protein marker of pyroptosis was also significantly reduced in all resuscitated animals receiving Alda1 treatment. Moreover, the severity of oxidative stress indicated by the changes of 4-hydroxy-2-nonenal and malondialdehyde was significantly decreased in the heart and brain in all animals treated with Alda-1 compared to the CPR group. Thus, Alda-1 mitigated postresuscitation cardiac and neurological dysfunction and injuries possibly by inhibiting oxidative stress-mediated NLRP3 inflammasome activation and pyroptosis in a swine model of CA and resuscitation.

Heparin-free adventitia pulmonary oxygenation in the treatment of trauma complicated with severe pulmonary infection: a case report.

The application of Venovenous (VV) extracorporeal membrane oxygenation (ECMO) in trauma and patients with severe bleeding tendency has been controversial. However, VV ECMO without anticoagulation contributes to reducing the risk of bleeding during ECMO maintenance. VV ECMO serves critical roles in therapy of patients with severe pulmonary infection and failure in conventional therapy. The common peripheral catheterization approach for VV ECMO is femoral vein-internal jugular vein catheterization, and bilateral femoral vein catheterization can also achieve the purpose of respiratory support for patients with limited cervical catheterization. In this case report, we described a patient with post-traumatic cervical spinal cord injury and severe pulmonary infection who was successfully treated with heparin-free intravenous ECMO.

A retrospective study of sepsis-associated encephalopathy: epidemiology, clinical features and adverse outcomes.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a common complication of sepsis that may result in worse outcomes. This study was designed to determine the epidemiology, clinical features, and risk factors of SAE. METHODS: This was a retrospective study of all patients with sepsis who were admitted to the Critical Care Medicine Department of Hangzhou First People's Hospital Affiliated with Zhejiang University School of Medicine from January 2015 to December 2019. RESULTS: A total of 291 sepsis patients were screened, and 127 (43.6%) were diagnosed with SAE. There were significant differences in median age, proportion of underlying diseases such as hypertension, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, gastrointestinal infections, detection rate of Enterococcus, and 28-day mortality between the SAE and non-SAE groups. Both the SOFA score and APACHE II score were independent risk factors for SAE in patients with sepsis. All 127 SAE patients were divided into survival and non-survival groups. The age, SOFA score, and APACHE II score were independently associated with 28-day mortality in SAE patients. CONCLUSION: In the present retrospective study, nearly half of patients with sepsis developed SAE, which was closely related to poor outcomes. Both the SOFA score and APACHE II score were independent risk factors for predicting the occurrence and adverse outcome of SAE.

Development and validation of a nomogram for predicting 28-day mortality in patients with ischemic stroke.

BACKGROUND/AIM: We aimed to construct a validated nomogram model for predicting short-term (28-day) ischemic stroke mortality among critically ill populations. MATERIALS AND METHODS: We collected raw data from the Medical Information Mart for Intensive Care IV database, a comprehensive repository renowned for its depth and breadth in critical care information. Subsequently, a rigorous analytical framework was employed, incorporating a 10-fold cross-validation procedure to ensure robustness and reliability. Leveraging advanced statistical methodologies, specifically the least absolute shrinkage and selection operator regression, variables pertinent to 28-day mortality in ischemic stroke were meticulously screened. Next, binary logistic regression was utilized to establish nomogram, then applied concordance index to evaluate discrimination of the prediction models. Predictive performance of the nomogram was assessed by integrated discrimination improvement (IDI) and net reclassification index (NRI). Additionally, we generated calibration curves to assess calibrating ability. Finally, we evaluated the nomogram's net clinical benefit using decision curve analysis (DCA), in comparison with scoring systems clinically applied under common conditions. RESULTS: A total of 2089 individuals were identified and assigned into training (n = 1443) or validation (n = 646) cohorts. Various identified risk factors, including age, ethnicity, marital status, underlying metastatic solid tumor, Charlson comorbidity index, heart rate, Glasgow coma scale, glucose concentrations, white blood cells, sodium concentrations, potassium concentrations, mechanical ventilation, use of heparin and mannitol, were associated with short-term (28-day) mortality in ischemic stroke individuals. A concordance index of 0.834 was obtained in the training dataset, indicating that our nomogram had good discriminating ability. Results of IDI and NRI in both cohorts proved that our nomogram had positive improvement of predictive performance, compared to other scoring systems. The actual and predicted incidence of mortality showed favorable concordance on calibration curves (P > 0.05). DCA curves revealed that, compared with scoring systems clinically used under common conditions, the constructed nomogram yielded a greater net clinical benefit. CONCLUSIONS: Utilizing a comprehensive array of fourteen readily accessible variables, a prognostic nomogram was meticulously formulated and rigorously validated to provide precise prognostication of short-term mortality within the ischemic stroke cohort.

LncRNA MSTRG.13,871/miR155-5p/Grip1 network involved in the post-cardiac arrest brain injury.

Post-cardiac arrest brain (PCABI) is a severe medical condition characterized by a significant risk of neurological impairment and death. Nevertheless, the specific process and essential molecules responsible for its development are not fully understood. Profiling based on competing endogenous RNAs (ceRNA) has been implicated in the onset and progression of neurological disorders, yet its role in PCABI remains unclear. In this study, we performed RNA transcriptome sequencing analysis to identify differentially expressed genes in the rat model for cardiac arrest and cardiopulmonary resuscitation (CA/CPR). A hub ceRNA regulatory network was constructed using miRWalk 2.0 and Cytohubba plug-in in Cytoscape. Subsequently, real-time quantitative reverse transcription-polymerase chain reaction and dual-luciferase activity assays validated MSTRG.13,871, miR-155-5p, and Grip1 as differentially expressed in CA/CPR group, with MSTRG.13,871 capable of targeting both miR-155-5p and Grip1. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed the ceRNA network enrichment in immunoregulation mechanisms such as mitochondrion, apoptotic process, and negative regulation cell death. Our research highlights the mechanism of PCABI by revealing a critical regulatory axis involving MSTRG.13,871-miR-155-5p-Grip1 in the hippocampus CA1 region after CA/CPR in rats, proposing a feasible controlled mechanism, which may serve as a theoretical basis for designing innovative therapies.

A nomogram to predict in-hospital mortality of gastrointestinal bleeding patients in the intensive care unit.

Background: Gastrointestinal bleeding (GIB) is a common condition in clinical practice, and predictive models for patients with GIB have been developed. However, assessments of in-hospital mortality due to GIB in the intensive care unit (ICU), especially in critically ill patients, are still lacking. This study was designed to screen out independent predictive factors affecting in-hospital mortality and thus establish a predictive model for clinical use. Methods: This retrospective study included 1,442 patients with GIB who had been admitted to the ICU. They were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) 1.0 database and divided into a training group and a validation group in a ratio of 7:3. The main outcome measure was in-hospital mortality. Least absolute shrinkage and section operator (LASSO) regression was used to screen out independent predictors and create a nomogram. Results: LASSO regression picked out nine independent predictors: heart rate (HR), activated partial thromboplastin time (aPTT), acute physiology score III (APSIII), sequential organ failure assessment (SOFA), cerebrovascular disease, acute kidney injury (AKI), norepinephrine, vasopressin, and dopamine. Our model proved to have excellent predictive value with regard to in-hospital mortality (the area under the receiver operating characteristic curve was 0.906 and 0.881 in the training and validation groups, respectively), as well as a good outcome on a decision curve analysis to assess net benefit. Conclusion: Our model effectively predicts in-hospital mortality in patients with GIB, indicating that it may prove to be a valuable tool in future clinical practice.

Fascinating polyphenol lignin extracted from sawdust via a green and recyclable solvent route.

Due to the complexity, heterogeneity and recalcitrant structure of lignin, the extraction of multifunctional lignin directly from lignocellulose is still a challenge. Here, a green and recyclable route was proposed to separate high-quality lignin and tailor its functionalities. Through tuning the components of deep eutectic solvent (DES) and separation procedures, DES extracted lignin (DESL) exhibited high purity of 99.6 %, yield of 83.2 % and phenolic hydroxyl content of 8.33 wt%. The results of FTIR and 13C NMR demonstrated that DESL possessed more oxygen-containing reactive groups compared with commercial lignin (CL), enabling DESL with more superior functional activities. DESL exhibited higher antioxidant activity with the DPPH capture rate of 73.2 %. Meanwhile, DESL showed strong bactericidal effects against E. coli (100 %) and S. aureus (100 %) due to higher phenolic hydroxyl content, which could destroy bacterial cell membranes and inhibit bacterial metabolism by interacting with phospholipid layer and protein. Additionally, DESL displayed strong UV absorption and could be blended with polyurethane to enhance UV shielding property of polyurethane composite film with >50 of UPF value. In summary, DES treatment is a suitable strategy for high-quality lignin separation, which opens a broad spectrum of possibilities for lignin valorization.

Strong and flexible lignocellulosic film fabricated via a feasible molecular remodeling strategy.

Biomass-derived sustainable film is a promising alternative to synthetic plastic, but hampered by strength, toughness and flexibility trade-off predicament. Here, a feasible and scalable strategy was proposed to fabricate strong and flexible lignocellulosic film through molecular reconstruction of cellulose and lignin. In this strategy, polyphenol lignin was absorbed and wrapped on the surface of cellulose fiber, forming strong interfacial adhesion and cohesion via intramolecular and intermolecular hydrogen bonding. Further, covalent ether bond was generated between the hydroxyl groups of lignocellulose to form chemical cross-linking network induced by epichlorohydrin (ECH). The synergistic effect of hydrogen bonding and stable chemical cross-linking enabled the resultant lignocellulosic film (ELCF) with outstanding mechanical strength of 132.48 MPa, the elongation at break of 9.77 %, and toughness of 9.77 MJ·m-3. Notably, the integration of polyphenol lignin synergistically improved the thermal stability, water resistance, UV-blocking performances of ELCF. Importantly, after immersion for 30 d, ELCF still possessed high wet strength of 70.38 MPa, and elongation at break of 7.70 %, suggesting excellent and durable mechanical performances. Moreover, ELCF could be biodegraded in the natural soil. Therefore, this study provides a new and versatile approach to reconstruct highly-performance lignocellulosic films coupling strength, toughness with flexibility for promising plastic replacement.

Development and verification of a nomogram for predicting short-term mortality in elderly ischemic stroke populations.

Stroke is a major healthcare problem worldwide, particularly in the elderly population. Despite limited research on the development of prediction models for mortality in elderly individuals with ischemic stroke, our study aimed to address this knowledge gap. By leveraging data from the Medical Information Mart for Intensive Care IV database, we collected comprehensive raw data pertaining to elderly patients diagnosed with ischemic stroke. Through meticulous screening of clinical variables associated with 28-day mortality, we successfully established a robust nomogram. To assess the performance and clinical utility of our nomogram, various statistical analyses were conducted, including the concordance index, integrated discrimination improvement (IDI), net reclassification index (NRI), calibration curves and decision curve analysis (DCA). Our study comprised a total of 1259 individuals, who were further divided into training (n = 894) and validation (n = 365) cohorts. By identifying several common clinical features, we developed a nomogram that exhibited a concordance index of 0.809 in the training dataset. Notably, our findings demonstrated positive improvements in predictive performance through the IDI and NRI analyses in both cohorts. Furthermore, calibration curves indicated favorable agreement between the predicted and actual incidence of mortality (P > 0.05). DCA curves highlighted the substantial net clinical benefit of our nomogram compared to existing scoring systems used in routine clinical practice. In conclusion, our study successfully constructed and validated a prognostic nomogram, which enables accurate short-term mortality prediction in elderly individuals with ischemic stroke.

Application of Visual Artificial Airway in Patients with ARDS Assisted by Pulmonary Ultrasound.

Objective: To explore the application of pulmonary ultrasound in visual nursing of artificial airway in patients with acute respiratory distress syndrome (ARDS). Methods: Seventy-eight ARDS patients with mechanical ventilation admitted from February 2021 to January 2022 were included and divided into the intervention group and the control group. The control group was given routine airway nursing, and the intervention group was given visual airway nursing management through lung ultrasound. The arterial blood gas analysis indexes, mechanical ventilation time, ICU treatment time, total hospitalization time, aspiration, and the incidence of ventilator-associated pneumonia (VAP) were compared between the two groups. Results: After treatment, PaO2, PaCO2, SPO2, and oxygenation indexes were significantly improved compared with those before treatment, and the indexes in the intervention group were better than those in the control group after treatment, and the differences were statistically significant (P < 0.05). The mechanical ventilation time (5.39 ± 0.68 vs. 7.92 ± 0.59 days), ICU treatment time (8.05 ± 1.14 vs. 10.71 ± 1.16 days), and total hospitalization time (12.05 ± 2.20 vs. 15.68 ± 2.18 days) in the intervention group were significantly shorter than those in the control group (P < 0.05). The incidences of aspiration (2.56% vs. 15.38%) and VAP (5.13% vs. 20.51%) in the intervention group was significantly lower than that in the control group (P < 0.05). Conclusion: The application of visual artificial airway management assisted by lung ultrasound in ARDS patients can shorten the treatment time and hospitalization time of mechanical ventilation, reduce the incidence of aspiration and VAP, and improve the prognosis of patients.

Rat model of asphyxia-induced cardiac arrest and resuscitation.

Neurologic injury after cardiopulmonary resuscitation is the main cause of the low survival rate and poor quality of life among patients who have experienced cardiac arrest. In the United States, as the American Heart Association reported, emergency medical services respond to more than 347,000 adults and more than 7,000 children with out-of-hospital cardiac arrest each year. In-hospital cardiac arrest is estimated to occur in 9.7 per 1,000 adult cardiac arrests and 2.7 pediatric events per 1,000 hospitalizations. Yet the pathophysiological mechanisms of this injury remain unclear. Experimental animal models are valuable for exploring the etiologies and mechanisms of diseases and their interventions. In this review, we summarize how to establish a standardized rat model of asphyxia-induced cardiac arrest. There are four key focal areas: (1) selection of animal species; (2) factors to consider during modeling; (3) intervention management after return of spontaneous circulation; and (4) evaluation of neurologic function. The aim was to simplify a complex animal model, toward clarifying cardiac arrest pathophysiological processes. It also aimed to help standardize model establishment, toward facilitating experiment homogenization, convenient interexperimental comparisons, and translation of experimental results to clinical application.

ALDA-1 TREATMENT ALLEVIATES LUNG INJURY AFTER CARDIAC ARREST AND RESUSCITATION IN SWINE.

ABSTRACT: Introduction: Alda-1, an aldehyde dehydrogenase 2 (ALDH2) activator, has been shown to protect the lung against a variety of diseases including regional ischemia-reperfusion injury, severe hemorrhagic shock, hyperoxia, and so on. The present study was designed to investigate the effectiveness of Alda-1 treatment in alleviating lung injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in swine. Methods: A total of 24 swine were randomized into three groups: sham (n = 6), CA/CPR (n = 10), and CA/CPR + Alda-1 (n = 8). The swine model was established by 8 min of electrically induced and untreated CA, and then 8 min of manual CPR. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 min after CA/CPR. After CA/CPR, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index (OI) were regularly evaluated for 4 h. At 24 h after resuscitation, lung ALDH2 activity was detected, and its injury score, apoptosis, and ferroptosis were measured. Results: After experiencing the same procedure of CA and CPR, five swine in the CA/CPR group and six swine in the CA/CPR + Alda-1 group restored spontaneous circulation. Subsequently, significantly increased ELWI and PVPI, and markedly decreased OI were observed in these two groups compared with the sham group. However, all of them were gradually improved and significantly better in the swine treated with the Alda-1 compared with the CA/CPR group. Tissue analysis indicated that lung ALDH2 activity was significantly decreased in those swine experiencing the CA/CPR procedure compared with the sham group; nevertheless, its activity was significantly greater in the CA/CPR + Alda-1 group than in the CA/CPR group. In addition, lung injury score, and its apoptosis and ferroptosis were significantly increased in the CA/CPR and CA/CPR + Alda-1 groups compared with the sham group. Likewise, Alda-1 treatment significantly decreased these pathological damages in lung tissue when compared with the CA/CPR group. Conclusions: Alda-1 treatment was effective to alleviate lung injury after CA/CPR in a swine model, in which the protective role was possibly related to the inhibition of cell apoptosis and ferroptosis. It might provide a novel therapeutic target and a feasible therapeutic drug for lung protection after CA/CPR.

A Standardized Multimodal Neurological Monitoring Protocol-Guided Cerebral Protection Therapy for Venoarterial Extracorporeal Membrane Oxygenation Supported Patients.

Background: The main objective of this study was to investigate the role of a multimodal neurological monitoring (MNM)-guided protocol in the precision identification of neural impairment and long-term neurological outcomes in venoarterial extracorporeal membrane oxygenation (VA-ECMO) supported patients. Methods: We performed a cohort study that examined adult patients who underwent VA-ECMO support in our center between February 2010 and April 2021. These patients were retrospectively assigned to the "with MNM group" and the "without MNM group" based on the presence or absence of MNM-guided precision management. The differences in ECMO-related characteristics, evaluation indicators (precision, sensitivity, and specificity) of the MNM-guided protocol, and the long-term outcomes of the surviving patients were measured and compared between the two groups. Results: A total of 63 patients with VA-ECMO support were retrospectively assigned to the without MNM group (n = 35) and the with MNM group (n = 28). The incidence of neural impairment in the without MNM group was significantly higher than that in the with MNM group (82.1 vs. 54.3%, P = 0.020). The MNM group exhibited older median ages [52.5 (39.5, 65.3) vs. 31 (26.5, 48.0), P = 0.008], a higher success rate of ECMO weaning (92.8 vs. 71.4%, P = 0.047), and a lower median duration of building ECMO [40.0 (35.0, 52.0) vs. 58.0 (48.0, 76.0), P = 0.025] and median ECMO duration days [5.0 (4.0, 6.2) vs. 7.0 (5.0, 10.5), P = 0.018] than the group without MNM. The MNM-guided protocol exhibited a higher precision rate (82.1 vs. 60.0%), sensitivity (95.7 vs. 78.9%), and specificity (83.3 vs. 37.5%) in identifying neural impairment in VA-ECMO support patients. There were significant differences in the long-term outcomes of survivors at 1, 3 and 6 months after discharge between the two groups (P < 0.05). However, the results showed no significant differences in ICU length of stay (LOS), hospital LOS, survival to discharge, or 28-day mortality between the two groups (P > 0.05). Conclusion: The MNM-guided protocol is conducive to guiding intensivists in the improvement of cerebral protection therapy for ECMO-supported patients to detect and treat potential neurologic impairment promptly, and then improving long-term neurological outcomes after discharge.

Two cases of intestinal perforation due to mesenteric artery embolism during extracorporeal membrane oxygenation and intra-aortic balloon pumping.

The patient in case 1 was a 50-year-old man who presented to the emergency department of the local hospital with chest pain and syncope for 3 hours due to acute myocardial infarction. He underwent cardiopulmonary resuscitation (CPR) followed by extracorporeal membrane oxygenation (ECMO), and intestinal perforation was detected on day 9. The patient in case 2 was a 58-year-old man who was admitted to the hospital with abdominal pain lasting for 3 days. He also required CPR and ECMO for cardiogenic shock, and intestinal perforation was identified on day 7 of ECMO. We believe that this case report will be important to alert clinicians to the possibility of this complication and to encourage early detection and intervention to improve prognosis. Conventionally, the gastrointestinal tract has received secondary attention in patients receiving ECMO support because the vital organs tend to be considered first. However, this case report illustrates the importance of monitoring gastrointestinal function in patients undergoing ECMO.

Gene model-related m6A expression levels predict the risk of preeclampsia.

BACKGROUND: This is the first study to explore the potential functions and expression patterns of RNA N6-methyladenosine (m6A) and potential related genes in preeclampsia. METHODS: We identified two m6A modification patterns through unsupervised cluster analysis and validated them by principal component analysis. We quantified the relative abundance of specific infiltrating immunocytes using single-sample gene set enrichment analysis (ssGSEA) and the Wilcoxon test. To screen hub genes related to m6A regulators, we performed weighted gene coexpression network analysis. Functional enrichment analysis was conducted for differential signalling pathways and cellular processes. Preeclampsia patients were grouped by consensus clustering based on differentially expressed hub genes and the relationship between different gene-mediated classifications and clinical features. RESULTS: Two m6A clusters in preeclampsia, cluster A and cluster B, were determined based on the expression of 17 m6A modification regulators; ssGSEA revealed seven significantly different immune cell subtypes between the two clusters. A total of 1393 DEGs and nine potential m6A-modified hub genes were screened. We divided the patients into two groups based on the expression of these nine genes. We found that almost all the patients in m6A cluster A were classified into hub gene cluster 1 and that a lower gestational age may be associated with more m6A-associated events. CONCLUSIONS: This study revealed that hub gene-mediated classification is consistent with m6A modification clusters for predicting the clinical characteristics of patients with preeclampsia. Our results provide new insights into the molecular mechanisms of preeclampsia.

Case Report: Extracorporeal Membrane Oxgenation for Rapidly Progressive Interstitial Lung Disease Associated With Clinically Amyopathic Dermatomyositis in a Post-partum Woman.

Background: Clinically amyopathic dermatomyositis (CADM) presented with rapid progressive interstitial lung disease (RP-ILD) is rare. Here, we present a case of a post-partum female with CADM complicated by severe RP-ILD managed with venovenous extracorporeal membrane oxygenation (V-V ECMO). Case Summary: A 36-year-old woman was referred to a local hospital with cough and fever. She had a history of facial erythema and cough since an induction of labor for a stillborn fetus 2 months ago. Her status developed into RP-ILD with mediastinal emphysema and subcutaneous emphysema after admission, and V-V ECMO was initiated. After several failed attempts to wean the patient from ECMO, a decision was made to place the patient on the lung transplant waitlist. She underwent a double lung transplant on ECMO day 31 and received tacrolimus as an immunosuppressive regimen. The patient presented with positive anti-MDA5 and anti-Ro-52 antibodies and a high ferritin level, all of which indicated the presence of clinically amyopathic dermatomyositis (CADM). The patient was weaned from ECMO at 3 days after transplantation, but the patient's state of consciousness deteriorated, and head CT was considered for posterior reversible encephalopathy syndrome (PRES). After the temporary cessation of calcineurin inhibitors and a dosage reduction, the patient's state of consciousness returned to normal. Because of another disturbance of consciousness, the patient declined further treatment and was discharged 14 days after transplantation. Conclusion: Early recognition of CADM can effectively improve patients' prognosis. ECMO should be considered as a supportive therapy in patients in acute respiratory failure secondary to RP-ILD.

Clinical Characteristics of 10 Pregnant and Postpartum Women With Extracorporeal Membrane Oxygenation: A Retrospective Study.

Background: The aim of study was to summarize the clinical characteristics and experience of extracorporeal membrane oxygenation (ECMO) in pregnant and postpartum patients. Methods and Results: We retrospectively reviewed 131 consecutive ECMO patients at our center from May 2015 to May 2021. A total of 10 Chinese patients were pregnant or postpartum at the time of ECMO initiation. Patients ranged in age from 25 to 36 years (median age 30.5 years). The ECMO duration ranged from 3 to 31 days (median duration 8 days). There was a stabilizing trend of acid-base balance and decreasing lactic acid over the 3 days following ECMO initiation. Seven (70%) patients survived at least 48 h after weaning from ECMO. Four (40%) patients survived until discharge, and four (40%) fetuses survived until discharge. Conclusion: ECMO provides a suitable temporary cardiopulmonary support for pregnant and postpartum patients. ECMO shows a favorable effect on short-term stability in critical obstetric patients.

Mesenchymal Stem Cells Alleviate Post-resuscitation Cardiac and Cerebral Injuries by Inhibiting Cell Pyroptosis and Ferroptosis in a Swine Model of Cardiac Arrest.

Following cardiopulmonary resuscitation (CPR), the ensuing cardiac and cerebral injuries contribute to the poor outcome of cardiac arrest (CA) victims, in which the pathogenetic process is possibly driven by cell pyroptosis and ferroptosis. Mesenchymal stem cells (MSCs) have been shown to be a promising strategy for post-resuscitation cardiac and cerebral protection in rat, but its effectiveness in the clinically relevant swine model and the potential protective mechanism remain unknown. The present study was designed to investigate whether MSCs administration could alleviate post-resuscitation cardiac and cerebral injuries through the inhibition of cell pyroptosis and ferroptosis in swine. Twenty-four male domestic swine were randomly divided into three groups: sham, CPR, and MSC. A dose of 2.5×106/kg of MSCs derived from human embryonic stem cells was intravenously infused at 1.5, and 3 days prior to CA. The animal model was established by 8 min of CA and then 8 min of CPR. After resuscitation, cardiac, cerebral function and injury biomarkers were regularly evaluated for a total of 24 h. At 24 h post-resuscitation, pyroptosis-related proteins (NLRP3, ASC, cleaved caspase-1, GSDMD), proinflammatory cytokines (IL-1ß, IL-18), ferroptosis-related proteins (ACSL4, GPX4) and iron deposition in the heart, cortex and hippocampus were measured. Consequently, significantly greater cardiac, cerebral dysfunction and injuries after resuscitation were observed in the CPR and MSC groups compared with the sham group. However, the severity of cardiac and cerebral damage were significantly milder in the MSC group than in the CPR group. In addition, the expression levels of NLRP3, ASC, cleaved caspase-1, GSDMD and ACSL4, the contents of IL-1ß and IL-18, and the level of iron deposition were significantly higher while the expression level of GPX4 was significantly lower in the heart, cortex and hippocampus in all resuscitated animals compared with the sham group. Nevertheless, MSCs administration significantly decreased post-resuscitation cardiac, cerebral pyroptosis and ferroptosis compared to the CPR group. Our results showed that the administration of MSCs significantly alleviated post-resuscitation cardiac and cerebral injuries in swine, in which the protective effects were related to the inhibition of cell pyroptosis and ferroptosis.

Estimation of the reproductive number of novel coronavirus (COVID-19) and the probable outbreak size on the Diamond Princess cruise ship: A data-driven analysis.

BACKGROUNDS: Up to February 16, 2020, 355 cases have been confirmed as having COVID-19 infection on the Diamond Princess cruise ship. It is of crucial importance to estimate the reproductive number (R0) of the novel virus in the early stage of outbreak and make a prediction of daily new cases on the ship. METHOD: We fitted the reported serial interval (mean and standard deviation) with a gamma distribution and applied "earlyR" package in R to estimate the R0 in the early stage of COVID-19 outbreak. We applied "projections" package in R to simulate the plausible cumulative epidemic trajectories and future daily incidence by fitting the data of existing daily incidence, a serial interval distribution, and the estimated R0 into a model based on the assumption that daily incidence obeys approximately Poisson distribution determined by daily infectiousness. RESULTS: The Maximum-Likelihood (ML) value of R0 was 2.28 for COVID-19 outbreak at the early stage on the ship. The median with 95% confidence interval (CI) of R0 values was 2.28 (2.06-2.52) estimated by the bootstrap resampling method. The probable number of new cases for the next ten days would gradually increase, and the estimated cumulative cases would reach 1514 (1384-1656) at the tenth day in the future. However, if R0 value was reduced by 25% and 50%, the estimated total number of cumulative cases would be reduced to 1081 (981-1177) and 758 (697-817), respectively. CONCLUSION: The median with 95% CI of R0 of COVID-19 was about 2.28 (2.06-2.52) during the early stage experienced on the Diamond Princess cruise ship. The future daily incidence and probable outbreak size is largely dependent on the change of R0. Unless strict infection management and control are taken, our findings indicate the potential of COVID-19 to cause greater outbreak on the ship.