Cerebral Neural Changes in Venous-Arterial Extracorporeal Membrane Oxygenation Survivors.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is used as temporary cardiorespiratory support in patients with critical ailments, but very little is known about the functional cerebral changes in ECMO survivors. Degree centrality (DC), a graph-based assessment of network organization, was performed to explore the neural connectivity changes in ECMO survivors compared to controls and their correlation with cognitive and neurological measures. METHODS: This exploratory observational study was conducted from August 2020 to May 2022. ECMO survivors and controls underwent functional magnetic resonance imaging (fMRI) of the brain. We performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity with other voxels. DC was measured by the fMRI graph method and comparisons between the two groups were performed. All participants underwent neuropsychological assessment (Montreal Cognitive Assessment, MoCA). Blood serum neuron-specific enolase and the Glasgow Coma Scale (GCS) were assessed in ECMO survivors. RESULTS: DC values in the right insula and right precuneus gyrus were lower in ECMO survivors and higher in the right medial superior frontal gyrus compared to controls (all p < 0.001). Decreased connectivity in the right insular and right precuneus gyrus correlated with total MoCA scores, delayed recollection, and calculation (all p < 0.05). Increased serum NSE levels, GCS score, and GCS-motor response correlated with decreased connectivity in the right insular and right precuneus gyrus and increased connectivity in the right medial superior frontal gyrus (all p < 0.05). CONCLUSIONS: We showed that both functional impairment and adaptation were observed in survivors of ECMO, suggesting that neural connectivity changes may provide insights into the mechanisms that may potentially link ECMO survivors to neurological and cognitive disorders.

The correlation between serum Cyclophilin A level and severity, prognosis of craniocerebral injury.

Background: To investigate the value of serum Cyclophilin A(Cyp A) in evaluating the prognosis of patients with different severity of craniocerebral injury. Methods: The clinical data of patients with craniocerebral injury treated in the Department of Emergency from July 2014 to August 2017 were collected. The patients were divided into survival group and death group, good neurological function group and poor neurological function group with 28-day prognosis and were divided into mild (13-15) group, moderate (9-12) group, and severe (3-8) group with Glasgow Coma Scale (GCS) score. Clinical parameters such as Cyp A and mortality in groups and the relationship between Cyp A and GCS score were compared and its predictive value for prognosis was analyzed with Binary Logistics regression, Cox proportional hazards model and kaplan-meier survival curve. Results: In a single-center retrospective study, 503 patients were enrolled, including 365 males and 138 females; serum Cyp A in the survival group was significantly smaller than the death group [18.7 (10.1, 51.5) ng/mL vs. 149.8 (79.5, 194.4) ng/mL, P < 0.005]. There were significant differences in mortality and Cyp A levels between patients with different severity of craniocerebral injury (P < 0.001). Serum Cyp A levels were negatively correlated with GCS scores in all patients with craniocerebral injury, mild, moderate, or severe craniocerebral injury (r = -0.844, r = -0.256, r = -0.540, r = -0.531, P < 0.001). Predictive value of Serum Cyp A level for all patients with craniocerebral injury, mild, moderate, and severe craniocerebral injury is 0.890, 0.789, 0.806, and 0.833, respectively. Logistics regression analysis showed that lactate (OR = 1.260, 95%CI: 1.023-1.551) and Cyp A (OR = 1.021, 95%CI: 1.011-1.031) were positively correlated with death (P < 0.05), Lactic acid (HR 1.115; 95%CI:1.001-1.243; P = 0.048), GCS score (HR 0.888; 95% CI: 0.794-0.993; P = 0.038), Cyp A levels (HR 1.009; 95% CI: 1.004-1.013; P < 0.001) had a significant effect on short-term mortality. Similar results were seen when neurologic function was used as the outcome. Kaplan-meier survival curve analysis found survival rate of patients with Cyp A level below the cut-off value was significantly higher. Conclusion: Serum Cyp A has a certain predictive value for the prognosis of patients with different severity of craniocerebral injury. Among them, patients with severe craniocerebral injury have the highest predictive value and mild craniocerebral injury patients have the least.

Characterization of Necroptosis-Related Molecular Subtypes and Therapeutic Response in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most common malignant tumors with high morbidity and mortality and is usually associated with therapeutic resistance and poor prognosis because of individual biological heterogeneity. There is an unmet need to screen for reliable parameters, especially immunotherapy-related biomarkers to predict the patient's outcomes. Necroptosis is a special caspase-independent form of necrotic cell death associated with the pathogenesis, progression, and prognosis of multiple tumors but the potential connection between necroptosis-related genes (NRGs) and LUAD still remains unclear. In this study, we expounded mutational and transcriptional alterations of 67 NRGs in 522 LUAD samples and proposed a consensus-clustering subtype of these patients into two cohorts with distinct immunological and clinical prognosis characteristics. Cluster B patients were associated with a better prognosis and characterized by relatively lower expression of NRGs, higher immune scores in the tumor microenvironment (TME), more mild clinical stages, and downregulated expression of immunotherapy checkpoints. Subsequently, the NRG score was further established to predict the overall survival (OS) of LUAD patients using univariate Cox, LASSO, and multivariate Cox regression analyses. The immunological characteristics and potential predictive capability of NRG scores were further validated by 583 LUAD patients in external datasets. In addition to better survival and immune-activated conditions, low-NRG-score cohorts exhibited a significant positive correlation with the mRNA stem index (mRNAsi) and tumor mutation burden (TMB) levels. Combined with classical clinical characteristics and NRG scores, we successfully defined a novel necroptosis-related nomogram to accurately predict the 1/3/5-year survival rate of individual LUAD patients, and the potential predictive capability was further estimated and validated in multiple test datasets with high AUC values. Integrated transcriptomic analysis helps us seek vital NRGs and supplements a novel clinical application of NRG scores in predicting the overall survival and therapeutic benefits for LUAD patients.

Delaying effect of humidity on leaf unfolding in Europe.

Understanding the drivers of plant phenology is critical to predict the impact of future warming on terrestrial ecosystem carbon cycling and feedbacks to climate. Using indoor growth chambers, air humidity is reported to influence spring phenology in temperate trees. However, previous studies have not investigated the effect of air humidity on the spring phenology using long-term and large-scale ground observations. Therefore, the role of humidity in spring phenology in temperate trees still remains poorly understood. Here, we synthesized 229,588 records of leaf unfolding dates in eight temperate tree species, including four early-successional and four late-successional species, at 1716 observation sites during 1951-2015 in Europe, and comprehensively analyzed the effect of humidity on the spring phenology. We found that rising humidity significantly delayed spring leaf unfolding for all eight temperate tree species. Leaf unfolding was more sensitive to humidity in early-successional species compared to late-successional species. In addition, the delaying effect of humidity on leaf unfolding increased as temperature warmed over the past 65 years. Our results provide evidence that spring leaf unfolding of temperate trees was significantly delayed by rising humidity. The delaying effect of humidity may restrict earlier spring phenology induced by warming, especially for early-successional species, under future climate warming scenarios in temperate forests.

Contrasting temporal variations in responses of leaf unfolding to daytime and nighttime warming.

Earlier spring phenological events have been widely reported in plants under global warming. Recent studies reported a slowdown in the warming-induced advanced spring phenology in temperate regions. However, previous research mainly focused on daily mean temperature, thus neglecting the asymmetric phenological responses to daytime and nighttime temperature. Using long-term records of leaf unfolding in eight deciduous species at 1300 sites across central Europe, we assessed and compared the effects of daytime temperature, nighttime temperature, and photoperiod on leaf unfolding during 1951-1980 and 1981-2013. Although leaf unfolding was advanced by daytime warming during 1951-2013, the advancing responses of leaf unfolding significantly decreased from 1951-1980 to 1981-2013 due to a lower accumulation of chilling units by daytime warming. Nighttime warming delayed leaf unfolding during 1951-1980 but advanced it during 1981-2013 due to a higher accumulation of chilling units by nighttime warming. In contrast, critical daylength and plasticity of leaf unfolding dates remained unchanged between 1951 and 2013. Our study provided evidence that daytime warming instead of nighttime warming accounts for the slowdown in the advancing spring phenology and implied that nighttime warming-induced earlier spring phenology may be buffering the slowdown of the advanced spring phenology by daytime warming. The response of spring phenology to nighttime temperature may override that to daytime temperature under the actual trends in global warming.

Hemorrhage and venous thromboembolism in critically ill patients with COVID-19.

OBJECTIVE: The majority of patients with COVID-19 showed mild symptoms. However, approximately 5% of them were critically ill and require intensive care unit admission for advanced life supports. Patients in the intensive care unit were high risk for venous thromboembolism and hemorrhage due to the immobility and anticoagulants used during advanced life supports. The aim of the study was to report the incidence and treatments of the two complications in such patients. METHOD: Patients with COVID-19 (Group 1) and patients with community-acquired pneumonia (Group 2) that required intensive care unit admission were enrolled in this retrospective study. Their demographics, laboratory results, ultrasound findings and complications such as venous thromboembolism and hemorrhage were collected and compared. RESULTS: Thirty-four patients with COVID-19 and 51 patients with community-acquired pneumonia were included. The mean ages were 66 and 63 years in Groups 1 and 2, respectively. Venous thromboembolism was detected in 6 (18%) patients with COVID-19 and 18 (35%) patients with community-acquired pneumonia (P = 0.09). The major type was distal deep venous thrombosis. Twenty-one bleeding events occurred in 12 (35%) patients with COVID-19 and 5 bleeding events occurred in 5 (10%) patients with community-acquired pneumonia, respectively (P = 0.01). Gastrointestinal system was the most common source of bleeding. With the exception of one death due to intracranial bleeding, blood transfusion with or without surgical/endoscopic treatments was able to manage the bleeding in the remaining patients. Multivariable logistic regression showed increasing odds of hemorrhage with extracorporeal membrane oxygenation (odds ratio: 13.9, 95% confidence interval: 4.0-48.1) and COVID-19 (odds ratio: 4.7, 95% confidence interval: 1.2-17.9). CONCLUSION: Venous thromboembolism and hemorrhage were common in both groups. The predominant type of venous thromboembolism was distal deep venous thrombosis, which presented a low risk of progression. COVID-19 and extracorporeal membrane oxygenation were risk factors for hemorrhage. Blood transfusion with or without surgical/endoscopic treatments was able to manage it in most cases.

Application of extracorporeal membrane oxygenation to treatment of serious tracheal stenosis caused by relapsing polychondritis: a case report and literature review.

Relapsing polychondritis (RP) is a multisystemic rheumatic disease characterized by widespread and potentially destructive inflammatory lesions of the cartilage. The rarity of this disease and the lack of pathological diagnostic laboratory tests can occasionally lead to delayed diagnosis. We herein describe a 51-year-old woman with RP. She was sent to our hospital 4 days after the development of an upper respiratory tract infection with difficulty breathing. Her clinical condition significantly improved after the performance of extracorporeal membrane oxygenation support in an awake state, implantation of a tracheal stent, and administration of steroid therapy. Airway involvement of RP may be life-threatening. In this case, endotracheal intubation would have undoubtedly been very dangerous. Extracorporeal membrane oxygenation can be performed in an awake state to maintain oxygenation and improve the chance of survival.

Failure of early extubation among cases of coronavirus disease-19 respiratory failure: Case report and clinical experience.

RATIONALE: Extubation strategy for mechanically ventilated patients with Coronavirus Disease 19 is different from that for patients with other viral pneumonia. We reported 2 cases of Coronavirus Disease 19 receiving tracheal intubation twice during the hospitalization. PATIENT CONCERNS: Two elderly patients with onset of fever and upper respiratory tract infection were confirmed as Coronavirus Disease 19, 1 of whom had chronic obstructive pulmonary disease previously. With active antiviral and noninvasive respiratory supportive therapy, there was no improvement, thus mechanical ventilation (MV) was adopted. Combining with symptomatic and supportive treatment, their oxygenation recovered and then extubation was carried out. However, 96 hours later, they underwent endotracheal intubation again due to their Coronavirus Disease 19 progression. DIAGNOSIS: Critically ill Coronavirus Disease 19 requiring tracheal intubation owing to respiratory failure with lung.javascript. INTERVENTIONS: Initial Strategy for respiratory failure included endotracheal intubation, MV, antiviral treatment and cortisol in both cases. When extubation criteria were satisfied, early discontinuation of MV was conducted, then rehabilitation exercise and nutritional support followed. However, 96 hours later, the disease progressed leading to respiratory failure again, thus reintubation was performed. Later, veno-venous extracorporeal membrane oxygenation was performed owing to aggravation of respiratory failure, assisted by prone position treatment and sputum drainage, then status became stable and stepped into recovery stage. OUTCOMES: Both patients underwent reintubation, and their MV time and Intensive care unit residence time were prolonged. Through prone position treatment, sputum drainage and awake extracorporeal membrane oxygenation strategy, patient has been transferred to rehabilitation unit in Case 1, and patient in Case 2 has been in recovery stage as well with stable pulmonary status and was expected to receive evaluation in recent future. LESSONS: Course of Coronavirus Disease 19 is relatively longer, and failure rate of simple early extubation seemes higher. To reduce the likelihood of reintubation and iatrogenic injury, individualized assessment is recommended.