Perioperative oxygenation impairment related to type a aortic dissection.

Type A aortic dissection (TAAD) is a life-threatening disease with high mortality and poor prognosis, usually treated by surgery. There are many complications in its perioperative period, one of which is oxygenation impairment (OI). As a common complication of TAAD, OI usually occurs throughout the perioperative period of TAAD and requires prolonged mechanical ventilation (MV) and other supportive measures. The purpose of this article is to review the risk factors, mechanisms, and treatments of type A aortic dissection-related oxygenation impairment (TAAD-OI) so as to improve clinicians' knowledge about it. Among risk factors, elevated body mass index (BMI), prolonged extracorporeal circulation (ECC) duration, higher inflammatory cells and stored blood transfusion stand out. A reduced occurrence of TAAD-OI can be achieved by controlling these risk factors such as suppressing inflammatory response by drugs. As for its mechanism, it is currently believed that inflammatory signaling pathways play a major role in this process, including the HMGB1/RAGE signaling pathway, gut-lung axis and macrophage, which have been gradually explored and are expected to provide evidences revealing the specific mechanism of TAAD-OI. Numerous treatments have been investigated for TAAD-OI, such as nitric oxide (NO), continuous pulmonary perfusion/inflation, ulinastatin and sivelestat sodium, immunomodulation intervention and mechanical support. However, these measures are all aimed at postoperative TAAD-OI, and not all of the therapies have shown satisfactory effects. Treatments for preoperative TAAD-OI are not currently available because it is difficult to correct OI without correcting the dissection. Therefore, the best solution for preoperative TAAD-OI is to operate as soon as possible. At present, there is no specific method for clinical application, and it relies more on the experience of clinicians or learns from treatments of other diseases related to oxygenation disorders. More efforts should be made to understand its pathogenesis to better improve its treatments in the future.

Mortality risk factors in patients receiving ECPR after cardiac arrest: Development and validation of a clinical prognostic prediction model.

BACKGROUND: Previous studies have shown an increasing trend of extracorporeal cardiopulmonary resuscitation (ECPR) use in patients with cardiac arrest (CA). Although ECPR have been found to reduce mortality in patients with CA compared with conventional cardiopulmonary resuscitation (CCPR), the mortality remains high. This study was designed to identify the potential mortality risk factors for ECPR patients for further optimization of patient management and treatment selection. METHODS: We conducted a prospective, multicentre study collecting 990 CA patients undergoing ECPR in 61 hospitals in China from January 2017 to May 2022 in CSECLS registry database. A clinical prediction model was developed using cox regression and validated with external data. RESULTS: The data of 351 patients meeting the inclusion criteria before October 2021 was used to develop a prediction model and that of 68 patients after October 2021 for validation. Of the 351 patients with CA treated with ECPR, 227 (64.8%) patients died before hospital discharge. Multivariate analysis suggested that a medical history of cerebrovascular diseases, pulseless electrical activity (PEA)/asystole and higher Lactate (Lac) were risk factors for mortality while aged 45-60, higher pH and intra-aortic balloon pump (IABP) during ECPR have protective effects. Internal validation by bootstrap resampling was subsequently used to evaluate the stability of the model, showing moderate discrimination, especially in the early stage following ECPR, with a C statistic of 0.70 and adequate calibration with GOF chi-square = 10.4 (p = 0.50) for the entire cohort. Fair discrimination with c statistic of 0.65 and good calibration (GOF chi-square = 6.1, p = 0.809) in the external validation cohort demonstrating the model's ability to predict in-hospital death across a wide range of probabilities. CONCLUSION: Risk factors have been identified among ECPR patients including a history of cerebrovascular diseases, higher Lac and presence of PEA or asystole. While factor such as age 45-60, higher pH and use of IABP have been found protective against in-hospital mortality. These factors can be used for risk prediction, thereby improving the management and treatment selection of patients for this resource-intensive therapy.

Advances of mesenchymal stem cells and their derived extracellular vesicles as a promising therapy for acute respiratory distress syndrome: from bench to clinic.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury characterized by diffuse alveolar damage. The period prevalence of ARDS was 10.4% of ICU admissions in 50 countries. Although great progress has been made in supportive care, the hospital mortality rate of severe ARDS is still up to 46.1%. Moreover, up to now, there is no effective pharmacotherapy for ARDS and most clinical trials focusing on consistently effective drugs have met disappointing results. Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have spawned intense interest of a wide range of researchers and clinicians due to their robust anti-inflammatory, anti-apoptotic and tissue regeneration properties. A growing body of evidence from preclinical studies confirmed the promising therapeutic potential of MSCs and their EVs in the treatment of ARDS. Based on the inspiring experimental results, clinical trials have been designed to evaluate safety and efficacy of MSCs and their EVs in ARDS patients. Moreover, trials exploring their optimal time window and regimen of drug administration are ongoing. Therefore, this review aims to present an overview of the characteristics of mesenchymal stem cells and their derived EVs, therapeutic mechanisms for ARDS and research progress that has been made over the past 5 years.

Prevalence of burnout among perfusionists in China: A nationwide survey.

BACKGROUND: Burnout has gained increasing attention worldwide as a phenomenon that affects health care professionals. However, there is a lack of relevant research about its impact on practitioners in the field of cardiovascular perfusion in China. This study investigated the prevalence of and the factors associated with the burnout affecting perfusionists in mainland China. METHODS: This national cross-sectional study included perfusionists from 31 provinces in mainland China. Participants were asked to complete a self-administered questionnaire, which included three parts: (1) demographic information, (2) work-related information, and (3) dissatisfaction with work and sources of pressure. The levels of burnout were calculated, and logistic regression was used to analyze the factors associated with burnout. RESULTS: The questionnaire, created by the survey program "Questionnaire Star", was sent to 2211 perfusionists in mainland China. A final sample of 1813 perfusionists participated in the survey, with a participation rate of 82.0% (1813/2211). The prevalence of burnout and severe burnout was 86.0% (1559/1813, 95%CI: 84.3%-87.5%) and 13.3% (241/1813, 95%CI: 11.8%-15.0%), respectively. The logistic regression analysis revealed that age [20-29 years, odds ratio (OR) = 1; 30-39 years, OR = 2.009; 40-49 years, OR = 2.220], educational background (bachelor and below, OR = 1; postgraduate, OR = 1.472), and professional background (others, OR = 1; surgery, OR = 1.283; anesthesiology, OR = 2.004) were associated with burnout. We also found that age (20-29 years, OR = 1; 30-39 years, OR = 1.928), professional background (others, OR = 1; surgery, OR = 1.734; anesthesiology, OR = 2.257), annual cardiopulmonary bypass (CPB) case load in the most recent 3 years (< 50, OR = 1; 50-100, OR = 1.613; 100-300, OR = 1.702; ≥300, OR = 2.637), and income level [< 5000 (RMB/month), OR = 1; 5000-10,000, OR = 0.587; 10,000-20,000, OR = 0.366] were associated with severe burnout among perfusionists. CONCLUSIONS: Cardiovascular perfusionists in mainland China experience high rates of burnout. Age, the professional background, annual CPB caseload in the most recent 3 years, and income level are independently associated with the burnout rates experienced by these health care professionals.

EXTRACORPOREAL CARDIOPULMONARY RESUSCITATION WITH THERAPEUTIC HYPOTHERMIA MITIGATES KIDNEY INJURY AFTER CARDIAC ARREST IN RATS.

ABSTRACT: Many patients with cardiac arrest (CA) experience severe kidney injury after the return of spontaneous circulation. This study aimed to compare the renal protective effect of conventional cardiopulmonary resuscitation (CCPR), extracorporeal cardiopulmonary resuscitation (ECPR), and ECPR with therapeutic hypothermia (ECPR+T) in a CA rat model. Twenty-four adult male Sprague-Dawley rats were randomly and equally allocated into the sham, CCPR, ECPR, and ECPR+T groups. The sham group underwent basic surgical procedures without asphyxia-induced CA. The other three groups were treated with asphyxiation to establish the CA model. Subsequently, they were rescued using three different therapeutic methods. The end points were 1 h after return of spontaneous circulation or death. Renal injury was evaluated by histopathology. Oxidative stress, endoplasmic reticulum stress, necroptosis, inflammatory, and apoptosis-related genes, and proteins were detected using western blotting, ELISA, and assay kit. Compared with CCPR, ECPR and ECPR+T alleviated oxidative stress by upregulating nuclear factor erythroid 2-related factor 2, superoxide dismutase, glutathione and downregulating heme oxygenase-1, and malondialdehyde. Expression of endoplasmic reticulum stress-related proteins, glucose-regulated protein 78, and CCAAT/enhancer-binding protein homologous protein was lower in ECPR and ECPR+T groups than that in the CCPR group, along with levels of TNF-α, IL-6, and IL-ß, and necroptosis proteins (receptor-interacting serine/threonine kinases 1 and 3). Furthermore, the ECPR and ECPR+T groups had significantly increased B-cell lymphoma 2 and decreased B-cell lymphoma 2-associated X levels compared with the CCPR group. Extracorporeal cardiopulmonary resuscitation and ECPR+T alleviate kidney damage after CA in rats compared with CCPR. Furthermore, ECPR+T had a better renal protective effect.

The Relationship Between Short-Term Mean Arterial Pressure Variability and Mortality in Critically Ill Patients.

Background: Increased or decreased blood pressure variability may affect the perfusion of tissues and organs, leading to acute kidney injury and death. This study was conducted to explore the relationship between mean arterial pressure variability and short- and long-term mortality in critically ill patients. Methods: We used patient data from the MIMIC-III database for cohort study. According to the recorded mean arterial pressure during the first 24 h in the intensive care unit, we calculated each patient's two variability parameters -coefficient of variation and average real variability. The primary outcome was in-hospital mortality and the secondary outcomes were 28-day mortality and 1-year mortality. We conducted smooth spline models to examine the possible nonlinear associations between blood pressure variability and mortality. According to the smoothing curve, we further developed a two-piecewise linear regression model to find out the threshold effect. Multivariable logistic regression or Cox proportional hazards model was used to evaluate the relationship. Kaplan-Meier survival analysis for 28-day and 1-year mortality was performed. Subgroup analysis explored the factors modifying the relationship between them. Results: A total of 12,867 patients were enrolled in the study, 1,320 in-hospital death, 1,399 28-day death, and 2,734 1-year death occurred. The smooth spline showed death risk was the lowest when average real variability was around 7.2 mmHg. After adjusting for covariates, logistic or Cox regression showed the highest MAP variability level was strongly associated with increased mortality in the hospital (odds ratio: 1.44; 95% CI, 1.21∼1.72), at 28 days (hazard ratio: 1.28; 95% CI, 1.1∼1.5), and at 1 year (hazard ratio: 1.27; 95% CI, 1.14∼1.42) compared with the second level of average real variability group. The survival curve plot showed patients with higher average real variability had a higher risk of 28-day and 1-year mortality. This relationship remained remarkable in patients with low or high Sequential Organ Failure Assessment scores in the sensitivity analysis. The two-piecewise linear regression model showed that lower ARV was a risk factor for 28-day (HR 0.72, 95% CI, 0.57∼0.91) and 1-year mortality (HR 0.81, 95% CI, 0.68∼0.96) when ARV was less than 7.2 mmHg, higher ARV was a risk factor for 28-day mortality (HR 1.1, 95% CI, 1.04∼1.17) and 1-year mortality (HR 1.07, 95% CI, 1.02∼1.12) when ARV was greater than 7.2 mmHg. Conclusion: Blood pressure variability predicts mortality in critically ill patients. Individuals with higher or lower mean arterial pressure average real variability during the first day in ICU may have an increased risk of death.

Inflammatory alveolar macrophage-derived microvesicles damage lung epithelial cells and induce lung injury.

Emerging evidence has demonstrated that several microvesicles (MVs) are secreted in bronchoalveolar lavage fluid (BALF) during the pathogenesis of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the impact of alveolar macrophage (AM)-derived MVs on epithelial cells and their in vivo effects on ALI/ARDS require further exploration. In this study, MVs were isolated from BALF of mice or mouse alveolar macrophage (MHS) cells by sequential centrifugation and then delivered to epithelial cells or mice. Enzyme-linked immunosorbent assay revealed that BALF-derived MVs (BALF-MVs) and MHS-derived MVs (AM-MVs) were rich in tumor necrosis factor-α (TNF-α) at the early stage of lung injury. In vitro, both inflammatory BALF-MVs and AM-MVs decreased the expression of α subunit of epithelial sodium channel (α-ENaC), γ-ENaC, and Na+,K+-ATPase α1 and ß1 in lung epithelial cells. However, antibodies against TNF-α inhibited the effects of inflammatory AM-MVs in epithelial cells. In vivo, the inflammatory AM-MVs, delivered intratracheally to mice, impaired lung tissues and increased the injury score. They also resulted in decreased alveolar fluid clearance and increased lung wet weight/dry weight ratio. Furthermore, inflammatory AM-MVs downregulated the α-ENaC, γ-ENaC, and Na+,K+-ATPase α1 and ß1 levels in lung tissues. According to our results, inflammatory AM-derived MVs may potentially contribute to lung injury and pulmonary edema, thereby indicating a potential novel therapeutic approach against ALI/ARDS based on AM-MVs.

A single-center analysis of outcomes, risk factors, and new valves in Asian patients treated with early transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) continues to expand as an optimal treatment in Western countries; however, Asian countries have been slower to adopt this procedure. This research aimed to explore the outcomes and status of early TAVI performed at a single center in Asia, and provide comparative outcomes of the newly designed Chinese valves. METHODS: We enrolled 175 consecutive patients who successfully underwent TAVI from September 2012 to January 2018 at Fuwai Hospital (Beijing, China). After a preliminary assessment of age, we included 109 older patients (≥69 years) who underwent surgical aortic valve replacement (SAVR) during the same period. The primary endpoint was all-cause mortality. The inverse probability of treatment weighting (IPTW) was used to reduce potential bias. Cox regression was used to identify the risk factors of a poor prognosis. RESULTS: The TAVI cohort had higher rates of all-cause mortality [11.4% vs. 2.4%, hazard ratio (HR): 4.79, 95% confidence interval (CI): 1.47 to 15.57, IPTW-adjusted P=0.009] and permanent pacemaker implantation (PPI; 14.6% vs. 1.6%, HR: 9.98, 95% CI: 2.71 to 36.67, IPTW-adjusted P<0.001) at 3 years than the SAVR cohort. In the multivariable Cox regression analysis based on the entire sample, liver disease was associated with all-cause mortality (HR: 5.080, 95% CI: 1.067 to 24.174, P=0.041). A smoking history was associated with an increased risk of postoperative heart failure (HF) (HR: 4.902, 95% CI: 1.265 to 18.999, P=0.022). Additionally, age (HR: 1.141, 95% CI: 1.010 to 1.288, P=0.034) and diabetes (HR: 7.301, 95% CI: 2.414 to 22.079, P<0.001) were identified as predictors of postoperative stroke. In the new valve subgroups, the 1-year composite endpoints were 38.2% (Venus A), 35.3% (TaurusOne), 34% (J-Valve), and 28% (VitaFlow) (P=0.857). CONCLUSIONS: Not all TAVI procedures had satisfactory outcomes compared with SAVR when initiated. At first, our center faced some challenges in delivering TAVI, and this is probably one of the reasons why the use of TAVI has developed slowly in Asia. Further investigations are needed to explore the underlying factors precluding the rapid expansion of TAVI in Asia.

Electrical storm after correction of an uncomplicated congenital atrial septal defect in an adult: a case report.

BACKGROUND: There is a paucity of published literature describing electrical storm after the correction of uncomplicated atrial septal defect (ASD) in an adult. CASE PRESENTATION: We present a 49-year-old woman with a congenital ASD combined with mild tricuspid regurgitation who denied any history of arrhythmia or other medical history. She suffered from electrical storm (≥ 3 episodes of ventricular tachycardias or ventricular fibrillations) in the early stage after ASD repair with combined tricuspid valvuloplasty. During electrical storm, her electrolytes were within normal ranges and no ischemic electrocardiographic changes were detected, which suggested that retained air embolism or acute coronary thrombosis were unlikely. Additionally, echocardiographic findings and her central venous pressure (5-8 mmHg during the interval between attacks) failed to support the diagnosis of pericardial tamponade. After a thorough discussion, the surgeons conducted an emergent re-exploration and repeated closure of the ASD with combined DeVega's annuloplasty. Eventually, the patient recovered uneventfully, without reoccurring arrhythmias during follow-up. Although we fail to determine the definite cause, we speculate that the causes probably are iatrogenic injury of the conduction system due to a rare anatomic variation, poor intraoperative protection, latent coronary distortion during tricuspid valvuloplasty, or idiopathic or secondary abnormalities of the conduction system. CONCLUSIONS: For most surgeons, performing re-exploration without a known etiology is a difficult decision to make. This case illustrates that re-exploration could be an option when electrical storm occurs in the early stage postoperatively. Nevertheless, surgeons should assess the benefit-risk ratio when taking this unconventional measure.

General Anesthesia Increased the Risk of Atrial Fibrillation and Acute Kidney Injury in Transcatheter Aortic Valve Replacement.

PURPOSE: To examine key impacts of anesthesia on new-onset atrial fibrillation (AF) and acute kidney injury (AKI) in transcatheter aortic valve replacement (TAVR). METHODS: All consecutive patients who underwent transfemoral, transapical, and transaortic TAVR in Fuwai Hospital from 2012 to 2018 were retrospectively analyzed and dichotomized into 2 groups: TAVR under conscious sedation (CS) and under general anesthesia (GA). The primary endpoint was a composite of all-cause mortality, stroke, AF, permanent pacemaker implantation, myocardial infarction, heart failure, high-grade atrioventricular block, and AKI at 1 year. Binary logistic regression and adjusted multilevel logistic regression were performed to analyze the predictors of AF and AKI. RESULTS: A total of 107 patients were under CS and 66 patients under GA. No significant difference was observed in the composite endpoint (51.5% vs. 41.2%, GA vs. CS, P = .182) and ≥ mild paravalvular leakage (36.4% vs. 31.4%, GA vs. CS, P = .589) at 1 year. However, the GA group had a significantly higher rate of intensive care unit (ICU) admission (84.8% vs. 6.5%, P < .001), AKI (28.8% vs. 14.0%, P = .018), new-onset AF (15.2% vs. 5.5% at 1 year, P = .036). Multivariable analysis revealed GA to be the significant predictor of new-onset AF (odds ratio 3.237, 95% confidence interval 1.059 to 9.894, P = .039) and AKI (odds ratio 2.517, 95% confidence interval 1.013 to 6.250, P = .047). CONCLUSION: GA was associated with higher rates of ICU admission, postoperative AKI, and new-onset AF. The results may provide new evidence that CS challenges universal GA.

Propofol suppresses lung cancer tumorigenesis by modulating the circ-ERBB2/miR-7-5p/FOXM1 axis.

BACKGROUND: Propofol is a commonly used anesthetic for cancer surgery. Previous studies have shown that propofol has an anticancer role in various cancers, including lung cancer. This study aimed to investigate the role of propofol in lung cancer and its underlying mechanism. METHODS: Cell proliferation was determined by cell counting kit-8 (CCK-8) and colony formation assays. Flow cytometry and transwell assays were used to detect cell apoptosis and invasion, respectively. Glycolysis was evaluated by detecting glucose consumption, lactate production and ATP/ADP ratios. The levels of circular RNA erb-b2 receptor tyrosine kinase 2 (circ-ERBB2), microRNA-7-5p (miR-7-5p) and forkhead box M1 (FOXM1) were tested by quantitative real-time PCR and Western blot. The binding relationship between miR-7-5p and circ-ERBB2/FOXM1 was verified by dual-luciferase reporter assay. Moreover, in vivo experiments were performed by establishing a mouse xenograft model. RESULTS: Propofol suppressed cell proliferation, invasion and glycolysis and expedited apoptosis in lung cancer cells. Circ-ERBB2 and FOXM1 were upregulated, while miR-7-5p was decreased in lung cancer tissues and cells. Propofol suppressed lung cancer cell progression by regulating circ-ERBB2. Additionally, miR-7-5p directly interacted with circ-ERBB2 and FOXM1. Also, propofol played an antitumor role in lung cancer via modulating miR-7-5p or FOXM1. Moreover, circ-ERBB2 knockdown enhanced the suppressive effect of propofol on tumor growth in vivo. CONCLUSIONS: Propofol inhibited lung cancer progression via mediating circ-ERBB2/miR-7-5p/FOXM1 axis, which might provide an effective therapeutic target for lung cancer therapy.

Extracorporeal Cardiopulmonary Resuscitation in Children of Asia Pacific: A Retrospective Analysis of Extracorporeal Life Support Organization Registry.

BACKGROUND: Recent advances in extracorporeal membrane oxygenation (ECMO) have led to increasing interest in its use during cardiopulmonary resuscitation (CPR). However, decisions regarding extracorporeal CPR (ECPR) in children are difficult as a result of limited studies, especially in Asia Pacific. The objective of this study was to investigate trends in survival and demographic details for children with ECPR in Asia Pacific recorded in the Extracorporeal Life Support Organization (ELSO) registry from 1999 to 2016 and identify the risk factors associated with in-hospital mortality. METHODS: The data of children younger than 18 years of age who received ECPR over the past 18 years in Asia Pacific were retrospectively analyzed. The data were extracted from the ELSO registry and divided into two 9-year groups (Group 1: 1999-2007 and Group 2: 2008-2016) to assess temporal changes using univariate analysis. Then, univariate and multiple logistic regression analyses were performed between survivors and nonsurvivors to identify factors independently associated with in-hospital mortality. RESULTS: A total of 321 children were included in final analysis, with an overall survival rate of 50.8%. Although survival rates were similar between Group 1 and Group 2 (43.1% vs. 52.5%, χ2 = 1.67, P = 0.196), the median age (1.7 [0.3, 19.2] months for Group 1 vs. 5.6 [0.8, 64.9] months for Group 2, t = -2.93, P = 0.003) and weight (3.7 [3.0, 11.5] kg for Group 1 vs. 6.0 [3.4, 20.3] kg for Group 2, t = -3.14, P = 0.002) of children increased over time, while the proportion of congenital heart disease (75.9% for Group 1 vs. 57.8% for Group 2, χ2 = 6.52, P = 0.011) and cardiogenic shock (36.2% for Group 1 vs. 7.2% for Group 2, χ2 = 36.59, P < 0.001) decreased. Patient conditions before ECMO were worse, while ECMO complications decreased across time periods, especially renal complications. Multiple logistic regression analysis of ECMO complications showed that disseminated intravascular coagulation (DIC), myocardial stunning, and neurological complications were independently associated with increased odds of hospital mortality. CONCLUSIONS: The broader indications and decreased complication rates make EPCR to be applicated more and more extensive in children in Asia Pacific region. ECMO complications such as myocardial stunning are independently associated with decreased survival.

Effects of pumpless extracorporeal lung assist on hemodynamics, gas exchange and inflammatory cascade response during experimental lung injury.

Pumpless extracorporeal lung assist (pECLA) has been reported to efficiently remove the systemic CO2 production and provide mild to moderate oxygenation, thereby allowing for ventilator settings and modes prioritizing oxygenation and lung protection. However, an adequate bypass flow, the capacity to provide respiratory support and the effect on the inflammatory cascade response and tissue perfusion require further study to be determined. After induction of acute lung injury (ALI) by oleic acid injection, pECLA was implemented in 12 anaesthetized and mechanically ventilated dogs for 48 h. Improved oxygenation [partial oxygen pressure (PaO2) and oxygen saturation (SaO2) was measured by arterial blood gas analysis, and increased by 29 and 18%, respectively] and CO2 elimination (partial CO2 pressure decreased by 43.35%) were obtained after pECLA implementation. A maximum arterio-venous shunt flow of up to 25% of the foundational CO resulted in stable hemodynamics. The pECLA procedure did not elicit any further increase in the concentration of tumor necrosis factor-α, interleukin (IL)-6, IL-8 and endothelin-1 compared with that in the group subjected to oleic acid injection only. In addition, the pECLA procedure had no effect on lactate levels and urine production. In conclusion, pECLA is an efficient and promising strategy for providing a mild to moderate oxygenation and adequate decarboxylation, while avoiding excessive inflammatory cascade response and tissue hypoperfusion in an experimental ALI model.

Decellularized Rat Lung Scaffolds Using Sodium Lauryl Ether Sulfate for Tissue Engineering.

Perfusion decellularization with detergents is effective to maintain the architecture and proteins of extracellular matrix (ECM) for use in the field of lung tissue engineering (LTE). However, it is unclear which detergent is ideal to produce an acellular lung scaffold. In this study, we obtained two decellularized rat lung scaffolds using a novel detergent sodium lauryl ether sulfate (SLES) and a conventional detergent sodium dodecyl sulfate (SDS). Both decellularized lung scaffolds were assessed by histology, immunohistochemistry, scanning electron microscopy, DNA quantification, sulfated glycosaminoglycans (GAGs) quantification and western blot. Subsequently, the scaffolds were implanted subcutaneously in rats for 6 weeks and were evaluated via hematoxylin and eosin staining and Masson staining. Results indicated that SLES was effective to remove cells; moreover, lungs decellularized with SLES showed better preservation of sulfated GAGs, lung architecture, and ECM proteins than SDS. After 6 weeks, SLES scaffolds demonstrated a significantly greater potential for cell infiltration and blood vessel formation compared with SDS scaffolds. Taken together, we conclude that SLES is a promising detergent to produce an acellular scaffold using LTE for eventual transplantation.

Incidence, Risk Factors, and Outcomes of Hyperbilirubinemia in Adult Cardiac Patients Supported by Veno-Arterial ECMO.

The aims of this study were to evaluate the incidence, risk factors, and outcomes of hyperbilirubinemia in cardiac patients with veno-arterial (VA) ECMO. Data on 89 adult patients with cardiac diseases who received VA ECMO implantation in our hospital were retrospectively reviewed. All patients were divided into the following three groups: 24 in normal group (N, total bilirubin [TBIL] ≤3 mg/dL), 30 in high bilirubin group (HB, 6 mg/dL ≥ TBIL > 3 mg/dL), and 35 in severe high bilirubin group (SHB, TBIL > 6 mg/dL). lg(variables + 1) was performed for nonnormally distributed variables. The incidence of hyperbilirubinemia (>3 mg/dL) was 73%. In a multiple linear regression analysis, lg(peak TBIL + 1) was significantly associated with lg(peak AST + 1) (b-coefficient 0.188, P = 0.001), lg(peak pFHb + 1) (b-coefficient 0.201, P = 0.003), and basic TBIL (b-coefficient 0.006, P = 0.009). Repeated measurement analysis of variance revealed that the main effect for three groups in pFHb and lg(AST + 1) was significant at first 3 days during ECMO. The patients in SHB had low platelets during ECMO and low in-hospital survival rate. Hyperbilirubinemia remains common in patients with VA ECMO and is associated with low platelets and high in-hospital mortality. Hemolysis and liver dysfunction during ECMO and basic high bilirubin levels are risk factors of hyperbilirubinemia.

Exosomes from iPSCs Delivering siRNA Attenuate Intracellular Adhesion Molecule-1 Expression and Neutrophils Adhesion in Pulmonary Microvascular Endothelial Cells.

The pro-inflammatory activation of pulmonary microvascular endothelial cells resulting in continuous expression of cellular adhesion molecules, and subsequently recruiting primed neutrophils to form a firm neutrophils-endothelium (PMN-EC) adhesion, has been examined and found to play a vital role in acute lung injury (ALI). RNA interference (RNAi) is a cellular process through harnessing a natural pathway silencing target gene based on recognition and subsequent degradation of specific mRNA sequences. It opens a promising approach for precision medicine. However, this application was hampered by many obstacles, such as immunogenicity, instability, toxicity problems, and difficulty in across the biological membrane. In this study, we reprogrammed urine exfoliated renal epithelial cells into human induced pluripotent stem cells (huiPSCs) and purified the exosomes (Exo) from huiPSCs as RNAi delivery system. Through choosing the episomal system to deliver transcription factors, we obtained a non-integrating huiPSCs. Experiments in both vitro and vivo demonstrated that these huiPSCs possess the pluripotent properties. The exosomes of huiPSCs isolated by differential centrifugation were visualized by transmission electron microscopy (TEM) showing a typical exosomal appearance with an average diameter of 122 nm. Immunoblotting confirmed the presence of the typical exosomal markers, including CD63, TSG 101, and Alix. Co-cultured PKH26-labeled exosomes with human primary pulmonary microvascular endothelial cells (HMVECs) confirmed that they could be internalized by recipient cells at a time-dependent manner. Then, electroporation was used to introduce siRNA against intercellular adhesion molecule-1 (ICAM-1) into exosomes to form an Exo/siRNA compound. The Exo/siRNA compound efficiently delivered the target siRNA into HMVECs causing selective gene silencing, inhibiting the ICAM-1 protein expression, and PMN-EC adhesion induced by lipopolysaccharide (LPS). These data suggest that huiPSCs exosomes could be used as a natural gene delivery vector to transport therapeutic siRNAs for alleviating inflammatory responses in recipient cells.

Plasma Free Hemoglobin Is a Predictor of Acute Renal Failure During Adult Venous-Arterial Extracorporeal Membrane Oxygenation Support.

OBJECTIVE: Hemolysis is a common and severe complication during extracorporeal membrane oxygenation (ECMO). Increased plasma free hemoglobin (PFHb) is related to renal injury. The aim of this study was to investigate whether increased PFHb during adult venous-arterial ECMO was associated with acute renal failure (ARF). DESIGN: A retrospective, observational, single-center study. SETTING: Fuwai Hospital in Beijing, China. PARTICIPANTS: The study comprised 84 venous-arterial ECMO patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 84 consecutive adult patients (≥18 years) with cardiac diseases requiring venous-arterial ECMO support were studied retrospectively. Demographics of patients, clinical and ECMO characteristics, and PFHb level were collected within the first 3 days after ECMO. ARF was defined as a≥300% rise in serum creatinine from baseline or application of dialysis. Repeated measurement analysis of variance revealed that the main effect for the non-ARF group and ARF group in PFHb (p = 0.002) was significant. A significant main effect for time points (p<0.001) and time×group interaction (p = 0.014) in PFHb was obtained. In a multiple logistic regression model, peak PFHb during ECMO (odds ratio 1.052, 95% confidence interval 1.016-1.089, p = 0.005) was a risk factor for ARF during ECMO and patients who underwent heart transplantation (odds ratio 0.240, 95% confidence interval 0.060-0.964, p = 0.044) experienced less ARF. There was a linear correlation between peak serum creatinine and peak PFHb (Spearman's r = 0.223, p = 0.042). CONCLUSIONS: Increased PFHb is a predictor of ARF among adult patients on venous-arterial ECMO support.

Predictors of Acute Renal Failure During Extracorporeal Membrane Oxygenation in Pediatric Patients After Cardiac Surgery.

Acute renal failure (ARF) is associated with increased mortality in pediatric extracorporeal membrane oxygenation (ECMO). The aim of this study was to identify predictors of ARF during ECMO in pediatric patients after cardiac surgery. A retrospective study analyzed 42 children (≤15 years) after cardiac surgery requiring venous-arterial ECMO between December 2008 and December 2014 at Fuwai Hospital. ARF was defined as ≥300% rise in serum creatinine (SCr) concentration from baseline or application of dialysis. Multivariate logistic regression was performed to identify the predictors of ARF during ECMO. A total of 42 children (age, interquartile range [IQR], 13.0 [7.2-29.8] months; weight, IQR, 8.5 [6.7-11.0] kg) after cardiac surgery requiring ECMO were included in this study. The total survival rate was 52.4%, and the incidence of ARF was 40.5%. As the result of univariate analysis, ECMO duration, cardiopulmonary resuscitation, maximum free hemoglobin (FHB) during ECMO, lactate level, and mean blood pressure before initiation of ECMO were entered in multiple logistic regression analysis. In multiple logistic regression analysis, FHB during ECMO (OR 1.136, 95% CI 1.023-1.261) and lactate level before initiation of ECMO (OR 1.602, 95% CI 1.025-2.502) were risk factors for ARF during ECMO after pediatric cardiac surgery. There was a linear correlation between maximum SCr and maximum FHB (Pearson's r = 0.535, P = 0.001). Maximum SCr during ECMO has also a linear correlation with lactate level before initiation of ECMO (Pearson's r = 0.342, P = 0.044). Increased FHB during ECMO and high lactate level before initiation of ECMO were risk factors for ARF during ECMO in pediatric patients after cardiac surgery.

Differentiation of Urine-Derived Human Induced Pluripotent Stem Cells to Alveolar Type II Epithelial Cells.

Human alveolar type II (AT II) epithelial cells are valuable for the cellular therapy of lung disease. Human induced pluripotent stem cells (iPSCs) have the ability to generate AT II cells that can be used in modeling and treatment of lung disease caused by dysfunction of AT II cells. In this study, we present a simple, effective, and noninvasive way of obtaining human iPSCs from exfoliated renal epithelial cells, which exist in urine. Alkaline phosphatase (AP) staining, immunofluorescence staining, karyotyping, and teratoma experiments have proved that these iPSCs are pluripotent. Urinary iPSCs (UiPSCs) can differentiate into AT II cells with our four-step induction protocol. These cells have phenotypic properties similar to mature human AT II cells, such as outstretched and epithelium-like morphology and the specific expression markers of AT II cells (surfactant proteins A, B, and C). This study indicates that AT II cells can be generated from UiPSCs and these cells may be useful for the study of human lung development and regenerative medicine.