Clinical characteristics of extracorporeal cardiopulmonary resuscitation in China: a multicenter retrospective study.

PURPOSE: Extracorporeal cardiopulmonary resuscitation (ECPR) might markedly increase the survival of selected patients with refractory cardiac arrest. But the application situation and indications remained unclear. MATERIALS AND METHODS: We respectively reviwed all adult patients who underwent ECPR from January 2017 to March 2021. Patient characteristics, initiation and management of ECMO, complications, and outcomes were collected and compared between the survivors and nonsurvivors. LASSO regression was used to screen risk factors. Multivariate logistic regression was performed with several parameters screened by LASSO regression. RESULTS: Data were reported from 42 ECMO centers covering 19 provinces of China. A total of 648 patients were included in the study, including 491 (75.8%) males. There were 11 ECPR centers in 2017, and the number increased to 42 in 2020. The number of patients received ECPR increased from 33 in 2017 to 274 in 2020, and the survival rate increased from 24.2% to 33.6%. Neurological complications, renal replacement therapy, epinephrine dosage after ECMO, recovery of spontaneous circulation before ECMO, lactate clearance and shockable rhythm were risk factors independently associated with outcomes of whole process. Sex, recovery of spontaneous circulation before ECMO, lactate, shockable rhythm and causes of arrest were pre-ECMO risk factors independently affecting outcomes. CONCLUSIONS: From January 2017 to March 2021, the numbers of ECPR centers and cases in mainland China increased gradually over time, as well as the survival rate. Pre-ECMO risk factors, especially recovery of spontaneous circulation before ECMO, shockable rhythm and lactate, are as important as post-ECMO management,. Neurological complications are vital risk factors after ECMO that deserved close attention. TRIAL REGISTRATION: NCT04158479, registered on 2019/11/08. https://clinicaltrials.gov/NCT04158479.

Esmolol increases the fecal abundance of Lactobacillus in a rat model of sepsis.

BACKGROUND: Disorders of the gut microbiome could be responsible for the progression of multiple organ dysfunction syndrome. In this study, we examined the effect of esmolol on the gut microbiome in a rat model of sepsis induced by cecal ligation and puncture (CLP). METHODS: The animals (n = 32) were randomly divided into 3 groups: Sham group (sham operation + normal saline treatment, n = 8), CLP group (cecal ligation and puncture + normal saline treatment, n = 12), and CLP + ESM group (cecal ligation and puncture + esmolol treatment, n = 12). After 24 h, feces in the colon were collected for 16S rRNA gene sequencing and nitric oxide analysis. In addition, colon was removed for immunohistochemical staining of inducible nitric oxide synthase (iNOS). RESULTS: Four rats in the CLP group and two rats in the CLP + ESM group died. The abundance of Lactobacillus in the CLP + ESM group was higher than CLP group (P = 0.048). In the linear discriminant analysis effect size analysis, Norank f Muribaculaceae, Escherichia-Shigella and Lactobacillus were the predominant bacteria in the Sham group, CLP group and CLP + ESM group, respectively. The iNOS expression in colonocytes stained by brown in the CLP group were much more than Sham group (P = 0.001). Compared to CLP group, the iNOS expression in colonocytes reduced after esmolol treatment (P = 0.013). The concentration of nitric oxide in colon feces was different in Sham group, CLP group and CLP + ESM group (1.31 ± 0.15µmmol/l vs. 1.98 ± 0.27µmmol/l vs. 1.51 ± 0.14µmmol/l, P = 0.001). In addition, the concentration of nitric oxide in CLP group was higher than Sham group (P = 0.001) or CLP + ESM group (P = 0.001). CONCLUSIONS: Esmolol increased the fecal abundance of Lactobacillus in a rat model of sepsis. Moreover, esmolol reduced the iNOS expression of colonocytes and the nitric oxide concentration of colon feces.

[Exploration and practice of building tele-critical care system].

OBJECTIVE: To look for the problems faced in the construction of the tele-critical care system, explore the framework of construction of the tele-critical care system, and verify the application effects of the established tele-critical care system. METHODS: Through literature review and on-site investigation and demonstration, the causes affecting the construction of the tele-critical care system were explored. Through on-site investigation of the actual situation of the critical care department in relevant hospitals, arguing and choosing intended intensive care unit (ICU) and cooperative third-party communication and equipment companies, and through the Internet of Things and 5G communication technology, a tele-critical care system with the core hospital of the group as the center and the member institutes within the group as the nodes was built. Via the established tele-critical care system, activities such as tele-monitoring, visual remote ward rounds, remote consultation, remote teaching were carried out to verify the functions of the system. RESULTS: The insufficient cognition of relevant personnel, tele-medicine practice certification requirements, information security issues and the barriers of equipment information integration were the main causes affecting the construction of tele-critical care system. There were five parts in the tele-critical care system architecture foundations, including bed unit equipment and audio and video information collection system, lossless and secure transmission of collected information, real-time display of information in the remote center, real-time staff interaction between the centre and the nodal hospitals, and information cloud storage. It has been verified that patients' diagnostic and treatment information can be transmitted safely, losslessly and in real-time by a special line through private 5G network. Through this system, real-time and stable upload of audio and video information of patients and application information of monitors, ventilators and infusion work stations can be achieved; combined with tele-conference connections to conduct two-way communication with local medical staff, real-time tele-monitoring, visual remote ward rounds, remote consultation, remote teaching and other functions can be achieved. CONCLUSIONS: The tele-critical care system we established is feasible to construct within the medical group and can safely and effectively realize the functions of real-time tele-monitoring, visual remote ward rounds, remote consultation, and remote teaching.

Chemotherapy-induced adenosine A2B receptor expression mediates epigenetic regulation of pluripotency factors and promotes breast cancer stemness.

Rationale: Triple-negative breast cancer (TNBC) is characterized by its unique molecular profile, aggressive nature and lack of targeted therapy. Chemotherapy induces expression of pluripotency factors and mediates an active induction of breast cancer stem cells (BCSCs) in TNBC, which potentiates the risk of tumor recurrence and metastasis and increases patient mortality. Adenosine receptor 2B (A2BR) expression and activation of its downstream signaling pathway has been implied to promote breast cancer metastasis. This study is to investigate the role of A2BR in the regulation of chemotherapy-induced BCSC enrichment. Methods: We generated shRNA-mediated A2BR knockdown subclones in TNBC cell lines and evaluated the effect on the BCSC phenotype by Aldefluor and mammosphere assays in vitro. We performed chromatin immunoprecipitation (ChIP) assay to investigate recruitment of transcription factor FOXO3 and histone modification enzymes KDM6A and p300 to the regulatory regions of pluripotency factors, as well as levels of histone modification marks H3K27ac and H3K27me3 on these regions. We employed both xenograft model and genetically engineered, autochthonous breast cancer model to evaluate the effect of A2BR on chemotherapy-induced BCSC enrichment in vivo. Results: We demonstrated that chemotherapy increased protein level of A2BR, which contributed to chemotherapy-induced pluripotency factor expression and BCSC enrichment in TNBC. A2BR mediated activation of p38 MAPK and nuclear translocation of chromatin remodeling factor SMARCD3, which interacted and recruited histone demethylase KDM6A and histone acetyltransferase p300 specifically to the pluripotency factor genes NANOG, SOX2 and KLF4. Recruitment of KDM6A and p300 decreased histone H3K27me3 and increases H3K27ac marks, and increased transcription factor FOXO3 binding to NANOG, SOX2 and KLF4 genes, leading to transcriptional activation of these genes and BCSC specification. Genetic or pharmacological inhibition of A2BR blocked chemotherapy-mediated epigenetic activation of pluripotency factor genes and BCSC enrichment in vitro and in vivo, and delayed tumor recurrence after chemotherapy was discontinued. Conclusion: Chemotherapy-induced A2BR expression mediates epigenetic activation of pluripotency factors and promotes breast cancer stemness. Targeting A2BR in combination with chemotherapy may block BCSC enrichment and improve outcome in TNBC.