Impact of an enhanced recovery after surgery program integrating cardiopulmonary rehabilitation on post-operative prognosis of patients treated with CABG: protocol of the ERAS-CaRe randomized controlled trial.

BACKGROUND: Coronary artery bypass grafting is associated with a high occurrence of postoperative cardiopulmonary complications. Preliminary evidence suggested that enhanced recovery after surgery can effectively reduce the occurrence of postoperative cardiopulmonary complications. However, enhanced recovery after surgery with systematic integration of cardiopulmonary rehabilitation (ERAS-CaRe) into for Coronary artery bypass grafting has not been evaluated so far. We thus design the ERAS-CaRe randomized-controlled trial to evaluate possible superiority of embedding cardiopulmonary rehabilitation in ERAS over ERAS alone as well as to investigate effects of differential timing of cardiopulmonary rehabilitation within enhanced recovery after surgery (pre-, post-, perio-operative) on post-operative cardiopulmonary complications following Coronary artery bypass grafting surgery. METHODS: ERAS-CaRe is a pragmatic, randomized-controlled, parallel four-arm, clinical trial. Three hundred sixty patients scheduled for Coronary artery bypass grafting in two Chinese hospitals will be grouped randomly into (i) Standard enhanced recovery after surgery or (ii) pre-operative ERAS-CaRe or (iii) post-operative ERAS-CaRe or (iv) perio-operative ERAS-CaRe. Primary outcome is the occurrence of cardiopulmonary complications at 10 days after Coronary artery bypass grafting. Secondary outcomes include the occurrence of other individual complications including cardiac, pulmonary, stroke, acute kidney injury, gastrointestinal event, ICU delirium rate, reintubation rate, early drainage tube removal rate, unplanned revascularization rate, all-cause mortality, ICU readmission rate, plasma concentration of myocardial infarction-related key biomarkers etc. DISCUSSION: The trial is designed to evaluate the hypothesis that a cardiopulmonary rehabilitation based enhanced recovery after surgery program reduces the occurrence of cardiopulmonary complications following Coronary artery bypass grafting and to determine optimal timing of cardiopulmonary rehabilitation within enhanced recovery after surgery. The project will contribute to increasing the currently limited knowledge base in the field as well as devising clinical recommendations. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trials Registry on 25 August 2023 (ChiCTR2300075125; date recorded: 25/8/2023, https://www.chictr.org.cn/ ).

Anti-angiogenic effect of exo-LncRNA TUG1 in myocardial infarction and modulation by remote ischemic conditioning.

The successful use of exosomes in therapy after myocardial infarction depends on an improved understanding of their role in cardiac signaling and regulation. Here, we report that exosomes circulating after myocardial infarction (MI) carry LncRNA TUG1 which downregulates angiogenesis by disablement of the HIF-1α/VEGF-α axis and that this effect can be counterbalanced by remote ischemic conditioning (RIC). Rats with MI induced through left coronary artery ligation without (MI model) and with reperfusion (ischemia/reperfusion I/R model) were randomized to RIC, or MI (I/R) or sham-operated (SO) control. Data from one cohort study and one randomized-controlled trial of humans with MI were also utilized, the former involving patients who had not received percutaneous coronary intervention (PCI) and the latter patients with PCI. Exosome concentrations did not differ between intervention groups (RIC vs. control) in rats (MI and I/R model) as well as humans (with and without PCI). However, MI and I/R exosomes attenuated HIF-1α, VEGF-α, and endothelial function. LncRNA TUG1 was increased in MI and I/R exosomes, but decreased in SO and RIC exosomes. HIF-1α expression was downregulated with MI and I/R exosomes but increased with RIC exosomes. Exosome inhibition suppressed HIF-1α upregulation through RIC exosomes. VEGF-α was identified as HIF-1α-regulated target gene. Knockdown of HIF-1α decreased VEGF-α, endothelial cell capability, and tube formation. Overexpression of HIF-1α exerted opposite effects. Transfection and co-transfection of 293 T cells with exosome-inhibitor GW4869 and HIF-1α inhibitor si-HIF-1α confirmed the exosomal-LncRNA TUG1/HIF-1α/VEGF-α pathway. LncRNA TUG1 is a potential therapeutic target after MI with or without reperfusion through PCI.

Distinctive Gut Microbiota Alteration Is Associated with Poststroke Functional Recovery: Results from a Prospective Cohort Study.

Objectives: Functional prognosis is potentially correlated with gut microbiota alterations following the dysregulation of the gut-microbiota-brain axis after stroke. This study was designed to explore the poststroke alterations of gut microbiota and potential correlations between gut microbiota and global functions. Methods: A total of thirty-eight patients with stroke and thirty-five healthy demographics-matched controls were recruited. Their fecal DNAs were extracted, and the V3-V4 regions of the conserved bacterial 16S RNA were amplified and sequenced on the Illumina MiSeq platform. Microbial composition, diversity indices, and species cooccurrence were compared between groups. Random forest and receiver operating characteristic analysis were used to identify potential diagnostic biomarkers. Relationships between discriminant bacteria and poststroke functional outcomes were estimated. Results: Higher alpha diversity of gut microbiota was observed in poststroke patients as compared to the healthy controls (p < 0.05). Beta diversity showed that microbiota composition in the poststroke group was significantly different from that in the control group. Relative abundance of nine genera increased significantly in poststroke patients, while 82 genera significantly decreased (p < 0.05). The accuracy, specificity, and susceptibility of the optimal model consisted of the top 10 discriminant species were 93%, 100%, and 86%, respectively. Subgroup analysis showed that bacterial taxa abundant between subacute and chronic stroke patients were overall different (p < 0.05). The modified Rankin scale (mRS) (r = -0.370, p < 0.05), Fugl-Meyer assessment (FMA) score (r = 0.364, p < 0.05), water swallow test (WST) (r = 0.340, p < 0.05), and Barthel index (BI) (r = 0.349, p < 0.05) were significantly associated with alterations of distinctive gut microbiota. Conclusions: The gut microbiota in patients with stroke was significantly changed in terms of richness and composition. Significant associations were detected between alterations of distinctive gut microbiota and global functional prognosis. It would facilitate novel treatment target selection in the context of stroke while the causal relationships between distinctive gut microbiota alterations and functional variations need to be further verified with well-designed studies.

Can Cardiopulmonary Rehabilitation Facilitate Weaning of Extracorporeal Membrane Oxygenation (CaRe-ECMO)? Study Protocol for a Prospective Multidisciplinary Randomized Controlled Trial.

Background: Mortality of patients suffering from critical illness has been dramatically improved with advanced technological development of extracorporeal membrane oxygenation (ECMO) therapy. However, the majority of ECMO-supported patients failed to wean from ECMO therapy. As one of several options, cardiopulmonary rehabilitation serves as effective intervention in the improvement of cardiovascular and respiratory function in various major critical illness. Nonetheless, its role in facilitating ECMO weaning has not yet been explored. The purpose of this study is to investigate the effectiveness of cardiopulmonary rehabilitation on rate of ready for ECMO weaning in ECMO-supported patients (CaRe-ECMO). Methods: The CaRe-ECMO trial is a randomized controlled, parallel group, clinical trial. This trial will be performed in a minimum number of 366 ECMO-supported eligible patients. Patients will be randomly assigned to either: (1) the CaRe-ECMO group, which will be treated with usual care including pharmacotherapy, non-pharmacotherapy, and specific nursing for ECMO therapy and the CaRe-ECMO program; or (2) the control group, which will receive usual care only. The CaRe-ECMO program consists of protocolized positioning, passive range of motion (PROM) training, neuromuscular electrical stimulation (NMES), surface electrical phrenic nerve stimulation (SEPNS), and pulmonary rehabilitation. The primary outcome of the CaRe-ECMO trial is the rate of ready for ECMO weaning at CaRe-ECMO day 7 (refers to 7 days after the CaRe-ECMO program initiation). Secondary outcomes include rate of ECMO and mechanical ventilation weaning, total length in day of ready for ECMO weaning, ECMO weaning and mechanical ventilation, all-cause mortality, rate of major post-ECMO complications, ECMO unit length of stay (LOS) and hospital LOS, total cost for hospitalization, cerebral performance category (CPC), activities of daily living (ADL), and health-related quality of life (HRQoL). Discussion: The CaRe-ECMO is designed to answer the question "whether cardiopulmonary rehabilitation can facilitate weaning of ECMO (CaRe-ECMO)." Should the implementation of the CaRe-ECMO program result in superior primary and secondary outcomes as compared to the controls, specifically the add-on effects of cardiopulmonary rehabilitation to the routine ECMO practice for facilitating successful weaning, the CaRe-ECMO trial will offer an innovative treatment option for ECMO-supported patients and meaningfully impact on the standard care in ECMO therapy. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05035797.

Correlation between the Serum Platelet-Derived Growth Factor, Angiopoietin-1, and Severity of Coronary Heart Disease.

BACKGROUND: The expression of the platelet-derived growth factor (PDGF), angiopoietin-1 (Ang-1) in patients with coronary artery disease of different studies was inconsistent. This study was to investigate the expression of the PDGF and Ang-1 in peripheral blood and coronary artery in patients with acute coronary syndrome (ACS) and the relationship between the expression of the PDGF and Ang-1 and the severity of coronary artery disease. METHODS: A total of 81 patients with acute coronary syndrome undergoing coronary angiography were enrolled from September 2012 to December 2013. Patients with ACS included 61 patients with acute myocardial infarction (AMI group) and 20 patients with unstable angina pectoris (UAP group). The 29 patients who were hospitalized for chest pain undergoing coronary angiography without stenosis and with TIMI level 3 blood flow were selected as the control group. During coronary arteriography (CAG) or percutaneous coronary intervention (PCI), blood in the peripheral artery and in the local coronary artery was collected from all the patients. Serum PDGF and Ang-1 levels were measured by ELISA. We calculated the Gensini score of each patient with CHD according to the result of CAG. Patients with ACS were followed up, and the major adverse cardiovascular and cerebrovascular adverse events were recorded. RESULTS: In peripheral blood, the concentration of the PDGF was significantly elevated in the ACS group than that of the control group. The level of the PDGF in the AMI group was significantly higher than that in the UAP group. In coronary artery blood, the level of the PDGF in the ACS group was significantly higher than that of the UAP group. There was no significant difference in the concentration of Ang-1 in peripheral blood between patients with coronary heart disease and the control group. The concentration of Ang-1 in the coronary artery was significantly lower than that in peripheral blood. The coronary Ang-1 concentrations in the ACS group were significantly higher than those in the UAP group. The concentrations of the PDGF and Ang-1 in peripheral and coronary artery blood were positively correlated with the severity of coronary lesions. Patients with MACCE had higher PDGF and Ang-1 levels in the coronary sinus. CONCLUSION: The serum PDGF concentration in patients with acute coronary syndrome was significantly increased, especially in the local coronary artery. The serum Ang-1 in the coronary artery was significantly increased in patients with acute myocardial infarction and was related to the degree of coronary artery stenosis. Coronary sinus PDGF and Ang-1 levels can reflect the severity of lesions in patients with acute coronary syndrome.