Risk factors for sternal wound infection after median sternotomy: A nested case-control study and time-to-event analysis.

Although potential risk factors for sternal wound infection (SWI) have been extensively studied, the onset time of SWI and different risk factors for superficial and deep SWI were rarely reported. This nested case-control study aims to compare the onset time and contributors between superficial and deep SWI. Consecutive adult patients who underwent cardiac surgery through median sternotomy in a single center from January 2011 to January 2021 constituted the cohort. The case group was those who developed SWI as defined by CDC and controls were matched 6:1 per case. Kaplan-Meier analysis, LASSO and univariate and multivariate Cox regressions were performed. A simple nomogram was established for clinical prediction of the risk of SWI. The incidence of SWI was 1.1% (61 out of 5471) in our cohort. Totally 366 controls were matched to 61 cases. 26.2% (16 of 61) SWI cases were deep SWI. The median onset time of SWI was 35 days. DSWI had a longer latency than SSWI (median time 46 days vs. 32 days, p = 0.032). Kaplan-Meier analyses showed different time-to-SWI between patients with and without DM (p = 0.0011) or MI (p = 0.0019). Multivariate Cox regression showed that BMI (HR = 1.083, 95% CI: 1.012-1.116, p = 0.022), DM (HR = 2.041, 95% CI: 1.094-3.805, p = 0.025) and MI (HR = 2.332, 95% CI: 1.193-4.557, p = 0.013) were independent risk factors for SWI. Superficial SWI was only associated with BMI (HR = 1.089, 95% CI: 1.01-1.175, p = 0.027), while deep SWI was associated with DM (HR = 3.271, 95% CI: 1.036-10.325, p = 0.043) and surgery time (HR = 1.004, 95% CI: 1.001-1.008, p = 0.027). The nomogram for SWI prediction had an AUC of 0.67, good fitness and clinical effectiveness as shown by the calibration curve and decision curve analyses. BMI, DM and MI were independent risk factors for SWI. DSWI had a longer latency and different risk factors compared to SSWI. The nomogram showed a fair performance and good effectiveness for the clinical prediction of SWI.

Robotic Level IV Inferior Vena Cava Thrombectomy Using an Intrapericardial Control Technique: Is It Safe Without Cardiopulmonary Bypass?

PURPOSE: We introduce an intrapericardial control technique using a robotic approach in the surgical treatment of renal tumor with level IV inferior vena cava thrombus to decrease the severe complications associated with cardiopulmonary bypass and deep hypothermic circulatory arrest. MATERIALS AND METHODS: Eight patients with level IV inferior vena cava thrombi not extending into the atrium underwent transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy obviating cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass-free group) by an expert team comprising urological, hepatobiliary, and cardiovascular surgeons. The central diaphragm tendon and pericardium were transabdominally dissected until the intrapericardial inferior vena cava were exposed and looped proximal to the cranial end of the thrombi under intraoperative ultrasound guidance. As controls, 14 patients who underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass (cardiopulmonary bypass group) and 25 patients who underwent open thrombectomy with cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass/deep hypothermic circulatory arrest group) were included. Clinicopathological, operative, and survival outcomes were retrospectively analyzed. RESULTS: Eight robot-assisted inferior vena cava thrombectomies were successfully performed without cardiopulmonary bypass, with 1 open conversion. The median operation time and first porta hepatis occlusion time were shorter, and estimated blood loss was lower in the cardiopulmonary bypass-free group as compared to the cardiopulmonary bypass group (540 vs 586.5 minutes, 16.5 vs 38.5. minutes, and 2,050 vs 3,500 mL, respectively). Severe complications (level IV-V) were also lower in the cardiopulmonary bypass-free group than in cardiopulmonary bypass and cardiopulmonary bypass/deep hypothermic circulatory arrest groups (25% vs 50% vs 40%). Oncologic outcomes were comparable among the 3 groups in short-term follow-up. CONCLUSIONS: Pure transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass/deep hypothermic circulatory arrest represents as an alternative minimally invasive approach for selected level IV inferior vena cava thrombi.

The Establishment of Hypertrophic Cardiomyopathy Diagnosis Model via Artificial Neural Network and Random Decision Forest Method.

Hypertrophic cardiomyopathy is a hereditary disease characterized by asymmetric ventricular hypertrophy as the key anatomical feature. Currently, there exists no effective method for the early diagnosis of hypertrophic cardiomyopathy. In this analysis, we incorporated multiple GEO datasets containing RNA profiles of hypertrophic cardiomyopathic patient tissues, identified 642 differentially expressed genes, and performed GO and KEGG analyses. Furthermore, we narrowed down 46 characteristic genes from these differentially expressed genes using random decision forests and conducted transcription factor regulation analysis on them. Using 40 genes that showed overlap between the training set and the verification set, the artificial neural network was trained, and the final MPS scoring model was constructed, and a receiver-operating characteristic (ROC) curve was drawn. We used the MPS model to predict the verification dataset and drew the ROC curve, which demonstrated the good prediction performance of the model. In conclusion, this study combines a random decision forest and artificial neural network to build a diagnostic model for hypertrophic cardiomyopathy to predict the disease, aiming at early detection and treatment, prolonging the survival time, and improving the quality of life of patients.

Circular RNA circFADS2 is overexpressed in sepsis and suppresses LPS-induced lung cell apoptosis by inhibiting the maturation of miR-15a-5p.

BACKGROUND: Circular RNA circFADS2 plays protective roles in LPS-induced inflammation, which promotes sepsis, suggesting its involvement in sepsis. METHODS: Expression of circFADS2, mature miR-15a-5p, and miR-15a-5p precursor in plasma samples from sepsis patients and healthy controls was determined by RT-qPCR. The circFADS2 expression vector was transfected in lung cells, followed by the measurement of the expression levels of mature miR-15a-5p and miR-15a-5p precursor to study the role of circFADS2 in miR-15a-5p maturation. Cell apoptosis was analyzed by cell apoptosis assay. RESULTS: CircFADS2 was upregulated in sepsis and inversely correlated with mature miR-15a-5p, but not miR-15a-5p precursor. In lung cells, circFADS2 overexpression decreased the level of mature miR-15a-5p, but not miR-15a-5p precursor. LPS treatment decreased miR-15a-5p expression and increased circFADS2 level. Cell apoptosis analysis showed that circFADS2 overexpression reduced miR-15a-5p overexpression-induced apoptosis of LPS-treated lung cells. CONCLUSIONS: CircFADS2 is upregulated in sepsis to suppress LPS-induced lung cell apoptosis by inhibiting miR-15a-5p maturation.

Robotically assisted coronary artery bypass graft surgery versus drug-eluting stents for patients with stable isolated proximal left anterior descending disease.

OBJECTIVE: To compare the midterm outcomes of patients with isolated left anterior descending disease (iLAD) who underwent robotically assisted coronary artery bypass graft (R-CABG) and percutaneous coronary intervention (PCI) with drug eluting stents (DES). METHOD: Clinic data was collected in 223 patients who underwent R-CABG in our hospital between July, 2007 to November, 2014. Cardiology Database System of our hospital was used to identify 4047 patients who underwent PCI with DES for LAD lesion between April, 2011 to November, 2014. Total 496 patients received DES and 108 patients underwent R-CABG after screening. Patients were propensity matched into 108 R-CABG and DES pairs according to vital statistic. Mortality, myocardial infarction (MI), stroke, repeat target lesion revascularization (r-TLR), main adverse cardiac and cerebral events (MACCE), and angina relief were compared across pairs. RESULT: Kaplan-Meier estimates for R-CABG and DES had no significant difference in mortality (p = 1.00), MI (p = .32), Stroke (p = .80), and MACCE (p = .47), but the rate of r-TLR (p = .03) were lower in R-CABG group. Patients who underwent R-CABG had better angina relief (p = .02), lower rate of arrhythmia (p < .001), and recurrent angina (p = .02) after operation compared patients received DES. CONCLUSION: R-CABG offers lower r-TLR rate and better angina relief compared with DES for revascularization in patients with isolated proximal LAD stenosis and there was no difference in mortality, MI, stroke, and MACCE between them.

Extracorporeal membrane oxygenation (ECMO) for critically ill patients with coronavirus disease 2019 (COVID-19): A retrospective cohort study.

PURPOSE: The role of extracorporeal membrane oxygenatio (ECMO) for rescue therapy of respiratory failure in critically ill coronavirus disease 2019 (COVID-19) patients remains controversial. We aimed to evaluate the clinical outcomes of ECMO in the treatment of COVID-19 compared with conventional ventilation support. METHODS: In this retrospective cohort study, data were collected on extremely critical patients with COVID-19 from January 2020 to March 2020 in intensive care unit of a hospital in charge by national rescue team in Wuhan, China, the epicenter of pandemic. Patients were classified into the ECMO group and the conventional ventilation non-ECMO group. Clinical characteristics, technical characteristics, laboratory results, mortality, and complications of the two groups were analyzed. RESULTS: 88 patients with extremely critical COVID-19 were screened; 34 received ECMO support and 31 received conventional ventilation support. Both groups had comparable characteristics at baseline in terms of age, gender, and comorbidities. Before ECMO or conventional therapy, patients in the two groups had sever acute respiratory distress syndrome with a mean partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2 /FiO2 ) ratio of 69.6 and 75.4, respectively. At the time of reporting, patients in the ECMO had significantly lower in-hospital mortality compared with the control group (58.8 vs. 93.5%, p = .001). CONCLUSION: ECMO is shown to decrease the mortality of extremely critical ill COVID-19 patients compared with the conventional treatment. Although complications occurred frequently, ECMO could still be a rescue therapy for the treatment of COVID-19 during the pandemic.

Surgical Experience of Primary Cardiac Tumor: Single-Institution 23-Year Report.

BACKGROUND Primary cardiac tumors are rare but have favorable surgical prognosis. Previous studies have been small series studies with limited surgical approaches. To date, few studies have examined the clinical features associated with different surgical procedures. MATERIAL AND METHODS In a search of the cardiovascular surgery database of our institution, we retrospectively identified 225 patients who had cardiac tumor resection from January 1993 to May 2016. The patients' clinical characteristics and operation information were reviewed, and the operation parameters, postoperative complications, and short-term prognosis among robotic, mini-thoracotomy, and conventional procedures in our center were compared. RESULTS A total of 228 operations were performed, including 156 traditional open surgeries (68.4%), 60 robotically assisted neoplasm resections (26.3%), and 12 mini-thoracotomy procedures (5.3%). Among 232 lesions, myxoma (94.8%) was the most common neoplasm, and the remainders were fibroma (1.3%) and lipoma (0.9%). Operative complications occurred in 36 patients (15.8%). Arrhythmia (8.8%) was the first common complication, and delayed mechanical ventilation (4.8%) ranked second. The overall risk of recurrence of myxoma was 2.7%. The cardiopulmonary bypass (CPB) time in the mini-thoracotomy group was longer than in the robotic group (p=0.034) and the conventional group (p=0.002). There were no significant differences in cross clamp time (p=0.266) or complications (p=0.835) among the three groups. The in-hospital survival rate was 100% in all patients. There were no significant differences in main adverse events among the three groups at six-month follow-up (p=0.285). CONCLUSIONS Prognosis for cardiac neoplasm surgical resection is favorable for primary cardiac tumors. The minimally invasive surgery of cardiac tumor resection can be an alternative to conventional operations in selected patients.

Superior vena cava drainage improves upper body oxygenation during veno-arterial extracorporeal membrane oxygenation in sheep.

INTRODUCTION: Differential hypoxia is a pivotal problem in patients with femoral veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) support. Despite recognition of differential hypoxia and attempts to deliver more oxygenated blood to the upper body, the mechanism of differential hypoxia as well as prevention strategies have not been well investigated. METHODS: We used a sheep model of acute respiratory failure that was supported with femoral VA ECMO from the inferior vena cava to the femoral artery (IVC-FA), ECMO from the superior vena cava to the FA (SVC-FA), ECMO from the IVC to the carotid artery (IVC-CA) and ECMO with an additional return cannula to the internal jugular vein based on the femoral VA ECMO (FA-IJV). Angiography and blood gas analyses were performed. RESULTS: With IVC-FA, blood oxygen saturation (SO2) of the IVC (83.6 ± 0.8%) was higher than that of the SVC (40.3 ± 1.0%). Oxygen-rich blood was drained back to the ECMO circuit and poorly oxygenated blood in the SVC entered the right atrium (RA). SVC-FA achieved oxygen-rich blood return from the IVC to the RA without shifting the arterial cannulation. Subsequently, SO2 of the SVC and the pulmonary artery increased (70.4 ± 1.0% and 73.4 ± 1.1%, respectively). Compared with IVC-FA, a lesser difference in venous oxygen return and attenuated differential hypoxia were observed with IVC-CA and FA-IJV. CONCLUSIONS: Differential venous oxygen return is a key factor in the etiology of differential hypoxia in VA ECMO. With knowledge of this mechanism, we can apply better cannula configurations in clinical practice.

Zhuang-Gu-Fang intervenes vasculogenic and osteogenic coupling in GK rats through Notch1/Noggin/VEGF pathway.

Background: Zhuang-Gu-Fang (ZGF) has been proved to treat osteoporosis in ovariectomized rats by increasing osteogenic related factors Leptin, Ghrelin and Peptide YY(PYY). However, the mechanism of ZGF in the treatment of diabetic osteoporosis (DOP) remains unclear. The aim of this study was to explore the therapeutic effect of ZGF on DOP and its potential molecular mechanism. Methods: Using GK rats as models, the pharmacodynamic effects of ZGF on bone loss were evaluated by hematoxylin-eosin (H&E) staining and micro-computed.tomography (micro-CT). The expression levels of CD31 and endomucin (Emcn) were detected by immunofluorescence to assess the role of ZGF in angiogenic osteogenic coupling. Finally, real-time quantitative PCR (RT-PCR) and Western Blot (WB)were used to detect the expression levels of osteogenic and angiogenesis-related genes and proteins Notch1, Noggin and vascular endothelial growth factor (VEGF). Results: Administration of ZGF demonstrated a significant mitigation of bone loss attributable to elevated glucose levels. H&E staining and micro-CT showed that ZGF notably improved the integrity of the trabecular and cortical bone microarchitecture. Moreover, ZGF was found to augment the density of type H vessels within the bone tissue, alongside elevating the expression levels of Osterix, a transcription factor pivotal for bone formation. Furthermore, our findings suggest that ZGF facilitates the activation of the Notch1/Noggin/VEGF pathway, indicating a potential mechanism through which ZGF exerts its osteoprotective effects. Conclusion: Our results suggest that ZGF potentially facilitates the formation of type H vessels through the Notch1/Noggin/VEGF pathway. This action not only enhances angiogenic-osteogenic coupling but also contributes to the improvement of bone structure and density. Consequently, ZGF emerges as a promising therapeutic agent for the prevention and management of DOP, offering a novel approach by leveraging angiogenesis-dependent osteogenesis.

Yidiyin, a Chinese herbal decoction, improves erectile dysfunction in diabetic patients and rats through the NO-cGMP pathway.

The nitric-oxide (NO)-cyclic-guanosine-monophosphate (cGMP) pathway plays a key role in penile erection. Erectile dysfunction (ED) is a complication in male diabetic patients that impacts their quality of 1ife. Recently, Yidiyin, a Chinese herbal decoction, is used to treat diabetic ED, but convincing evidence is lacking, and the potential mechanisms remain uncertain. In the study, diabetic ED patients had low scores on international index of erectile function-5 (IIEF-5), and administration of Yidiyin and hypoglycemic drugs for 16 weeks ameliorated patients' scores on IIEF-5 more than the hypoglycemic drug alone. Moreover, streptozotocin-induced diabetes severely impaired rats' erectile function and the activity of the NO-cGMP pathway in the corpora cavernosum, and treatment with Yidiyin for 4 weeks obviously increased the rats' erectile function, remarkably enhanced the activity of nitric oxide synthase (NOS), and elevated the contents of NO and cGMP. Our findings indicate that Yidiyin improves diabetic ED probably by enhancing the NO-cGMP pathway.

Large-conductance Ca2 +-activated K+ channel ß1-subunit maintains the contractile phenotype of vascular smooth muscle cells.

Background: Vascular smooth muscle cells (VSMCs) phenotype switching is very important during the pathogenesis and progression of vascular diseases. However, it is not well understood how normal VSMCs maintain the differentiated state. The large-conductance Ca2+-activated K+ (BKCa) channels are widely expressed in VSMCs and regulate vascular tone. Nevertheless, there is limited understanding of the role of the BKCa channel in modulation of the VSMC phenotype. Methods and results: We assessed BKCa channel expression levels in normal and injured carotid arteries from rats of the balloon-injury model. A strong decrease of BKCa-ß1 was seen in the injured carotid arteries, accompanied by a parallel decrease of the VSMC contractile markers. BKCa-ß1 in primary rat aortic VSMCs was decreased with the increase of passage numbers and the stimulation of platelet-derived growth factor (PDGF)-BB. Conversely, transforming growth factor ß upregulated BKCa-ß1. Meanwhile, the BKCa-ß1 level was positively associated with the levels of VSMC contractile proteins. Intravenous injection of PDGF-BB induced downregulation of BKCa-ß1 expression in the carotid arteries. Knockdown of BKCa-ß1 favored VSMC dedifferentiation, characterized by altered morphology, abnormal actin fiber organization, decreased contractile proteins expression and reduced contractile ability. Furthermore, the resultant VSMC dedifferentiated phenotype rendered increased proliferation, migration, enhanced inflammatory factors levels, and matrix metalloproteinases activity. Studies using primary cultured aortic VSMCs from human recapitulated key findings. Finally, protein level of BKCa-ß1 was reduced in human atherosclerotic arteries. Conclusion: BKCa-ß1 is important in the maintenance of the contractile phenotype of VSMCs. As a novel endogenous defender that prevents pathological VSMC phenotype switching, BKCa-ß1 may serve as a potential therapeutic target for treating vascular diseases including post-injury restenosis and atherosclerosis.

Nosocomial Infections During Extracorporeal Membrane Oxygenation in Pediatric Patients: A Multicenter Retrospective Study.

Objective: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients with respiratory and/or cardiac failure. This study aimed to investigate the epidemiology and risk factors of nosocomial infection (NI) in pediatric patients who underwent ECMO for respiratory and/or circulatory failure. Methods: Medical records for patients that were administered underwent ECMO support at Xiangya Second Hospital of Central South University, The Sixth Medical Center of PLA General Hospital, and Children's Hospital Affiliation of Zhengzhou University, from September 2012 to December 2019 were retrospectively reviewed. Clinical data of the patients who developed NI were collected and analyzed. Univariate and multivariate logistic regressions were performed to identify the independent predictive factors of NI during ECMO. Results: A total of 54 first episodes of NI were identified in the 190 patients on ECMO, including 32 cases of respiratory tract infections, 20 cases of bloodstream infections, and 2 cases of surgical site wound infections. Gram-negative pathogens were the dominant pathogens isolated, accounting for 92.6% of the NI. The incidence of ECMO-related NI was 47.6 cases per 1,000 ECMO days. In the univariate logistic regression, ECMO mode, ECMO duration, ICU duration, and peritoneal dialysis were associated with the development of NI in patients with ECMO support. However, in the multivariate analysis, only ECMO duration (OR = 2.46, 95%CI: 1.10, 5.51; P = 0.029), ICU duration (OR = 1.35, 95%CI: 1.05, 1.59; P = 0.017) and peritoneal dialysis (OR = 2.69, 95%CI: 1.08, 5.73; P = 0.031) were the independent predictive factors for NI during ECMO support. Conclusion: This study identified the significant correlation between ECMO-related NI and ECMO duration, ICU duration, and peritoneal dialysis. Appropriate preventive measures are needed for hospitals to reduce the incidence of ECMO in pediatric patients.

Large-Conductance Calcium-Activated Potassium Channel Opener, NS1619, Protects Against Mesenteric Artery Remodeling Induced by Agonistic Autoantibodies Against the Angiotensin II Type 1 Receptor.

Background Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AAs) extensively exist in patients with hypertensive diseases and have been demonstrated to play crucial roles in the pathophysiological process of vascular remodeling. However, the treatment options are limited. The large-conductance calcium-activated potassium (BK) channel is a critical regulator and potential therapeutic target of vascular tone and architecture. We have previously observed that AT1-AAs have an inhibitory effect on BK channels. However, whether BK channel dysfunction is involved in AT1-AAs-induced vascular remodeling and the therapeutic effect of BK channel opener is unclear. Methods and Results In our study, mesenteric arteries from AT1-AAs-positive rats exhibited increased wall thickness, narrowing of the arteriolar lumen, and increased collagen accumulation. Patch clamp test results showed that the voltage sensitivity of BK channel declined in mesenteric arteriolar smooth muscle cells from AT1-AAs-positive rats. Experiments with freshly isolated mesenteric arteriolar smooth muscle cells showed that AT1-AAs reduced the opening probability, open levels, open dwell time, and calcium sensitivity of BK channel. Experiments with HEK293T cells transfected with GFP-ZERO-BK α-subunit plasmids suggested a BK channel α-subunit-dependent mechanism. BK channel α-subunit deficient, namely KCNMA1-/- rats showed a phenotype of mesenteric artery remodeling. The administration of NS1619, a specific BK channel opener targeting the α-subunit, reversed the phenotypic transition and migration induced by AT1-AAs in cultured mesenteric arteriolar smooth muscle cells. Finally, perfusion of NS1619 significantly relieved the pathological effects induced by AT1-AAs in vivo. Conclusions In summary, we provide compelling evidence that BK channel α-subunit dysfunction mediates AT1-AAs-induced mesenteric artery remodeling. Preservation of BK channel activity may serve as a potential strategy for the treatment of AT1-AAs-induced maladaptive resistance artery remodeling.

Ginsenoside Rg1 interferes with the progression of diabetic osteoporosis by promoting type H angiogenesis modulating vasculogenic and osteogenic coupling.

Ginsenoside Rg1 (Rg1) has been demonstrated to have antidiabetic and antiosteoporotic activities. The aim of this study was to investigate the protective effect of Rg1 against diabetic osteoporosis and the underlying mechanism. In vitro, we found that Rg1 increased the number of osteoprogenitors and alleviated high glucose (HG) induced apoptosis of osteoprogenitors by MTT assays and flow cytometry. qRT‒PCR and western blot analysis suggested that Rg1 can also promote the secretion of vascular endothelial growth factor (VEGF) by osteoprogenitors and promote the coupling of osteogenesis and angiogenesis. Rg1 can also promote the proliferation of human umbilical vein endothelial cells (HUVECs) cultured in high glucose, enhance the angiogenic ability of endothelial cells, and activate the Notch pathway to promote endothelial cells to secrete the osteogenesis-related factor Noggin to regulate osteogenesis, providing further feedback coupling of angiogenesis and osteogenesis. Therefore, we speculated that Rg1 may have similar effects on type H vessels. We used the Goto-Kakizaki (GK) rat model to perform immunofluorescence staining analysis on two markers of type H vessels, Endomucin (Emcn) and CD31, and the osteoblast-specific transcription factor Osterix, and found that Rg1 stimulates type H angiogenesis and bone formation. In vivo experiments also demonstrated that Rg1 promotes VEGF secretion, activates the Noggin/Notch pathway, increases the level of coupling between type H vessels and osteogenesis, and improves the bone structure of GK rats. All of these data reveal that Rg1 is a promising candidate drug for treating diabetic osteoporosis as a potentially bioactive molecule that promotes angiogenesis and osteointegration coupling.

Machine Learning-Based Personalized Risk Prediction Model for Mortality of Patients Undergoing Mitral Valve Surgery: The PRIME Score.

Background: Mitral valve surgery (MVS) is an effective treatment for mitral valve diseases. There is a lack of reliable personalized risk prediction models for mortality in patients undergoing mitral valve surgery. Our aim was to develop a risk stratification system to predict all-cause mortality in patients after mitral valve surgery. Methods: Different machine learning models for the prediction of all-cause mortality were trained on a derivation cohort of 1,883 patients undergoing mitral valve surgery [split into a training cohort (70%) and internal validation cohort (30%)] to predict all-cause mortality. Forty-five clinical variables routinely evaluated at discharge were used to train the models. The best performance model (PRIME score) was tested in an externally validated cohort of 220 patients undergoing mitral valve surgery. The model performance was evaluated according to the area under the curve (AUC). Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were compared with existing risk strategies. Results: After a median follow-up of 2 years, there were 133 (7.063%) deaths in the derivation cohort and 17 (7.727%) deaths in the validation cohort. The PRIME score showed an AUC of 0.902 (95% confidence interval [CI], 0.849-0.956) in the internal validation cohort and 0.873 (95% CI: 0.769-0.977) in the external validation cohort. In the external validation cohort, the performance of the PRIME score was significantly improved compared with that of the existing EuroSCORE II (NRI = 0.550, [95% CI 0.001-1.099], P = 0.049, IDI = 0.485, [95% CI 0.230-0.741], P < 0.001). Conclusion: Machine learning-based model (the PRIME score) that integrate clinical, demographic, imaging, and laboratory features demonstrated superior performance for the prediction of mortality patients after mitral valve surgery compared with the traditional risk model EuroSCORE II. Clinical Trial Registration: [http://www.clinicaltrials.gov], identifier [NCT05141292].

MicroRNA-375-3p in endothelial progenitor cells-derived extracellular vesicles relieves myocardial injury in septic rats via BRD4-mediated PI3K/AKT signaling pathway.

OBJECTIVE: Sepsis can induce myocardial dysfunctions and endothelial progenitor cells (EPCs)-derived extracellular vesicles (EVs) can attenuate sepsis. Concerning to that, this article is intended to decode whether microRNA (miR)-375-3p in EPCs-EVs could affect myocardial injury in sepsis. METHODS: Rat bone marrow-derived EPCs and EPCs-EVs were harvested. A rat model of sepsis was established by cecal ligation and puncture. Septic rats were injected with EPCs-EVs that interfered with miR-375-3p, after which cardiac function, inflammatory response, pathological damage, oxidative stress and apoptosis were detected in myocardial tissues. miR-375-3p, bromodomain 4 (BRD4), phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) expression in myocardial tissues, and their reciprocals were identified. RESULTS: Septic rats expressed reduced miR-375-3p and elevated BRD4 in myocardial tissues. EPCs-EVs improved cardiac function, suppressed inflammation, oxidative stress and apoptosis, as well as attenuated the pathological damage of myocardial tissues in septic rats. Up-regulated/down-regulated miR-375-3p in EPCs-EVs relieved/deteriorated myocardial injury in septic rats. miR-375-3p targeted BRD4 to activate PI3K/AKT pathway, thereafter to ameliorate myocardial injury in septic rats. CONCLUSION: It is illustrated that miR-375-3p in EPCs-EVs activates BRD4-mediated PI3K/AKT signaling pathway to ameliorate myocardial injury in septic rats, which provides a therapeutic target for myocardial injury in sepsis.

Severe Patients With ARDS With COVID-19 Treated With Extracorporeal Membrane Oxygenation in China: A Retrospective Study.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis affecting over 200 countries worldwide. Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the management of COVID-19-associated end-stage respiratory failure. However, the exact effect of ECMO in the management of these patients, especially with regards to complications and mortality, is unclear. Methods: This is the largest retrospective study of ECMO treated COVID-19 patients in China. A total of 50 ECMO-treated COVID-19 patients were recruited. We describe the main characteristics, the clinical features, ventilator parameters, ECMO-related variables and management details, and complications and outcomes of COVID-19 patients with severe acute respiratory distress syndrome (ARDS) that required ECMO support. Results: For those patients with ECMO support, 21 patients survived and 29 died (mortality rate: 58.0%). Among those who survived, PaO2 (66.3 mmHg [59.5-74.0 mmHg] and PaO2/FiO2 (68.0 mmHg [61.0-76.0 mmHg]) were higher in the survivors than those of non-survivors (PaO2: 56.8 mmHg (49.0-65.0 mmHg), PaO2/FiO2 (58.2 mmHg (49.0-68.0 mmHg), all P < 0.01) prior to ECMO. Patients who achieved negative fluid balance in the early resuscitation phase (within 3 days) had a higher survival rate than those who did not (P = 0.0003). Conclusions: In this study of 50 cases of ECMO-treated COVID-19 patients, a low PO2/FIO2 ratio before ECMO commencement may indicate a poor prognosis. Negative fluid balance in the early resuscitation phase during ECMO treatment was a predictor of increased survival post-ECMO treatment.

Zhuang-Gu-Fang Treats Osteoporosis in Ovariectomized Rats by Increasing the Osteogenesis-Related Factors Leptin, Ghrelin, and PYY.

Zhuang-Gu-Fang is a Chinese medicinal compound mixture, which is mainly composed of traditional remedies like the Epimedium Herb, Astragalus, and Eucommia among many others. The study is aimed at investigating the therapeutic effect of Zhuang-Gu-Fang in ovariectomized rats. Fifty six-month-old Wistar rats were randomly selected and divided into 5 groups (n = 10), namely, model group, positive group, low-dose Chinese medicine group, medium-dose group, and high-dose group. Another 10 sham operation Wistar rats were taken as a negative control group. After 3 months of intervention, the bone mineral density (BMD), procollagen type I N-peptide (PINP), beta C-terminal cross-linked telopeptides of type I collagen carboxyl-terminal peptide (ß-CTX), Leptin, Ghrelin, and Peptide YY (PYY) of each group were measured. Besides, the ultrastructure of bone structure and osteoblasts was also observed by transmission electron microscopy. Western blot method was used to detect the expression levels of Leptin and Ghrelin in bone tissue, and RT-PCR detected the mRNA expression levels of Leptin and Ghrelin. BMD test indicated that Zhuang-Gu-Fang could effectively prevent the loss of tibia bone in ovariectomized rats. Histomorphology analysis showed that Zhuang-Gu-Fang could preserve trabecular bone structure integrity and improve osteoblast ultrastructure. Notably, the study found out that Zhuang-Gu-Fang worked through balancing the bone metabolism via increasing bone formation/resorption ratio. Additionally, Zhuang-Gu-Fang highlighted the recovery effects in multiple levels of osteogenesis- and osteanagenesis-related factors Leptin, Ghrelin, and PYY. Conclusively, the study proved the therapeutic potential of the Zhuang-Gu-Fang for postmenopausal osteoporosis (PMOP) and further revealed that its therapeutic effect was related to the balance of bone metabolism and the recovery effects of bone-related factors Leptin, Ghrelin, and PYY.

Robot-assisted Level III-IV Inferior Vena Cava Thrombectomy: Initial Series with Step-by-step Procedures and 1-yr Outcomes.

BACKGROUND: Level III-IV robot-assisted inferior vena cava (IVC) thrombectomy (RA-IVCT) has been reported in limited series. OBJECTIVE: To report our initial series of level III-IV RA-IVCT with step-by-step procedures and 1-yr outcomes. DESIGN, SETTING, AND PARTICIPANTS: From November 2014 to January 2018, 13 patients with level III-IV IVC tumor thrombi underwent RA-IVCT with a minimum of 1-yr follow-up. SURGICAL PROCEDURE: Level III RA-IVCT requires liver mobilization and clamping of first porta hepatis (FPH), and suprahepatic and infradiaphragmatic IVC. Level IV RA-IVCT requires establishment of cardiopulmonary bypass (CPB). Thoracoscopy-assisted thrombectomy was performed for the intra-atrium part of the thrombus under CPB. Infradiaphragmatic RA-IVCT was completed in a manner similar to that of level III RA-IVCT. MEASUREMENTS: Detailed techniques were described for various scenarios. Baseline and perioperative outcomes were reported, and descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: Median operative time was 465 (interquartile range [IQR]: 338-567) min. Median estimated intraoperative blood loss was 2000 (IQR: 1000-3000) ml. The rates of intraoperative blood transfusion and postoperative transformation to the intensive care unit ward were 92.3% and 100%, respectively. Median FPH blocking time was 40 (IQR: 25-60) min and the CPB time was 72 (IQR: 51-87) min. Three cases had grade IV complications, including two vascular injuries that were treated with intraoperative endoscopic sutures and one perioperative death. The perioperative mortality rate was 7.7%. During an 18-mo follow-up, two patients died and one patient progressed. CONCLUSIONS: Although the risks involved are high, level III-IV RA-IVCT is feasible and serves as an alternative minimally invasive method for selected patients. It also requires more complex techniques and multidisciplinary cooperation. PATIENT SUMMARY: We studied the treatment of patients with level III-IV inferior vena cava (IVC) tumor thrombi using a robotic approach. This technique was feasible for well-selected patients. However, level III-IV robot-assisted IVC thrombectomy requires more complex techniques and multidisciplinary cooperation.