Comparison of surgical and conservative treatment outcomes for type a aortic intramural hematoma.

OBJECTIVE: This study aimed to compare hospital and long-term clinical outcomes associated with various treatment methods for Stanford A type aortic intramural hematoma (IMH) to provide a reference for clinical decision-making. METHODS: In this single-center cohort study, we retrospectively analyzed 73 patients with Type A IMH treated at our center from August 1, 2018 to August 1, 2021. Among these patients, 26 were treated conservatively, and 47 underwent surgical intervention. We next compared this IMH cohort with 154 patients with acute type A aortic dissection (AD) who were treated surgically during the same study period. RESULTS: Computed tomography angiography revealed that the diameter of the ascending aorta of IMH patients treated with surgery was higher than IMH patients treated with conservative therapy (44.92 ± 7.58 mm vs. 51.22 ± 11.85 mm, P < 0.05), while there was no significant difference in other clinical parameters. The in-hospital mortality of patients with IMH who underwent surgical treatment was lower than those undergoing conservative treatment (0% vs. 11.5%, P < 0.05). The long-term mortality of the conservative IMH group was higher than the surgical IMH group (26.1% vs. 8.5%, P < 0.05). There was no significant difference in the surgical parameters and postoperative complications between AD and IMH surgery patients. The proportion of circulatory arrest time in the lower body (19.98 ± 9.39 min vs. 17.51 ± 3.97 min) and arch involvement (98 (63.6%) vs. 22 (46.8%)) in the IMH surgery group was lower than in the AD surgery group (P < 0.05). CONCLUSIONS: Compared with conservative treatment, surgical treatment of IMH significantly improves the survival rate of patients. Thus, surgical intervention should be considered the primary treatment option if feasible. Furthermore, The safety of IMH surgery can be guaranteed just like AD. But we still need in the future evidence on bigger samples.

CARMA3 Deficiency Aggravates Angiotensin II-Induced Abdominal Aortic Aneurysm Development Interacting Between Endoplasmic Reticulum and Mitochondria.

BACKGROUND: Abdominal aortic aneurysm (AAA) is life threatening and associated with vascular walls' chronic inflammation. However, a detailed understanding of the underlying mechanisms is yet to be elucidated. CARMA3 assembles the CARMA3-BCL10-MALT1 (CBM) complex in inflammatory diseases and is proven to mediate angiotensin II (Ang II) response to inflammatory signals by modulating DNA damage-induced cell pyroptosis. In addition, interaction between endoplasmic reticulum (ER) stress and mitochondrial damage is one of the main causes of cell pyroptosis. METHODS: Male wild type (WT) or CARMA3-/- mice aged 8 to 10 weeks were subcutaneously implanted with osmotic minipumps, delivering saline or Ang II at the rate of 1 µg/kg/min for 1, 2, and 4 weeks. RESULTS: We discovered that CARMA3 knockout promoted formation of AAA and prominently increased diameter and severity of the mice abdominal aorta infused with Ang II. Moreover, a significant increase in the excretion of inflammatory cytokines, expression levels of matrix metalloproteinases (MMPs) and cell death was found in the aneurysmal aortic wall of CARMA3-/- mice infused with Ang II compared with WT mice. Further studies found that the degree of ER stress and mitochondrial damage in the abdominal aorta of CARMA3-/- mice was more severe than that in WT mice. Mechanistically, CARMA3 deficiency exacerbates the interaction between ER stress and mitochondrial damage by activating the p38MAPK pathway, ultimately contributing to the pyroptosis of vascular smooth muscle cells (VSMCs). CONCLUSIONS: CARMA3 appears to play a key role in AAA formation and might be a potential target for therapeutic interventions of AAA.

Stomatin-like protein 2 deficiency exacerbates adverse cardiac remodeling.

Myocardial fibrosis, oxidative stress, and autophagy both play key roles in the progression of adverse cardiac remodeling. Stomatin-like protein 2 (SLP-2) is closely related to mitochondrial function, but little is known about its role and mechanism in cardiac remodeling. We developed doxorubicin (Dox), angiotensin (Ang) II, and myocardial ischemia-reperfusion (I/R) injury induced cardiac remodeling model and Dox treated H9C2 cell injury model using SLP-2 knockout (SLP-2-/-) mice and H9C2 cells with low SLP-2 expression. We first examined cardiac functional and structural changes as well as levels of oxidative stress, apoptosis and autophagy. We found that SLP-2 deficiency leads to decreased cardiac function and promotes myocardial fibrosis. After Dox and Ang II treatment, SLP-2 deficiency further aggravated myocardial fibrosis, increased myocardial oxidative stress and apoptosis, and activated autophagy by inhibiting PI3K-Akt-mTOR signaling pathway, ultimately exacerbating adverse cardiac remodeling. Similarly, SLP-2 deficiency further exacerbates adverse cardiac remodeling after myocardial I/R injury. Moreover, we extracted cardiomyocyte mitochondria for proteomic analysis, suggesting that SLP-2 deficiency may be involved in myocardial I/R injury induced adverse cardiac remodeling by influencing ubiquitination of intramitochondrial proteins. In addition, the oxidative stress, apoptosis and autophagy levels of H9C2 cells with low SLP-2 expression were further enhanced, and the PI3K-Akt-mTOR signaling pathway was further inhibited under Dox stimulation. Our results suggest that SLP-2 deficiency promotes myocardial fibrosis, disrupts normal mitochondrial function, overactivates autophagy via PI3K-Akt-mTOR signaling pathway, affects the level of ubiquitination, leads to irreversible myocardial damage, and ultimately exacerbates adverse cardiac remodeling.

Ythdf2 promotes pulmonary hypertension by suppressing Hmox1-dependent anti-inflammatory and antioxidant function in alveolar macrophages.

Pulmonary hypertension (PH) is a devastating disease characterized by irreversible pulmonary vascular remodeling (PVR) that causes right ventricular failure and death. The early alternative activation of macrophages is a critical event in the development of PVR and PH, but the underlying mechanisms remain elusive. Previously we have shown that N6-methyladenosine (m6A) modifications of RNA contribute to phenotypic switching of pulmonary artery smooth muscle cells and PH. In the current study, we identify Ythdf2, an m6A reader, as an important regulator of pulmonary inflammation and redox regulation in PH. In a mouse model of PH, the protein expression of Ythdf2 was increased in alveolar macrophages (AMs) during the early stages of hypoxia. Mice with a myeloid specific knockout of Ythdf2 (Ythdf2Lyz2 Cre) were protected from PH with attenuated right ventricular hypertrophy and PVR compared to control mice and this was accompanied by decreased macrophage polarization and oxidative stress. In the absence of Ythdf2, heme oxygenase 1 (Hmox1) mRNA and protein expression were significantly elevated in hypoxic AMs. Mechanistically, Ythdf2 promoted the degradation of Hmox1 mRNA in a m6A dependent manner. Furthermore, an inhibitor of Hmox1 promoted macrophage alternative activation, and reversed the protection from PH seen in Ythdf2Lyz2 Cre mice under hypoxic exposure. Together, our data reveal a novel mechanism linking m6A RNA modification with changes in macrophage phenotype, inflammation and oxidative stress in PH, and identify Hmox1 as a downstream target of Ythdf2, suggesting that Ythdf2 may be a therapeutic target in PH.

I-κB kinase-ε deficiency improves doxorubicin-induced dilated cardiomyopathy by inhibiting the NF-κB pathway.

Dilated cardiomyopathy (DCM) can lead to heart expansion and severe heart failure, but its specific pathogenesis is still elusive. In many cardiovascular diseases, I-κB kinase-ε (IKKε) has been recognized as a pro-inflammatory molecule. In this study, wild-type mice (WT, n = 14) and IKKε knockout mice (IKKε-KO, n = 14) were intraperitoneally injected with a cumulative dose of 25 mg/kg with Dox or Saline five times in 30 days. Finally, the experimental mice were divided into WT + Saline group、WT + DOX group、IKKε-KO + Saline group and IKKε-KO + Dox group. Echocardiography was performed to assess cardiac structure and function. Moreover, the mechanism was validated by immunohistochemistry and western blotting. Our results demonstrated that compared to WT + Dox mice, IKKε-KO + Dox mice exhibited attenuation of dilated cardiomyopathy-related morphological changes and alleviation of heart failure. Additionally, compared to the WT mice after Dox-injected, the expression of fibrosis and proinflammatory were decreased in IKKε-KO mice, and the expression of cardiac gap junction proteins was much higher in IKKε-KO mice. Further testing found that pyroptosis and apoptosis in the myocardium were also ameliorated in IKKε-KO mice compared to WT mice after Dox was injected. Mechanistically, our results showed that deficiency of IKKε might inhibit the phosphorylation of IκBα, p65, RelB, and p100 in mouse heart tissues after Dox stimulation. In summary, our research suggests that IKKε might play an essential role in the development of Dox-induced dilated cardiomyopathy and may be a potential target for the treatment of dilated cardiomyopathy in the future.

Deficiency of CARMA3 attenuates the development of bleomycin induced pulmonary fibrosis.

BACKGROUND: Pulmonary fibrosis (PF) has attracted more and more attention due to its irreversibility and high mortality rate. Currently, there is no effective treatment option is available to reverse the disease. Caspase recruitment domain-containing membrane-associated guanylate kinase protein (CARMA3) has been recognized as a proinflammatory molecule involved in many lung diseases, such as Allergic airway inflammation and lung cancer. Bleomycin (Bleo), as an alkaline sugar peptide antibiotics, is often used as a first-line anti-tumor agent. Its toxic effect is to induce pulmonary fibrosis (PF) and its clinical symptoms, so it has been widely used in the construction of pulmonary fibrosis model. METHODS: Wild type mice (WT, n = 20) and CARMA3 knockout mice (CARMA3-KO, n = 20) were generated and injected with bleomycin or saline via trachea. The severity of fibrosis was evaluated by fibrosis markers and lung histological morphology. Furthermore, the amount of alveolar epithelial cells and inflammation in lung tissue were examined. Finally, epithelial-mesenchymal transition was further investigated. RESULTS: We found CARMA3 expression in the mice alveolar epithelial cells. And compared with WT mice, CARMA3-KO mice showed reduced deposition of collagen fibers, inflammation and destruction of alveolar epithelial cells in lung tissue. In addition, after bleomycin induction, the expressions of proinflammatory factors and collagen-related factors in CARMA3-KO mice were much lower than those in WT mice. The epithelial-mesenchymal transformation phenotype was also improved in CARMA3-KO mice compared to WT mice. CONCLUSION: Our Results shows that CARMA3 plays an important role in the pathogenesis of bleomycin-induced pulmonary fibrosis. CARMA3 could alleviate the fibrosis by improving inflammation, deposition of collagen and damage of alveolar epithelial cells, which revealed that CARMA3 may be a potential target for pulmonary fibrosis.

Stomatin-Like Protein-2: A Potential Target to Treat Mitochondrial Cardiomyopathy.

Stomatin-like protein-2 (SLP-2) is a mitochondrial-associated protein that is abundant in cardiomyocytes. Many reports have shown that SLP-2 plays an important role in mitochondria. The treatment of mitochondrial cardiomyopathy (MCM) needs further improvement, so the relationship between SLP-2 and MCM is worth exploring. This study reviewed some protective mechanisms of SLP-2 on mitochondria. Published studies have shown that SLP-2 protects mitochondria by stabilising the function of optic atrophy 1 (OPA1), promoting mitofusin (Mfn) 2 expression, interacting with prohibitins and cardiolipin, forming SLP-2-PARL-YME1L (SPY) complex, and stabilising respiratory chain complexes, suggesting that SLP-2 is a new potential target for the treatment of MCM. However, the specific mechanism of SLP-2 needs to be confirmed by further research.

[Clinical outcomes of radial artery as the second arterial conduit in coronary artery bypass].

Objective: To examine the clinical experience and outcomes of coronary artery bypass grafting (CABG) using radial artery as the second arterial graft. Methods: Totally 585 patients in whom both left internal thoracic artery and radial artery as arterial conduits were used in CABG in Department of Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University from April 2008 to August 2019 were consecutively enrolled. There were 436 males and 149 females, aging (63±10) years (range: 36 to 86 years). There were 40.7% (238/585) of patients had diabetes and 75.6% (442/585) of them had multivessel disease (two-vessel or three-vessel diseases). From January 2017, transit time flow measurement was performed on every patient. Demographic and perioperative data were retrospectively collected, as well as follow-up data for patients who underwent CABG from January 2014 to August 2019. Analysis were made on their early and late outcomes. Results: 81.9%(479/585) Most patients in this cohort (81.9%) received on-pump CABG and 11 patients had intraoperative intro-aortic balloon counterpulsation (prior to CABG) support. Forty-three patients had concomitant valve procedures. The number of distal anastomosis was 3.6±0.9 (range: 2 to 6) and number of arterial distal anastomosis was 2.1±0.3. Radial artery was anastomosed to left obtuse marginal artery in 95.8% (560/585) patients. All target vessels for radial artery conduit had significant proximal stenosis (>70%) and 72.5% (424/585) of target vessels had proximal stenosis which was >90%. Intraoperative transit-time flow measurement of 151 cases showed that radial artery conduits had a flow of (29.8±10.2) ml/minutes (range: 10 to 150 ml/min), and pulsatility index of 2.5±1.4 (range: 0.7 to 5.0). There was no operative death. Two in-hospital death occurred more than 30 days after index surgery. There was no perioperative myocardial infarction. There were 188 patients who received CABG from January 2014 to August 2019 followed-up for a median duration of 3.2 years. There were two noncardiac death. No patient had myocardial infarction or to receive myocardial revascularization. Conclusions: Radial artery as the second arterial conduit is a safe and effective strategy for CABG. Good selection of target vessel and intraoperative transit-time flow measurement may help achieve good patency, as well as the short and mid-term outcome.

LncRNA AC061961.2 overexpression inhibited endoplasmic reticulum stress induced apoptosis in dilated cardiomyopathy rats and cardiomyocytes via activating wnt/ß-catenin pathway.

Down-regulated lncRNA AC061961.2 in dilated cardiomyopathy (DCM) patients was previous reported. Whether AC061961.2 has regulatory effect on DCM still need exploration. Here, we tried to investigate the effect of AC061961.2 on DCM. After DCM model rat was established through injecting Adriamycin, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS) were measured by echocardiography. Histopathological changes and apoptosis were detected by hematoxylin-eosin, Masson staining, and TUNEL. After cardiomyocytes were isolated and identified by immunofluorescence, DCM cell model was established by injecting adriamycin. After transfected with overexpressed-AC061961.2 plasmids, cell apoptosis was detected by flow cytometry. The expressions of AC061961.2, ß-catenin, Axin2, c-Myc, CRP78, CHOP, Caspase-3, Bcl-2, and Bax in cardiomyocytes and heart tissues were detected by RT-qPCR or western blot. LVEDD and LVESD were increased while LVEF and LVFS were decreased in DCM rats. The histopathological of heart tissues showed a typical sign of DCM. Apoptosis were increased in heart tissues of DCM rats. In DCM rats, the expressions of AC061961.2, ß-catenin, Axin2, c-Myc, and Bcl-2 were decreased, the expressions of CRP78, CHOP, Caspase-3, and Bax were increased. After the overexpression of AC061961.2, levels of ß-catenin, Axin2, c-Myc, and Bcl-2 were increased, while levels of CRP78, CHOP, Caspase-3, and Bax were decreased, compared with that in DCM cardiomyocytes. LncRNA AC061961.2 overexpression inhibited endoplasmic reticulum stress induced apoptosis in DCM rats and cardiomyocytes via activating Wnt/ß-catenin pathway.

A Novel Molecular Mechanism of IKKε-Mediated Akt/mTOR Inhibition in the Cardiomyocyte Autophagy after Myocardial Infarction.

Autophagy of cardiomyocytes after myocardial infarction (MI) is an important factor affecting the prognosis of MI. Excessive autophagy can lead to massive death of cardiomyocytes, which will seriously affect cardiac function. IKKε plays a crucial role in the occurrence of autophagy, but the functional role in MI remains largely unknown. To evaluate the impact of IKKε on the autophagy of cardiomyocytes after MI, MI was induced by surgical left anterior descending coronary artery ligation in IKKε knockout (KO) mice and wild-type (WT) mice. Starvation of H9c2 cells with IKKε siRNA and rescued with IKKε overexpressed afterwards to test the mechanism of IKKε in autophagy in vitro. Our results demonstrated that the expression of IKKε was upregulated in mice myocardial tissues which were consistent with cardiomyocyte autophagy after MI. Significantly, the IKKε KO mice showed increased infarct size, decreased viable cardiomyocytes, and exacerbated cardiac dysfunction when compared with the wild-type mice. Western blot and electron micrography analysis also revealed that loss of IKKε induces excessive cardiomyocyte autophagy and reduced the expression of p-Akt and p-mTOR. Similar results were observed in IKKε siRNA H9c2 cells in vitro which were under starvation injury. Notably, the levels of p-Akt and p-mTOR can restore in IKKε rescued cells. In conclusion, our results indicated that IKKε protects cardiomyocyte survival by reduced autophagy following MI via regulation of the Akt/mTOR signaling pathway. Thus, our study suggests that IKKε might represent a potential therapeutic target for the treatment of MI.

High expression levels and localization of Sox5 in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a disease that can lead to heart expansion and severe heart failure, but the specific pathogenesis remains unclear. Sox5 is a member of the Sox family with a key role in cardiac function. However, the role of Sox5 in DCM remains unclear. In the present study, wild­type mice were intraperitoneally injected with doxorubicin (Dox) to induce DCM, and heart specimens from human patients with DCM were used to investigate the preliminary role of Sox5 in DCM. The present study demonstrated that, compared with control human hearts, the hearts of patients with DCM exhibited high expression levels of Sox5 and activation of the wnt/ß­catenin pathway. This result was consistent with Dox­induced DCM in mice. Furthermore, in Dox­treated mice, apoptosis was activated during the development of DCM. Inflammation and collagen deposition also increased in DCM mice. The results of the present study indicate that Sox5 may be associated with the development of DCM. Sox5 may be a novel potential factor that regulates DCM.

Downregulation of AC061961.2, LING01-AS1, and RP11-13E1.5 is associated with dilated cardiomyopathy progression.

This study aimed to explore long noncoding RNAs (lncRNAs) implicated in dilated cardiomyopathy (DCM). Ten samples of failing hearts collected from the left ventricles of patients with DCM undergoing heart transplants, and ten control samples obtained from normal heart donors were included in this study. After sequencing, differentially expressed genes (DEGs) and lncRNAs between DCM and controls were screened, followed with functional enrichment analysis and weighted gene coexpression network analysis (WGCNA). Five key lncNRAs were validated through real-time polymerase chain reaction (PCR). Total 1,398 DEGs were identified, including 267 lncRNAs. WGCNA identified seven modules that were significantly correlated with DCM. The top 50 genes in the three modules (black, dark-green, and green-yellow) were significantly correlated with DCM disease state. Four core enrichment lncRNAs, such as AC061961.2, LING01-AS1, and RP11-557H15.4, in the green-yellow module were associated with neurotransmitter secretion. Five core enrichment lncRNAs, such as KB-1299A7.2 and RP11-13E1.5, in the black module were associated with the functions of blood circulation and heart contraction. AC061961.2, LING01-AS1, and RP11-13E1.5 were confirmed to be downregulated in DCM tissues by real-time PCR. The current study suggests that downregulation of AC061961.2, LING01-AS1, and RP11-13E1.5 may be associated with DCM progression, which may serve as key diagnostic biomarkers and therapeutic targets for DCM.

Stomatin-like protein-2 relieve myocardial ischemia/reperfusion injury by adenosine 5'-monophosphate-activated protein kinase signal pathway.

Previous studies have shown that stomatin-like protein-2 (SLP-2) could regulate mitochondrial biogenesis and function. The study was designed to explore the contribution of SLP-2 to the myocardial ischemia and reperfusion (I/R) injury. Anesthetized rats were treated with SLP-2 and subjected to ischemia for 30 minutes before 3 hours of reperfusion. An oxygen-glucose deprivation/reoxygenation model of I/R was established in H9C2 cells. In vivo, SLP-2 significantly improved cardiac function recovery of myocardial I/R injury rats by increasing fractional shortening and ejection fraction. SLP-2 pretreatment alleviated infarct area and myocardial apoptosis, which was paralleled by decreasing the level of cleaved caspase-3 and the ratio of Bax/Bcl-2, increasing the content of superoxide dismutase and reducing oxidative stress damage in serum. In addition, SLP-2 increased the level of ATP and stabilized mitochondrial potential (Ψm). The present in vitro study revealed that overexpression with SLP-2 reduced H9C2 cells apoptosis, accompanied by an increased level of ATP, the ratio of mitochondrial DNA/nuclear DNA, activities of complex II and V, and decreased the production of mitochondrial reactive oxygen species. Simultaneously, SLP-2 activated the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway in myocardial I/R injury rats and H9C2 cells. This study revealed that SLP-2 mediates the cardioprotective effect against I/R injury by regulating AMPK signaling pathway.

Regulatory role of IKKɑ in myocardial ischemia/reperfusion injury by the determination of M1 versus M2 polarization of macrophages.

The IκB kinase (IKK) complex plays a well-documented role in cancer and immune system. This function has been widely attributed to its role as the master regulator of the NF-κB family. Particularly, IKKɑ, a member of IKK complex, is reported to have various regulating effects in inflammatory and malignant diseases. However, its role as well as its mechanism of function in macrophages following myocardial ischemia and reperfusion (I/R) injury remains unexplored. In vivo, sham or I/R operations were performed on macrophage-specific IKKɑ knockout (mIKKɑ-/-) mice and their IKKɑflox/flox littermates. We ligated the left anterior descending (LAD) coronary artery of I/R groups simulating ischemia for 30 min, followed by a reperfusion period of 3 days and 7 days, respectively. The hearts of mIKKɑ-/- mice exhibited significantly increased inflammation and macrophage aggregation as compared to their IKKɑflox/flox littermates. Moreover, in the mIKKɑ-/- group subjected to I/R macrophages had a tendency to polarize to M1 phenotype. In vitro, we stimulated RAW264.7 cells with Lipopolysaccharides (LPS) after infection by the lentivirus, either knocking-down or overexpressing IKKɑ. We discovered that a deficiency of IKKɑ in RAW264.7 caused increased expression of pro-inflammatory markers compared to normal RAW264.7 after LPS stimulation. Inversely, pro-inflammatory factors were inhibited with IKKɑ overexpression. Mechanistically, IKKɑ directly combined with RelB to regulate macrophage polarization. Furthermore, IKKɑ regulated MEK1/2-ERK1/2 and downstream p65 signaling cascades after LPS stimulation. Overall, our data reveals that IKKɑ is a novel mediator protecting against the development of myocardial I/R injury via negative regulation of macrophage polarization to M1 phenotype. Thus, IKKɑ may serve as a valuable therapeutic target for the treatment of myocardial I/R injury.

Risk factors for early death in primary malignant cardiac tumors: An analysis of over 40 years and 500 patients.

OBJECTIVES: To investigate risk factors contributing to early death in patients diagnosed with primary malignant cardiac tumors (PMCTs) and derive better understanding of these poorly characterized individuals. METHOD: Data from the Surveillance, Epidemiology and End-Results (SEER) registries on 564 patients diagnosed with PMCTs between 1973 and 2014 were analyzed. Early death was defined as survival of ≤3 months from the time of diagnosis. Two-tailed χ2 or fisher's exact test were used for association between categorical variables and occurrence of early death. Logistic regression analysis was used to assess independent risk factors of early death. Time trends in early death rates of PMCTs were described using scatter plot. RESULTS: Of the 564 patients with PMCTs, early death was identified in 214 individuals (37.9%). Patients with unspecified soft tissue sarcomas and blood vessel tumors had the highest risk of early death. Age > 80 years and non-consent for surgery were strong predictors of early death in all PMCT subtypes. In sarcomas, disadvantaged income was associated with an increase in early mortality, while black race was associated with a reduction in early mortality. In mesotheliomas and others, male sex was a risk factor for early mortality, while Hispanic ethnicity was associated with a reduction in early mortality. Percentages of early death slightly decreased over the past 40 years. CONCLUSIONS: Predictors of early death are primarily related to age older than 80 years, no surgery and specific histopathology types but also include disadvantaged socioeconomic status and male sex. Initiatives to identify those at risk and develop preventive interventions should be prioritized.

The midterm results of coronary endarterectomy in patients with diffuse coronary artery disease.

BACKGROUND: Diffuse coronary artery disease is a challenge for both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Coronary artery endarterectomy (CE) coupled with CABG is an alternative method to achieve complete revascularization. The mid- and long-term results of CE are largely questionable. The aim is to evaluate the early and mid-term graft patency of concomitant coronary artery endarterectomy and CABG. METHODS: A total of 304 patients who had undergone concomitant CE and CABG for diffuse coronary artery disease were identified from our database. A total of 238 patients (1) with complete operative records, (2) with good graft flow during surgery, (3) who were discharged, (4) with a one-year/ three-year follow-up were included in our study. The follow-up information was obtained directly from our out-patient department and by telephone contact. The categorical and continuous values were analyzed by Chi Square test and student's test respectively. RESULTS: CE was performed on 238 patients who represented a total of 269 target coronary vessels. The mean age of the patients was 67.8 ± 6.8 years old; male to female patient ratio was 170:68. The mean intensive care unit stay was 1.7 ± 8 days, and mean post-operative length of hospital stay was 11 ± 3 days. The average follow up time was 41.8 ± 21.4 months. At follow-up, the overall graft patency was 78.4% at one year and 69.8% at three years. The left coronary graft patency rate was significantly higher than the right coronary graft patency rate (87.4% vs 73.1% at one-year and 78.2% vs 64.8% at three years). There was no significant difference in graft patency rates between the on-pump CE + CABG vs off-pump CE + CABG groups at one year (80.0% vs 76.9%) and at three years (92.3% vs 91.7%). At the one-year follow up, 92.3% of grafts showed grade A patency in the on-pump group versus 91.7% in the off-pump group; 7.7% of grafts showed grade B patency in the on-pump group versus 8.3% in the off-pump group. At the three-year follow up, 80.6% of grafts showed grade A patency in the on-pump group versus 77.4% in the off-pump group; 19.4% of grafts showed grade B patency in the on-pump group versus 22.6% in the off -pump group. The Predictors of better graft patency are use of LIMA graft, CE on LAD, and intra-operative graft flow meter and PI. CONCLUSIONS: In patients with diffuse coronary disease, CE is a safe and feasible technique for a select group of patients with excellent mid-term survival rates and graft patency rates. CE produces better overall results when performed on the LAD, and grafted over with the LIMA. Similar outcomes are obtained with both on-pump and off-pump surgery. For a select group of patients, coronary endarterectomy (CE) offers an alternative choice of coronary artery reconstruction and complete coronary revascularization.

Does full sternotomy have more significant impact than the cardiopulmonary bypass time in patients of mitral valve surgery?

BACKGROUND: Over the past decade, minimally invasive mitral valve surgery (MIMVS) has grown in popularity. Less invasive approaches to mitral valve surgery are increasingly used for improved cosmesis. We sought to compare these minimally invasive approaches fairly with conventional full sternotomy approaches by using propensity-matching methods. METHODS: From January 2011 to January 2017, a total of 1120 isolated mitral valve operations were performed at our institution. Data were retrospectively collected on all patients, and a logistic regression model was created to predict selection to a minimally invasive versus conventional sternotomy approach. Propensity scores were then generated based on the regression model and matched pairs created using 1:1 nearest neighbor matching. There were 165 matched pairs in the analysis (sternotomy, n = 165;MIMVS, n = 165). Clinical outcomes included bypass and cross-clamp time, length of hospitalization, morbidity, and mortality. Patient details and follow-up outcomes were compared using multivariate, and Kaplan-Meier analyses. RESULTS: The minimally invasive approach led to slightly longer cardiopulmonary bypass time (99 ± 25 vs 88 ± 17 min, p <0.001), and cross-clamp time (65 ± 13 vs 49 ± 11 min, p<0.001). Overall, no significant differences existed among major in-hospital complications between groups. There were no differences between the matched groups in 30-day mortality (1.2% vs 0.6%, p >0.05). However, Chest tube drainage was lower at 6 and 24 h after a minimally invasive approach (30 ± 5 mL) and 120 ± 20 mL than after conventional sternotomy 175 ± 50 mL and 400 ± 150 mL at these times (p < 0.001). Transfusion was less frequent after minimally invasive surgery than after conventional surgery (15.7% vs 40.6%, p < 0.001). Patients undergoing minimally invasive surgery spent less time on ventilation support (6.2 ± 1.1 h vs 10.4 ± 2.7, p < 0.001). The multivariable regression analysis showed the full sternotomy was an independent risk factor for the propensity-adjusted likelihood of postoperative transfusion, re-exploration for bleeding, and postoperative ventilation support (p < 0.05). But the duration of cardiopulmonary bypass time was not an independent risk factor. The mean duration of survival follow-up was 4.4 ± 1.2 years. However, comparison of survival curves between the two groups revealed no significant difference (P = 0.203). With regard to freedom from valve-related morbidity, there was no significant difference between groups (P = 0 .574). CONCLUSION: Within that portion of the spectrum of mitral valve surgery in which propensity matching was possible, minimally invasive mitral valve surgery has cosmetic, blood product use, and respiratory advantages over conventional surgery, and no apparent detriments. However, minimally invasive mitral valve surgery required a slightly longer cardiopulmonary bypass time and cross-clamp time. Minimally invasive mitral valve surgery represents a safe and effective surgical technique that we believe should be used more routinely in the surgical management of mitral valve disease. MIMVS provides equally durable midterm results as the standard sternotomy approach.

Expression and role of neutrophil gelatinase-associated lipocalin (NGAL) signaling pathways in the early stage of vein graft restenosis of a pig model / 中国胸心血管外科临床杂志

@#Objective     To investigate the expression of neutrophil gelatinase-associated lipocalin (NGAL) signaling pathways in the early stage of porcine vein graft restenosis, and to explore the possible role and mechanism in the early vein graft restenosis after coronary artery bypass surgery. Methods     We selected 18 ordinary healthy pigs weighing 25-30 kg and collected samples of the vein graft of pigs at the preoperation and postoperative days 7, 14 and 30. Hematoxylin-eosin (HE) staining and Masson staining, immunohistochemical method were used to observe the neointimal hyperplasia, the migration of smooth muscle cells and and vascular remodeling of the vein bypass graft. The expression changes of NGAL, matrix metalloprotenase (MMP)9, MMP2 and tissue inhibitor of metalloproteinase (TIMP)1 in different periods of the vein bypass graft was tested. Results     By HE and Masson staining, with the passing of modeling time, degradation of collagen matrix in the vein graft, gradually thickening of muscle fibers and the migration to the inner membrance and vascular remodeling caused the vascular stenosis. By immunohistochemistry, NGAL, MMP9  and MMP2 of normal vein in the model were seldom expressed and even did not express. At 14 days after the modeling, NGAL expression in the membrane layer of blood vessels began to appear, peaked at postoperative 30 days, and began to appear in the inner membrance. MMP9, MMP2 expression began to appear at postoperative 7 days, peaked at postoperative 14 days, and tended to decline at postoperative 30 days. TIMP1 expression was less in normal vascular walls and at the 14 days after the modeling, expression peaked in the vein graft. Conclusion     NGAL, MMP9, MMP2 and TIMP1 may be involved in the formation of early vascular graft restenosis. NGAL as initiator, results in the expression of MMP9 and MMP2, and participates in the degradation of collagen matrix and the migration of smooth muscle cells in vein grafts. TIMP1 as a negative factor, may play an important role in maintaining their own balance.

Targeted Metagenome Based Analyses Show Gut Microbial Diversity of Inflammatory Bowel Disease patients.

Inflammatory bowel disease (IBD) is a multifactorial disease including both genetic and environmental factors. We compared the diversity of intestinal microbesamong a cohort of IBD patients to study the microbial ecological effects on IBD. Fecal samples from patients were sequenced with next generation sequence technology at 16S rDNA region. With statistical tools, microbial community was investigated at different level. The gut microbial diversity of Crohn's disease (CD) patients and colonic polyp (CP) patients significantly different from each other. However, the character of ulcerative colitis (UC) patients has of both CD and CP features. The microbial community from IBD patients can be very different (CD patient) or somewhat similar (UC patients) to non-IBD patients. Microbial diversity can be an important etiological factor for IBD clinical phenotype.

Prevalence of primary cardiac tumor malignancies in retrospective studies over six decades: a systematic review and meta-analysis.

The incidence of patients diagnosed with primary malignant cardiac tumors (PMCTs) has increased greatly in the past few decades. Whether this rising prevalence is due to overdiagnosis or an increased malignancy rate of primary cardiac tumors (PCTs) remains unclear. Therefore, we performed a systematic review and meta-analysis of published retrospective studies to determine whether the malignancy rate has been increasing over time. Published studies containing relevant data between 1956 and 2014 were evaluated. Two authors searched for all retrospective studies that included patients diagnosed with PCT and PMCT. Two other investigators independently extracted the data, and discrepancies were resolved by consensus. A random-effects meta-analysis model and cumulative meta-analysis model were used to evaluate the pooled prevalence and trend of dynamic change in PCT malignancies. The effects of time, study period and sample size were studied using a logit-linear regression model with robust error variance and a time variable. Thirty-eight studies involving 5,586 patients were analyzed. The pooled prevalence of PMCT among the patients diagnosed with PCT was 9.9% (95% CI, 8.4% to 11.4%) (I2=70%; P< 0.001), and this prevalence has been stable since around 2003. In the regression model, the malignancy odds ratio remained stable from 1975 onward, and no time effect was observed. Our study confirms that PMCT is uncommon, and the prevalence of PCT malignancies remained stable in the past few decades. The clinically observed increase in incidence is unlikely to reflect a true population-level increase in tumorigenesis. This result strongly suggests that the observed increase in incidence of PMCT most likely reflects increased diagnostic detection over time.