The activator protein-1 complex governs a vascular degenerative transcriptional programme in smooth muscle cells to trigger aortic dissection and rupture.

BACKGROUND AND AIMS: Stanford type A aortic dissection (AD) is a degenerative aortic remodelling disease marked by an exceedingly high mortality without effective pharmacologic therapies. Smooth muscle cells (SMCs) lining tunica media adopt a range of states, and their transformation from contractile to synthetic phenotypes fundamentally triggers AD. However, the underlying pathomechanisms governing this population shift and subsequent AD, particularly at distinct disease temporal stages, remain elusive. METHODS: Ascending aortas from nine patients undergoing ascending aorta replacement and five individuals undergoing heart transplantation were subjected to single-cell RNA sequencing. The pathogenic targets governing the phenotypic switch of SMCs were identified by trajectory inference, functional scoring, single-cell regulatory network inference and clustering, regulon, and interactome analyses and confirmed using human ascending aortas, primary SMCs, and a ß-aminopropionitrile monofumarate-induced AD model. RESULTS: The transcriptional profiles of 93 397 cells revealed a dynamic temporal-specific phenotypic transition and marked elevation of the activator protein-1 (AP-1) complex, actively enabling synthetic SMC expansion. Mechanistically, tumour necrosis factor signalling enhanced AP-1 transcriptional activity by dampening mitochondrial oxidative phosphorylation (OXPHOS). Targeting this axis with the OXPHOS enhancer coenzyme Q10 or AP-1-specific inhibitor T-5224 impedes phenotypic transition and aortic degeneration while improving survival by 42.88% (58.3%-83.3% for coenzyme Q10 treatment), 150.15% (33.3%-83.3% for 2-week T-5224), and 175.38% (33.3%-91.7% for 3-week T-5224) in the ß-aminopropionitrile monofumarate-induced AD model. CONCLUSIONS: This cross-sectional compendium of cellular atlas of human ascending aortas during AD progression provides previously unappreciated insights into a transcriptional programme permitting aortic degeneration, highlighting a translational proof of concept for an anti-remodelling intervention as an attractive strategy to manage temporal-specific AD by modulating the tumour necrosis factor-OXPHOS-AP-1 axis.

A meta-analysis comparing the diagnostic performance of computed tomography-derived fractional flow reserve and coronary computed tomography angiography at different levels of coronary artery calcium score.

OBJECTIVES: The impact of coronary calcification on the diagnostic accuracy of computed tomography-derived fractional flow reserve (CT-FFR) and coronary computed tomography angiography (CCTA) remains a crucial consideration. This meta-analysis aims to compare the diagnostic performance of CT-FFR and CCTA at different levels of coronary artery calcium score (CACS). METHODS AND RESULTS: We searched PubMed, Embase, and the Cochrane Library for relevant articles on CCTA, CT-FFR, and invasive fractional flow reserve (FFR). Ten studies were included to evaluate the diagnostic performance of CT-FFR and CCTA at the per-patient and per-vessel levels in four CACS groups. Invasive FFR was used as the reference standard. Except for the CACS ≥ 400 group, the AUC of CT-FFR was higher than those of CCTA in other subgroups of CACS (in CACS < 100 (per-patient, 0.9 (95% CI 0.87-0.92) vs. 0.32 (95% CI 0.28-0.36); per-vessel, 0.92 (95% CI 0.89-0.94) vs. 0.66 (95% CI 0.62-0.7); both p < 0.001), CACS ≥ 100 (per-patient, 0.86 (95% CI 0.82-0.88) vs. 0.44 (95% CI 0.4-0.48); per-vessel, 0.88 (95% CI 0.85-0.9) vs. 0.51 (95% CI 0.46-0.55); both p < 0.001), and CACS < 400 (per-patient, 0.9 (95% CI 0.87-0.93) vs. 0.74 (95% CI 0.7-0.78), p < 0.001; per-vessel, 0.8 (95% CI 0.76-0.83) vs. 0.74 (95% CI 0.7-0.78); p = 0.02)). CONCLUSIONS: CT-FFR demonstrates superior diagnostic performance in low CACS groups (CACS < 400) than CCTA in detecting hemodynamic stenoses in patients with coronary artery disease (CAD). CLINICAL RELEVANCE STATEMENT: Computed tomography-derived fractional flow reserve might be utilized to determine the necessity of invasive coronary angiography in coronary artery disease patients with coronary artery calcium score < 400. KEY POINTS: • There is a lack of meta-analysis comparing the diagnostic performance of computed tomography-derived fractional flow reserve and coronary computed tomography angiography at different levels of calcification. • Computed tomography-derived fractional flow reserve only has a better diagnostic performance than coronary computed tomography angiography with low amounts of coronary calcium. • For the low coronary artery calcium score group, computed tomography-derived fractional flow reserve might be a good non-invasive method to detect hemodynamic stenoses in coronary artery disease patients.

Scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair in rheumatic mitral disease.

OBJECTIVE: We aimed to evaluate the mitral valve calcification and mitral structure detected by cardiac computed tomography (cardiac CT) and establish a scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair (EGMR) and guide surgical strategy in rheumatic mitral disease (RMD). MATERIALS AND METHODS: This is a retrospective bi-center cohort study. Based on cardiac CT, mitral valve calcification and mitral structure in RMD were quantified and evaluated. The primary outcome was EGMR. A logical regression algorithm was applied to the scoring model. RESULTS: A total of 579 patients were enrolled in our study from January 1, 2019, to August 31, 2022. Of these, 443 had baseline cardiac CT scans of adequate quality. The calcification quality score, calcification and thinnest part of the anterior leaflet clean zone, and papillary muscle symmetry were the independent CT factors of EGMR. Coronary artery disease and pulmonary artery pressure were the independent clinical factors of EGMR. Based on the above six factors, a scoring model was established. Sensitivity = 95% and specificity = 95% were presented with a cutoff value of 0.85 and 0.30 respectively. The area under the receiver operating characteristic of external validation set was 0.84 (95% confidence interval [CI] 0.73-0.93). CONCLUSIONS: Mitral valve repair is recommended when the scoring model value > 0.85 and mitral valve replacement is prior when the scoring model value < 0.30. This model could assist in guiding surgical strategies for RMD. CLINICAL RELEVANCE STATEMENT: The model established in this study can serve as a reference indicator for surgical repair in rheumatic mitral valve disease. KEY POINTS: • Cardiac CT can reflect the mitral structure in detail, especially for valve calcification. • A model based on cardiac CT and clinical factors for predicting early good mitral valve repair was established. • The developed model can help cardiac surgeons formulate appropriate surgical strategies.

Surgical Treatment for Type A Aortic Dissection after Endovascular Aortic Repair: A 12-year, Single-Center Study.

OBJECTIVE: This study aims to investigate the clinical manifestations, operative techniques, and outcomes of patients who undergo open repair after thoracic endovascular aortic repair (TEVAR). METHODS: From January 2010 to June 2022, 113 consecutive type A aortic dissection (TAAD) patients underwent secondary open operation after TEVAR at our institution, and the median interval from primary intervention to open surgery was 12 (1.9-48.0) months. We divided the patients into two groups (RTAD (retrograde type A dissection) group, N = 56; PNAD (proximal new aortic dissection) group, N = 57) according to their anatomical features. Survival analysis during the follow-up was evaluated using a Kaplan-Meier survival curve and a log-rank test. RESULTS: The 30-day mortality was 6.2% (7/113), the median follow-up period was 31.7 (IQR 14.7-65.6) months, and the overall survival at 1 year, 5 years, and 10 years was 88.5%, 88.5%, and 87.6%, respectively. Fourteen deaths occurred during the follow-up, but there were no late aorta-related deaths. Three patients underwent total thoracoabdominal aortic replacement 1 year after a second open operation. The RTAD group had a smaller ascending aorta size (42.5 ± 7.7 mm vs 48.4 ± 11.4 mm; P < .01) and a closer proximal landing zone (P < .01) compared to the PNAD group. However, there were no differences in survival between the two groups. CONCLUSIONS: TAAD can present as an early or a late complication after TEVAR due to stent-grafting-related issues or disease progression. Open operation can be performed to treat TAAD, and this has acceptable early and mid-term outcomes. Follow-up should become mandatory for patients after TEVAR because these patients are at increased risk for TAAD.

Chinese Additive Anti-inflammatory Action for Aortopathy & Arteriopathy (5A) Registry protocol: rationale, design and methodology.

BACKGROUND: Acute aortic syndrome (AAS) is a life-threatening condition. Inflammation plays a key role in the pathogenesis, development and progression of AAS, and is associated with significant mortality and morbidity. Understanding the inflammatory responses and inflammation resolutions is essential for an appropriate management of AAS. METHOD: Thirty Chinese cardiovascular centers have collaborated to create a multicenter observational registry (named Chinese Additive Anti-inflammatory Action for Aortopathy & Arteriopathy [5A] registry), with consecutive enrollment of adult patients who underwent surgery for AAS that was started on Jan 1, 2016 and will be ended on December 31, 2040. Specially, the impact of inflammation and anti-inflammatory strategies on the early and late adverse events are investigated. Primary outcomes are severe systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), Sequential Organ Failure Assessment (SOFA) scores at 7 days following this current surgery. Secondary outcomes are SISR, 30-day mortality, operative mortality, hospital mortality, new-onset stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. DISCUSSION: The analysis of this multicenter registry will allow our better knowledge of the prognostic importance of preoperative inflammation and different anti-inflammatory strategies in adverse events after surgery for AAS. This registry is expected to provide insights into novel different inflammatory resolutions in management of AAS beyond conventional surgical repair. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04398992 (Initial Release: 05/19/2020).

The immunoproteasome subunit ß2i ameliorates myocardial ischemia/reperfusion injury by regulating Parkin-Mfn1/2-mediated mitochondrial fusion.

Mitochondrial dynamics are critical for maintaining mitochondrial morphology and function during cardiac ischemia and reperfusion (I/R). The immunoproteasome complex is an inducible isoform of the proteasome that plays a key role in modulating inflammation and some cardiovascular diseases, but the importance of immunoproteasome catalytic subunit ß2i (also known as LMP10 or MECL1) in regulating mitochondrial dynamics and cardiac I/R injury is largely unknown. Here, using ß2i-knockout (KO) mice and rAAV9-ß2i-injected mice, we discovered that ß2i expression and its trypsin-like activity were significantly attenuated in the mouse I/R myocardium and in patients with myocardial infarction (MI). Moreover, ß2i-KO mice exhibited greatly enhanced I/R-mediated cardiac dysfunction, infarct size, myocyte apoptosis and oxidative stress accompanied by excessive mitochondrial fission due to Mfn1/2 and Drp1 imbalance. Conversely, cardiac overexpression of ß2i in mice injected with recombinant adeno-associated virus 9 (rAAV9)-ß2i ameliorated cardiac I/R injury. Mechanistically, I/R injury reduced ß2i expression and activity, which increased the expression of the E3 ligase Parkin protein and promoted the degradation of mitofusin 1/2 (Mfn1/2), leading to excessive mitochondrial fission. In conclusion, our data suggest for the first time that ß2i exerts a protective role against cardiac I/R injury and that increasing ß2i expression may be a new therapeutic option for cardiac ischemic disease in clinical practice. Graphical abstract showing how the immunoproteasome subunit ß2i ameliorates myocardial I/R injury by regulating Parkin-Mfn1/2-mediated mitochondrial fusion.

Development of a High-Field "Brick" Mass Spectrometer with Extended Mass Range and Capable of Characterizing Native Proteins.

One of the main challenges of analyzing intact proteins on an ion trap mass spectrometer is the mass range limitation, especially for miniature mass spectrometers. In this study, a high-field frequency scanning ion trap miniature mass spectrometer, namely the high-field "Brick" mass spectrometer, was developed to analyze intact proteins. A high-voltage broadband radio frequency (rf) amplifier was designed with a maximum output of 900 Vp-p over a frequency range of 130-700 kHz. Compared to the 600 Vp-p rf amplifier equipped in the conventional "Brick" mass spectrometer, the mass range of the instrument could be extended from 2000 to over 8000 Th. Sensitivity and mass resolution for native protein analyses were also evaluated and compared. Various proteins as well as their mixtures were analyzed on the high-field "Brick" mass spectrometer. The noncovalent interaction between protein-ligand complexes, lysozyme with triN-acetylchitotriose, was also analyzed. In addition, a hybrid ion scan mode was explored to further expand the mass range of the instrument at both low- and high-mass ends. In the hybrid ion scan mode, both rf frequency and amplitude were tuned, and a mass range from 100 to 12,000 Th was realized. As a result, both small drugs and proteins could be analyzed in a single mass scan. As proof-of-concept demonstrations, a mixture of atenolol and bovine serum albuminand oligomers of transferrin were analyzed.

Smart Miniature Mass Spectrometer Enabled by Machine Learning.

Similar to smartphones, smart or automatic level is also a critical feature for a miniature mass spectrometer. Compared to large-scale instruments, miniature mass spectrometers often have a lower mass resolution and larger mass drift, making it challenging to identify molecules with close mass-charge ratios. In this work, a miniature mass spectrometer (the Brick-V model) was combined with intelligent algorithms to realize rapid and accurate identification. This Brick-V mass spectrometer developed in our lab was equipped with a vacuum ultraviolet photoionization (VUV-PI) source, which ionizes volatile organic compounds (VOCs) with minor fragments. Machine learning would be especially helpful when analyzing samples with multiple characteristic peaks. Four machine learning algorithms were tested and compared in terms of precision, recall, balanced F score (F1 score), and accuracy. After optimization, the multilayer perceptron (MLP) method was selected and first applied for the automatic identification and differentiation of ten different fruits. By recognizing the pattern of multiple VOCs diffused from fruits, an average accuracy of 97% was achieved. This system was further applied to determine the freshness of strawberries, and strawberry picking at different times (especially during the first 24 h at room temperature of winter) could be well discriminated. After building a database of 63 VOCs, a rapid method to identify compounds in the database was established. In this method, molecular ions, fragment ions, and dimer ions in the full mass spectrum were all utilized in the machine learning program. A satisfactory prediction accuracy for the 63 VOCs could be achieved (>99%).

Programmable gear-based mechanical metamaterials.

Elastic properties of classical bulk materials can hardly be changed or adjusted in operando, while such tunable elasticity is highly desired for robots and smart machinery. Although possible in reconfigurable metamaterials, continuous tunability in existing designs is plagued by issues such as structural instability, weak robustness, plastic failure and slow response. Here we report a metamaterial design paradigm using gears with encoded stiffness gradients as the constituent elements and organizing gear clusters for versatile functionalities. The design enables continuously tunable elastic properties while preserving stability and robust manoeuvrability, even under a heavy load. Such gear-based metamaterials enable excellent properties such as continuous modulation of Young's modulus by two orders of magnitude, shape morphing between ultrasoft and solid states, and fast response. This allows for metamaterial customization and brings fully programmable materials and adaptive robots within reach.

HbA1c is related to microcirculation blood perfusion in patients with coronary microvascular disease using stress perfusion cardiac magnetic resonance: An observational study.

BACKGROUND: In coronary microvascular disease (CMD) patients, the incidence of major adverse cardiovascular events (MACEs) in patients with myocardial perfusion reserve index (MPRI) ≤ 1.47 is three times higher than that in MPRI > 1.47. We investigated whether the increase of glycated hemoglobin A1c (HbA1c) could increase the risk of MPRI ≤1.47 in diabetic and non-diabetic patients. METHODS: From November 2019, patients with ischemic symptoms but without obstructive coronary disease were screened. Use MPRI measured by stress perfusion cardiac magnetic resonance (CMR) to reflect microcirculation blood perfusion, and MPRI <2.5 were included. The patients were divided into two groups based on MPRI was greater or <1.47. The risk factors for CMD were explored using logistic regression analysis. RESULTS: A total of 80 patients with an MPRI of 1.69 ± 0.79 were included. CMD patients with an MPRI of ≤1.47(n = 33) were higher than MPRI of >1.47(n = 47) in age, presence of diabetes mellitus, fasting blood glucose levels and HbA1c levels (P < 0.05). In non-diabetic patients, increased HbA1c was associated with the risk of MPRI≤1.47 (OR = 0.017, 95%CI: 0.050-1.107, P = 0.045). Compared with non-diabetic patients with HbA1c < 6.0, non-diabetic patients with HbA1c ≥ 6.0 increased the risk of MPRI of ≤1.47 (OR = 0.219, 95%CI: 0.069-0.697, P = 0.010). In diabetic patients, HbA1c was not associated with the risk of MPRI of ≤1.47 (OR = 1.043, 95%CI: 0.269, 4.044, P = 0.952). And compared with non-diabetic patients with HbA1c <6.0, diabetic patients with HbA1c <6.0 (OR = 0.917, 95%CI: 0.233-3.610, P = 0.901) or ≥6.0 (OR = 0.326, 95%CI: 0.073-1.446, P = 0.140), the risk of MPRI ≤ 1.47 was not further increased. CONCLUSIONS: In non-diabetic patients, elevated HbA1c is related to MPRI≤1.47(a value increased incidence of MACEs). Therefore, in patients with undiagnosed diabetes, early management of glycosylated hemoglobin is very important. TRIAL REGISTRATION: This clinical trial has been registered in the Chinese clinical Trial Registry with an identifier: ChiCTR1900025810.

High preoperative bradykinin level is a risk factor for severe postoperative hypoxaemia in acute aortic dissection surgery.

NEW FINDINGS: What is the central question of this study? Hypoxaemia can lead to increased postoperative mortality in patients: what are the independent risk factors for severe hypoxaemia after acute Stanford type A aortic dissection? What is the main finding and its importance? Severe postoperative hypoxaemia was found in 36.4% of patients, and it was determined that high preoperative bradykinin levels and increased BMI were independent predictors of severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. For obese patients with high preoperative bradykinin levels, more attention should be paid to preventing severe postoperative hypoxaemia. ABSTRACT: Severe hypoxaemia after cardiac surgery is associated with serious complications and a high risk of mortality. The purpose of this study is to investigate the independent risk factors of severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. We collected 77 patients with acute Stanford type A aortic dissection who underwent surgical treatment. The primary outcome was severe postoperative hypoxaemia (PaO2 /FiO2  ≤ 100 mmHg), and a multivariate logistic regression analysis was performed to assess the independent predictors of risk for this. A mixed-effects analysis of variance model and a receiver operating characteristic (ROC) curve were generated to evaluate the predictive probabilities of risk factors for severe postoperative hypoxaemia. A total of 36.4% of patients developed severe postoperative hypoxaemia. The multivariate logistic regression analysis identified high preoperative bradykinin level (odds ratio (OR) = 55.918, P < 0.001) and increased body mass index (BMI; OR = 1.292, P = 0.032) as independent predictors of severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. The mixed-effect analysis of variance model and ROC curve indicated that high preoperative bradykinin level and BMI were significant predictors of severe postoperative hypoxaemia (area under the ROC curve = 0.834 and 0.764, respectively). High preoperative bradykinin levels and obesity were independent risk factors for severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. For obese patients with high levels of bradykinin before surgery, clinicians should actively take measures to block bradykinin-mediated inflammatory reactions.

Efficient Correction of a Hypertrophic Cardiomyopathy Mutation by ABEmax-NG.

[Figure: see text].

Mammalian sterile 20-like kinase 1 acts as a candidate biomarker of mortality of emergency surgical repair for acute type a aortic dissection.

BACKGROUND: Acute type A aortic dissection (ATAAD) is a life-threatening pathological change of the aorta. Patients who have undergone aortic surgery are usually at high risk of mortality. AIM: We investigated the predictive value of serum Mammalian sterile 20-like kinase 1 (MST1) as a biomarker for the risk of mortality of ATAAD patients. METHODS: In this retrospective cohort study, we analyzed 160 consecutive ATAAD patients who had undergone emergency surgery from July 2016 to April 2017. Medical records and blood samples were collected and analyzed. ELISA assays were performed to detect the concentrations of several proteins including MST1. The relationship between these potential biomarkers and the primary endpoint of death was evaluated using Cox proportional hazard regression analysis. RESULTS: Compared with a low level (< 1330.8 ng/L), high serum MST1 level (≥ 1330.8 ng/L) was positively associated with the 30-day mortality (OR = 5.233, 95%CI, 1.843-14.862, P < 0.01) and retained predictive after adjustment for sex, age, BMI, nasopharyngeal temperature and deep hypothermia circulatory arrest time (OR = 4.628 95% CI, 1.572-13.625, P < 0.01). A pre-existing basic clinical prediction model was improved with the inclusion of preoperative serum MST1. Specifically, the area under the ROC curve for base model (history of cerebrovascular disease, creatinine, time of operation) was 0.708 (95%CI, 0.546-0.836) and markedly increased to 0.823 when taking MST1 into consideration (95%CI, 0.700-0.912, P = 0.02). CONCLUSION: Our study suggests that high preoperative circulating MST1, with a concentration greater than 1330.8 ng/L, was correlated with the 30-day mortality of ATAAD patients who underwent emergency surgery.

The prognostic study of mental stress-induced myocardial ischemia in coronary revascularization patients with depression/anxiety: rationale and design.

BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) frequently occurs in patients with coronary artery disease (CAD), and is even more common in patients with co-occurring CAD and depression/anxiety. MSIMI appears to be a poor prognostic factor for CAD, but existing data on depression/anxiety patients are limited. METHODS: This cohort study will consecutively screen 2,647 CAD patients between 2023 and 2025. Included subjects will need to have received coronary revascularization and also have depression and/or anxiety at baseline. This study will enroll 360 subjects who meet the criteria. Two mental stress tests will be carried out in each patient at 1 month and 1 year timelines after coronary revascularization, using Stroop color word tests. MSIMI will be assessed by 99 m-Tc-sestamibi myocardial perfusion imaging. The endothelial function will be assessed by EndoPAT. Furthermore, we will dynamically monitor patients' health and mental conditions every 3 months. The mean follow-up time will be 1 year. The primary endpoint is the major adverse cardiac events, a composite of all-cause death, cardiac death, myocardial infarction, stroke, or unplanned revascularization. Secondary endpoints will include overall health and mental conditions. The reproducibility of mental stress combined with myocardial perfusion for detecting MSIMI and comparisons between coronary stenosis and ischemic segments will also be included. CONCLUSIONS: This cohort study will provide information on MSIMI outcomes in CAD patients who also have comorbid depression/anxiety after revascularization. In addition, understanding the long-term dynamics of MSIMI and the match between coronary stenosis and ischemia will provide insight into MSIMI mechanisms. TRAIL REGISTRATION: ChiCTR2200055792, 2022.1.20, www.medresman.org.cn.

Development of PROTAC degrader probe of CDK4/6 based on DCAF16.

Treatment of breast cancer has greatly evolved during the last decades, but triple negative breast cancer (TNBC) with a higher degree of malignancy cannot be directly and effectively treated. Abnormal cell cycle is generally found in human breast cancer and other malignant tumors, and cyclin-dependent kinases (CDK) 4/6, a cell cycle-related regulatory nuclear protein, is deemed as an effective target for breast cancer treatment so far. Since DCAF16 E3 ligase is also mainly distributed in the nucleus, in this study, by combining Palbociclib and DCAF16 E3 ligase ligand KB02 with different linkers, a series of DCAF16 based CDK4/6 degraders were designed and synthesized. Among them, compound A4 showed potent inhibitory activity against CDK4/6, and decreased the level of CDK4/6 protein in MDA-MB-231 cells in a concentration- and time-dependent manner. Moreover, the toxicity of A4 in normal cells showed 7 times lower than that of Palbociclib, and A4 exhibits therapeutic potential in MDA-MB-231 xenograft models in vivo. These findings indicate that A4, as a novel CDK4/6 degrader based on DCAF16, is worthy of further investigating for the treatment of TNBC.

Metabolomic analysis reveals the metabolic disturbance in aortic dissection: Subtype difference and accurate diagnosis.

BACKGROUND AND AIMS: Aortic dissection (AD), a severe clinical emergency with high mortality, is easily misdiagnosed as are other cardiovascular diseases. This study aimed at discovering plasma metabolic markers with the potential to diagnose AD and clarifying the metabolic differences between two subtypes of AD. METHODS AND RESULTS: To facilitate the diagnosis of AD, we investigated the plasma metabolic profile by metabolomic approach. A total 482 human subjects were enrolled in the study: 80 patients with AD (50 with Stanford type A and 30 with Stanford type B), 198 coronary artery disease (CAD) patients, and 204 healthy individuals. Plasma samples were submitted to targeted metabolomic analysis. The partial least-squares discriminant analysis models were constructed to illustrate clear discrimination of AD patients with CAD patients and healthy control. Subsequently, the metabolites that were clinically relevant to the disturbances in AD were identified. Twenty metabolites induced the separation of AD patients and healthy control, 9 of which caused the separation of CAD patients and healthy control. There are 11 metabolites specifically down-regulated in AD group. Subgroup analysis showed that the levels of glycerol and uridine were dramatically lower in the plasma of patients with Stanford type A AD than those in the healthy control or Stanford type B AD groups. CONCLUSION: This study characterized metabolomic profiles specifically associated with the pathogenesis and development of AD. The findings of this research may potentially lead to earlier diagnosis and treatment of AD.

Safety and efficacy of fibrinogen concentrate in aortic arch surgery involving moderate hypothermic circulatory arrest.

OBJECTIVE: Bleeding is a common complication of cardiac surgery, especially aortic arch surgery involving moderate hypothermic circulatory arrest. Fibrinogen concentrate has been increasingly used to treat coagulopathic bleeding in cardiac surgery, although its effectiveness and safety are unknown. The aim of this prospective study was to investigate the safety and efficacy of fibrinogen concentrate in patients with acute type A aortic dissection. METHODS: From July 2020 to August 2021, 84 patients with acute type A aortic dissection who underwent emergency aortic arch surgery involving MHCA and whose intraoperative fibrinogen level was less than 1.5 g/L were included in this study. Fifty-four patients who were supplemented with fibrinogen concentrate were included in the FC treatment group. Thirty patients were included in the non-FC treatment group. The primary endpoints included the required volumes of individual allogeneic blood products (RBCs, FFP, and PC), volumes of cumulative drainage within 24 and 48 h, and total volumes after infusion of FC, as well as reoperation rates due to bleeding. The secondary endpoint for the study was the incidence of serious adverse events from the infusion of FC to day 45. The serious adverse events defined for the evaluation of the safety of FC were death, pulmonary embolism and other thromboembolic or ischaemic events. The clinical data, routine laboratory tests and plasma fibrinogen levels were obtained at 5 time points. RESULTS: We observed rapid increases in the plasma fibrinogen level and subsequent improvement in haemostasis after the administration of fibrinogen concentrate. The mean fibrinogen level increased from 1.36 ± 0.75 g/L to 2.91 ± 0.76 g/L in the fibrinogen concentrate treatment group. The patients in the fibrinogen concentrate treatment group demonstrated lower volumes of cumulative postoperative drainage and transfused allogeneic blood products than the nonfibrinogen concentrate treatment group. There were no serious adverse events in the fibrinogen concentrate treatment group during hospitalization. CONCLUSION: Fibrinogen concentrate was effective at increasing the plasma fibrinogen level and significantly reduced the volumes of transfused allogeneic blood products and blood loss in patients with aortic arch surgery. There were no serious adverse events in the patients who received fibrinogen concentrate treatment. PERSPECTIVE STATE: The safety and efficacy of fibrinogen concentrate were investigated in acute type A aortic dissection patients with aortic arch surgery. Fibrinogen concentrate was effective at increasing the plasma fibrinogen level and significantly reduced the volumes of transfused allogeneic blood products and blood loss; there were no serious adverse events in the patients who received fibrinogen concentrate treatment.

A scoring model based on clinical factors to predict postoperative moderate to severe acute respiratory distress syndrome in Stanford type A aortic dissection.

BACKGROUND: Postoperative acute respiratory distress syndrome (ARDS) after type A aortic dissection is common and has high mortality. However, it is not clear which patients are at high risk of ARDS and an early prediction model is deficient. METHODS: From May 2015 to December 2017, 594 acute Stanford type A aortic dissection (ATAAD) patients who underwent aortic surgery in Anzhen Hospital were enrolled in our study. We compared the early survival of MS-ARDS within 24 h by Kaplan-Meier curves and log-rank tests. The data were divided into a training set and a test set at a ratio of 7:3. We established two prediction models and tested their efficiency. RESULTS: The oxygenation index decreased significantly immediately and 24 h after TAAD surgery. A total of 363 patients (61.1%) suffered from moderate and severe hypoxemia within 4 h, and 243 patients (40.9%) suffered from MS-ARDS within 24 h after surgery. Patients with MS-ARDS had higher 30-day mortality than others (log-rank test: p-value <0.001). There were 30 variables associated with MS-ARDS after surgery. The XGboost model consisted of 30 variables. The logistic regression model (LRM) consisted of 11 variables. The mean accuracy of the XGBoost model was 70.7%, and that of the LRM was 80.0%. The AUCs of XGBoost and LRM were 0.764 and 0.797, respectively. CONCLUSION: Postoperative MS-ARDS significantly increased early mortality after TAAD surgery. The LRM model has higher accuracy, and the XGBoost model has higher specificity.

Comparing perioperative outcomes following off-pump multi-vessel minimally invasive via a single left intercostal space incision with median sternotomy coronary artery bypass grafting: A single-center retrospective cohort study.

BACKGROUND: The perioperative outcomes following off-pump multi-vessel minimally invasive surgery (MICS) coronary artery bypass grafting (CABG) via a single left intercostal space incision has not been well evaluated. METHOD: From July 2019 to January 2022, a total of 444 patients with multi-vessel coronary artery disease (CAD) were enrolled and divided into MICS (n = 179) and sternotomy CABG (n = 265). Perioperative outcomes were compared between these two groups, including intraoperative blood loss, postoperative first 24 h drainage, ventilation duration, length of stay (LOS) in ICU and total LOS in hospital. Intraoperative blood flow of graft vessels were measured by transit-time flow measurement after vascular anastomosis and mean flow (MF) and pulsatile index (PI) were compared. RESULTS: There were no significant differences in preoperative profiles between these two groups except younger and lower proportion of female in MICS. No significant difference in the number of graft vessels was observed between MICS (3.18 ± 0.74) and sternotomy CABG (3.28 ± 0.86). Compared to sternotomy CABG, patients with MICS showed longer operation duration [(4.33 ± 0.86) h versus (5.10 ± 1.09) h], fewer intraoperative blood loss [700 (600, 900) mL versus 500 (200, 700) mL], fewer postoperative first 24 h drainage [400 (250, 500) mL versus 300 (200, 400) mL], shorter postoperative ventilation duration [16.5 (12.5, 19.0) h versus 15.0 (12.0, 17.0) h], LOS in ICU [20.0 (16.0, 23.0) h versus 18.0 (15.0, 20.0) h] and total LOS in hospital [(14.5 ± 3.9) d versus (12.6 ± 2.7) d] (all p < .001). MI and PI of graft vessels were similar and no significant differences in major perioperative complications and mortality were observed between MICS and sternotomy CABG (all p > .05). CONCLUSION: Off-pump multi-vessel MICS may be an alternative treatment for patients with multi-vessel CAD with better perioperative outcomes than sternotomy CABG.

Does intensive blood pressure control benefit type B aortic dissection patients who undergoing surgical repair?

OBJECTIVES: The aim of this research is to determine the optimum blood pressure (BP) control goal for hypertensive type B aortic dissection (TBAD) patients undergoing surgery. METHODS: Between January 2019 and April 2021, 259 hypertensive TBAD patients undergoing surgery were included in the research. 98 patients received intensive BP control with a target of systolic BP (SBP) < 120 mmHg, and 161 received standard BP control targeting SBP between 120 and 140 mmHg. Clinical data from two groups were compared. RESULTS: Patients who received intensive BP control experienced a significantly higher incidence of acute kidney injury (AKI) postoperatively (21/98, 21.4% vs 14/161, 8.7%, p = 0.004). The intensive group took more anti-hypertensive drugs per day compared with the standard group (1.9 vs 1.5, p < 0.001). Triple-drug combination treatment was more frequent in the intensive group (38.8% vs 14.3%, p < 0.001), as were angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB; 67.3% vs 44.7%, p 0.001), and thiazide-like diuretic (44.9% vs 18.0%, p < 0.001). CONCLUSIONS: Intensive BP control treatment increases the incidence of AKI and raises the utilization of the anti-hypertensive drug, but did not reduce the operative mortality and late mortality in TBAD patients undergoing surgical repair.