Diagnosis of fetal arrhythmia in echocardiography imaging using deep learning with cyclic loss.

Background: Fetal arrhythmias frequently co-occur with congenital heart disease in fetuses. The peaks observed in M-mode fetal echocardiograms serve as pivotal diagnostic markers for fetal arrhythmias. However, speckles, artifacts, and noise pose notable challenges for accurate image analysis. While current deep learning networks mainly overlook cardiac cyclic information, this study concentrated on the integration of such features, leveraging contextual constraints derived from cardiac cyclical features to improve diagnostic accuracy. Methods: This study proposed a novel deep learning architecture for diagnosing fetal arrhythmias. The architecture presented a loss function tailored to the cardiac cyclical information and formulated a diagnostic algorithm for classifying fetal arrhythmias. The training and validation processes utilized a dataset comprising 4440 patches gathered from 890 participants. Results: Incorporating cyclic loss significantly enhanced the performance of deep learning networks in predicting peak points for diagnosing fetal arrhythmia, resulting in improvements ranging from 7.11% to 14.81% in F1-score across different network combinations. Particularly noteworthy was the 18.2% improvement in the F1-score for the low-quality group. Additionally, the precision of diagnosing fetal arrhythmia across four categories exhibited improvement, with an average improvement rate of 20.6%. Conclusion: This study introduced a cyclic loss mechanism based on the cardiac cycle information. Comparative evaluations were conducted using baseline methods and state-of-the-art deep learning architectures with the fetal echocardiogram dataset. These evaluations demonstrated the proposed framework's superior accuracy in diagnosing fetal arrhythmias. It is also crucial to note that further external testing is essential to assess the model's generalizability and clinical value.

Causal Relationships between Lymphocyte Subsets and Risk of Coronary Artery Disease: A Two-Sample Mendelian Randomization Study.

Background: Currently, the causal relationship between lymphocyte subsets and coronary artery disease (CAD) remains unclear. Therefore, we utilized Mendelian randomization (MR) to assess the association between lymphocyte subsets and CAD. Methods: We performed a two-sample MR analysis using publicly available genome-wide association studies (GWAS) datasets. The primary method of analysis to comprehensively evaluate causal effects was the inverse variance-weighted (IVW) method. The four additional MR approaches were MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analysis incorporated Cochran's Q and MR-Egger intercept tests to identify residual heterogeneity and potential horizontal pleiotropy, respectively. The MR-PRESSO distortion test was applied to identify potential pleiotropic outliers. Leave-one-out analysis confirmed that no single single-nucleotide polymorphism (SNP) significantly affected the MR estimate. We conducted reverse MR analysis to investigate the impact of variables correlated with outcomes in forward MR analysis. Results: The IVW method revealed a significant positive association between B cell count and CAD (odds ratio (OR) = 1.08 (95% CI: 1.04, 1.11), p = 2.67 × 10-5). A similar association was observed between B cell count and myocardial infarction (MI) (OR = 1.07 (95% CI: 1.03, 1.11), p = 5.69 × 10-4). Sensitivity analyses detected no outliers, heterogeneity, or pleiotropy. The reverse MR analysis was conducted to investigate the impact of CAD and MI on B cell count, and the IVW results showed no statistical significance. Conclusions: Our study suggests that a higher absolute B cell count is linked to an increased risk of CAD and MI.

Feasibility and Exploration of a Standardized Protocol for Cardiac CT Assessment of Rheumatic Mitral Disease.

Rheumatic mitral valve disease often requires surgical interventions, such as percutaneous mitral commissurotomy, surgical mitral valve repair, or replacement, especially in severe cases. This necessitates a precise preoperative assessment of the extent of mitral valve disease. Currently, transthoracic echocardiography, the gold standard for preoperative assessment, has limitations, such as restricted acoustic windows and dependence on the operator, which can affect the evaluation of subvalvular structures and calcification of the mitral valve. Previous studies have shown that cardiac computed tomography (CT), with its high resolution, strong multiplanar reconstruction capabilities, and sensitivity to calcifications, can effectively overcome these limitations. Therefore, this study aims to summarize and evaluate the effectiveness of cardiac CT in examining mitral valve leaflets, annulus, and subvalvular structures. It also reviews the feasibility and guiding significance of using cardiac CT to assess characteristic rheumatic mitral valve lesions.

Development and validation of a clinical diagnostic model for myocardial ischaemia in borderline coronary lesions based on optical pumped magnetometer magnetocardiography: a prospective observational cohort study.

OBJECTIVES: To develop and validate a clinical diagnostic model based on optical pumped magnetometer magnetocardiography (OPM-MCG) for the detection of myocardial ischaemia in patients with borderline coronary lesions prior to invasive coronary angiography (ICA). DESIGN: Prospective observational cohort study. SETTING: Single centre of the China National Clinical Research Centre for Cardiovascular Disease (NCCMRC). PARTICIPANTS: Adults with borderline coronary lesions on ICA (n=141). INTERVENTIONS: Underwent OPM-MCG before ICA and fractional flow reserve measurement. RESULTS: Five parameters were included in the final diagnostic model: MAgmax-TT, δDtsum-PN, δAgsum-C, δArsum-N and δArmin-N. 1000 bootstrap replications showed that the area under the receiver operating characteristic curve and 95% CI of the diagnostic model were 0.864 (0.803-0.925), with a sensitivity of 79.4%, specificity of 80.8%, positive predictive value of 79.4% and negative predictive value of 80.8%. Decision curve analysis showed a net benefit from the predictive model when the threshold probability of an ischaemic patient was >12%, suggesting the potential utility of the model in the real world. CONCLUSIONS: A nomogram based on five OPM-MCG parameters was developed to assess myocardial ischaemia in patients with borderline coronary lesions and has the potential to reduce the need for unnecessary ICA. TRIAL REGISTRATION NUMBER: China Clinical Trial Registry (ChiCTR2300072382).

Short-term outcomes of mild (≥30 ℃) vs. moderate hypothermic circulatory arrest in aortic arch surgery.

Background: Hypothermia and antegrade cerebral perfusion (ACP) strategies in open aortic arch surgery (AAS) have improved significantly. The significance of the gradual temperature rise to mild hypothermia is quite apparent, however, its safety remains a challenge. Therefore, our objective was to explore the safety and efficacy of mild hypothermic circulatory arrest (Mi-HCA, ≥30 ℃). Methods: This retrospective cohort study enrolled in a total of 372 patients, and was performed at the Beijing Anzhen Hospital between January 2017 and November 2022. Among the 372 patients, 81 received AAS at ≥30 ℃, and the remaining 291 received the same at 22-29.9 ℃. Most acute type A aortic dissection (ATAAD) patients received total arch replacement (TAR) and frozen elephant trunk (FET) operation. Results: Mi-HCA patients exhibited strongly augmented systemic temperature (26.19±1.63 vs. 31.40±0.79 ℃, P<0.01). The surgical, cardiopulmonary bypass (CPB), cross-clamp, circulatory arrest, and ACP durations were drastically diminished among Mi-HCA patients (all P<0.01). Moreover, the major adverse events (MAEs) incidence of Mi-HCA patients was significantly decreased (25.43% vs. 14.81%, P<0.05). Simultaneously, the Mi-HCA strategy also exhibited enhanced protection of blood cells, as well as myocardial and hepatic function. Nevertheless, multivariate logistic regression analysis revealed that Mi-HCA strategy (≥30 ℃) was not a stand-alone risk factor for MAEs following AAS. Conclusions: The short-term outcomes and safety of Mi-HCA, in combination with ACP, in AAS are satisfactory. Additionally, relative to the traditional moderate hypothermic circulatory arrest (MHCA) approach, it can substantially decrease operation duration while improving patient clinical outcomes.

Inflammatory signature-based theranostics for acute lung injury in acute type A aortic dissection.

Acute lung injury (ALI) is a serious adverse event in the management of acute type A aortic dissection (ATAAD). Using a large-scale cohort, we applied artificial intelligence-driven approach to stratify patients with different outcomes and treatment responses. A total of 2,499 patients from China 5A study database (2016-2022) from 10 cardiovascular centers were divided into 70% for derivation cohort and 30% for validation cohort, in which extreme gradient boosting algorithm was used to develop ALI risk model. Logistic regression was used to assess the risk under anti-inflammatory strategies in different risk probability. Eight top features of importance (leukocyte, platelet, hemoglobin, base excess, age, creatinine, glucose, and left ventricular end-diastolic dimension) were used to develop and validate an ALI risk model, with adequate discrimination ability regarding area under the receiver operating characteristic curve of 0.844 and 0.799 in the derivation and validation cohort, respectively. By the individualized treatment effect prediction, ulinastatin use was significantly associated with significantly lower risk of developing ALI (odds ratio [OR] 0.623 [95% CI 0.456, 0.851]; P = 0.003) in patients with a predicted ALI risk of 32.5-73.0%, rather than in pooled patients with a risk of <32.5 and >73.0% (OR 0.929 [0.682, 1.267], P = 0.642) (Pinteraction = 0.075). An artificial intelligence-driven risk stratification of ALI following ATAAD surgery were developed and validated, and subgroup analysis showed the heterogeneity of anti-inflammatory pharmacotherapy, which suggested individualized anti-inflammatory strategies in different risk probability of ALI.

Management strategies and outcomes in pregnancy-related acute aortic dissection: a multicentre cohort study in China.

BACKGROUND: Acute aortic dissection (AD) in pregnancy poses a lethal risk to both mother and fetus. However, well-established therapeutic guidelines are lacking. This study aimed to investigate clinical features, outcomes and optimal management strategies for pregnancy-related AD. METHODS: We conducted a retrospective multicentre cohort study including 67 women with acute AD during pregnancy or within 12 weeks postpartum from three major cardiovascular centres in China between 2003 and 2021. Patient characteristics, management strategies and short-term outcomes were analysed. RESULTS: Median age was 31 years, with AD onset at median 32 weeks gestation. Forty-six patients (68.7%) had type A AD, of which 41 underwent immediate surgery. Overall maternal mortality was 10.4% (7/67) and fetal mortality was 26.9% (18/67). Compared with immediate surgery, selective surgery was associated with higher risk of composite maternal and fetal death (adjusted RR: 12.47 (95% CI 3.26 to 47.73); p=0.0002) and fetal death (adjusted RR: 8.77 (95% CI 2.33 to 33.09); p=0.001). CONCLUSIONS: Immediate aortic surgery should be considered for type A AD at any stage of pregnancy or postpartum. For pregnant women with AD before fetal viability, surgical treatment with the fetus in utero should be considered. Management strategies should account for dissection type, gestational age, and fetal viability. TRIAL REGISTRATION NUMBER: NCT05501145.

The predictive value of coronary computed tomography angiography-derived fractional flow reserve for perioperative cardiac events in lung cancer surgery.

PURPOSE: As a non-invasive coronary functional examination, coronary computed tomography angiography (CCTA)-derived fractional flow reserve (CT-FFR) showed predictive value in several non-cardiac surgeries. This study aimed to evaluate the predictive value of CT-FFR in lung cancer surgery. METHOD: We retrospectively collected 227 patients from January 2017 to June 2022 and used machine learning-based CT-FFR to evaluate the stable coronary artery disease (CAD) patients undergoing lung cancer surgery. The major adverse cardiac event (MACE) was defined as perioperative myocardial injury (PMI), myocardial infarction, heart failure, atrial and ventricular arrhythmia with hemodynamic disorder, cardiogenic shock and cardiac death. The multivariate logistic regression analysis was performed to identify risk factors for MACE and PMI. The discriminative capacity, goodness-of-fit, and reclassification improvement of prediction model were determined before and after the addition of CT-FFR≤0.8. RESULTS: The incidence of MACE was 20.7 % and PMI was 15.9 %. CT-FFR significantly outperformed CCTA in terms of accuracy for predicting MACE (0.737 vs 0.524). In the multivariate regression analysis, CT-FFR≤0.8 was an independent risk factor for both MACE [OR=10.77 (4.637, 25.016), P<0.001] and PMI [OR=8.255 (3.372, 20.207), P<0.001]. Additionally, we found that the performance of prediction model for both MACE and PMI improved after the addition of CT-FFR. CONCLUSIONS: CT-FFR can be used to assess the risk of perioperative MACE and PMI in patients with stable CAD undergoing lung cancer surgery. It adds prognostic information in the cardiac evaluation of patients undergoing lung cancer surgery.

Radiomics Analysis of CTO Plaques for Predicting Successful Guidewire Crossing Within 30 Minutes of PCI.

BACKGROUND: Coronary computed tomography angiography provides valuable information for evaluating the difficulty of chronic total occlusion (CTO) percutaneous coronary intervention. This study aimed to investigate the value of CTO plaque characteristics derived from radiomics analysis for predicting the difficulty of percutaneous coronary intervention. METHODS: Patients with CTO were retrospectively enrolled from a hospital as training and internal test sets and from the other 2 territory hospitals as external test sets. Radiomics characteristics were extracted from the CTO segment on coronary computed tomography angiography. Radiomics and combined models were developed to predict successful guidewire crossing within 30 minutes (guidewire success) of CTO percutaneous coronary intervention. Subgroup analysis was conducted to investigate the influence of potential risk factors on the radiomics model performance. RESULTS: A total of 551 patients (median, 60; interquartile range, 52.00-66.00 years, 460 men) with 565 CTO lesions were finally enrolled. In the training, internal test, and external test sets, 203 of 357, 85 of 149, and 38 of 59 CTO lesions achieved guidewire success, respectively. Six radiomics features were selected for constructing the radiomics model. In the external test set, the area under the receiver operating characteristic curve of the radiomics model was significantly higher than prior prediction models (P<0.05 for all) with the area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity of 0.86, 74.58%, 81.58%, and 61.90%, respectively. The performance of the radiomics model was dependent on calcification, CTO location, adjacent branch(es), and operator caseload. CONCLUSIONS: CTO characteristics revealed by radiomics analysis can be used as effective imaging biomarkers for predicting guidewire success. However, the performance of the radiomics model depends on anatomic and operator factors.

STING-mediated IL-6 Inhibits OATP1B1 Expression via the TCF4 Signaling Pathway in Cholestasis.

Background and Aims: Organic anion-transporting polypeptides (OATPs) play a crucial role in the transport of bile acids and bilirubin. In our previous study, interleukin 6 (IL-6) reduced OATP1B3 levels in cholestatic disease. However, it remains unclear whether IL-6 inhibits OATP1B1 expression in cholestatic diseases. This study aimed to investigate whether IL-6 can inhibit OATP1B1 expression and explore the underlying mechanisms. Methods: The effect of stimulator of interferon genes (STING) signaling on inflammatory factors was investigated in a cholestatic mouse model using RT-qPCR and enzyme-linked immunosorbent assay. To assess the impact of inflammatory factors on OATP1B1 expression in hepatocellular carcinoma, we analyzed OATP1B1 expression by RT-qPCR and Western Blot after treating PLC/PRF/5 cells with TNF-α, IL-1ß, and IL-6. To elucidate the mechanism by which IL-6 inhibits OATP1B1 expression, we examined the expression of the OATP1B1 regulator TCF4 in PLC/PRF/5 and HepG2 cells using RT-qPCR and Western Blot. The interaction mechanism between ß-catenin/TCF4 and OATP1B1 was investigated by knocking down ß-catenin/TCF4 through siRNA transfection. Results: The STING inhibitor decreased inflammatory factor levels in the cholestatic mouse model, with IL-6 exhibiting the most potent inhibitory effect on OATP1B1. IL-6 downregulated ß-catenin/TCF4, leading to decreased OATP1B1 expression. Knocking-down ß-catenin/TCF4 counteracted the ß-catenin/TCF4-mediated repression of OATP1B1. Conclusions: STING-mediated IL-6 up-regulation may inhibit OATP1B1, leading to reduced transport of bile acids and bilirubin by OATP1B1. This may contribute to altered pharmacokinetics in patients with diseases associated with increased IL-6 production.

Inflammatory Trajectory and Anti-Inflammatory Pharmacotherapy in Frozen Elephant Trunk-Treated Acute Type I Aortic Dissection.

Background: Acute DeBakey type I aortic dissection is associated with high morbidity and mortality. Little is known regarding the role of leukocyte trajectory in prognosis. Methods: We included adult acute DeBakey type I aortic dissection patients with emergency frozen elephant trunk and total arch replacement in 2 cardiovascular centers (2020-2022). We used latent class mixed model to group patients according to their leukocyte patterns from hospital admission to the first 5 days after surgery. We investigated the association of leukocyte trajectory and 30-day and latest follow-up mortality (October 31, 2023), exploratorily analyzing the effects of ulinastatin treatment on outcome. Results: Of 255 patients included, 3 distinct leukocyte trajectories were identified: 196 in group I (decreasing trajectory), 34 in group II (stable trajectory), and 25 in group III (rising trajectory). Overall, 30-day mortality was 25 (9.8%), ranging from 8.2% (16/196) in group I, 8.8% (3/34) in group II, to 24.0% (6/25) in group III (P for trend = .036). Group III was associated with higher mortality both at 30 days (adjusted hazard ratio, 3.260; 95% CI, 1.071-9.919; P = .037) and at the last follow-up (adjusted hazard ratio, 2.840; 95% CI, 1.098-7.345; P = .031) compared with group I. Conclusions: Distinct and clinically relevant groups can be identified by analyzing leukocyte trajectories, and a rising trajectory was associated with higher short-term and midterm mortality.

Comparison of Mitral Valve Repair Versus Percutaneous Mitral Balloon Commissurotomy for Patients With Rheumatic Heart Disease: A Single-Centre Study.

BACKGROUND: Percutaneous mitral balloon commissurotomy (PMBC) is the standard treatment option for patients with rheumatic mitral stenosis (MS), according to current guidelines. This study aimed to compare the outcomes of rheumatic mitral valve repair (rMVR) and PMBC in this patient population. METHODS: Baseline, clinical, and follow-up data from 703 patients with rheumatic heart disease who underwent PMBC or rMVR at the current centre were collected and analysed. A 1:1 propensity score (PS) matching method was used to balance the differences in baseline characteristics between the two groups. The primary outcome was mitral valve reoperation, and the secondary outcome was all-cause mortality. RESULTS: Propensity score matching generated 101 patient pairs for comparison. In the matched population, there were no significant differences in the early clinical outcomes between the groups. The median follow-up time was 40.9 months. Overall, patients in the rMVR group had a statistically significantly lower risk of mitral valve reoperation than those in the PMBC group (HR 0.186; 95% CI 0.041-0.835; p=0.028). Regarding all-cause mortality, no statistically significant differences were observed between the rMVR and PMBC groups (HR 4.065; 95% CI 0.454-36.374; p=0.210). CONCLUSIONS: Compared with PMBC, rMVR has more advantages for the correction of valve lesions; therefore, it may offer a better prognosis than PMBC in select patients with rheumatic MS. However, this finding needs to be verified in future studies with larger sample sizes and longer follow-up periods.

Discovery of L15 as a novel Vif PROTAC degrader with antiviral activity against HIV-1.

Viral infectivity factor (Vif) has been recognized as a new therapeutic target for human immunodeficiency virus-1 (HIV-1) infected patients. In our previous work, we have synthesized a novel class of Vif inhibitors with 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold, which show obvious activity in HIV-1 infected cells and are also effective against drug-resistant strains. Proteolytic targeting chimera (PROTAC) utilizes the ubiquitin-proteasome system to degrade target proteins, which is well established in the field of cancer, but the antiviral PROTAC molecules are rarely reported. In order to explore the effectiveness of PROTAC in the antiviral area, we designed and synthesized a series of degrader of HIV-1 Vif based on 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold. Among them, L15 can degrade Vif protein obviously in a dose-dependent manner and shows certain antivirus activity. Meanwhile, molecular dynamics simulation indicated that the ternary complex formed by L15, Vif, and E3 ligase adopted a reasonable binding mode and maintained a stable interaction. This provided a molecular basis and prerequisite for the selective degradation of the Vif protein by L15. This study reports the HIV-1 Vif PROTAC for the first time and represents the proof-of-concept of PROTACs-based antiviral drug discovery in the field of HIV/ acquired immune deficiency syndrome (AIDS).

Does Higher Temperature During Moderate Hypothermic Circulatory Arrest Increase the Risk of Paraplegia in Acute DeBakey I Aortic Dissection Patients?

BACKGROUND: In this study, we sought to assess the safety of high-moderate (24.1-28.0°C) and low-moderate (20.1-24.0°C) systemic hypothermia during circulatory arrest (MHCA) in patients with acute DeBakey I aortic dissection (DeBakey I AAD), particularly concerning spinal cord protection. METHODS: From 2009 to 2020, 1759 patients with DeBakey I AAD who underwent frozen elephant trunk and total arch replacement surgery at a tertiary centre were divided into preoperative malperfusion (viscera, spinal cord, or lower extremities) and nonmalperfusion subgroups. The baseline differences were balanced with the use of propensity score matching. Prognoses were compared between those who were subjected to high-MHCA (nasopharyngeal temperature 24.1-28.0°C) and low-MHCA (nasopharyngeal temperature 20.1-24.0°C). RESULTS: In the nonmalperfusion subgroup (n = 1389), 469 pairs of matched patients showed lower in-hospital mortality and incidence of acute kidney injury in the high-MHCA group than in the low-MHCA group: in-hospital mortality 7.0% vs 10.2% (P = 0.01); acute kidney injury, 57.1% vs 64.6% (P < 0.01). The duration of mechanical ventilation was shorter in the high-MHCA group than that in the low-MHCA group (P = 0.03). No significant difference in the incidence of paraplegia was observed between the 2 groups. In the malperfusion subgroup (n = 370), 112 pairs of matched patients showed a higher incidence of paraplegia in the high-MHCA group than in the low-MHCA group (15.9% vs 6.5%; P = 0.04). CONCLUSIONS: The safety of high-MHCA, a commonly used temperature management strategy during aortic arch surgery, was recognised in most patients with DeBakey I AAD. However, among patients with preoperative distal organ malperfusion, low-MHCA may be more appropriate owing to an increased risk of postoperative paraplegia associated with high-MHCA.

Novel Amphiphilic PROTAC with Enhanced Pharmacokinetic Properties for ALK Protein Degradation.

Advancements in anticancer strategies spotlight proteolysis targeting chimera (PROTAC) technology, yet it is hindered by poor water solubility and bioavailability. This study introduces a novel amphiphilic PROTAC, B1-PEG, synthesized through PEGylation of an optimized PROTAC molecule, B1, to enhance its properties. B1-PEG is engineered to self-organize into micelles in water and releases its active form in response to the tumor-specific high GSH environment. Comparative pharmacokinetic analysis revealed B1-PEG's superior bioavailability at 84.8%, outperforming the unmodified PROTAC molecule B1. When tested in a H3122 xenograft mouse model, B1-PEG significantly regressed tumors, underscoring its potential as a formidable candidate in targeted cancer therapy. Our findings offer a promising direction for overcoming bioavailability limitations in PROTAC drug design.

Discovery of Novel Proteolysis-Targeting Chimera Molecules as Degraders of Programmed Cell Death-Ligand 1 for Breast Cancer Therapy.

The immune checkpoint blockade represents a pivotal strategy for tumor immunotherapy. At present, various programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) monoclonal antibodies have been successfully applied to tumor treatment. Additionally, numerous small molecule inhibitors of the PD-1/PD-L1 interaction have also been developed, with some advancing into clinical trials. Here, a novel PD-L1 proteolysis-targeting chimera (PROTAC) library was designed and synthesized utilizing the PD-L1 inhibitor BMS202 and the E3 ligand PG as foundational components. Among these, we identified a highly potent molecule PA8 for PD-L1 degradation in 4T1 cells (DC50 = 0.609 µM). Significantly, compound PA8 potentially inhibits 4T1 cell growth both in vitro and in vivo. Further mechanistic studies revealed that PA8 effectively promoted the immune activation of model mice. Thus, these results suggest that PA8 could be a novel strategy for cancer immunotherapy in the 4T1 tumor model. Although PA8 exhibits weaker degradation activity in some human cancer cells, it still provides a certain basis for further research on PD-L1 PROTAC.

Operative Mortality After Type A Aortic Dissection Surgery: Differences Based on Sex and Age.

Background: There is controversy regarding sex differences in short-term mortality in acute type A aortic dissection (ATAAD). Objectives: This study aimed to investigate the impact of sex differences on 30-day operative mortality after ATAAD surgery and to determine if other covariates modify the association. Methods: Consecutive patients (N = 5670) with surgically repaired ATAAD were identified from the multicenter China 5A study. The primary outcome was operative mortality. The age dependency was modeled using a cubic spline curve. Results: There were 1,503 females (26.5%) and 4,167 males (73.5%). Females were older and had a lower percentage of comorbidities compared with males. Females had higher mortality compared to males (10.2% vs 8.2%, P = 0.019); however, there was no difference after propensity analyses (adjusted OR: 1.334 [95% CI: 0.918-1.938]). There was an interaction with sex and age (P interaction = 0.035): older age was associated with higher odds of operative mortality among females (OR: 1.045 [95% CI: 1.029-1.061]) compared with males (OR: 1.025 [95% CI: 1.016-1.035]). The risk of mortality for males and females appears to diverge at 55 years of age (P interaction = 0.019): females under 55 years of age had similar odds to males (OR: 0.852 [95% CI: 0.603-1.205]) but higher odds when over 55 years (OR: 1.420 [95% CI: 1.096-1.839]) compared to males. Conclusions: Under the age of 55 years, females have similar odds of operative mortality compared with males; however, over the age of 55 years females have higher odds than males. Understanding differences in risk allows for individualized treatment strategies. (Additive Anti-inflammatory Action for Aortopathy & Arteriopathy; NCT04398992).

Clinical outcomes of the type II hybrid procedure for the repair of extensive aortic arch pathology.

Background: Type II hybrid arch repair (HAR) has been used for the repair of extensive aortic arch pathology. The aim of this study was to retrospectively analyze single-stage hybrid treatment involving replacement of the ascending aorta, arch debranching, and zone 0 stent graft deployment. Methods: We retrospectively analyzed clinical data from 41 patients with acute and chronic aortic disease who underwent a type II hybrid arch procedure at Beijing Anzhen Hospital and Beijing Chaoyang Hospital from January 2020 to August 2022. The femoral arteries and right axillary arteries were used as cannulation sites to decrease the risk of malperfusion. During surgery, the nasopharyngeal temperature was lowered to 30 ℃. Demographic, perioperative, and late results data were retrieved and analyzed. Results: The mean age of the patients was 54.9±11.1 years, and 31 patients (75.6%) were men. In all cases, zone 0 stent graft deployment was successful, with no in-hospital mortality. The median follow-up time was 10.5 [interquartile range (IQR), 4.8-17.6] months, and the survival rate was 94.9% during follow-up. Complications included cerebral infarction (3 patients, 7.3%) and renal failure requiring dialysis (3 patients, 7.3%). There were no occurrences of paraplegia, and no stent-related complications occurred during the follow-up period. Conclusions: The single-stage hybrid arch procedure achieved satisfactory early results and represents a less invasive approach for treating complex diffuse aortic disease that affects the arch. This strategy is an important technical advance in the treatment of high-risk patients with extensive aortic arch pathology.

Bradykinin induces acute kidney injury after hypothermic circulatory arrest through the repression of the Nrf2-xCT pathway.

Postoperative acute kidney injury (AKI) is a common complication in patients undergoing deep hypothermic circulatory arrest (HCA); however, its underlying pathogenesis is unclear. In this study, we established a rat cardiopulmonary bypass model and demonstrated that hypothermia during HCA, rather than circulatory arrest, was responsible for the occurrence of AKI. By recruiting 56 patients who underwent surgery with HCA and analyzing the blood samples, we found that post-HCA AKI was associated with an increase in bradykinin. Animal experiments confirmed this and showed that hypothermia during HCA increased bradykinin levels by increasing kallikrein expression. Mechanistically, bradykinin inhibited the Nrf2-xCT pathway through B2R and caused renal oxidative stress damage. Application of Icatibant, a B2R inhibitor, reversed changes in the Nrf2-xCT pathway and oxidative stress damage. Finally, Icatibant reversed hypothermia-induced AKI in vivo. This finding reveals the pathogenesis of AKI after HCA and helps to provide therapeutic strategy for patients with post-HCA AKI.