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1.
PNAS Nexus ; 3(9): pgae371, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39234501

RESUMEN

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.

2.
Heart ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266045

RESUMEN

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.

3.
Circ Cardiovasc Imaging ; 17(8): e016117, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39163378

RESUMEN

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.


Asunto(s)
Angiografía por Tomografía Computarizada , Angiografía Coronaria , Oclusión Coronaria , Intervención Coronaria Percutánea , Placa Aterosclerótica , Valor Predictivo de las Pruebas , Radiómica , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Crónica , Angiografía Coronaria/métodos , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/cirugía , Oclusión Coronaria/terapia , Vasos Coronarios/diagnóstico por imagen , Intervención Coronaria Percutánea/métodos , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
4.
Eur J Radiol ; 180: 111688, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39182273

RESUMEN

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.


Asunto(s)
Angiografía por Tomografía Computarizada , Enfermedad de la Arteria Coronaria , Reserva del Flujo Fraccional Miocárdico , Neoplasias Pulmonares , Valor Predictivo de las Pruebas , Humanos , Masculino , Femenino , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Angiografía por Tomografía Computarizada/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Complicaciones Posoperatorias/diagnóstico por imagen , Angiografía Coronaria/métodos , Factores de Riesgo , Aprendizaje Automático
5.
J Clin Transl Hepatol ; 12(8): 701-712, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39130625

RESUMEN

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.

6.
J Soc Cardiovasc Angiogr Interv ; 3(7): 101935, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39132007

RESUMEN

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.

7.
Heart Lung Circ ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38955596

RESUMEN

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.

8.
Bioorg Med Chem Lett ; 111: 129880, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38996941

RESUMEN

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).


Asunto(s)
Fármacos Anti-VIH , VIH-1 , Productos del Gen vif del Virus de la Inmunodeficiencia Humana , VIH-1/efectos de los fármacos , Productos del Gen vif del Virus de la Inmunodeficiencia Humana/antagonistas & inhibidores , Productos del Gen vif del Virus de la Inmunodeficiencia Humana/metabolismo , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/química , Humanos , Relación Estructura-Actividad , Estructura Molecular , Benzamidas/farmacología , Benzamidas/química , Benzamidas/síntesis química , Descubrimiento de Drogas , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Proteolisis/efectos de los fármacos , Simulación de Dinámica Molecular
9.
Can J Cardiol ; 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38981559

RESUMEN

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.

11.
JACC Adv ; 3(4): 100909, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38939657

RESUMEN

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).

12.
J Med Chem ; 67(12): 9842-9856, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38839424

RESUMEN

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.


Asunto(s)
Quinasa de Linfoma Anaplásico , Polietilenglicoles , Proteolisis , Animales , Humanos , Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Quinasa de Linfoma Anaplásico/metabolismo , Proteolisis/efectos de los fármacos , Ratones , Polietilenglicoles/química , Polietilenglicoles/farmacocinética , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Antineoplásicos/química , Antineoplásicos/síntesis química , Línea Celular Tumoral , Disponibilidad Biológica , Ensayos Antitumor por Modelo de Xenoinjerto , Micelas , Ratones Desnudos
13.
J Med Chem ; 67(13): 10589-10600, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38889052

RESUMEN

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.


Asunto(s)
Antineoplásicos , Antígeno B7-H1 , Neoplasias de la Mama , Proteolisis , Proteolisis/efectos de los fármacos , Animales , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Humanos , Ratones , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Descubrimiento de Drogas , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/química , Inhibidores de Puntos de Control Inmunológico/síntesis química , Acetamidas , Piridinas
14.
iScience ; 27(6): 110075, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38868208

RESUMEN

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.

15.
J Thorac Dis ; 16(5): 3260-3271, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38883664

RESUMEN

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.

16.
Front Cardiovasc Med ; 11: 1345761, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38720920

RESUMEN

Artificial intelligence (AI) has made significant progress in the medical field in the last decade. The AI-powered analysis methods of medical images and clinical records can now match the abilities of clinical physicians. Due to the challenges posed by the unique group of fetuses and the dynamic organ of the heart, research into the application of AI in the prenatal diagnosis of congenital heart disease (CHD) is particularly active. In this review, we discuss the clinical questions and research methods involved in using AI to address prenatal diagnosis of CHD, including imaging, genetic diagnosis, and risk prediction. Representative examples are provided for each method discussed. Finally, we discuss the current limitations of AI in prenatal diagnosis of CHD, namely Volatility, Insufficiency and Independence (VII), and propose possible solutions.

17.
J Chem Neuroanat ; 138: 102424, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38670441

RESUMEN

Neuroinflammation associated with microglial activation plays a role in the development of Parkinson's disease (PD). The upregulation of interferon regulatory factor 8 (IRF8) in microglia following peripheral nerve injury has been observed to induce microglial activation. This suggests the potential therapeutic significance of IRF8 in PD. This research aims to explore the effects of IRF8 on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and lipopolysaccharide (LPS)-induced neuroinflammation, along with its underlying mechanisms. The study examines the differential expression of IRF8 and its effects on neuropathological changes using a PD mouse model and a PD model established from BV2 cells in vitro. IRF8 was found to be prominently expressed in the substantia nigra pars compacta (SNpc) region of PD mice and LPS-stimulated BV2 cells, while the expression of tyrosine hydroxylase (TH) and dopamine (DA) content in the SNpc region of PD mice was notably reduced. MPTP treatment and LPS stimulation intensified microglial activation, inflammation, and activation of the AMPK/mTOR signaling pathway in vivo and in vitro, respectively. Upon IRF8 silencing in the PD mouse and cell models, the knockdown of IRF8 ameliorated MPTP-induced behavioral deficits, increased the counts of TH and Nissl-positive neurons and DA content, reduced the number of Iba-1-positive microglia, and reduced the content of inflammatory factors, possibly by inhibiting the AMPK/mTOR signaling pathway. Similar outcomes were observed in the PD cell model. In conclusion, the suppression of IRF8 alleviates neuroinflammation through regulating microglial activation in PD models in vivo and in vitro by the AMPK/mTOR signaling pathway.


Asunto(s)
Factores Reguladores del Interferón , Ratones Endogámicos C57BL , Microglía , Enfermedades Neuroinflamatorias , Enfermedad de Parkinson , Animales , Microglía/metabolismo , Ratones , Factores Reguladores del Interferón/metabolismo , Factores Reguladores del Interferón/genética , Masculino , Enfermedades Neuroinflamatorias/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Lipopolisacáridos , Serina-Treonina Quinasas TOR/metabolismo , Técnicas de Silenciamiento del Gen , Transducción de Señal/fisiología , Porción Compacta de la Sustancia Negra/metabolismo , Porción Compacta de la Sustancia Negra/patología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología
18.
Front Surg ; 11: 1329771, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38655210

RESUMEN

Objectives: The diameter, area, and volume of the true lumen and false lumen (FL) have been measured in previous studies to evaluate the extent of DeBakey type I aortic dissection. However, these indicators have limitations because of the irregular shapes of the true and false lumens and the constant oscillation of intimal flap during systole and diastole. The ratio of arch lengths seems to be a more reliable indicator. FL% was defined as the ratio of the arch length of FL to the circumference of the aorta at the different levels of the aorta. The purpose of this article was to investigate whether FL% is a predictor of the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk (FET) and total arch replacement. Methods: In this retrospective observational study, we analyzed a total of 344 patients with acute DeBakey type I aortic dissection that underwent FET and total arch replacement at our center from October 2015 to October 2019. The patients were divided into two groups by cluster analysis according to the perioperative course. Binary logistic regression analyses were performed to determine whether FL% could predict the severity of acute DeBakey type I aortic dissection. The area under the receiver operating characteristic curve (AUROC) was used to assess the power of the multivariate logistic regression model for the severity of acute DeBakey type I aortic dissection. Results: The patients in the ultra-high-risk group (109 patients) had significantly more severe clinical comorbidities and complications than the patients in the high-risk group (235 patients). The ascending aortic FL% [odds ratio (OR), 11.929 (95% CI: 1.421-100.11); P = 0.022], location of initial tear [OR, 0.68 (95% CI: 0.47-0.98); P = 0.041], the degree of left iliac artery involvement [OR, 1.95 (95% CI: 1.15-3.30); P = 0.013], and the degree of right coronary artery involvement [OR, 1.46 (95% CI: 1.01-2.12); P = 0.045] on preoperative computed tomography angiography were associated with the severity of acute DeBakey type I aortic dissection. The AUROC value of this multivariate logistic regression analysis was 0.940 (95% CI: 0.914-0.967; P < 0.001). The AUROC value of ascending aortic FL% was 0.841 (95% CI: 0.798-0.884; P < 0.001) for the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Conclusions: Ascending aortic FL% was validated as an essential radiologic index for assessing the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Higher values of ascending aortic FL% were more severe.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38488985

RESUMEN

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.

20.
Int J Surg ; 110(6): 3346-3356, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38445499

RESUMEN

BACKGROUND: Peripheral platelet-white blood cell ratio (PWR) integrating systemic inflammatory and coagulopathic pathways is a key residual inflammatory measurement in the management of acute DeBakey type I aortic dissection (AAD); however, trajectories of PWR in AAD is poorly defined. METHODS: Two AAD cohorts were included in two cardiovascular centers (2020-2022) if patients underwent emergency total arch replacement with frozen elephant trunk implantation. PWR data were collected over time at baseline and five consecutive days after surgery. Trajectory patterns of PWR were determined using the latent class mixed modelling (LCMM). Cox regression was used to determine independent risk factors. By adding PWR Trajectory, a user-friendly nomogram was developed for predicting mortality after surgery. RESULTS: Two hundred forty-six patients with AAD were included with a median follow-up of 26 (IRQ 20-37) months. Three trajectories of PWR were identified [cluster α 45(18.3%), ß105 (42.7%), and γ 96 (39.0%)]. Cluster γ was associated with higher risk of mortality at follow-up (crude HR, 3.763; 95% CI: 1.126-12.574; P =0.031) than cluster α. By the addition of PWR trajectories, an inflammatory nomogram, composed of age, hemoglobin, estimated glomerular filtration rate, and cardiopulmonary time was developed and internally validated, with adequate discrimination [the area under the receiver-operating characteristic curve 0.765, 95% CI: 0.660-0.869)], calibration, and clinical utility. CONCLUSION: Based on PWR trajectories, three distinct clusters were identified with short-term outcomes, and longitudinal residual inflammatory shed some light to individualize treatment strategies for AAD.


Asunto(s)
Disección Aórtica , Humanos , Disección Aórtica/cirugía , Disección Aórtica/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Pronóstico , Anciano , Inflamación/sangre , Recuento de Leucocitos , Nomogramas , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/mortalidad , Factores de Riesgo
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