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BACKGROUND: Stent malapposition (SM) following percutaneous coronary intervention (PCI) for myocardial infarction continues to present significant clinical challenges. In recent years, machine learning (ML) models have demonstrated potential in disease risk stratification and predictive modeling. HYPOTHESIS: ML models based on optical coherence tomography (OCT) imaging, laboratory tests, and clinical characteristics can predict the occurrence of SM. METHODS: We studied 337 patients from the Affiliated Hospital of Zunyi Medical University, China, who had PCI and coronary OCT from May to October 2023. We employed nested cross-validation to partition patients into training and test sets. We developed five ML models: XGBoost, LR, RF, SVM, and NB based on calcification features. Performance was assessed using ROC curves. Lasso regression selected features from 46 clinical and 21 OCT imaging features, which were optimized with the five ML algorithms. RESULTS: In the prediction model based on calcification features, the XGBoost model and SVM model exhibited higher AUC values. Lasso regression identified five key features from clinical and imaging data. After incorporating selected features into the model for optimization, the AUC values of all algorithmic models showed significant improvements. The XGBoost model demonstrated the highest calibration accuracy. SHAP values revealed that the top five ranked features influencing the XGBoost model were calcification length, age, coronary dissection, lipid angle, and troponin. CONCLUSION: ML models developed using plaque imaging features and clinical characteristics can predict the occurrence of SM. ML models based on clinical and imaging features exhibited better performance.
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Enfermedad de la Arteria Coronaria , Aprendizaje Automático , Intervención Coronaria Percutánea , Placa Aterosclerótica , Tomografía de Coherencia Óptica , Humanos , Estudios Retrospectivos , Masculino , Tomografía de Coherencia Óptica/métodos , Femenino , Persona de Mediana Edad , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/métodos , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/cirugía , China/epidemiología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Anciano , Stents , Infarto del Miocardio/diagnóstico , Valor Predictivo de las Pruebas , Factores de Riesgo , Medición de Riesgo/métodos , Angiografía CoronariaRESUMEN
BACKGROUND: There are several surgical options for osteonecrosis of the lunate, and confirming the effectiveness of various surgical methods remains challenging. Here, we present a case of stage IIIB osteonecrosis of the lunate repaired with a free medial femoral condyle osteocutaneous flap. CASE PRESENTATION: A 43-year-old male construction worker was admitted to our hospital due to right wrist pain, impaired mobility, and pain aggravated by activity for 10 months. The patient was diagnosed with stage IIIB osteonecrosis of the lunate based on the orthopantomogram and magnetic resonance imaging of the right wrist. Considering the patient's medical history, physical examination, auxiliary examination, and wishes, reconstruction was performed using a free medial femoral condyle osteocutaneous flap. After the flap survived completely, the K-wires were removed one month after the operation, the external brace was removed two months after the operation, and functional wrist rehabilitation was initiated. After six months of follow-up, the wrist swelling and pain resolved, and the reconstructed lunate bone was viable. Additionally, the last follow-up was conducted in the sixth month after surgery; the affected hand grip strength improved from about 70% (28 kg) to 80% (32 kg) compared with the healthy side (40 kg); the visual analog scale score decreased from 6.5 points before the operation to 1 point; and the MAYO score increased from 60 points before the operation to 85 points. CONCLUSIONS: The success of this case reinforces the potential of the free medial femoral condyle osteocutaneous flap as a new treatment option for stage IIIB osteonecrosis of the lunate and further expands the existing treatment options. Using a free medial femoral condyle osteocutaneous flap to reconstruct the lunate and restore the carpal anatomy may.
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Fémur , Colgajos Tisulares Libres , Hueso Semilunar , Osteonecrosis , Humanos , Masculino , Adulto , Osteonecrosis/cirugía , Osteonecrosis/diagnóstico por imagen , Fémur/cirugía , Fémur/diagnóstico por imagen , Fémur/patología , Hueso Semilunar/cirugía , Hueso Semilunar/diagnóstico por imagen , Colgajos Tisulares Libres/trasplante , Resultado del Tratamiento , Procedimientos de Cirugía Plástica/métodos , Trasplante Óseo/métodosRESUMEN
BACKGROUND: Hypoxia-induced pulmonary artery hypertension (HPH) is a complication of chronic hypoxic lung disease and the third most common type of pulmonary artery hypertension (PAH). Epigenetic mechanisms play essential roles in the pathogenesis of HPH. N6-methyladenosine (m6A) is an important modified RNA nucleotide involved in a variety of biological processes and an important regulator of epigenetic processes. To date, the precise role of m6A and regulatory molecules in HPH remains unclear. METHODS: HPH model and pulmonary artery smooth muscle cells (PASMCs) were constructed from which m6A changes were observed and screened for AlkB homolog 5 (Alkbh5). Alkbh5 knock-in (KI) and knock-out (KO) mice were constructed to observe the effects on m6A and evaluate right ventricular systolic pressure (RVSP), left ventricular and septal weight [RV/(LV + S)], and pulmonary vascular remodeling in the context of HPH. Additionally, the effects of Alkbh5 knockdown using adenovirus were examined in vitro on m6A, specifically in PASMCs with regard to proliferation, migration and cytochrome P450 1A1 (Cyp1a1) mRNA stability. RESULTS: In both HPH mice lung tissues and hypoxic PASMCs, a decrease in m6A was observed, accompanied by a significant up-regulation of Alkbh5 expression. Loss of Alkbh5 attenuated the proliferation and migration of hypoxic PASMCs in vitro, with an associated increase in m6A modification. Furthermore, Alkbh5 KO mice exhibited reduced RVSP, RV/(LV + S), and attenuated vascular remodeling in HPH mice. Mechanistically, loss of Alkbh5 inhibited Cyp1a1 mRNA decay and increased its expression through an m6A-dependent post-transcriptional mechanism, which hindered the proliferation and migration of hypoxic PASMCs. CONCLUSION: The current study highlights the loss of Alkbh5 impedes the proliferation and migration of PASMCs by inhibiting post-transcriptional Cyp1a1 mRNA decay in an m6A-dependent manner.
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In current clinical practice, radiotherapy (RT) is prescribed as a pre-determined total dose divided over daily doses (fractions) given over several weeks. The treatment response is typically assessed months after the end of RT. However, the conventional one-dose-fits-all strategy may not achieve the desired outcome, owing to patient and tumor heterogeneity. Therefore, a treatment strategy that allows for RT dose personalization based on each individual response is preferred. Multiple strategies have been adopted to address this challenge. As an alternative to current known strategies, artificial intelligence (AI)-derived mechanism-independent small data phenotypic medicine (PM) platforms may be utilized for N-of-1 RT personalization. Unlike existing big data approaches, PM does not engage in model refining, training, and validation, and guides treatment by utilizing prospectively collected patient's own small datasets. With PM, clinicians may guide patients' RT dose recommendations using their responses in real-time and potentially avoid over-treatment in good responders and under-treatment in poor responders. In this paper, we discuss the potential of engaging PM to guide clinicians on upfront dose selections and ongoing adaptations during RT, as well as considerations and limitations for implementation. For practicing oncologists, clinical trialists, and researchers, PM can either be implemented as a standalone strategy or in complement with other existing RT personalizations. In addition, PM can either be used for monotherapeutic RT personalization, or in combination with other therapeutics (e.g. chemotherapy, targeted therapy). The potential of N-of-1 RT personalization with drugs will also be presented.
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Neoplasias , Medicina de Precisión , Humanos , Medicina de Precisión/métodos , Neoplasias/radioterapia , Inteligencia Artificial , Fenotipo , Dosificación RadioterapéuticaRESUMEN
Acute coronary syndrome (ACS), a significant cardiovascular disease threat, has garnered increased focus concerning its etiological mechanisms. Thin-cap fibroatheroma (TCFA) are central to ACS pathogenesis, characterized by lipid-rich plaques, profuse foam cells, cholesterol crystals, and fragile fibrous caps predisposed to rupture. While TCFAs may be latent and asymptomatic, their pivotal role in ACS risk is undeniable. High-resolution imaging techniques like Optical coherence tomography (OCT) and Intravascular ultrasound (IVUS) are instrumental for effective TCFA detection. Therapeutic strategies encompass pharmacological and interventional measures, including antiplatelet agents, statins, and Percutaneous Coronary Intervention (PCI), aiding in plaque stabilization, inflammation reduction, and rupture risk mitigation. Despite the strong correlation between TCFAs and adverse prognoses in ACS patients, early detection and rigorous treatment significantly enhance patient prognosis and diminish cardiovascular events. This review aims to encapsulate recent advancements in TCFA research within ACS, covering formation mechanisms, clinical manifestations, and prognostic implications.
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Síndrome Coronario Agudo , Placa Aterosclerótica , Tomografía de Coherencia Óptica , Ultrasonografía Intervencional , Humanos , Síndrome Coronario Agudo/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Placa Aterosclerótica/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodosRESUMEN
BACKGROUND: The latest information regarding the awareness of atrial fibrillation (AF) remains limited in China. OBJECTIVES: The present study aimed to understand the variation and disparity in awareness of AF in China. METHODS: The cross-sectional study used data from the 2020 nationwide epidemiology survey on AF among adults aged 18 years or older in mainland China to assess the prevalence of AF awareness. The awareness of AF diagnostic methods and outcomes was also assessed using an interviewer-administered questionnaire. RESULTS: Of the 114,039 adults responding to the survey, 1463 (age-standardized prevalence, 55.3% (95% confidence interval [CI], 47.7-62.9%) and 10,202 (8.2%, 95%CI 5.4-10.9%) were aware of AF in participants with and without AF, respectively. Of these, 36.4% (95%CI 30.0-42.9%) and 6.3% (95%CI 3.6-9.1%) considered electrocardiogram as a method of diagnosing AF, and 30.0% (95% CI 3.2-8.2%) and 5.2% (95%CI 2.7-7.6%) considered stroke as an outcome of AF. The proportion of participants who being aware of AF varied significantly across sociodemographic and cardiovascular disease subgroups, and was almost consistently lower in rural areas than those in urban areas. Overall, lack of AF awareness was associated with rural areas, geographical region, lower education levels, and without history and had no risk factors of cardiovascular disease. CONCLUSIONS: Nearly half of adults with AF, and >90% non-AF population are unaware of AF in China, with significant variation and disparity. Focused public health initiatives are needed to improve awareness and knowledge of AF among high-risk populations.
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Fibrilación Atrial , Accidente Cerebrovascular , Adulto , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Estudios Transversales , Accidente Cerebrovascular/epidemiología , Factores de Riesgo , China/epidemiología , PrevalenciaRESUMEN
Background: The relationship between neointimal characteristics of in-stent restenosis (ISR) and periprocedural myocardial injury (PMI) remains unclear. Therefore, this study aimed to investigate the relationship between PMI and neointimal characteristics of ISR by using optical coherence tomography (OCT). Methods: This was a retrospective study. We enrolled 140 patients diagnosed with ISR with normal baseline high-sensitivity troponin T (hs-cTnT) levels who underwent OCT and subsequent revascularization by means of drug-coated balloon (DCB) or drug-eluting stent (DES) between October 2018 and October 2022 in the Affiliated Hospital of Zunyi Medical University. Based on the 4th universal definition of myocardial infarction, patients whose hs-cTnT were increased five times above the upper reference limit (URL) after percutaneous coronary interventions (PCI) were deemed to PMI. The patients were subdivided into PMI (n=53) and non-PMI (n=87) groups. In the univariable analysis, variables in the baselines, angiography characteristics and OCT findings were analyzed with binary logistic regression. A P value of <0.2 was included in the multivariable model. Multivariable logistic regression analysis was used to identify the independent predictors of PMI. Results: The prevalence of intra-intimal microvessels in patients with PMI was higher than in those without PMI (58.5% vs. 32.2%, P=0.003). The ratio of intra-stent plaque rupture (PR) was also higher in patients with PMI (60.4% vs. 40.2%, P=0.021). Multivariable logistic regression analysis showed that intra-intimal microvessels [odds ratio (OR): 3.193, 95% confidence interval (CI): 1.280-7.966; P=0.013] and intra-stent PR (OR: 2.124, 95% CI: 1.153-4.732; P=0.035) were independently associated with PMI. Conclusions: Intra-intimal microvessels and intra-stent PR were independently associated with PMI. Accurate identification and recognition of intra-intimal microvessels and intra-stent PR may be helpful in preventing PMI.
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Graves' ophthalmopathy (GO), or thyroid eye disease (TED), is the most frequent extrathyroidal manifestation of Graves' disease (GD). Inflammation and subsequent aberrant tissue remodeling with fibrosis are important pathogenesis. There are many proposed mechanisms and molecular pathways contributing to tissue remodeling and fibrosis in GO, including adipogenesis, fibroblast proliferation and myofibroblasts differentiation, oxidative stress, endoplasmic reticulum (ER) stress, hyaluronan (HA) and glycosaminoglycans (GAGs) accumulation in the extracellular matrix (ECM) and new concepts of epigenetics modification, such as histone modification, DNA methylation, non-coding RNAs, and gut microbiome. This review summarizes the current understanding of ECM proteins and associated tissue remodeling in the pathogenesis and potential mediators for the treatment of GO.
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Enfermedad de Graves , Oftalmopatía de Graves , Humanos , Oftalmopatía de Graves/genética , Oftalmopatía de Graves/metabolismo , Órbita/metabolismo , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Enfermedad de Graves/metabolismo , FibrosisRESUMEN
The morphological characteristics of in-stent restenosis (ISR) in relation to varying degrees of area stenosis have not been comprehensively examined. This study aimed to explore the tissue characteristics of patients experiencing ISR with different degrees of area stenosis through the utilization of optical coherence tomography (OCT). In total, 230 patients with ISR who underwent OCT were divided into the following three groups: area stenosis (AS) < 70% (n = 26); 70-80% (n = 119) and AS ≥ 80% (n = 85). Among the 230 patients, the clinical presentation as stable angina was 61.5% in AS < 70%, followed by 47.2% in 70% < AS ≤ 80%, and 31.8% in AS ≥ 80% (P = 0.010). The OCT findings showed that heterogeneous neointima, ISNA, LRP, neointima rupture, TCFA-like pattern, macrophage infiltration, red and white thrombus was more common with AS increased. Ordinal logistic regression analysis showed that higher AS was associated with previous dyslipidemia (odds ratio [OR], 4.754; 95% confidence interval [CI], 1.419-15.927, P = 0.011), neointimal rupture (OR: 3.640; 95% CI, 1.169-11.325, P = 0.026), red thrombus (OR: 4.482; 95% CI, 1.269-15.816, P = 0.020) and white thrombus (OR: 5.259; 95% CI, 1.660-16.659, P = 0.005). Patients with higher degrees of area stenosis in the context of ISR exhibited a greater number of discernible morphological characteristics as identified through OCT analysis. Furthermore, previous dyslipidemia, neointimal rupture, white thrombus and red thrombus were highly associated with and the progression of ISR lesions.
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Reestenosis Coronaria , Vasos Coronarios , Neointima , Intervención Coronaria Percutánea , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Stents , Tomografía de Coherencia Óptica , Humanos , Masculino , Femenino , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/etiología , Reestenosis Coronaria/patología , Persona de Mediana Edad , Anciano , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo , Resultado del Tratamiento , Estudios Retrospectivos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/patología , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/patología , Estenosis Coronaria/terapia , Rotura EspontáneaRESUMEN
Aims: Artificial intelligence-driven small data platforms such as CURATE.AI hold potential for personalized hypertension care by assisting physicians in identifying personalized anti-hypertensive doses for titration. This trial aims to assess the feasibility of a larger randomized controlled trial (RCT), evaluating the efficacy of CURATE.AI-assisted dose titration intervention. We will also collect preliminary efficacy and safety data and explore stakeholder feedback in the early design process. Methods and results: In this open-label, randomized, pilot feasibility trial, we aim to recruit 45 participants with primary hypertension. Participants will be randomized in 1:1:1 ratio into control (no intervention), home blood pressure monitoring (active control; HBPM), or CURATE.AI arms (intervention; HBPM and CURATE.AI-assisted dose titration). The home treatments include 1 month of two-drug anti-hypertensive regimens. Primary endpoints assess the logistical (e.g. dose adherence) and scientific (e.g. percentage of participants for which CURATE.AI profiles can be generated) feasibility, and define the progression criteria for the RCT in a 'traffic light system'. Secondary endpoints assess preliminary efficacy [e.g. mean change in office blood pressures (BPs)] and safety (e.g. hospitalization events) associated with each treatment protocol. Participants with both baseline and post-treatment BP measurements will form the intent-to-treat analysis. Following their involvement with the CURATE.AI intervention, feedback from CURATE.AI participants and healthcare providers will be collected via exit survey and interviews. Conclusion: Findings from this study will inform about potential refinements of the current treatment protocols before proceeding with a larger RCT, or potential expansion to collect additional information. Positive results may suggest the potential efficacy of CURATE.AI to improve BP control. Trial registration number: NCT05376683.
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AIMS: A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well-known HR-lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF. METHODS AND RESULTS: This multicentre, single-arm, prospective, observational study enrolled Chinese patients with chronic HF. The primary outcome was change from baseline in HR at 1 and 6 months, measured by pulse counting. Effectiveness was also evaluated using laboratory tests, the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (CSS) and overall summary score (OSS), and New York Heart Association (NYHA) class. Treatment-emergent adverse events (TEAEs) were assessed. A post hoc analysis examined the effectiveness and safety of ivabradine combined with an angiotensin receptor-neprilysin inhibitor (ARNI) or beta-blocker. A total of 1003 patients were enrolled [mean age 54.4 ± 15.0 years, 773 male (77.1%), mean baseline HR 88.5 ± 11.3 b.p.m., mean blood pressure 115.7/74.4 ± 17.2/12.3 mmHg, mean left ventricular ejection fraction 30.9 ± 7.6%, NYHA Classes III and IV in 48.8% and 22.0% of patients, respectively]. HR decreased by a mean of 12.9 and 16.1 b.p.m. after 1 and 6 months, respectively (both P < 0.001). At Month 6, improvements in the KCCQ CSS and OSS of ≥5 points were observed in 72.1% and 74.1% of patients, respectively (both P < 0.001). Left ventricular ejection fraction increased by 12.1 ± 11.6 (P < 0.001), and 66.7% of patients showed improvement in NYHA class (P < 0.001). At Month 6, the overall proportion of patients in NYHA Classes III and IV was reduced to 13.5% and 2.1%, respectively. Serum brain natriuretic peptide (BNP) and N-terminal pro-BNP changed by -331.9 ng/L (-1238.6, -134.0) and -1113.8 ng/L (-2202.0, -297.2), respectively (P < 0.001). HR reductions and improvements in NYHA and KCCQ scores with ivabradine were similar with and without use of ARNIs or beta-blockers. Of 498 TEAEs in 296 patients (29.5%), 73 TEAEs in 55 patients (5.5%) were considered related to ivabradine [most frequent sinus bradycardia (n = 7) and photopsia (n = 7)]. TEAEs were reported in a similar number of patients in ARNI and beta-blocker subgroups (21.9-35.6%). CONCLUSIONS: Ivabradine treatment reduced HR and improved cardiac function and health-related quality of life in Chinese patients with chronic HF. Benefits were seen irrespective of whether or not patients were also taking ARNIs or beta-blockers. Treatment was well tolerated with a similar profile to previous ivabradine studies.
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Fármacos Cardiovasculares , Insuficiencia Cardíaca , Trastornos de la Visión , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Antagonistas Adrenérgicos beta/uso terapéutico , Benzazepinas , Fármacos Cardiovasculares/uso terapéutico , China , Ivabradina/uso terapéutico , Estudios Prospectivos , Calidad de Vida , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular Izquierda , FemeninoRESUMEN
Neoatherosclerosis is a major cause of stent failure after percutaneous coronary intervention. Metabolism such as hyperuricemia is associated with in-stent restenosis (ISR). However, the association between serum uric acid (sUA) levels and in-stent neoatherosclerosis (ISNA) has never been validated.A total of 216 patients with 220 ISR lesions who had undergone optical coherence tomography (OCT) of culprit stents were included in this study. According to their sUA levels, eligible patients were divided into two groups [normal-sUA group: sUA < 7 mg/dL, n = 126, and high-sUA group: sUA ≥ 7 mg/dL, n = 90]. OCT findings were analyzed and compared between the normal- and high-sUA groups.The incidence of ISNA (63.0% versus 43.0%, P = 0.004) was significantly higher in the high-sUA group than in the normal-sUA group. Lipid plaques (66.3% versus 43.0%, P < 0.001) and thin-cap fibroatheroma (38.0% versus 18.0%, P = 0.001) were observed more frequently in the restenotic tissue structure in patients in the high-sUA group than in those in the normal-sUA group. Meanwhile, univariate (OR: 1.208, 95% CI: 1.037-1.407; P = 0.015) and multivariate (OR: 1.254, 95% CI: 1.048-1.501; P = 0.013) logistic regression analyses indicated that sUA levels were an independent risk factor for ISNA after adjusting for relevant risk factors.The high-sUA levels were an independent risk factor for the occurrence of neoatherosclerosis in patients with ISR via OCT.
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Aterosclerosis , Reestenosis Coronaria , Intervención Coronaria Percutánea , Placa Aterosclerótica , Humanos , Ácido Úrico , Reestenosis Coronaria/etiología , Reestenosis Coronaria/complicaciones , Placa Aterosclerótica/complicaciones , Stents/efectos adversos , Aterosclerosis/etiología , Tomografía de Coherencia Óptica/métodos , Intervención Coronaria Percutánea/efectos adversos , Constricción Patológica/patología , Vasos Coronarios/patologíaRESUMEN
BACKGROUND: Monocyte-to-high-density lipoprotein cholesterol ratio (MHR) is an independent predictor of atherosclerosis and in-stent restenosis (ISR). However, the association between MHR and the incidence of in-stent neoatherosclerosis (ISNA) remains to be validated. METHODS: This study included 216 patients with acute coronary syndrome who had 220 ISR lesions and had undergone optical coherence tomography (OCT). All eligible patients were divided into three groups according to their MHR tertile level. OCT characteristics were comparatively analyzed between groups of different MHR levels, and univariate and multivariate logistic regression analyses were constructed to assess correlations between MHR level and ISNA as well as in-stent thin-cap fibroatheroma (TCFA). A receiver operating characteristic curve was used to determine the optimal MHR thresholds for predicting ISNA and in-stent TCFA. RESULTS: The incidence of ISNA (70.3% vs. 61.1% vs. 20.3%, P < 0.001) and in-stent TCFA (40.5% vs. 31.9% vs. 6.8%, P < 0.001) was the highest in the third tertile, followed by the second and first tertiles, respectively. Multivariate analysis revealed that MHR was independently associated with ISNA (odds ratio [OR], 7.212; 95% confidence interval [CI], 1.287-40.416; P = 0.025) and in-stent TCFA (OR, 5.610; 95% CI, 1.743-18.051; P = 0.004) after adjusting for other clinical factors. The area under the curve was 0.745 (95% CI, 0.678-0.811; P < 0.001) for the prediction of ISNA and 0.718 (95% CI, 0.637-0.778; P < 0.001) for the prediction of in-stent TCFA. CONCLUSION: MHR levels are an independent risk factor for ISNA.
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Aterosclerosis , Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/patología , Tomografía de Coherencia Óptica/métodos , Monocitos/patología , Aterosclerosis/patología , Stents/efectos adversos , Lipoproteínas HDL , Colesterol , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/complicaciones , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Valor Predictivo de las Pruebas , Angiografía Coronaria/efectos adversosRESUMEN
Tacrolimus is a potent immunosuppressant used after pediatric liver transplant. However, tacrolimus's narrow therapeutic window, reliance on physicians' experience for the dose titration, and intra- and inter-patient variability result in liver transplant patients falling out of the target tacrolimus trough levels frequently. Existing personalized dosing models based on the area-under-the-concentration over time curves require a higher frequency of blood draws than the current standard of care and may not be practically feasible. We present a small-data artificial intelligence-derived platform, CURATE.AI, that uses data from individual patients obtained once daily to model the dose and response relationship and identify suitable doses dynamically. Retrospective optimization using 6 models of CURATE.AI and data from 16 patients demonstrated good predictive performance and identified a suitable model for further investigations.Clinical Relevance- This study established and compared the predictive performance of 6 personalized tacrolimus dosing models for pediatric liver transplant patients and identified a suitable model with consistently good predictive performance based on data from pediatric liver transplant patients.
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Trasplante de Hígado , Tacrolimus , Humanos , Niño , Tacrolimus/uso terapéutico , Estudios Retrospectivos , Inteligencia Artificial , Inmunosupresores/uso terapéuticoRESUMEN
Hypoxia, characterized by reduced oxygen concentration, is a significant stressor that affects the survival of aerobic species and plays a prominent role in cardiovascular diseases. From the research history and milestone events related to hypoxia in cardiovascular development and diseases, The "hypoxia-inducible factors (HIFs) switch" can be observed from both temporal and spatial perspectives, encompassing the occurrence and progression of hypoxia (gradual decline in oxygen concentration), the acute and chronic manifestations of hypoxia, and the geographical characteristics of hypoxia (natural selection at high altitudes). Furthermore, hypoxia signaling pathways are associated with natural rhythms, such as diurnal and hibernation processes. In addition to innate factors and natural selection, it has been found that epigenetics, as a postnatal factor, profoundly influences the hypoxic response and progression within the cardiovascular system. Within this intricate process, interactions between different tissues and organs within the cardiovascular system and other systems in the context of hypoxia signaling pathways have been established. Thus, it is the time to summarize and to construct a multi-level regulatory framework of hypoxia signaling and mechanisms in cardiovascular diseases for developing more therapeutic targets and make reasonable advancements in clinical research, including FDA-approved drugs and ongoing clinical trials, to guide future clinical practice in the field of hypoxia signaling in cardiovascular diseases.
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Enfermedades Cardiovasculares , Sistema Cardiovascular , Humanos , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/terapia , Hipoxia/genética , Oxígeno , Epigénesis GenéticaRESUMEN
In an era of increasing need for precision medicine, machine learning has shown promise in making accurate acute myocardial infarction outcome predictions. The accurate assessment of high-risk patients is a crucial component of clinical practice. Type 2 diabetes mellitus (T2DM) complicates ST-segment elevation myocardial infarction (STEMI), and currently, there is no practical method for predicting or monitoring patient prognosis. The objective of the study was to compare the ability of machine learning models to predict in-hospital mortality among STEMI patients with T2DM. We compared six machine learning models, including random forest (RF), CatBoost classifier (CatBoost), naive Bayes (NB), extreme gradient boosting (XGBoost), gradient boosting classifier (GBC), and logistic regression (LR), with the Global Registry of Acute Coronary Events (GRACE) risk score. From January 2016 to January 2020, we enrolled patients aged > 18 years with STEMI and T2DM at the Affiliated Hospital of Zunyi Medical University. Overall, 438 patients were enrolled in the study [median age, 62 years; male, 312 (71%); death, 42 (9.5%]). All patients underwent emergency percutaneous coronary intervention (PCI), and 306 patients with STEMI who underwent PCI were enrolled as the training cohort. Six machine learning algorithms were used to establish the best-fit risk model. An additional 132 patients were recruited as a test cohort to validate the model. The ability of the GRACE score and six algorithm models to predict in-hospital mortality was evaluated. Seven models, including the GRACE risk model, showed an area under the curve (AUC) between 0.73 and 0.91. Among all models, with an accuracy of 0.93, AUC of 0.92, precision of 0.79, and F1 value of 0.57, the CatBoost model demonstrated the best predictive performance. A machine learning algorithm, such as the CatBoost model, may prove clinically beneficial and assist clinicians in tailoring precise management of STEMI patients and predicting in-hospital mortality complicated by T2DM.
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Diabetes Mellitus Tipo 2 , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/etiología , Medición de Riesgo/métodos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Intervención Coronaria Percutánea/efectos adversos , Teorema de Bayes , Mortalidad Hospitalaria , Aprendizaje AutomáticoRESUMEN
ABSTRACT: The mechanism of in-stent restenosis (ISR) remains elusive, and in-stent neoatherosclerosis (ISNA) may hold siginificant pathophysiological implications. Nevertheless, the correlation between ISNA and the progression of untreated coronary segments affected by native atherosclerosis remains incompletely investigated. This study enrolled 225 patients diagnosed with coronary heart disease and multivessel disease (MVD). These patients underwent successful percutaneous coronary intervention (PCI) and intraoperative placement of drug-eluting stent (DES), followed by optical coherence tomography (OCT) assessment of the culprit stent. The mechanism of ISR was emamined through qualitative and quantitative analysis of OCT imaging. A significantly higher proportion of patients in the ISR with non-target lesion progression (N-TLP) group exhibited lipid plaque formation compared to the ISR without N-TLP group (69.0% versus 39.8%, P < 0.001). The incidence of thin-cap fibroatheroma (TCFA) (33.3% versus 11.4%, P = 0.001) and ISNA (60.7% versus 38.6%, P < 0.001) was markedly elevated in the ISR with N-TLP group compared to the ISR without N-TLP group. Regarding manifestations, heterogeneous hyperplasia was predominantly observed in the ISR with N-TLP group (76.2% versus 38.6%, P < 0.001), while homogeneous hyperplasia was primarily presented in the ISR without N-TLP group (61.4% versus 23.8%, P < 0.001). Patients displaying notable progression of naturally occurring atherosclerosis manifest histomorphological features of ISR, primarily characterized by heterogeneous intimal hyperplasia and a higher prevalence of ISNA. In contrast, patients without substantial progression of naturally occurring atherosclerosis exhibit histomorphologic features of ISR primarily characterized by homogeneous intimal hyperplasia.
RESUMEN
Cyclin-dependent kinases (CDKs) regulate cell cycle progression and the transcription of a number of genes, including lipid metabolism-related genes, and aberrant lipid metabolism is involved in prostate carcinogenesis. Previous studies have shown that CDK13 expression is upregulated and fatty acid synthesis is increased in prostate cancer (PCa). However, the molecular mechanisms linking CDK13 upregulation and aberrant lipid metabolism in PCa cells remain largely unknown. Here, we showed that upregulation of CDK13 in PCa cells increases the fatty acyl chains and lipid classes, leading to lipid deposition in the cells, which is positively correlated with the expression of acetyl-CoA carboxylase (ACC1), the first rate-limiting enzyme in fatty acid synthesis. Gain- and loss-of-function studies showed that ACC1 mediates CDK13-induced lipid accumulation and PCa progression by enhancing lipid synthesis. Mechanistically, CDK13 interacts with RNA-methyltransferase NSUN5 to promote its phosphorylation at Ser327. In turn, phosphorylated NSUN5 catalyzes the m5C modification of ACC1 mRNA, and then the m5C-modified ACC1 mRNA binds to ALYREF to enhance its stability and nuclear export, thereby contributing to an increase in ACC1 expression and lipid deposition in PCa cells. Overall, our results disclose a novel function of CDK13 in regulating the ACC1 expression and identify a previously unrecognized CDK13/NSUN5/ACC1 pathway that mediates fatty acid synthesis and lipid accumulation in PCa cells, and targeting this newly identified pathway may be a novel therapeutic option for the treatment of PCa.
Asunto(s)
Acetil-CoA Carboxilasa , Neoplasias de la Próstata , Humanos , Masculino , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Proteína Quinasa CDC2 , Ácidos Grasos , Lípidos , Metiltransferasas , Proteínas Musculares , Próstata/metabolismo , Neoplasias de la Próstata/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Neoatherosclerosis (NA) is a significant contributor to late stent failure; however, predictors of late in-stent restenosis (ISR) with NA have not been systematically reported. This study aimed to identify predictors of NA incidence and plaque vulnerability in patients with late ISR and the role of low-density lipoprotein cholesterol (LDL-C) levels in this process. A total of 216 patients with 216 lesions who underwent optical coherence tomography (OCT) before interventional procedure for late drug-eluting stent ISR were enrolled and divided into NA and non-NA groups based on OCT findings. Results showed that higher LDL-C levels were associated with NA, thin-cap fibroatheroma (TCFA), intimal disruption, plaque erosion, and thrombosis. Multivariate regression analysis revealed that the LDL-C level was an independent risk factor for NA and TCFA. The LDL-C levels exhibited a significant predictive value for NA and TCFA, surpassing other factors such as stent age and other lipid types. In conclusion, a high LDL-C level is an independent predictor of NA incidence and plaque vulnerability in patients with late ISR.
Asunto(s)
Aterosclerosis , Enfermedad de la Arteria Coronaria , Reestenosis Coronaria , Stents Liberadores de Fármacos , Enfermedades de las Válvulas Cardíacas , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/patología , Stents Liberadores de Fármacos/efectos adversos , LDL-Colesterol , Tomografía de Coherencia Óptica/métodos , Neointima , Valor Predictivo de las Pruebas , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/etiología , Reestenosis Coronaria/patología , Aterosclerosis/patología , Constricción Patológica/complicaciones , Enfermedades de las Válvulas Cardíacas/complicaciones , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/complicacionesRESUMEN
ABSTRACT: Cardiac macrophages with different polarization phenotypes regulate ventricular remodeling and neovascularization after myocardial infarction (MI). Annexin A2 (ANXA2) promotes macrophage polarization to the repair phenotype and regulates neovascularization. However, whether ANXA2 plays any role in post-MI remodeling and its underlying mechanism remains obscure. In this study, we observed that expression levels of ANXA2 were dynamically altered in mouse hearts upon MI and peaked on the second day post-MI. Using adeno-associated virus vector-mediated overexpression or silencing of ANXA2 in the heart, we also found that elevation of ANXA2 in the infarcted myocardium significantly improved cardiac function, reduced cardiac fibrosis, and promoted peri-infarct angiogenesis, compared with controls. By contrast, reduction of cardiac ANXA2 exhibited opposite effects. Furthermore, using in vitro coculture system, we found that ANXA2-engineered macrophages promoted cardiac microvascular endothelial cell (CMEC) proliferation, migration, and neovascularization. Mechanistically, we identified that ANXA2 interacted with yes-associated protein (YAP) in macrophages and skewed them toward pro-angiogenic phenotype by inhibiting YAP activity. In addition, ANXA2 directly interacted with integrin ß3 in CMECs and enhanced their growth, migration, and tubule formation. Our results indicate that increased expression of ANXA2 could confer protection against MI-induced injury by promoting neovascularization in the infarcted area, partly through the inhibition of YAP in macrophages and activation of integrin ß3 in endothelial cells. Our study provides new therapeutic strategies for the treatment of MI injury.