LPS induces RGS-1 to promote infectious intracranial aneurysm formation and rupture by accelerating smooth muscle cell phenotypic switching.

OBJECTIVE: Patients with infectious intracranial aneurysms (IIAs) have high mortality rates. Sepsis is an important condition that induces IIA. Smooth muscle cell (SMC) phenotypic switching may have a critical effect on sepsis-induced IIA, but its role remains unclear. Hence, we aimed to identify sepsis-induced target genes involved in SMC phenotypic switching and their underlying mechanisms. METHODS AND RESULTS: RNA sequencing and bioinformatics analyses of samples from patients with intracranial aneurysms and sepsis identified RGS-1 as a common differentially expressed gene (DEG) involved in SMC phenotypic switching. Experimental verification demonstrated that lipopolysaccharide (LPS), a critical molecule in sepsis, increased RGS-1 levels, promoted SMC phenotypic switching and proliferation, and upregulated the expression of matrix metalloproteinases and inflammatory factors. Furthermore, qRT-PCR and immunofluorescence experiments confirmed that RGS-1 knockdown under LPS stimulation inhibited SMC phenotypic switching, cell proliferation, and decreases in matrix metalloproteinases and inflammatory factors. Mechanistically, western blotting, bioinformatics analyses, and chip assays revealed that RGS-1 activates the JNK-P38 pathway to promote SMC phenotypic switching and is regulated by the transcription factor STAT1. CONCLUSION: LPS induces RGS-1 to promote IIA formation and rupture by accelerating SMC phenotypic switching.

Experience sharing of a case of dual atrioventricular nodal non-reentrant tachycardia: Case report.

RATIONALE: Tachycardia is a common arrhythmia in clinical practice, and its pathogenesis is mostly related to reentry. However, there are also a few tachycardia that are not related to reentry. Actively clarifying the pathogenesis of these non-reentry related tachycardia is of great significance for its treatment. PATIENT CONCERNS: A 55-year-old female patient presented with recurrent palpitations with a fastest heart rate of 180 beats/minute 10 years ago. DIAGNOSIS: Dual atrioventricular nodal non-reentrant tachycardia (DAVNNT). INTERVENTIONS: DAVNNT can be cured by radiofrequency ablation of atrioventricular nodal slow path modification. OUTCOMES: The tachycardia has stopped. CONCLUSION: DAVNNT is a rare disease in clinical practice. Its characteristic is not reentration-related arrhythmias, but the phenomenon of increased heart rate caused by electrical conduction down the double pathway of atrioventricular nodal tract and subsequent pathway. Electrophysiological examination helps to clarify the diagnosis and pathogenesis, and catheter ablation can cure the disease.

Systemic immune inflammation index is associated with in-stent neoatherosclerosis and plaque vulnerability: An optical coherence tomography study.

Background: In-stent neoatherosclerosis (ISNA) is identified as the primary cause of in-stent restenosis (ISR). The systemic immune inflammation index (SII), shows promise for predicting post-percutaneous coronary intervention (PCI) adverse cardiovascular events and is associated with coronary stenosis severity; however, its specific relationship with ISNA remains unclear. This study aimed to investigate the association between the SII and ISNA after drug-eluting stent (DES) implantation. Methods: This cross-sectional study included 195 participants with 195 ISR lesions who underwent optical coherence tomography (OCT)-guided PCI between August 2018 and October 2022. Participants were categorized based on the SII levels into Tertile 1 (SII <432.37, n = 65), Tertile 2 (432.37 ≤ SII ≤751.94, n = 65), and Tertile 3 (SII >751.94, n = 65). Baseline Clinical, angiographic, and OCT characteristics were analyzed. The association of the SII with ISNA and thin-fibroatheroma (TCFA) was investigated using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of the SII in detecting ISNA and TCFA. Results: Patients in Tertile 3 had a significantly higher incidences of ISNA and TCFA than did those in Tertile 1. Logistic regression analysis revealed the SII is an independent indicator of ISNA and TCFA in ISR lesions (P = 0.045 and P = 0.002, respectively). The areas under the ROC curves for ISNA and TCFA were 0.611 and 0.671, respectively. Conclusion: The SII is associated with ISNA and TCFA and may serve as an independent indicator in patients with ISR.

A case with rare complication of chronic puerperal uterine inversion and underwent operation reduction.

OBJECTIVE: Puerperal uterine inversion is a rare and severe complication and is associated with short cord, uncontrolled cord traction, placenta accreta, or uterine atony. CASE REPORT: A primigravida woman gave birth a 2770 gm newborn at term at our hospital, and clinically presented postpartum hemorrhage, hypovolemic shock, postpartum preeclampsia and urinary retention. She discharged 3 days postpartum, but she complained persist vaginal bleeding and lower abdominal pain for more than 1 month. Uterine inversion was diagnosed and laparoscope surgery for reduction was done. CONCLUSION: The non-specific clinical presentation made diagnosis of uterine inversion more difficult. Except pelvic examination, sonographic and hysteroscopic images were record in this article. Surgical intervention was performed. A fundus incision was effective for reduction and had low risk of bladder and bowel injury.

A Review of Pathophysiology and Therapeutic Strategies Targeting TGF-ß in Graves' Ophthalmopathy.

TGF-ß plays a pivotal role in the pathogenesis of GO by promoting orbital tissue remodeling and fibrosis. This process involves the stimulation of orbital fibroblasts, leading to myofibroblast differentiation, increased production of inflammatory mediators, and hyaluronan accumulation. Studies have elucidated TGF-ß's role in driving fibrosis and scarring processes through both canonical and non-canonical pathways, particularly resulting in the activation of orbital myofibroblasts and the excessive accumulation of extracellular matrix. Additionally, recent in vitro and in vivo studies have been summarized, highlighting the therapeutic potential of targeting TGF-ß signaling pathways, which may offer promising treatment interventions for GO. This review aims to consolidate the current understanding of the multifaceted role of TGF-ß in the molecular and cellular pathophysiology in Graves' ophthalmopathy (GO) by exploring its contributions to fibrosis, inflammation, and immune dysregulation. Additionally, the review investigates the therapeutic potential of inhibiting TGF-ß signaling pathways as a strategy for treating GO.

Non-target lesion progression: Unveiling critical predictors and outcomes in patients with in-stent restenosis.

BACKGROUND: Percutaneous coronary intervention (PCI) has become the primary treatment for coronary artery disease. However, while PCI effectively addresses severe stenosis or occlusive lesions in target vessels, the progression of non-target vessel plaque remains a critical determinant of long-term patient prognosis. AIMS: The purpose of this study was to investigate the impact of non-target vascular plaque progression on prognosis after PCI for ISR. METHODS: This study included 195 patients diagnosed with ISR and multivessel disease who underwent successful PCI with drug-eluting stent (DES) placement, along with intraoperative optical coherence tomography (OCT) assessment of the culprit stent. Subsequent rechecked coronary angiography categorized eligible patients into non-target lesion progression (N-TLP) and no-N-TLP groups. We evaluated the baseline morphological characteristics of N-TLP by OCT and investigated the relationship between N-TLP, non-culprit vessel-related major adverse cardiovascular events (NCV-MACE), and pan-vascular disease-related clinical events (PVD-CE) incidence. RESULTS: Multivariate logistic regression analysis revealed that diabetes mellitus (OR 3.616, 95% CI: 1.735-7.537; P = 0.001), uric acid level (OR 1.005, 95% CI: 1.001-1.009; P = 0.006), in-stent neoatherosclerosis (ISNA) (OR 1.334, 95% CI: 1.114-1.985; P = 0.047) and heterogeneous neointima morphology (OR 2.48, 95% CI: 1.18-5.43; P = 0.019) were independent predictors for N-TLP. Furthermore, N-TLP was associated with a high incidence of NCV-MACE (19.4% vs 6.9%, P = 0.009) and PVD-CE (83.9% [95% CI: 79.7%-88.3%] vs 93.1% [95% CI: 88.4%-98.0%], P = 0.038) after PCI in ISR patients. CONCLUSION: Diabetes, uric acid levels, ISNA, and heterogeneous neointima are predictive factors for subsequent rapid plaque progression, with N-TLP exacerbating the incidence of NCV-MACE and PVD-CE after PCI.

Machine Learning Constructed Based on Patient Plaque and Clinical Features for Predicting Stent Malapposition: A Retrospective Study.

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.

Free medial femoral condyle osteocutaneous flap for repairing stage IIIB osteonecrosis of the lunate: a case report.

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.

Loss of m6A demethylase ALKBH5 alleviates hypoxia-induced pulmonary arterial hypertension via inhibiting Cyp1a1 mRNA decay.

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.

Radiation therapy with phenotypic medicine: towards N-of-1 personalization.

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.

Thin-cap fibroatheroma in acute coronary syndrome: Implication for intravascular imaging assessment.

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.

Association between periprocedural myocardial injury and neointimal characteristics in patients with in-stent restenosis: an optical coherence tomography study.

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.

The Role of Fibrogenesis and Extracellular Matrix Proteins in the Pathogenesis of Graves' Ophthalmopathy.

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.

Variation and disparity in awareness of atrial fibrillation in China: A national cross-sectional study.

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.

Morphological characteristics of in-stent restenosis with different degrees of area stenosis: an optical coherence tomography study.

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.

CURATE.AI-assisted dose titration for anti-hypertensive personalized therapy: study protocol for a multi-arm, randomized, pilot feasibility trial using CURATE.AI (CURATE.AI ADAPT trial).

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.

Effectiveness and safety of ivabradine in Chinese patients with chronic heart failure: an observational study.

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.

Association Between Serum Uric Acid Levels and Neoatherosclerosis.

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.

Association of the monocytes to high-density lipoprotein cholesterol ratio with in-stent neoatherosclerosis and plaque vulnerability: An optical coherence tomography study.

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.

Comparing the Performance of Multiple Small-Data Personalized Tacrolimus Dosing Models for Pediatric Liver Transplant: A Retrospective Study.

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.