Non-coding RNAs in leukemia drug resistance: new perspectives on molecular mechanisms and signaling pathways.

Like almost all cancer types, timely diagnosis is needed for leukemias to be effectively cured. Drug efflux, attenuated drug uptake, altered drug metabolism, and epigenetic alterations are just several of the key mechanisms by which drug resistance develops. All of these mechanisms are orchestrated by up- and downregulators, in which non-coding RNAs (ncRNAs) do not encode specific proteins in most cases; albeit, some of them have been found to exhibit the potential for protein-coding. Notwithstanding, ncRNAs are chiefly known for their contribution to the regulation of physiological processes, as well as the pathological ones, such as cell proliferation, apoptosis, and immune responses. Specifically, in the case of leukemia chemo-resistance, ncRNAs have been recognized to be responsible for modulating the initiation and progression of drug resistance. Herein, we comprehensively reviewed the role of ncRNAs, specifically its effect on molecular mechanisms and signaling pathways, in the development of leukemia drug resistance.

Exosomes for angiogenesis induction in ischemic disorders.

Ischaemic disorders are leading causes of morbidity and mortality worldwide. While the current therapeutic approaches have improved life expectancy and quality of life, they are unable to "cure" ischemic diseases and instate regeneration of damaged tissues. Exosomes are a class of extracellular vesicles with an average size of 100-150 nm, secreted by many cell types and considered a potent factor of cells for paracrine effects. Since exosomes contain multiple bioactive components such as growth factors, molecular intermediates of different intracellular pathways, microRNAs and nucleic acids, they are considered as cell-free therapeutics. Besides, exosomes do not rise cell therapy concerns such as teratoma formation, alloreactivity and thrombotic events. In addition, exosomes are stored and utilized more convenient. Interestingly, exosomes could be an ideal complementary therapeutic tool for ischemic disorders. In this review, we discussed therapeutic functions of exosomes in ischemic disorders including angiogenesis induction through various mechanisms with specific attention to vascular endothelial growth factor pathway. Furthermore, different delivery routes of exosomes and different modification strategies including cell preconditioning, gene modification and bioconjugation, were highlighted. Finally, pre-clinical and clinical investigations in which exosomes were used were discussed.

The Significant Role of microRNAs in Gliomas Angiogenesis: A Particular Focus on Molecular Mechanisms and Opportunities for Clinical Application.

MicroRNAs (miRNAs) are non-coding RNAs with only 20-22 nucleic acids that inhibit gene transcription and translation by binding to mRNA. MiRNAs have a diverse set of target genes and can alter most physiological processes, including cell cycle checkpoints, cell survival, and cell death mechanisms, affecting the growth, development, and invasion of various cancers, including gliomas. So optimum management of miRNA expression is essential for preserving a normal biological environment. Due to their small size, stability, and capability of specifically targeting oncogenes, miRNAs have emerged as a promising marker and new biopharmaceutical targeted therapy for glioma patients. This review focuses on the most common miRNAs associated with gliomagenesis and development by controlling glioma-determining markers such as angiogenesis. We also summarized the recent research about miRNA effects on signaling pathways, their mechanistic role and cellular targets in the development of gliomas angiogenesis. Strategies for miRNA-based therapeutic targets, as well as limitations in clinical applications, are also discussed.

Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy.

Combined chemotherapy is a treatment method based on the simultaneous use of two or more therapeutic agents; it is frequently necessary to produce a more effective treatment for cancer patients. Such combined treatments often improve the outcomes over that of the monotherapy approach, as the drugs synergistically target critical cell signaling pathways or work independently at different oncostatic sites. A better prognosis has been reported in patients treated with combination therapy than in patients treated with single drug chemotherapy. In recent decades, 5-fluorouracil (5-FU) has become one of the most widely used chemotherapy agents in cancer treatment. This medication, which is soluble in water, is used as the first line of anti-neoplastic agent in the treatment of several cancer types including breast, head and neck, stomach and colon cancer. Within the last three decades, many studies have investigated melatonin as an anti-cancer agent; this molecule exhibits various functions in controlling the behavior of cancer cells, such as inhibiting cell growth, inducing apoptosis, and inhibiting invasion. The aim of this review is to comprehensively evaluate the role of melatonin as a complementary agent with 5-FU-based chemotherapy for cancers. Additionally, we identify the potential common signaling pathways by which melatonin and 5-FU interact to enhance the efficacy of the combined therapy. Video abstract.

Anti-Mullerian hormone and cardiometabolic status: a systematic review.

BACKGROUND: To summarise the relationship between Anti-mullerian hormone (AMH) levels and cardiometabolic status in different populations. METHODS: PubMed, Scopus, and Embase were searched for retrieving observational studies published up to February 2022 investigating the relationship between AMH level and cardiometabolic status. RESULTS: Of 3,643 studies retrieved from databases, a total of 37 observational studies were included in this review. The majority of the included studies revealed an inverse association between AMH and lipid profiles, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and a positive correlation with high-density lipoprotein (HDL). While some studies have revealed a significant inverse association between AMH and glycemic parameters, including fasting plasma glucose (FPG), fasting insulin, and HOMA-IR, others found no such relationships. There is also an inconsistency among studies regarding the association of AMH with adiposity indices and blood pressure. Evidence indicates a significant association between AMH and some vascular markers, such as intima-media thickness and coronary artery calcification. Of 3 studies evaluating the relationship between AMH and cardiovascular events, two studies showed an inverse relationship between AMH levels and cardiovascular (CVD), whereas another study showed no significant association. CONCLUSIONS: The results of this systematic review suggest that serum AMH levels can be associated with CVD risk. This may provide new insight into the use of AMH concentrations as a predictive marker for assessing the risk of cardiovascular disease, although more well-design longitudinal studies are still necessary for this area. Future studies on this topic will hopefully provide an opportunity to run a meta-analysis; it will increase the persuasiveness of this interpretation.

Adjunctive therapy with lipid-lowering agents in COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been controversial in this regard. In this systematic review, we assessed the effect of these medications as adjunctive therapy in COVID-19 by the inclusion of randomized controlled trials (RCTs). METHODS: We searched four international databases including PubMed, the Web of Science, Scopus, and Embase for RCTs in April 2023. The primary outcome was mortality, while other efficacy indices were considered secondary outcomes. In order to estimate the pooled effect size of the outcomes, considering the odds ratio (OR) or standardized mean difference (SMD) and 95% confidence interval (CI), random-effect meta-analyses was conducted. RESULTS: Ten studies involving 2,167 COVID-19 patients using statins, omega-3 fatty acids, fenofibrate, PCSK9 inhibitors, and nicotinamide as intervention compared to control or placebo, were included. No significant difference was found in terms of mortality (OR 0.96, 95% CI 0.58 to 1.59, p-value = 0.86, I2 = 20.4%) or length of hospital stay (SMD -0.10, 95% CI -0.78 to 0.59, p-value = 0.78, I2 = 92.4%) by adding a statin to the standard of care. The trend was similar for fenofibrate and nicotinamide. PCSK9 inhibition, however, led to decreased mortality and an overall better prognosis. Omega-3 supplementation showed contradicting results in two trials, suggesting the need for further evaluation. CONCLUSION: Although some observational studies found improved outcomes in patients using lipid-lowering agents, our study found no benefit in adding statins, fenofibrate, or nicotinamide to COVID-19 treatment. On the other hand, PCSK9 inhibitors can be a good candidate for further assessment. Finally, there are major limitations in the use of omega-3 supplements in treating COVID-19 and more trials are warranted to evaluate this efficacy.

Evaluating the pure effect of weight on cardiac function in patients with cardiac syndrome X.

BACKGROUND: Obese patients have more coronary artery disease (CAD) risk factors that may affect myocardial function. We aimed to assess the ability of echocardiography-derived conventional parameters, left atrial strain, and global longitudinal strain to detect early diastolic and systolic dysfunction in obese individuals with almost no CAD risk factors. METHOD: We studied 100 participants with structurally normal hearts, ejection fractions above 50%, almost normal coronary arteries in coronary angiogram (syndrome X), and no cardiovascular risk factor except dyslipidemia. Participants were classified as normal-weight (BMI < 25.0 kg/m2 , n = 28) and high-weight (BMI ≥ 25.0 kg/m2 , n = 72). Conventional echocardiographic parameters and two-dimensional speckle tracking (2DSTE) were used to measure peak LA strain and global longitudinal strain to evaluate diastolic and systolic function, respectively. RESULT: There was no significant difference in the standard and conventional echocardiographic parameters between the two groups. 2DSTE echocardiographic parameters of the longitudinal deformation of the LV myocardium were not significantly different within the two groups. However, there were significant differences between the subjects with normal-weight and high-weight in terms of LA strain (34.51 ± 8.98% vs. 39.06 ± 8.62%, p = .021). The normal-weight group had lower LA strain, in compression with the high-weight group. All echocardiographic parameters were in the normal range. CONCLUSION: In the present study we demonstrated that global longitudinal subendocardial deformations, for the evaluation of systolic function, and conventional echocardiographic parameters, for the evaluation of diastolic function, were not significantly different between normal- and high-weight groups. Although LA strain was higher among overweight patients, it was not above the normal range of diastolic dysfunction.

Coronary Artery Bypass Graft Surgery After Primary Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction.

OBJECTIVE: To determine whether primary percutaneous coronary intervention (PPCI) is associated with adverse outcomes following coronary artery bypass graft (CABG) among patients with ST-elevation myocardial infarction (STEMI). METHODS: Patients presenting with acute STEMI who underwent CABG between September 2015 and November 2020 were included. Among 354 patients, 222 (62.7%) underwent PPCI prior to CABG (PPCI+CABG group) and were compared with the rest of the patients (CABG only group). The effects of PPCI on primary endpoints---including in-hospital mortality, length of stay (LOS), and bleeding events---were investigated using the stabilised inverse probability weighting method (S-IPW). Further, in-hospital mortality in various PPCI subgroups was analysed using univariable regression. RESULTS: Patients with and without PPCI were comparable regarding their baseline and surgical characteristics, except that those without PPCI were more likely to have left-main disease (29.5% vs 16.2%, p-value=0.003). Among the PPCI+CABG group, 3.6% mortality and 55.9% bleeding events occurred, and the LOS was 7 [5-10] days. The respective figures for the CABG only group were 4.5%, 50.8%, and 7 [6-10.5] days. Primary percutaneous coronary intervention, as a whole, was not significantly associated with either morality (S-IPW odds ratio (S-IPW OR) 0.61; p=0.393), LOS logarithm (S-IPW ß -0.050; p=0.403), or bleeding events (S-IPW OR 1.06; p=0.821). Nevertheless, the unadjusted mortality risk was significantly higher in complicated PPCIs compared with the CABG only group (OR 7.50, 95% CI 2.03-27.77); it was also higher among some other PPCI subgroups, albeit non-significantly. CONCLUSION: This study found that PPCI did not confer additional risk regarding in-hospital mortality, LOS, or bleeding among patients with acute STEMI who underwent CABG. However, some PPCI subgroups, especially those with complicated PPCI, were at increased risk.

Estimating the burden of diseases attributable to lead exposure in the North Africa and Middle East region, 1990-2019: a systematic analysis for the Global Burden of Disease study 2019.

BACKGROUND: Lead exposure (LE) and its attributable deaths and disability-adjusted life years (DALYs) have declined in the recent decade; however, it remains one of the leading public health concerns, particularly in regions with low socio-demographic index (SDI) such as the North Africa and Middle East (NAME) region. Hence, we aimed to describe the attributable burden of the LE in this region. METHODS: Data on deaths, DALYs, years of life lost (YLLs), and years lived with disability (YLDs) attributable to LE in the NAME region and its 21 countries from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) 2019 study. RESULTS: In 2019, the age-standardized death and DALY rates attributable to LE were 23.4 (95% uncertainty interval: 15.1 to 33.3) and 489.3 (320.5 to 669.6) per 100,000 in the region, respectively, both of which were higher among men than women. The overall age-standardized death and DALY rates showed 27.7% and 36.8% decreases, respectively, between 1990 and 2019. In this period, Bahrain, the United Arab Emirates, and Turkey had the highest decreases in the age-standardized death and DALY rates, while Afghanistan, Egypt, and Yemen had the lowest ones. Countries within high SDI quintile had lower attributable burden to LE compared with the low SDI quintile. Cardiovascular diseases and chronic kidney diseases accounted for the 414.2 (258.6 to 580.6) and 28.7 (17.7 to 41.7) LE attributable DALYs per 100,000 in 2019, respectively. The attributable YLDs was 46.4 (20.7 to 82.1) per 100,000 in 2019, which shows a 25.7% reduction (-30.8 to -22.5%) over 1990-2019. CONCLUSIONS: The overall LE and its attributed burden by cause have decreased in the region from 1990-2019. Nevertheless, the application of cost-effective and long-term programs for decreasing LE and its consequences in NAME is needed.

BMI modifies HDL-C effects on coronary artery bypass grafting outcomes.

BACKGROUND: Despite the recognized implications of high-density lipoprotein cholesterol (HDL-C) in cardiovascular diseases, the role of body mass index (BMI) in HDL-C association with cardiovascular outcomes remains unclear. This study investigated the possible modifying implications of BMI on the correlation between HDL-C and coronary artery bypass grafting (CABG) outcomes. METHODS: The present cohort included isolated CABG patients (median follow-up: 76.58 [75.79-77.38] months). The participants were classified into three groups: 18.5 ≤ BMI < 25 (normal), 25 ≤ BMI < 30 (overweight), and 30 ≤ BMI < 35 (obese) kg/m2. Cox proportional hazard models (CPHs) and restricted cubic splines (RCSs) were applied to evaluate the relationship between HDL-C and all-cause mortality as well as major adverse cardio-cerebrovascular events (MACCEs) in different BMI categories. RESULTS: This study enrolled a total of 15,639 patients. Considering the final Cox analysis among the normal and overweight groups, HDL-C ≥ 60 was a significant protective factor compared to 40 < HDL-C < 60 for all-cause mortality (adjusted hazard ratio (aHR): 0.47, P: 0.027; and aHR: 0.64, P: 0.007, respectively). However, the protective effect of HDL-C ≥ 60 was no longer observed among patients with 30 ≤ BMI < 35 (aHR: 1.16, P = 0.668). RCS trend analyses recapitulated these findings; among 30 ≤ BMI < 35, no uniform inverse linear association was observed; after approximately HDL-C≈55, its increase was no longer associated with reduced mortality risk. RCS analyses on MACCE revealed a plateau effect followed by a modest rise in overweight and obese patients from HDL-C = 40 onward (nonlinear association). CONCLUSIONS: Very high HDL-C (≥ 60 mg/dL) was not related to better outcomes among obese CABG patients. Furthermore, HDL-C was related to the post-CABG outcomes in a nonlinear manner, and the magnitude of its effects also differed across BMI subgroups.

UBE2C: A pan-cancer diagnostic and prognostic biomarker revealed through bioinformatics analysis.

BACKGROUND: The diverse and complex attributes of cancer have made it a daunting challenge to overcome globally and remains to endanger human life. Detection of critical cancer-related gene alterations in solid tumor samples better defines patient diagnosis and prognosis, and indicates what targeted therapies must be administered to improve cancer patients' outcome. MATERIALS AND METHODS: To identify genes that have aberrant expression across different cancer types, differential expressed genes were detected within the TCGA datasets. Subsequently, the DEGs common to all pan cancers were determined. Furthermore, various methods were employed to gain genetic alterations, co-expression genes network and protein-protein interaction (PPI) network, pathway enrichment analysis of common genes. Finally, the gene regulatory network was constructed. RESULTS: Intersectional analysis identified UBE2C as a common DEG between all 28 types of studied cancers. Upregulated UBE2C expression was significantly correlated with OS and DFS of 10 and 9 types of cancer patients. Also, UBE2C can be a diagnostic factor in CESC, CHOL, GBM, and UCS with AUC = 100% and diagnose 19 cancer types with AUC ≥90%. A ceRNA network constructed including UBE2C, 41 TFs, 10 shared miRNAs, and 21 circRNAs and 128 lncRNAs. CONCLUSION: In summary, UBE2C can be a theranostic gene, which may serve as a reliable biomarker in diagnosing cancers, improving treatment responses and increasing the overall survival of cancer patients and can be a promising gene to be target by cancer drugs in the future.

Recent Insights into the Angioregulatory Role of Long Non-coding RNAs and Circular RNAs in Gliomas: From Signaling Pathways to Clinical Aspects.

The most prevalent and severe malignancy of the central nervous system within the brain is glioma. Glioma is a vascularized cancer, and angiogenesis is necessary for glioma growth, invasion, and recurrence. It is also believed that this factor is this factor to be accountable for therapy resistance in many cancers, including glioma. The process of angiogenesis, which plays a crucial role in both health and disease situations such as cancer, involves the creation of new blood vessels from pre-existing ones. Non-coding RNAs (ncRNAs) are unique molecules that have been found to possess a wide range of abilities to modify the expression of various genes. They carry out their gene-modulating roles at a variety of distinct levels, including post-transcriptional and post-translational levels. Long ncRNAs (lncRNAs) and circular RNAs (circRNAs) are a group of ncRNA that have attracted particular attention and are involved in the angiogenesis mechanism in cancer. Understanding the regulatory mechanisms of these RNAs in the angiogenesis process in gliomas provides unique fundamental information about the process of tumor-associated neovascularization. On the other hand, due to developments in the characterisation of lncRNAs and circRNAs, these novel structures may potentially be used in clinics as possible biomarkers for treatment strategies that target tumor angiogenesis. Throughout the review, new knowledge and views about the angioregulatory function of circRNAs and lncRNAs in gliomas have been presented. Additionally, we talk about the novel idea of ncRNA-based therapeutics for gliomas in the future.

Decoding common genetic alterations between Barrett's esophagus and esophageal adenocarcinoma: A bioinformatics analysis.

Background: Esophageal adenocarcinoma (EAC) is a common cancer with a poor prognosis in advanced stages. Therefore, early EAC diagnosis and treatment have gained attention in recent decades. It has been found that various pathological changes, particularly Barrett's Esophagus (BE), can occur in the esophageal tissue before the development of EAC. In this study, we aimed to identify the molecular contributor in BE to EAC progression by detecting the essential regulatory genes that are differentially expressed in both BE and EAC. Materials and methods: We conducted a comprehensive bioinformatics analysis to detect BE and EAC-associated genes. The common differentially expressed genes (DEGs) and common single nucleotide polymorphisms (SNPs) were detected using the GEO and DisGeNET databases, respectively. Then, hub genes and the top modules within the protein-protein interaction network were identified. Moreover, the co-expression network of the top module by the HIPPIE database was constructed. Additionally, the gene regulatory network was constructed based on miRNAs and circRNAs. Lastly, we inspected the DGIdb database for possible interacted drugs. Results: Our microarray dataset analysis identified 92 common DEGs between BE and EAC with significant enrichment in skin and epidermis development genes. The study also identified 22 common SNPs between BE and EAC. The top module of PPI network analysis included SCEL, KRT6A, SPRR1A, SPRR1B, SPRR3, PPL, SPRR2B, EVPL, and CSTA. We constructed a ceRNA network involving three specific mRNAs, 23 miRNAs, and 101 selected circRNAs. According to the results from the DGIdb database, TD101 was found to interact with the KRT6A gene. Conclusion: The present study provides novel potential candidate genes that may be involved in the molecular association between Esophageal adenocarcinoma and Barrett's Esophagus, resulting in developing the diagnostic tools and therapeutic targets to prevent progression of BE to EAC.

New Insights into the Long Non-coding RNAs Dependent Modulation of Heart Failure and Cardiac Hypertrophy: From Molecular Function to Diagnosis and Treatment.

Heart failure (HF) is a public health issue that imposes high costs on healthcare systems. Despite the significant advances in therapies and prevention of HF, it remains a leading cause of morbidity and mortality worldwide. The current clinical diagnostic or prognostic biomarkers, as well as therapeutic strategies, have some limitations. Genetic and epigenetic factors have been identified to be central to the pathogenesis of HF. Therefore, they might provide promising novel diagnostic and therapeutic approaches for HF. Long non-coding RNAs (lncRNAs) belong to a group of RNAs that are produced by RNA polymerase II. These molecules play an important role in the functioning of different cell biological processes, such as transcription and regulation of gene expression. LncRNAs can affect different signaling pathways by targeting biological molecules or a variety of different cellular mechanisms. The alteration in their expression has been reported in different types of cardiovascular diseases, including HF, supporting the theory that they are important in the development and progression of heart diseases. Therefore, these molecules can be introduced as diagnostic, prognostic, and therapeutic biomarkers in HF. In this review, we summarize different lncRNAs as diagnostic, prognostic, and therapeutic biomarkers in HF. Moreover, we highlight various molecular mechanisms dysregulated by different lncRNAs in HF.

Translational Approach Using Advanced Therapy Medicinal Products for Huntington's Disease.

Current therapeutic approaches for Huntington's disease (HD) focus on symptomatic treatment. Therefore, the unavailability of efficient disease-modifying medicines is a significant challenge. Regarding the molecular etiology, targeting the mutant gene or advanced translational steps could be considered promising strategies. The evidence in gene therapy suggests various molecular techniques, including knocking down mHTT expression using antisense oligonucleotides and small interfering RNAs and gene editing with zinc finger proteins and CRISPR-Cas9-based techniques. Several post-transcriptional and post-translational modifications have also been proposed. However, the efficacy and long-term side effects of these modalities have yet to be verified. Currently, cell therapy can be employed in combination with conventional treatment and could be used for HD in which the structural and functional restoration of degenerated neurons can occur. Several animal models have been established recently to develop cell-based therapies using renewable cell sources such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stromal cells, and neural stem cells. These models face numerous challenges in translation into clinics. Nevertheless, investigations in Advanced Therapy Medicinal Products (ATMPs) open a promising window for HD research and their clinical application. In this study, the ATMPs entry pathway in HD management was highlighted, and their advantages and disadvantages were discussed.

Role of long noncoding RNAs in pathological cardiac remodeling after myocardial infarction: An emerging insight into molecular mechanisms and therapeutic potential.

Myocardial infarction (MI) is the leading cause of heart failure (HF), accounting for high mortality and morbidity worldwide. As a consequence of ischemia/reperfusion injury during MI, multiple cellular processes such as oxidative stress-induced damage, cardiomyocyte death, and inflammatory responses occur. In the next stage, the proliferation and activation of cardiac fibroblasts results in myocardial fibrosis and HF progression. Therefore, developing a novel therapeutic strategy is urgently warranted to restrict the progression of pathological cardiac remodeling. Recently, targeting long non-coding RNAs (lncRNAs) provided a novel insight into treating several disorders. In this regard, numerous investigations have indicated that several lncRNAs could participate in the pathogenesis of MI-induced cardiac remodeling, suggesting their potential therapeutic applications. In this review, we summarized lncRNAs displayed in the pathophysiology of cardiac remodeling after MI, emphasizing molecular mechanisms. Also, we highlighted the possible translational role of lncRNAs as therapeutic targets for this condition and discussed the potential role of exosomes in delivering the lncRNAs involved in post-MI cardiac remodeling.

Predictive modeling for acute kidney injury after percutaneous coronary intervention in patients with acute coronary syndrome: a machine learning approach.

BACKGROUND: Acute kidney injury (AKI) is one of the preventable complications of percutaneous coronary intervention (PCI). This study aimed to develop machine learning (ML) models to predict AKI after PCI in patients with acute coronary syndrome (ACS). METHODS: This study was conducted at Tehran Heart Center from 2015 to 2020. Several variables were used to design five ML models: Naïve Bayes (NB), Logistic Regression (LR), CatBoost (CB), Multi-layer Perception (MLP), and Random Forest (RF). Feature importance was evaluated with the RF model, CB model, and LR coefficients while SHAP beeswarm plots based on the CB model were also used for deriving the importance of variables in the population using pre-procedural variables and all variables. Sensitivity, specificity, and the area under the receiver operating characteristics curve (ROC-AUC) were used as the evaluation measures. RESULTS: A total of 4592 patients were included, and 646 (14.1%) experienced AKI. The train data consisted of 3672 and the test data included 920 cases. The patient population had a mean age of 65.6 ± 11.2 years and 73.1% male predominance. Notably, left ventricular ejection fraction (LVEF) and fasting plasma glucose (FPG) had the highest feature importance when training the RF model on only pre-procedural features. SHAP plots for all features demonstrated LVEF and age as the top features. With pre-procedural variables only, CB had the highest AUC for the prediction of AKI (AUC 0.755, 95% CI 0.713 to 0.797), while RF had the highest sensitivity (75.9%) and MLP had the highest specificity (64.35%). However, when considering pre-procedural, procedural, and post-procedural features, RF outperformed other models (AUC: 0.775). In this analysis, CB achieved the highest sensitivity (82.95%) and NB had the highest specificity (82.93%). CONCLUSION: Our analyses showed that ML models can predict AKI with acceptable performance. This has potential clinical utility for assessing the individualized risk of AKI in ACS patients undergoing PCI. Additionally, the identified features in the models may aid in mitigating these risk factors.

Factors Affecting Late Atrial Fibrillation and Its Association With Coronary Artery Bypass Outcomes.

BACKGROUND: Although predictors and outcomes of postoperative atrial fibrillation (POAF) are well studied, evidence is lacking concerning postdischarge late/recurrent atrial fibrillation (AF). This study evaluated factors affecting late/recurrent AF and its association with coronary artery bypass grafting (CABG) outcomes in a real-world setting. METHODS: From 2012 through 2016, 5175 patients were included. Independent factors associated with late/recurrent AF were identified in a competing risk setting. Cox proportional hazard regression was used to evaluate the association between late/recurrent AF and study outcomes, consisting of all-cause mortality, major adverse cardio-cerebrovascular events, acute coronary syndrome, cerebrovascular events, and heart failure admissions. RESULTS: During a median follow-up of 60 months (quartile 1-quartile 3, 59.3-60.7 months), late/recurrent AF developed in 85 patients (1.64%). Independent factors associated with late/recurrent AF were age (subdistribution hazard ratio [sHR], 1.04; 95% CI, 1.02-1.07), left-ventricular ejection fraction (sHR, 0.97; 95% CI, 0.95-0.99), length of stay (sHR, 1.02; 95% CI, 1.01-1.04), and POAF (sHR, 4.02; 95% CI, 2.50-6.45). Late/recurrent AF was not significantly associated with all-cause mortality and major adverse cardio-cerebrovascular events at unadjusted or adjusted levels (adjusted hazard ratio, 0.80 [95% CI, 0.50-1.28] and 0.74 [95% CI, 0.48-1.13], respectively). Nevertheless, it significantly increased the unadjusted risk of cerebrovascular events (hazard ratio, 2.28; 95% CI, 01.07-4.87), which disappeared after adjustments. CONCLUSIONS: Patients with advanced age, a lower left-ventricular ejection fraction, and POAF are more likely to have late/recurrent clinical AF. Albeit counterintuitive, late/recurrent AF was not independently associated with worse midterm post-CABG outcomes. These observations need to be further elucidated in larger-scale studies and interpreted in the context of a developing country with limited resources for late AF surveillance.

Fragmented QRS, a strong predictor of mortality and major arrhythmic events in patients with nonischemic cardiomyopathy: A systematic review and meta-analysis.

Background and Aims: Fragmented QRS (fQRS), which is associated with rhythm disturbances, can predispose the heart to fatal ventricular arrhythmias. Recently, accumulating studies indicates that fQRS is associated with poor prognosis in various types of cardiomyopathies. Therefore, we assessed the association between fQRS with all-cause mortality and major arrhythmic events (MAEs) in patients with nonischemic cardiomyopathy, in this systematic review and meta-analysis study. Methods: We performed a comprehensive search in databases of PubMed/Medline, EMBASE, and Web of Science from the beginning to December 31, 2022. Published observational studies (cohorts, case-control, or analytical cross-sectional studies) were included that report the prognostic value of fQRS in patients with different types of nonischemic cardiomyopathies for MAEs (sudden cardiac death, sudden cardiac arrest, sustained ventricular tachycardia [VT], ventricular fibrillation [VF], and appropriate shock) and all-cause mortality. We pooled risk ratios (RRs) through raw data and adjusted hazard ratios (aHRs) using "Comprehensive Meta-Analysis" software, Version 2.0. Results: Nineteen cohort and three analytical cross-sectional studies were included in this meta-analysis involving a total of 4318 subjects with nonischemic cardiomyopathy (1279 with fQRS and 3039 without fQRS). FQRS was significantly associated with an increased risk of all-cause mortality in patients with nonischemic cardiomyopathy (pooled RR: 1.920; 95% confidence interval [CI]: 1.388-2.656, p < 0.0001/pooled HR: 1.729; 95% CI: 1.327-2.251, p < 0.0001). Also, the risk of developing MAEs in the presence of fQRS was significantly increased (pooled RR: 2.041; 95% CI: 1.644-2.533, p < 0.0001/pooled HR: 3.626; 95% CI: 2.119-6.204, p < 0.0001). In the subgroup analysis, the strongest association between fQRS presence and increased MAEs was observed in patients with hypertrophic cardiomyopathy (HCM) (pooled RR: 3.44; 95% CI: 2.07-5.71, p < 0.0001/pooled HR: 3.21; 95% CI: 2.04-5.06, p < 0.0001). Conclusion: Fragmented QRS could be a prognostic marker for all-cause mortality and MAEs in patients with various types of nonischemic cardiomyopathies, particularly HCM.

Caffeine Drug Interactions and its Clinical Implication After Acute Coronary Syndrome: A Literature Review.

The hemodynamic and cardiovascular impacts of coffee and caffeine have long been controversial. However, due to the worldwide popularity of coffee and caffeinated beverages, it is essential to understand how they affect the cardiovascular system, specifically in patients with a history of acute coronary syndrome. This literature review was conducted to explore the cardiovascular effects of coffee and caffeine and their interactions with common drugs after acute coronary syndrome and percutaneous coronary intervention. The evidence suggests that moderate coffee and caffeine consumption is not associated with cardiovascular disease in healthy individuals and patients with a history of acute coronary syndrome. The interactions of coffee or caffeine with common medications after acute coronary syndrome or percutaneous coronary intervention are less studied. However, based on the current human studies in this field, the only interaction is with the protective effect of statins on cardiac ischemia.