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Cyclization is a widely used approach to exert conformational restraint on linear peptide sequences. Herein, urea bridge chemistry was deployed to achieve side chain-to-side chain peptide cyclization on the Streptococcus pneumoniae CSP1-E1A peptide scaffold. To determine the effects of ring size and bridge position on the overall peptide conformation and find the ideal area within the CSP sequence for cyclization, we performed biological evaluation as well as secondary structure analysis on all the cyclic analogs. Biological evaluation results exhibited that even minor modifications to cyclic analogs for each of the cyclization positions could significantly alter the interaction between the peptide and its target receptor, ComD. Furthermore, structural analysis using circular dichroism (CD) and Trapped Ion Mobility Spectrometry (TIMS) emphasized the significance of incorporating the bridge position as a parameter to be modified, in addition to the traditional ring position and ring size parameters. Overall, our results showcase the importance of comprehensive conformational screening in fine-tuning the secondary structure of cyclic peptide analogs. This knowledge could be very useful for future studies aimed at optimizing peptide : protein interactions.

Background: Percutaneous coronary intervention (PCI) is considered the procedure of choice for patients with acute coronary syndrome (ACS), as it significantly improves cardiovascular outcomes. However, considerable uncertainty persists regarding the potential sex differences in PCI outcomes, due to conflicting results in previous studies., Objectives: This meta-analysis aims to evaluate potential sex-related differences in cardiovascular adverse outcomes after PCI among ACS patients., Methods: The primary outcome was major adverse cardiovascular events (MACE) and its components. Outcomes were examined in various time frames including: short-term (within 1 month after PCI), mid-term (within 1 year), and long-term (within >1 year). A random effects model was used to estimate risk ratios (RR) and 95% CIs., Results: Among 32 trials, at short-term, PCI was associated with a higher risk of MACE (risk ratio [RR]: 1.43; 95% CI: 1.10-1.86), all-cause mortality (RR: 2.51; 95% CI: 1.70-3.71), and myocardial infarction (RR: 1.33; 95% CI: 1.00-1.77) in women compared with men. Over the long-term, women had a higher risk of MACE (RR: 1.11; 95% CI: 1.01-1.22), all-cause mortality (RR: 1.29; 95% CI: 1.17-1.42), and cardiovascular mortality (RR: 1.30; 95% CI: 1.11-1.52), when compared with men. However, the analysis for stroke and repeat revascularization showed no significant difference between the 2 groups in the long- and short-term., Conclusions: In the meta-analysis of PCI-related trials in ACS, women have a higher risk of adverse cardiovascular outcomes compared with men., Competing Interests: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)

Background: Limited data exist on long-term outcomes after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). This meta-analysis aims to elucidate outcome trends following TAVR versus SAVR in patients with severe aortic stenosis and low-surgical risk., Methods and Results: A systematic search was conducted in PubMed, Embase, Scopus, and the Cochrane Library databases from inception until May 2024, to identify studies comparing TAVR versus SAVR in patients with low-surgical risk (Society of Thoracic Surgeons predicted risk of mortality score <4%). The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, stroke, disabling stroke, rehospitalization, myocardial infarction, aortic valve reintervention, permanent pacemaker implantation, and new-onset atrial fibrillation. Binary random-effects models were used to compare the risk of each outcome across various follow-up intervals and the risk of bias was assessed using the Cochrane Collaboration's Risk of Bias-2 tool. The meta-analysis included 6 randomized trials including 4682 patients. TAVR was associated with a lower risk of all-cause mortality than SAVR in the 30-day (hazard ratio [HR: 0.45] [95% CI: 0.26-0.77], I 2 : 0%) and 30-day to 1-year (HR: 0.55 [95% CI: 0.37-0.81], I 2 : 16%) follow-ups. However, the risk of all-cause mortality was similar during >1-year follow-ups. TAVR was associated with a significantly lower risk of cardiovascular mortality, disabling stroke, rehospitalization, new-onset atrial fibrillation, and a higher risk of permanent pacemaker implantation compared with SAVR during the 30-day follow-up., Conclusions: TAVR was associated with a lower risk of all-cause mortality within the first year of post-procedural follow-up compared with SAVR. However, the risk of all-cause mortality was similar in >1-year follow-ups.

Background: This study evaluated the association between bypass grafting with multiarterial grafts (MAG) and single arterial grafts (SAG) and all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE), overall and across different patient subgroups from a Middle Eastern nation., Methods: This single-center retrospective cohort study included 23,798 patients. MAG and SAG groups were balanced using inverse probability weighting (IPW). Associations between MAG and outcomes were assessed using Cox regression. A series of covariate-adjusted Cox models were conducted to evaluate the effect of MAG on outcomes at different levels of independent variables, including age, sex, and cardiovascular risk factors., Results: In the study population (73.9% were men, 65.11 ± 9.94 years), 986 patients (4.1%) underwent MAG. Compared with the SAG group, MAG had lower crude mortality (14.1% vs 21.6%) and MACCE (28.8% vs 34.7%) rates during a median follow-up of 9.23 years (quartile 1-quartile 3, 9.13-9.33 years). Although MAG was significantly associated with reduced risk of study outcomes at the univariate level, these associations disappeared after matching (all-cause mortality (IPW hazard ratio, 0.90; 95% CI, 0.67-1.22) and MACCEs (IPW hazard ratio, 0.94; 95% CI, 0.76-1.15). However, covariate-adjusted models indicated that MAG was associated with a significantly reduced risk of adverse events, particularly MACCEs, in men, younger patients, and those without risk factors., Conclusions: MAG was not associated with improved postsurgery outcomes among the total coronary artery bypass graft population. Our findings, however, should be interpreted in the context of a relatively low total institutional MAG burden. Choosing a second arterial conduit over saphenous vein grafts in specific patient subgroups might be reasonable. This hypothesis-generating finding should be investigated in future clinical trials in these patients., Competing Interests: Disclosures Mario Gaudino is on The Annals of Thoracic Surgery Editorial Board. The other authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Triglyceride-glucose index (TyG), a surrogate marker of insulin resistance (IR), could be a potential prognostic marker in patients with acute coronary syndromes (ACS). We evaluated the effect of the TyG index on major adverse cardiac and cerebrovascular events (MACCE) in patients with ACS undergoing percutaneous coronary intervention (PCI)., Methods: This registry-based cohort study was conducted at Tehran Heart Center from 2015 to 2021 and the median follow-up duration was 378 days. The primary outcome was MACCE and the secondary outcomes were MACCE components: all-cause mortality, myocardial infarction, stroke, target vessel revascularization, target lesion revascularization, and coronary artery bypass grafting. For comparison among TyG quartiles (Q), the log-rank test was used. Unadjusted and adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to describe the association between TyG quartiles and MACCE. A subgroup of euglycemic patients was also evaluated., Results: A total of 13,542 patients were included. Patients in the fourth TyG quartile (Q4) were younger, had higher mean BMI, and higher prevalence of hypertension, diabetes, and dyslipidemia. The adjusted Cox model showed that a 1-unit increment of the TyG index was associated with a significantly higher risk of MACCE (aHR 1.18, 95% CI 1.08 to 1.30, p < 0.001). Among TyG quartiles, there was a higher MACCE incidence in Q4 compared to Q1 (aHR 1.29, 95% CI 1.08 to 1.53, p = 0.005). In the euglycemic subgroup of the population, there was no significant association between MACCE incidence and a 1-unit increase in TyG or among TyG quartiles., Conclusion: Based on our findings, while higher TyG levels and quartiles were associated with higher rates of MACCE in ACS, there was no such effect in the euglycemic population. If confirmed in future studies, these results can be beneficial for clinicians to risk stratify these patients with an easy-to-use index and determine clinical plans based on their risk., (© 2024. The Author(s).)

Background: Machine learning (ML) models have the potential to accurately predict outcomes and offer novel insights into inter-variable correlations. In this study, we aimed to design ML models for the prediction of 1-year mortality after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome., Methods: This study was performed on 13,682 patients at Tehran Heart Center from 2015 to 2021. Patients were split into 70:30 for testing and training. Four ML models were designed: a traditional Logistic Regression (LR) model, Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Ada Boost models. The importance of features was calculated using the RF feature selector and SHAP based on the XGBoost model. The Area Under the Receiver Operating Characteristic Curve (AUC-ROC) for the prediction on the testing dataset was the main measure of the model's performance., Results: From a total of 9,073 patients with >1-year follow-up, 340 participants died. Higher age and higher rates of comorbidities were observed in these patients. Body mass index and lipid profile demonstrated a U-shaped correlation with the outcome. Among the models, RF had the best discrimination (AUC 0.866), while the highest sensitivity (80.9%) and specificity (88.3%) were for LR and XGBoost models, respectively. All models had AUCs of >0.8., Conclusion: ML models can predict 1-year mortality after PCI with high performance. A classic LR statistical approach showed comparable results with other ML models. The individual-level assessment of inter-variable correlations provided new insights into the non-linear contribution of risk factors to post-PCI mortality., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Transcatheter aortic valve implantation (TAVI) has been increasingly used in patients with severe aortic stenosis (AS). Since coronary artery disease (CAD) is common among these patients, it is crucial to choose the best method and timing of revascularization. This study aims to compare different timing strategies of percutaneous coronary intervention (PCI) in patients with severe AS undergoing TAVI to clarify whether PCI timing affects the patients' outcomes or not., Methods: A frequentist network meta-analysis was conducted comparing three different revascularization strategies in patients with CAD undergoing TAVI. The 30-day all-cause mortality, in-hospital mortality, all-cause mortality at 1 year, 30-day rates of myocardial infarction (MI), stroke, and major bleeding, and the need for pacemaker implantation at 6 months were analyzed in this study., Results: Our meta-analysis revealed that PCI during TAVI had higher 30-day mortality (RR = 2.46, 95% CI = 1.40-4.32) and in-hospital mortality (RR = 1.70, 95% CI = [1.08-2.69]) compared to no PCI. Post-TAVI PCI was associated with higher 1-year mortality compared to other strategies. While no significant differences in major bleeding or stroke were observed, PCI during TAVI versus no PCI (RR = 3.63, 95% CI = 1.27-10.43) showed a higher rate of 30-day MI., Conclusion: Our findings suggest that among patients with severe AS and CAD undergoing TAVI, PCI concomitantly with TAVI seems to be associated with worse 30-day outcomes compared with no PCI. PCI after TAVI demonstrated an increased risk of 1-year mortality compared to alternative strategies. Choosing a timing strategy should be individualized based on patient characteristics and procedural considerations., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: High-density lipoprotein cholesterol (HDL-C) is shown to be an independent protective factor against coronary artery diseases (CAD). Yet there are limited studies focusing on the association between HDL-C and coronary artery bypass graft (CABG) surgery outcomes., Hypothesis: Low levels of HDL-C are associated with higher incidence of adverse outcomes in patients undergoing CABG., Methods: This registry-based study included 17,772 patients who underwent elective isolated CABG between 2007 and 2017. Patients were classified into low and desirable HDL-C groups based on their serum HDL-C levels at admission and were followed for one-year post-surgery. The study population included 13,321 patients with low HDL-C and 4,451 with desirable HDL-C. proportional hazard Cox models were performed to evaluate the association between HDL-C levels and incidence of mortality as well as major adverse cardiovascular and cerebrovascular events (MACCE), while adjusting for potential confounders. Moreover, participants were stratified based on sex and the association was also investigated in each subgroup separately., Results: No significant difference was found between the groups regarding incidence of both mortality and MACCE, after adjusting with Inverse Probability Weighting (IPW) [HR (95%CI): 0.84 (0.46-1.53), p-value:0.575 and HR (95% CI): 0.91 (0.56-1.50), p-value:0.733, respectively]. According to the sex-based subgroup analysis, no significant association was observed after adjustment with IPW analysis. However, as we examined the association between the interaction of HDL-C levels, sex and cardiovascular outcomes, we found a significant association (HR;1.19 (95%CI: 1.04-1.45); p = 0.030)., Conclusion: HDL-C level was not associated with either mortality or MACCE during one year after CABG procedure. Sex-based analysis showed that in males, HDL-C is significantly more protective against these outcomes, compared to females. Further studies are necessary to elucidate the exact mechanisms mediating such association., (© 2024. The Author(s).)

Background: Unlike diabetes, the effect of prediabetes on outcomes in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) is not much investigated. We investigated the association between fasting glycemic status and major adverse cardiovascular and cerebrovascular events (MACCE) in patients with ACS undergoing PCI and had mid to long-term follow-up after coronary stenting., Methods: Registry-based retrospective cohort study included ACS patients who underwent PCI at the Tehran Heart Center from 2015 to 2021 with a median follow-up of 378 days. Patients were allocated into normoglycemic, prediabetic, and diabetic groups. The primary and secondary outcomes were MACCE and its components, respectively. Unadjusted and adjusted Cox models were used to evaluate the association between glycemic status and outcomes., Results: Among 13 682 patients, 3151 (23%) were prediabetic, and 5834 (42.6%) were diabetic. MACCE risk was significantly higher for diabetic versus normoglycemic (adjusted hazard ratio [aHR]: 1.22, 95% confidence interval [CI]: 1.06-1.41), but nonsignificantly higher for prediabetic versus normoglycemic (aHR: 0.95, 95% CI: 0.78-1.10). All-cause mortality risk was significantly higher in diabetic versus normoglycemic (aHR: 1.42, 95% CI: 1.08-1.86), but nonsignificantly higher for prediabetic versus normoglycemic (aHR: 1.15, 95% CI: 0.84-1.59). Among other components of MACCE, only coronary artery bypass grafting was significantly higher in diabetic patients, and not prediabetic, compared with normoglycemic., Conclusions: Prediabetic ACS patients undergoing PCI, unlike diabetics, are not at increased risk of MACCE and all-cause mortality. While prediabetic patients could be regarded as having the same risk as nondiabetics, careful consideration to provide more intensive pre- and post-PCI care in diabetic patients is mandatory., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

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., (© 2024. The Author(s).)

Metabolic syndrome (MetS) poses an additional risk for the development of coronary artery disease and major adverse cardiac and cerebrovascular events (MACCE). In this study, we investigated the association between MetS and its components and MACCE after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). The presence of MetS was calculated at baseline using the NCEP-ATP III criteria. The primary outcome was MACCE and its components were secondary outcomes. Unadjusted and adjusted Cox Regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) of the association between MetS or its components and MACCE and its components. A total of 13,459 ACS patients who underwent PCI (MetS: 7939 and non-MetS: 5520) with a mean age of 62.7 ± 11.0 years (male: 72.5%) were included and median follow-up time was 378 days. Patients with MetS had significantly higher MACCE risk (adjusted HR [aHR] 1.22, 95% CI 1.08-1.39). The only component of MACCE that exhibited a significantly higher incidence in MetS patients was myocardial infarction (aHR 1.43, 95% CI 1.15-1.76). MetS components that were significantly associated with a higher incidence of MACCE were hypertension and impaired fasting glucose. Having three MetS components did not increase MACCE (aHR 1.12, 95% CI 0.96-1.30) while having four (aHR 1.32, 95% CI 1.13-1.55) or five (aHR 1.42, 95% CI 1.15-1.75) MetS components was associated with a higher incidence of MACCE. MetS was associated with a higher risk of MACCE in ACS patients undergoing PCI. Among MACCE components, myocardial infarction was significantly higher in patients with MetS. Impaired fasting glucose and hypertension were associated with a higher risk of MACCE. Identifying these patterns can guide clinicians in choosing appropriate preventive measures., (© 2024. The Author(s).)

Background: Acute ST-elevation myocardial infarction (STEMI) is a leading cause of mortality and morbidity worldwide, and primary percutaneous coronary intervention (PCI) is the preferred treatment option., Hypothesis: Machine learning (ML) models have the potential to predict adverse clinical outcomes in STEMI patients treated with primary PCI. However, the comparative performance of different ML models for this purpose is unclear., Methods: This study used a retrospective registry-based design to recruit consecutive hospitalized patients diagnosed with acute STEMI and treated with primary PCI from 2011 to 2019, at Tehran Heart Center, Tehran, Iran. Four ML models, namely Gradient Boosting Machine (GBM), Distributed Random Forest (DRF), Logistic Regression (LR), and Deep Learning (DL), were used to predict major adverse cardiovascular events (MACE) during 1-year follow-up., Results: A total of 4514 patients (3498 men and 1016 women) were enrolled, with MACE occurring in 610 (13.5%) subjects during follow-up. The mean age of the population was 62.1 years, and the MACE group was significantly older than the non-MACE group (66.2 vs. 61.5 years, p < .001). The learning process utilized 70% (n = 3160) of the total population, and the remaining 30% (n = 1354) served as the testing data set. DRF and GBM models demonstrated the best performance in predicting MACE, with an area under the curve of 0.92 and 0.91, respectively., Conclusion: ML-based models, such as DRF and GBM, can effectively identify high-risk STEMI patients for adverse events during follow-up. These models can be useful for personalized treatment strategies, ultimately improving clinical outcomes and reducing the burden of disease., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: The prevalence of acute coronary syndrome (ACS) among young adults (premature ACS) has dramatically increased in recent years, especially in developing countries. Yet, the data on these patients' attributed risk factors and outcomes are inconsistent. In this study, we aimed to investigate these data in a cohort of premature ACS cases who underwent percutaneous coronary intervention (PCI) compared to older patients., Hypothesis: We hypothesize that premature ACS patients undergoing PCI will exhibit different risk factor profiles and outcomes compared to non-premature patients. specifically, we anticipate that premature patients do not necessarily have better outcomes than non-premature., Methods: Overall, 3142 and 10 399 patients were included in premature and non-premature groups, respectively. Patients' pre-operative, post-operative, and follow-up data were retrieved retrospectively from the Tehran Heart Center PCI databank., Results: The mean age of premature and non-premature cohorts was 48.39 and 67 years, respectively. Patients were predominantly male in both groups. Family history of coronary artery disease (CAD), dyslipidemia, smoking, and opium addiction were more prevalent among the younger cohort. After adjustment, in-hospital mortality in younger patients was considerably higher, with all-cause mortality and major cardiovascular and cerebrovascular events (MACCE) exhibiting no noticeable difference among the two groups., Conclusions: Risk factor profile is different in young patients, and traditional cardiovascular risk factors, such as hypertension and diabetes mellitus, are more prevalent among older adults. Younger age is not equivalent to a better prognosis; hence, similar or even more caution should be taken into consideration regarding secondary prevention for these patients., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: The no-reflow (NRF) phenomenon is the "Achilles heel" of interventionists after performing percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). No definitive treatment has been proposed for NRF, and preventive strategies are central to improving care for patients who develop NRF., Objectives: In this study, we aim to investigate the clinical prediction models developed to predict NRF in STEMI patients undergoing primary PCI., Design: Systematic review., Data Sources and Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were observed. Studies that developed clinical prediction modeling for NRF after primary PCI in STEMI patients were included. Data extraction was performed using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS) checklist. The Prediction Model Risk of Bias Assessment Tool (PROBAST) tool was used for critical appraisal of the included studies., Results: The three most common predictors were age, total ischemic time, and preoperative thrombolysis in myocardial infarction flow grade. Most of the included studies internally validated their developed model via various methods: random split, bootstrapping, and cross-validation. Only three studies (18%) externally validated their model. Six studies (37%) reported a calibration plot with or without the Hosmer-Lemeshow test. The reported area under the curve ranged from 0.648 to 0.925. The most common biases were in the statistical domain., Conclusion: Clinical prediction models aid in individualizing care for STEMI patients with NRF after primary PCI. Of the 16 included studies, we report four to have a low risk of bias and low concern with regard to our research question, which should undergo external validation with or without updating in future studies.

Aim: A considerable proportion of patients admitted with acute coronary syndrome (ACS) have no standard modifiable cardiovascular risk factors (SMuRFs: hypertension, diabetes mellitus, dyslipidemia, and cigarette smoking). The outcomes of this population following percutaneous coronary intervention (PCI) are debated. Further, sex differences within this population have yet to be established., Methods: This retrospective cohort study included 7,847 patients with ACS who underwent PCI. The study outcomes were in-hospital mortality, all-cause mortality, and major adverse cardio-cerebrovascular events (MACCE). The association between the absence of SMuRFs (SMuRF-less status) and outcomes among all the patients and each sex was assessed using logistic and Cox proportional hazard regressions., Results: Approximately 11% of the study population had none of the SMuRFs. During 12.13 [11.99-12.36] months of follow-up, in-hospital mortality (adjusted-odds ratio (OR):1.51, 95%confidence interval (CI): 0.91-2.65, P :0.108), all-cause mortality [adjusted-hazard ratio (HR): 1.01, 95%CI: 0.88-1.46, P : 0.731], and MACCE (adjusted-HR: 0.93, 95%CI:0.81-1.12, P : 0.412) did not differ between patients with and without SMuRFs. Sex-stratified analyses recapitulated similar outcomes between SMuRF+ and SMuRF-less men. In contrast, SMuRF-less women had significantly higher in-hospital (adjusted-OR: 3.28, 95%CI: 1.92-6.21, P  < 0.001) and all-cause mortality (adjusted-HR:1.41, 95%CI: 1.02-3.21, P : 0.008) than SMuRF+ women., Conclusions: Almost one in 10 patients with ACS who underwent PCI had no SMuRFs. The absence of SMuRFs did not confer any benefit in terms of in-hospital mortality, one-year mortality, and MACCE. Even worse, SMuRF-less women paradoxically had an excessive risk of in-hospital and one-year mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Sheikhy, Fallahzadeh, Jameie, Aein, Masoudkabir, Maghsoudi, Tajdini, Salarifar, Jenab, Pourhosseini, Mehrani, Alidoosti, Vasheghani-Farahani and Hosseini.)

Introduction: With the current high burden on the healthcare system and limited resources, the efficient utilization of facilities is of utmost importance. We sought to present the practice guideline used at a high prevalence tertiary cardiology center and compare its safety and efficacy performance with the single high-sensitivity cardiac troponin T strategy, conventional and modified HEART score., Methods: In this prospective cohort study, consecutive patients presenting to the emergency department with chest pain or an angina equivalent were recruited. The primary endpoints consisted of major adverse cardiac events at index visits and 30-day follow-up. Patients were managed according to the practice guideline, and sensitivity and negative predictive values were compared., Results: Of the total 1548 patients, the mean age was 50.4 ± 15.7 years. Ninety-nine (10.9%) patients were admitted at the index visit, and 89 patients were consequently diagnosed with acute coronary symptoms. Six (0.007%) patients experienced major adverse cardiac events within the 30-day follow-up among discharged patients. Among 911 patients with at least 1 troponin, using single high-sensitivity cardiac troponin T, HEART score, and modified HEART score would have further admitted 805, 450, and 609 patients, respectively. The negative predictive value for all 4 algorithms did not significantly differ (99.2% vs. 100% vs. 99.3% vs. 99.6%, respectively)., Conclusions: The Tehran Herat Center protocol was a relatively safe protocol with high efficacy. Despite the high safety of the other diagnostic pathways, the high volume of patients needing additional evaluation could impose a high burden on the health care system., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To assess the cost-effectiveness of sacubitril/valsartan compared with enalapril in patients with heart failure with reduced ejection (HFrEF)., Methods: A systematic literature search was conducted searching in major electronic databases from inception to January 1, 2021. All relevant full economic evaluation studies of sacubitril/valsartan versus enalapril for the treatment of patients with HFrEF were identified using ad hoc search strategies. Mortality, hospital admissions, quality-adjusted life years (QALYs), life-years (LYQs), annual drug costs, total lifetime costs, and incremental cost-effectiveness ratio (ICER) were considered as the outcomes. The quality of the included studies was assessed using the CHEERS checklist. This study was conducted and reported in accordance with the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines., Results: The initial search yielded a pool of 1026 articles, of which 703 unique articles were screened, 65 full-text articles were assessed for eligibility and 15 studies finally included in the qualitative synthesis. Studies show that sacubitril/valsartan reduces mortality and hospitalization rate. The mean of death risk ratio and hospitalization were computed at 0.843 and 0.844, respectively. Sacubitril/valsartan produced higher annual and total lifetime costs. The lowest and highest lifetime costs for sacubitril/valsartan were found in Thailand ($4,756) and Germany ($118,815), respectively. The lowest ICER was reported in Thailand ($4857/QALY) and the highest in the USA ($143,891/QALY)., Conclusion: Sacubitril/valsartan is associated with better outcomes and may be cost-effective compared to enalapril for the management of HFrEF. However, in developing countries such as Thailand, sacubitril-valsartan costs must be reduced to yield an ICER below the threshold., (Copyright © 2022 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Understanding bacterial communication mechanisms is imperative to improve our current understanding of bacterial infectivity and find alternatives to current modes of antibacterial therapeutics. Both Gram-positive and Gram-negative bacteria use quorum sensing (QS) to regulate group behaviours and associated phenotypes in a cell-density-dependent manner. Group behaviours, phenotypic expression and resultant infection and disease can largely be attributed to efficient bacterial communication. Of particular interest are the communication mechanisms of Gram-positive bacteria known as streptococci. This group has demonstrated marked resistance to traditional antibiotic treatment, resulting in increased morbidity and mortality of infected hosts and an ever-increasing burden on the healthcare system. Modulating circuits and mechanisms involved in streptococcal communication has proven to be a promising anti-virulence therapeutic approach that allows managing bacterial phenotypic response but does not affect bacterial viability. Targeting the chemical signals bacteria use for communication is a promising starting point, as manipulation of these signals can dramatically affect resultant bacterial phenotypes, minimizing associated morbidity and mortality. This review will focus on the use of modified peptide signals in modulating the development of proliferative phenotypes in different streptococcal species, specifically regarding how such modification can attenuate bacterial infectivity and aid in developing future alternative therapeutic agents.

Background: Recent research suggests a protective role for positive family history of premature cardiovascular disease (FHpCVD) in patients undergoing coronary artery bypass grafting. We aimed to further investigate this unlikely association., Methods: In this registry-based cohort study, patients who underwent first-time non-emergent coronary bypass surgery at Tehran Heart Center between 2007 and 2016 were included. Patients with and without FHpCVD were compared in terms of all-cause mortality and first non-fatal cardiovascular events (CVEs) comprising non-fatal acute coronary syndrome, non-fatal stroke or transient ischemic attack, and repeat coronary revascularization., Results: A total of 13,156 patients were included (mean age 60.83 ± 9.57, 74.5% male), among which 2684 (20.4%) patients had FHpCVD. Median follow-up was 77.7 months. FHpCVD was weakly associated with reduced all-cause mortality using inverse probability weight (IPW) method (hazard ratio [HR] = 0.853; 95% confidence interval [CI] 0.730-0.997; P = 0.046), and not associated with non-fatal CVEs considering death as the competing event (sub-distribution HR [SHR] = 1.124; 95% CI 0.999-1.265; P = 0.053). Within a subgroup of patients without previous myocardial infarction or revascularization (7403 cases; 56.3%), FHpCVD was associated with lower mortality (HR = 0.700; 95% CI 0.548-0.894; P = 0.004) and higher non-fatal CVEs (SHR = 1.197; 95% CI 1.019-1.405; P = 0.028), whereas among patients with previous coronary events, there was no association between FHpCVD and outcomes., Conclusions: FHpCVD was associated with lower all-cause mortality but higher non-fatal CVEs, especially in those without prior coronary events. Such discordance calls for caution in assuming a protective role for FHpCVD. The prognostic significance of FHpCVD needs further evaluation among surgical patients., (© 2022. The Author(s).)

Background: Coronary artery disease (CAD) is a universal public health challenge, more prominently so in the low- and middle-income countries. In this study, we aimed to determine prevalence and trends of CAD risk factors in patients with documented CAD and to determine their effects on the age of CAD diagnosis., Materials and Methods: We conducted a registry-based, serial cross-sectional study using the coronary angiography data bank of the Tehran Heart Center. Adult patients who had obstructive (> 50% stenosis) CAD were included in the study. The prevalence and 11-year trends of conventional CAD risk factors were analyzed by sex and age, and their adjusted effects on the age of CAD diagnosis were calculated., Results: From January 2005 to December 2015, data for 90,094 patients were included in this analysis. A total of 61,684 (68.5%) were men and 28,410 (31.5%) were women. Men were younger at diagnosis than women, with a mean age of 60.1 in men and 63.2 in women (p < 0.001), and had fewer risk factors at the time of diagnosis. Mean age at diagnosis had an overall increasing trend during the study period. Increasing trend was seen in body-mass index, hypertension prevalence, diabetes mellitus. All lipid profile components (total cholesterol, low-density lipoprotein cholesterol, triglycerides, and high-density lipoprotein cholesterol) decreased over time. Of particular interest, opium consumption was associated with 2.2 year earlier age of CAD diagnosis., Conclusion: The major results of this study (lower age of CAD diagnosis in men, lower age of diagnosis associated with most risk factors, and lower prevalence of serum lipids over time) were expected. A prominent finding of this study is confirming opium use was associated with a much younger age of CAD onset, even after adjusting for all other risk factors. In addition to recommendations for control of the traditional risk factors, spreading information about the potential adverse effect of opium use, which has only recently been associated with higher risk of CAD, may be necessary., (© 2021. The Author(s).)

Although the findings of some studies have been indicative of the direct relationship between the severity of clinical findings and imaging, reports have been published regarding inconsistency of clinical findings with imaging and laboratory evidence. Physicians treating these patients frequently report cases in which patients, sometimes in the recovery phase and despite improvements in imaging indices, suddenly deteriorate and in some instances suddenly expire. This letter aimed to draw attention to the role of pulmonary thromboembolism as a potential and possible cause of clinical deterioration in covid-19 patients.

Objective: A permanent pacemaker (PPM) is necessary for patients with a symptomatic third-degree or advanced second-degree atrioventricular (AV) block. An AV block due to medication use can often be reversed; however, subsequent relapse can occur and necessitate subsequent PPM implantation. The aim of this study was to explore the course and prognosis of patients with an AV block., Methods: This historical cohort study was conducted between January 2013 and June 2018. A total of 1900 patient records were analyzed and 1123 subjects with an AV block on admission were enrolled. The patients were categorized into 2 groups: Group 1 comprised patients with an AV block due to medication use (n=316, 28%) and Group 2 included patients with an AV block caused by other etiologies (n=807, 72%). Data of the cause of AV block, recurrence, and PPM implantation were analyzed. Patients in both groups who did not require a PPM during the index admission were followed up regarding subsequent implantation of a PPM., Results: AV conduction was recovered in 38 (12%) patients in Group 1 and 48 (6%) patients in Group 2 during the index hospitalization. However, recurrence of the AV block was observed in 18% of Group 1 patients and 40% of Group 2 patients. Only 25 patients in each group (4.5% of the whole study population) remained PPM-free during a median 3-year follow-up period., Conclusion: The study findings suggest that drug-induced AV blocks may not be as benign as previously thought. The high relapse rate indicates that watchful follow-up may be required despite discontinuation of the responsible medication and that consideration of earlier PPM implantation in cases of early recurrence may be warranted.

The adult myocardium has a limited regenerative capacity following heart injury, and the lost cells are primarily replaced by fibrotic scar tissue. Suboptimal efficiency of current clinical therapies to resurrect the infarcted heart results in injured heart enlargement and remodeling to maintain its physiological functions. These remodeling processes ultimately leads to ischemic cardiomyopathy and heart failure (HF). Recent therapeutic approaches (e.g., regenerative and nanomedicine) have shown promise to prevent HF postmyocardial infarction in animal models. However, these preclinical, clinical, and technological advancements have yet to yield substantial enhancements in the survival rate and quality of life of patients with severe ischemic injuries. This could be attributed largely to the considerable gap in knowledge between clinicians and nanobioengineers. Development of highly effective cardiac regenerative therapies requires connecting and coordinating multiple fields, including cardiology, cellular and molecular biology, biochemistry and chemistry, and mechanical and materials sciences, among others. This review is particularly intended to bridge the knowledge gap between cardiologists and regenerative nanomedicine experts. Establishing this multidisciplinary knowledge base may help pave the way for developing novel, safer, and more effective approaches that will enable the medical community to reduce morbidity and mortality in HF patients.

Background: Non-atherosclerotic spontaneous coronary artery dissection (SCAD) is a rare disease that predominantly affects women. It presents with acute chest pain, ventricular arrhythmias, and even sudden cardiac death., Case Summary: A 33-year-old man presented to emergency department with fatigue and cold sweat. He had no complaint of chest pain at the time of admission. He experienced a retrosternal chest pain 2 days ago after lifting a 30 pounds weight in the gym. Para-clinic results such as coronary computed tomography angiography and electrocardiogram were normal. However, coronary angiography showed multiple coronary dissections. We followed the patient for 4 months. He was asymptomatic except for one episode of chest pain during Tehran earthquake, while he was carrying his child to escape the room. Follow-up myocardial perfusion scan was negative for ischaemia., Discussion: Stressors such as intense exercise, emotional stress, and Valsalva manoeuvre may cause SCAD in otherwise healthy patient. As in our case, lifting heavy weights was the most likely reason for SCAD. Stable patients without ongoing chest pain will be followed conservatively.

Distinguishing ST-elevation myocardial infarction (STEMI) differential diagnoses is more challenging. Myopericarditis is one of these differentials that results from viral involvement of myocardium and pericardium of the heart. Myopericarditis in focal form can mimic acute STEMI in its electrocardiogram (ECG) features and elevated cardiac enzymes. Myocarditis patients may face thrombolytic related complications such as intracranial bleeding, myocardial rupture, and hemorrhagic cardiac tamponade. Furthermore, re-administration of streptokinase (a common thrombolytic agent in our country) is banned for at least six months of previous administration; however, it can save patients' lives in emergency conditions such as massive pulmonary embolism. It seems that, when dealing with a young patient presenting to emergency department with acute chest pain and ST segment elevation on ECG, we should consider focal myocarditis as an important but rare differential diagnosis of STEMI. In this report, we describe three cases of focal myocarditis, primarily misdiagnosed as STEMI.

Background: Brucellosis is the most common zoonotic infection in the world. Several antibiotics, separately or in combination, have been tried for treatment of human brucellosis. The inconsistencies between different treatment regimens warrants the need for a systematic review to inform clinical practice and future research., Objectives: To evaluate the effects of various antibiotic regimens, monotherapy or in combination with other antibiotics, for treating human brucellosis., Search Methods: We searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS until May 2012. We browsed the abstract books of several international infectious diseases conferences. We also checked the reference lists of all studies identified, Selection Criteria: We included the randomized controlled trials on the pharmaceutical interventions in treatment of acute, chronic, non-complicated, and complicated human brucellosis. The outcomes of interest were relapse, persistence of symptoms at the end of treatment, and adverse drug effects., Data Collection and Analysis: Two authors independently assessed the studies for inclusion, risk of bias, and extracted relevant data using pre-designed extraction forms. The findings of homogenous studies were pooled using fixed-effect meta-analysis., Main Results: In total we included 25 studies comparing various antibiotic regimens. Methods of allocation and concealment were inadequately described in half the studies, and only three were blinded. In comparisons of doxycycline plus rifampicin versus doxycycline plus streptomycin we found eight studies with 694 participants. For treatment failure, the doxycycline plus rifampicin regimen was less effective (risk ratio (RR) 1.91, 95% confidence interval (CI) 1.07 to 3.42, seven studies, 567 participants), relapse (RR 2.39, 95% CI 1.17 to 4.86), and minor adverse drug reactions (RR 1.38, 95% CI 0.99 to 1.92). In comparisons of doxycycline plus rifampicin against quinolone (ciprofloxacin or ofloxacin) plus rifampicin we found five studies of 336 participants. The pooled analysis did not demonstrate any significant difference between two regimens in terms of relapse and symptom persistence, but showed a non-significant higher risk of minor adverse reactions in doxycycline plus rifampicin (RR 1.80, 95% CI 0.78 to 4.18). Other comparisons were reported in a few heterogenous studies, and the pooled analyses, where applied, did not show any significant difference., Authors' Conclusions: Doxycycline (six weeks) plus streptomycin (two or three weeks) regimen is more effective regimen than doxycycline plus rifampicin (six weeks) regimen. Since it needs daily intramuscular (IM) injection, access to care and cost are important factors in deciding between two choices. Quinolone plus rifampicin (six weeks) regimen is slightly better tolerated than doxycycline plus rifampicin, and low quality evidence did not show any difference in overall effectiveness.

The aim of this research was to study the application and effectiveness of Enzyme Linked Immuno Receptor Assay (ELIRA) method for understanding the bioactivity of human Growth Hormone (hGH) in micro-titer plates. For this purpose, rabbit hepatocyte microsomes which contained hGH receptors were used for coating of ELISA micro-titer plates. Then hGH was interacted with coated receptors. Fractions of bounded complexes were identified by antibodies in an Enzyme-based substrate detection system. Different assay conditions such as: buffers, blocking agents, temperatures and times of incubation were analyzed. Our result indicated that, the carbonate coating buffer was not effective in receptor coating in ELIRA. Overnight incubation of hGH and hGH receptors in HEPES assay buffer and BSA blocking resulted in the lower linearity and correlations (R(2) = 0.46 to 0.85). However, 3 h incubation in Tris-HCl assay buffer at 30°C resulted in higher linearity and correlations (R(2) = 0.95 to 0.97). Finally, the coating of microwells by 250 μg/ml of microsome membranes in Tris buffer at 30°C for 3 hr and blocking by skim milk resulted to the best linearity and higher correlation, (R(2) = 0.985) and lower detection limit about 2 ng/ml of bioactive hGH.