Sex-based association between high-density lipoprotein cholesterol and adverse outcomes after coronary artery bypass grafting.

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.

Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications.

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

Developmental or Procedural Vena Cava Interruption and Venous Thromboembolism: A Review.

The inferior vena cava (IVC) and superior vena cava are the main conduits of the systemic venous circulation into the right atrium. Developmental or procedural interruptions of vena cava might predispose to stasis and deep vein thrombosis (DVT) distal to the anomaly and may impact the subsequent rate of pulmonary embolism (PE). This study aimed to review the various etiologies of developmental or procedural vena cava interruption and their impact on venous thromboembolism. A systematic search was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines per each clinical question. For management questions with no high-quality evidence and no mutual agreements between authors, Delphi methods were used. IVC agenesis is the most common form of congenital vena cava interruption, is associated with an increased risk of DVT, and should be suspected in young patients with unexpected extensive bilateral DVT. Surgical techniques for vena cava interruption (ligation, clipping, and plication) to prevent PE have been largely abandoned due to short-term procedural risks and long-term complications, although survivors of prior procedures are occasionally encountered. Vena cava filters are now the most commonly used method of procedural interruption, frequently placed in the infrarenal IVC. The most agreed-upon indication for vena cava filters is for patients with acute venous thromboembolism and coexisting contraindications to anticoagulation. Familiarity with different forms of vena cava interruption and their local and systemic adverse effects is important to minimize complications and thrombotic events.

Association of seizure with COVID-19 vaccines in persons with epilepsy: A systematic review and meta-analysis.

Seizure aggravation following coronavirus disease 2019 (COVID-19) vaccines is a major cause behind vaccine hesitancy among persons with epilepsy (PwE), resulting in lower immunization rates. We systematically reviewed seizure-activity-related events in PwE following COVID-19 vaccination. We systematically searched PubMed, Web of Science, Scopus, and Cochrane Library, until January 31, 2023, and included articles reporting seizure activity-related events in PwE receiving COVID-19 vaccination. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. The protocol was registered with PROSPERO (CRD42022312475). Outcomes included pooled incidence proportions of (a) increased seizure frequency, (b) status epilepticus (SE), and (c) change in seizure type. Of the 2207 studies, 16 entered the meta-analysis. The pooled incidence proportion of increased seizure frequency (16 studies-3245 PwE) was 5% (95% CI: 3%-7%, I2 = 52%). Regarding increased seizure frequency, no significant difference was observed between mRNA and viral vector (OR: 1.11, 95% CI: 0.49-2.52, I2 = 0%), and between mRNA and inactivated virus (OR: 1.60, 95% CI: 0.27-9.37; I2 = 0%). The pooled incidence proportion of SE (15 studies-2387 PwE) was 0.08% (95% CI: 0.02%-0.33%, I2 = 0%). Ultimately, the pooled incidence proportion of change in seizure type (7 studies-1172 PwE) was 1% (95% CI: 1%-2%, I2 = 0%). The meta-analysis revealed post-COVID-19-vaccination increased seizure frequency in 5% of PwE, with no difference between mRNA and viral vector or inactivated virus vaccines. Furthermore, we found 0.08% and 1% incidence proportions for postvaccination SE and change in seizure type, respectively. While noteworthy, these values are far less than reports for COVID-19 infection, emphasizing vaccination importance in preventing COVID-19 consequences in PwE.

Patterns of better breast cancer care in countries with higher human development index and healthcare expenditure: Insights from GLOBOCAN 2020.

Background: The huge burden of breast cancer (BC) necessitates the profound and accurate knowledge of the most recent cancer epidemiology and quality of care provided. We aimed to evaluate BC epidemiology and quality of care and examine the effects of socioeconomic development and healthcare expenditure on disparities in BC care. Methods: The results from the GLOBOCAN 2020 study were utilized to extract data on female BC, including incidence and mortality numbers, crude rates, and age-standardized rates [age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs)]. The mortality-to-incidence ratio (MIR) was calculated for different locations and socioeconomic stratifications to examine disparities in BC care, with higher values reflecting poor quality of care and vice versa. In both descriptive and analytic approaches, the human development index (HDI) and the proportion of current healthcare expenditure (CHE) to gross domestic product (CHE/GDP%) were used to evaluate the values of MIR. Results: Globally, 2,261,419 (95% uncertainty interval (UI): 2,244,260-2,278,710) new cases of female BC were diagnosed in 2020, with a crude rate of 58.5/100,000 population, and caused 684,996 (675,493-694,633) deaths, with a crude rate of 17.7. The WHO region with the highest BC ASIR (69.7) was Europe, and the WHO region with the highest ASMR (19.1) was Africa. The very high HDI category had the highest BC ASIR (75.6), and low HDI areas had the highest ASMR (20.1). The overall calculated value of female BC MIR in 2020 was 0.30, with Africa having the highest value (0.48) and the low HDI category (0.53). A strong statistically significant inverse correlation was observed between the MIR and HDI values for countries/territories (Pearson's coefficient = -0.850, p-value < 0.001). A significant moderate inverse correlation was observed between the MIR and CHE/GDP values (Pearson's coefficient = -0.431, p-value < 0.001). Conclusions: This study highlighted that MIR of BC was higher in less developed areas and less wealthy countries. MIR as an indicator of the quality of care showed that locations with higher healthcare expenditure had better BC care. More focused interventions in developing regions and in those with limited resources are needed to alleviate the burden of BC and resolve disparities in BC care.

Low bone mineral density, a neglected condition in North Africa and Middle East: estimates from the Global Burden of Disease Study, 1990-2019.

Due to the high prevalence of low bone mineral density in North Africa and Middle East region, estimating its attributable burden would help to a better understanding of this neglected condition for policymakers and health researchers. This study presented the number of attributable deaths has doubled from 1990 to 2019. PURPOSE: This study provides the latest estimates of the burden of low bone mineral density (BMD) from 1990 to 2019 in North Africa and Middle East (NAME) region. METHODS: The data were extracted from the global burden of disease (GBD) 2019 study to estimate epidemiological indices such as deaths, disability-adjusted life years (DALYs), and summary exposure value (SEV). SEV is a measure of the exposure of the population to a risk factor that considers the amount of exposure by the level of risk. RESULTS: Our findings showed that in 1990-2019, the number of deaths and DALYs attributable to low BMD had almost doubled in the region and caused 20,371 (95% uncertainty intervals: 14,848-24,374) deaths and 805,959 (630,238-959,581) DALYs in 2019. However, DALYs and death rates showed a decreasing trend after age standardization. Saudi Arabia had the highest, and Lebanon had the lowest age-standardized DALYs rates in 2019, with rates of 434.2 (329.6-534.3) and 90.3 (70.6-112.1) per 100,000, respectively. The highest burden attributable to low BMD was in the 90-94 and over 95 age groups. Also, there was a decreasing trend in age-standardized SEV to low BMD for both sexes. CONCLUSION: Despite the decreasing trend of age-standardized burden indices, considerable amounts of deaths and DALYs were attributable to low BMD, especially in the elderly population, in the region in 2019. As the positive effects of proper interventions will be detectable in the long term, robust strategies and comprehensive stable policies are the ultimate solutions to achieving desired goals.

Diagnostic models for the detection of intrauterine growth restriction and placental insufficiency severity based on magnetic resonance imaging of the placenta.

Purpose: We aimed to provide diagnostic models based on different parameters of placental magnetic resonance imaging (MRI) to detect intrauterine growth restriction (IUGR), as well as the severity of placental insufficiency. Material and methods: We included 44 foetuses with appropriate weight for gestational age (AGA) and 46 foetuses with documented IUGR, defined as the estimated foetal weight (EFW) below the 10th centile. Using Doppler ultrasound, IUGR cases were divided into 2 groups: 1) IUGR with severity signs: EFW < 3rd centile, or cerebroplacental ratio < 5th centile, or abnormal umbilical/uterine artery pulsatility index; and 2) non-severe IUGR without any of this criterion. For all these participants, placental MRI was performed in the third gestational trimester, and its parameters were compared between AGA and IUGR, as well as between the severe and non-severe IUGR groups. Two diagnostic models consisting of significant predictors were developed, and their performance was investigated with accuracy metrics. Results: The severity signs were detected in 25 (54.3%) IUGR cases. The diagnostic model for the differentiation of IUGR from AGA revealed an acceptable performance (area under the curve [AUC] of 0.749) and consisted of 2 variables: 1) the largest size of infarct ≥ 25 mm (odds ratio [OR] = 5.01, p = 0.001), and 2) thickness : volume ratio ≥ 0.043 (OR = 3.76, p = 0.027); while, the logistic regression model for detection of the severity signs was even better, with AUC = 0.862, and comprised of 2 predictors: 1) placental infarct percent ≥ 10% (OR = 26.73, p = 0.004), and 2) placental globular shape (OR = 5.40, p = 0.034). Conclusions: Placental MRI parameters can differentiate IUGR from AGA, and more precisely, assess the severity of placental insufficiency in IUGR foetuses.

Diffusion-weighted imaging (DWI) in diagnosis, staging, and treatment response assessment of multiple myeloma: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the role of diffusion-weighted imaging (DWI) in the initial diagnosis, staging, and assessment of treatment response in patients with multiple myeloma (MM). MATERIALS AND METHODS: A systematic literature review was conducted in PubMed, the Cochrane Library, EMBASE, Scopus, and Web of Science databases. The primary endpoints were defined as the diagnostic performance of DWI for disease detection, staging of MM, and assessing response to treatment in these patients. RESULTS: Of 5881 initially reviewed publications, 33 were included in the final qualitative and quantitative meta-analysis. The diagnostic performance of DWI in the detection of patients with MM revealed pooled sensitivity and specificity of 86% (95% CI: 84-89) and 63% (95% CI: 56-70), respectively, with a diagnostic odds ratio (OR) of 14.98 (95% CI: 4.24-52.91). The pooled risk difference of 0.19 (95% CI: - 0.04-0.42) was reported in favor of upstaging with DWI compared to conventional MRI (P value = 0.1). Treatment response evaluation and ADCmean value changes across different studies showed sensitivity and specificity of approximately 78% (95% CI: 72-83) and 73% (95% CI: 61-83), respectively, with a diagnostic OR of 7.21 in distinguishing responders from non-responders. CONCLUSIONS: DWI is not only a promising tool for the diagnosis of MM, but it is also useful in the initial staging and re-staging of the disease and treatment response assessment. This can aid clinicians with earlier initiation or change in treatment strategy, which could have prognostic significance for patients.

Meta-Analysis on the Association Between Nutritional Status and Outcomes After Transcatheter Aortic Valve Implantation.

Malnutrition is a common co-morbidity among candidates for transcatheter aortic valve implantation (TAVI). This study aimed to investigate the association between nutritional status determined by objective nutritional indices and outcomes of patients who underwent TAVI. We systematically searched PubMed, Embase, Web of Science, Scopus, and Cochrane Library from inception until April 18, 2022 to identify studies examining the association of preprocedural nutritional status with post-TAVI outcomes. Malnutrition was defined by objective nutritional indices-controlling nutritional index, nutritional risk index, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI). The primary end point was 1-year all-cause mortality. The review included 13 observational studies and 6,785 patients who underwent TAVI. Malnutrition was associated with a higher risk of 1-year all-cause mortality, as defined by either the controlling nutritional index (hazard ratio [HR] 2.70, 95% confidence interval [CI] 1.21 to 6.03, p = 0.015), GNRI (HR 1.79, 95% CI 1.09 to 2.93, p = 0.021), or PNI (HR 1.17, 95% CI 1.11 to 1.23, p <0.001). In the meta-analysis of adjusted results, lower GNRI was independently associated with higher 1-year mortality (HR 1.70, 95% CI 1.16 to 2.50, p = 0.006). Lower GNRI was associated with increased risk of acute kidney injury (relative risk [RR] 2.21, 95% CI 1.63 to 2.99, p <0.001) and 1-year cardiovascular mortality (RR 2.50, 95% CI 1.66 to 3.78, p <0.001). Lower PNI was associated with a higher risk of major vascular complications (RR 2.99, 95% CI 1.38 to 6.51, p = 0.006). In conclusion, baseline malnutrition, as assessed by objective indices, is associated with worse outcomes after TAVI. Future studies should focus on the value of nutritional assessment and interventions to improve nutritional status in patients who underwent TAVI.

Evaluation of the Practice Guideline Used for Rule-Out of Myocardial Infarction at a Tertiary Cardiology Center.

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.

Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High-risk Pulmonary Embolism: The CANARY Randomized Clinical Trial.

Importance: The optimal treatment of intermediate-high-risk pulmonary embolism (PE) remains unknown. Objective: To assess the effect of conventional catheter-directed thrombolysis (cCDT) plus anticoagulation vs anticoagulation monotherapy in improving echocardiographic measures of right ventricle (RV) to left ventricle (LV) ratio in acute intermediate-high-risk PE. Design, Setting, and Participants: The Catheter-Directed Thrombolysis vs Anticoagulation in Patients with Acute Intermediate-High-Risk Pulmonary Embolism (CANARY) trial was an open-label, randomized clinical trial of patients with intermediate-high-risk PE, conducted in 2 large cardiovascular centers in Tehran, Iran, between December 22, 2018, through February 2, 2020. Interventions: Patients were randomly assigned to cCDT (alteplase, 0.5 mg/catheter/h for 24 hours) plus heparin vs anticoagulation monotherapy. Main Outcomes and Measures: The proportion of patients with a 3-month echocardiographic RV/LV ratio greater than 0.9, assessed by a core laboratory, was the primary outcome. The proportion of patients with an RV/LV ratio greater than 0.9 at 72 hours after randomization and the 3-month all-cause mortality were among secondary outcomes. Major bleeding (Bleeding Academic Research Consortium type 3 or 5) was the main safety outcome. A clinical events committee, masked to the treatment assignment, adjudicated clinical outcomes. Results: The study was prematurely stopped due to the COVID-19 pandemic after recruiting 94 patients (mean [SD] age, 58.4 [2.5] years; 27 women [29%]), of whom 85 patients completed the 3-month echocardiographic follow-up. Overall, 2 of 46 patients (4.3%) in the cCDT group and 5 of 39 patients (12.8%) in the anticoagulation monotherapy group met the primary outcome (odds ratio [OR], 0.31; 95% CI, 0.06-1.69; P = .24). The median (IQR) 3-month RV/LV ratio was significantly lower with cCDT (0.7 [0.6-0.7]) than with anticoagulation (0.8 [0.7-0.9); P = .01). An RV/LV ratio greater than 0.9 at 72 hours after randomization was observed in fewer patients treated with cCDT (13 of 48 [27.0%]) than anticoagulation (24 of 46 [52.1%]; OR, 0.34; 95% CI, 0.14-0.80; P = .01). Fewer patients assigned to cCDT experienced a 3-month composite of death or RV/LV greater than 0.9 (2 of 48 [4.3%] vs 8 of 46 [17.3%]; OR, 0.20; 95% CI, 0.04-1.03; P = .048). One case of nonfatal major gastrointestinal bleeding occurred in the cCDT group. Conclusions and Relevance: This prematurely terminated randomized clinical trial of patients with intermediate-high-risk PE was hypothesis-generating for improvement in some efficacy outcomes and acceptable rate of major bleeding for cCDT compared with anticoagulation monotherapy and provided support for a definitive clinical outcomes trial. Trial Registration: ClinicalTrials.gov Identifier: NCT05172115.

Circular RNAs as prognostic and diagnostic biomarkers in renal cell carcinoma.

BACKGROUND: Circular RNAs (circRNAs) play pivotal roles in proliferation, apoptosis, migration, and invasion of renal cell carcinoma (RCC) cells. This study is aimed to systematically summarize the current evidence regarding the clinical implications of circRNAs in RCC patients. METHODS: A systematic search in PubMed, Embase, and Web of Science was performed until January 1, 2022. The correlation between the expression of circRNAs and clinicopathological, prognostic, and diagnostic features of RCC was evaluated using the meta-analysis. RESULTS: Ultimately, 41 studies with 3485 RCC patients were included in this study: 26 studies for clinicopathological features, 31 studies for prognosis, and eight studies for diagnosis. Altered expression of circRNAs was significantly associated with clinicopathological characteristics of RCC, including tumor size, tumor stage, lymph node metastasis, distant metastasis, and TNM stage. The tumor promoter circRNAs were associated with reduced overall survival (OS) (Hazard Ratio (HR) = 1.98, 95% confidence interval [CI] 1.68-2.34) and disease/progression/recurrence-free survival (DFS/PFS/RFS) (HR = 2.34, 95% CI 1.85-2.97). Contrarily, the tumor suppressor circRNAs were linked with better OS (HR = 0.49, 95% CI 0.40-0.60) and DFS/PFS/RFS (HR = 0.40, 95% CI 0.28-0.59). The pooled sensitivity and specificity of circRNAs for RCC diagnosis in tissue samples were both 0.84. These results in fluid samples (serum and urine) were 0.78 and 0.69, respectively. CONCLUSION: CircRNAs can serve as promising diagnostic and prognostic biomarkers for RCC.

Circular RNA MYLK as a prognostic biomarker in patients with cancers: A systematic review and meta-analysis.

BACKGROUND: Circular RNA (circRNA) myosin light chain kinase (circMYLK) has recently received increasing attention in cancer biology. Several studies have suggested that circMYLK expression is linked to prognosis and clinicopathological characteristics of various malignancies. AIMS: This study was carried out to systematically review the impact of circMYLK on the progression of multiple cancers and assess the significance of circMYLK in the prognosis and clinicopathological features of the patients. METHODS: PubMed, Web of Science, and Embase were systematically searched until July 2, 2021. For qualitative synthesis, the signaling pathways of circMYLK in the progression of different cancers were summarized. Regarding the meta-analysis, overall survival (OS) and eight clinicopathological characteristics of patients with cancers were addressed. Odds ratios (ORs) and hazard ratios (HRs) were calculated to assess the association of circMYLK with prognostic and clinicopathological features. RESULTS: Twelve studies investigating the role of circMYLK in cancer progression met the inclusion criteria. Among these, seven studies investigated the prognostic significance of circMYLK, and nine studies ascertained the clinicopathological importance of circMYLK in patients with various malignancies. CircMYLK acts as a tumor promoter circRNA, leading to migration, proliferation, invasion, and metastasis of neoplastic cells and inhibiting their apoptosis through interaction with several miRNAs and corresponding downstream signaling pathways. Overexpression of circMYLK was correlated with poor OS (HR = 1.75; 95% confidence interval [CI] 1.52-2.02) and larger tumor size (OR = 2.90; 95% CI 1.03-8.15), higher T stage (OR = 2.49; 95% CI 1.20-5.18), lymph node metastasis (OR = 2.55; 95% CI 1.41-4.62), and higher TNM stage (OR = 4.62; 95% CI 2.99-7.14). CONCLUSIONS: CircMYLK is involved in the progression of numerous cancers via different signaling pathways. This circRNA can serve as a promising prognostic biomarker for several types of malignancies. Furthermore, high expression of circMYLK is associated with advanced clinicopathological characteristics in various tumors.

Hospitalization, major complications and mortality in acute myocardial infarction patients during the COVID-19 era: A systematic review and meta-analysis.

Since the SARS-CoV-2 pandemic began, numerous studies have reported a concerning drop in the number of acute myocardial infarction (AMI) admissions. In the present systematic review and meta-analysis, we aimed to compare the rate of AMI admissions and major complication during the pandemic, in comparison with pre-pandemic periods. Three major databases (PubMed, Scopus, and Web of Science Core Collection) were searched. Out of 314 articles, 41 were entered into the study. Patients hospitalized for AMI were 35% less in the COVID-19 era compared with pre-pandemic periods, which was statistically significantly (OR = 0.65; 95% CI: 0.56-0.74; I2 = 99%; p < 0.001; 28 studies). Patients hospitalized for STEMI and NSTEMI were 29% and 34% respectively less in the COVID-19 era compared with periods before COVID-19, which was statistically significantly (OR = 0.71; 95% CI: 0.65 -0.78; I2 = 93%; p < 0.001; 22 studies, OR = 0.66; 95% CI: 0.58-0.73; I2 = 95%; p < 0.001; 14 studies). The overall rate of in-hospital mortality in AMI patients increased by 26% in the COVID-19 era, which was not statistically significant (OR = 1.26; 95% CI: 1.0-1.59; I2 = 22%; p < 0.001; six studies). The rate of in-hospital mortality in STEMI and NSTEMI patients increased by 15% and 26% respectively in the COVID-19 era, which was not statistically significant (OR = 1.15; 95% CI: 0.85-1.57; I2 = 48%; p = 0.035; 11 studies, OR = 1.35; 95% CI: 0.64-2.86; I2 = 45%; p = 0.157; 3 articles). These observations highlight the challenges in the adaptation of health-care systems with the impact of the COVID-19 pandemic.

Prognostic significance of CHADS2 and CHA2DS2-VASc scores to predict unfavorable outcomes in hospitalized patients with COVID-19.

Introduction: Owing to the imposed burden of the coronavirus disease 2019 (COVID-19),the need for stratifying the prognosis of patients has never been timelier. Hence, we aimed to ascertain the value of CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M (one point for male instead of female) scores to predict unfavorable outcomes in COVID-19 patients. Methods: We enrolled consecutive patients above 18 years of age with confirmed COVID-19,who were admitted between February 16 and November 1, 2020. The primary endpoint of this study was three-month all-cause mortality. The secondary endpoints were considered four major in-hospital clinical features, including acute respiratory distress syndrome, cardiac injury,acute kidney injury, and mechanical ventilation. Results: A total of 1,406 hospitalized COVID-19 patients were studied, among which 301(21.40%) patients died during the follow-up period. Regarding the risk scores, CHADS 2≥1,CHA2DS2-VASc≥2, and CHA2DS2-VASc-M≥2 were significantly associated with mortality. The performance of all risk scores for predicting mortality was satisfactory (area under the curve:0.668, 0.668, and 0.681, respectively). Appraising secondary endpoints, we found that all three risk scores were associated with increased risk of acute respiratory distress syndrome, cardiac injury, acute kidney injury, and mechanical ventilation. Lastly, we revealed that all risk scores were significantly correlated with serum levels of laboratory biomarkers. Conclusion: Our analysis illustrated that the CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-Mscores could aid prognostication of unfavorable outcomes in COVID-19 patients. Therefore,these easily calculable methods could be integrated into the overall therapeutic strategy to guide the COVID-19 management more accurately.

Combined anticancer effects of simvastatin and arsenic trioxide on prostate cancer cell lines via downregulation of the VEGF and OPN isoforms genes.

Arsenic trioxide (ATO) and statins have been demonstrated to have anti-neoplastic properties; however, the data regarding their combination therapy is limited. Thus, we aimed to study the effects of ATO, Simvastatin and their combination in proliferation, apoptosis and pathological angiogenesis in prostate cancer cell lines. The human prostate cell lines were treated with different concentrations of Simvastatin and ATO alone and combined to find effective doses and IC50 values. In addition, the percentage of apoptotic cells was evaluated by annexin/PI staining, and mRNA expression levels of the apoptotic gene, including OPN isoforms and VEGF, were investigated using real-time PCR. Our data displayed that Simvastatin (12 and 8 µM in PC3 and LNCaP cell lines respectively), ATO (8 and 5 µM in PC3 and LNCaP cell lines respectively), and also their combination (12 µM Simvastatin and 8 µM ATO in PC3, 8 µM Simvastatin and 5 µM ATO in LNCaP cell lines respectively) significantly increased the percentage of apoptotic cells. Also, we showed that the combination therapy by Simvastatin and ATO increased cell apoptosis and inhibited cell proliferation, providing anti-proliferative and anti-angiogenic properties, possibly via downregulation of the expression of VEGF and OPN genes. These results provide new perceptions regarding the anticancer roles of ATO and statins' combination therapy in prostate cancer.

Prognostic significance of positive family history in outcomes after coronary artery bypass grafting: Do we need to update our assumptions?

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.

Long-Term Impact of the COVID-19 Associated AKI: The Relationship between Kidney Recovery and Mortality in a 10-Month Follow-Up Cohort Study.

INTRODUCTION: Coronavirus-2019 disease (COVID-19)-associated acute kidney injury (AKI) and its short and mid-term effect on kidney has been well established in the previous literature, indicating a high number of AKI in hospitalized patients associated with high rates of mortality, followed by high rates of unresolved kidney injury at the time of discharge. However, the long-term impact of AKI and its resulting lack of recovery at the time of discharge has not been investigated. Herein, we sought to explore the possible relationship between AKI and unresolved kidney injury and post-discharge mortality. METHOD: In this cohort study, patients hospitalized with COVID-19 who survived until discharge were followed for a median of 9.6 months. AKI during hospitalization based on the staging according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria and kidney injury status at discharge and other comorbidities and mortality during the follow-up period were recorded. The desired association was investigated using Cox proportional hazards regression after adjustment for potential confounders. RESULT: Among 1,017 discharged patients, 298 patients (29.3%) experienced AKI during hospitalization according to KDIGO criteria, of whom 178 patients (59.7%) were diagnosed with unresolved kidney injury at the time of discharge. After adjusting for potential confounders, Cox regression indicated that AKI stage 3 (hazard ratio (HR): 4.56, 95% confidence interval (CI): 1.89-10.99, p = 0.001) and unresolved kidney injury at the time of discharge (HR: 2.09, 95% CI: 1.18-3.73, p = 0.011) were significantly associated with mortality during the post-discharge period. Additionally, Kaplan-Meier curves for overall survival indicated an increased risk of mortality in patients with stage 2, stage 3 AKI, and unresolved kidney injury at the time of discharge (p < 0.001). CONCLUSION: Overall, it was shown that patients with COVID-19 who develop AKI, mainly stage 2 and 3, and patients with unresolved kidney injury at the time of discharge, were at an increased risk of mortality, even after hospitalization for an extended period of time.

The interactions between adipose tissue secretions and Parkinson's disease: The role of leptin.

Leptin is a hormone that regulates appetite by acting on receptors in the hypothalamus, where it modifies food intake to maintain equilibrium with the body energy resources. Leptin and its receptors are widely distributed in the central nervous system, suggesting that they may give neuronal survival signals. The potential of leptin to decrease/increase neuronal damage and neuronal plasticity in Parkinson's diseases (PD) is the subject of this review, which outlines our current knowledge of how leptin acts in the brain. Although leptin-mediated neuroprotective signalling results in neuronal death prevention, it can affect neuroinflammatory cascades and also neuronal plasticity which contribute to PD pathology. Other neuroprotective molecules, such as insulin and erythropoietin, share leptin-related signalling cascades, and therefore constitute a component of the neurotrophic effects mediated by endogenous hormones. With the evidence that leptin dysregulation causes increased neuronal vulnerability to damage in PD, using leptin as a target for therapeutic modification is an appealing and realistic option.