Risk assessment for mortality in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: A retrospective cohort study.

Background and Aims: Primary percutaneous coronary intervention (PCI) is the treatment of choice in ST-elevation myocardial infarction (STEMI) patients. This study aims to evaluate predictors of in-hospital and long-term mortality among patients with STEMI undergoing primary PCI. Methods: In this registry-based study, we retrospectively analyzed patients with STEMI undergoing primary PCI enrolled in the primary angioplasty registry of Sina Hospital. Independent predictors of in-hospital and long-term mortality were determined using multivariate logistic regression and Cox regression analyses, respectively. Results: A total of 1123 consecutive patients with STEMI were entered into the study. The mean age was 59.37 ± 12.15 years old, and women constituted 17.1% of the study population. The in-hospital mortality rate was 5.0%. Multivariate analyses revealed that older age (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.02-1.10), lower ejection fraction (OR: 0.97, 95% CI: 0.92-0.99), lower mean arterial pressure (OR: 0.95, 95% CI: 0.93-0.98), and higher white blood cells (OR: 1.17, 95% CI: 1.06-1.29) as independent risk predictors for in-hospital mortality. Also, 875 patients were followed for a median time of 21.8 months. Multivariate Cox regression demonstrated older age (hazard ratio [HR] = 1.04, 95% CI: 1.02-1.06), lower mean arterial pressure (HR = 0.98, 95% CI: 0.97-1.00), and higher blood urea (HR = 1.01, 95% CI: 1.00-1.02) as independent predictors of long-term mortality. Conclusion: We found that older age and lower mean arterial pressure were significantly associated with the increased risk of in-hospital and long-term mortality in STEMI patients undergoing primary PCI. Our results indicate a necessity for more precise care and monitoring during hospitalization for such high-risk patients.

A Comprehensive Investigation of the Potential Role of Lipoproteins and Metabolite Profile as Biomarkers of Alzheimer's Disease Compared to the Known CSF Biomarkers.

Introduction: While cerebrospinal fluid (CSF) core biomarkers have been considered diagnostic biomarkers for a long time, special attention has been recently dedicated to lipoproteins and metabolites that could be potentially associated with Alzheimer's disease (AD) neurodegeneration. Herein, we aimed to investigate the relationship between the levels of CSF core biomarkers including Aß-42, TAU, and P-TAU and plasma lipoproteins and metabolites of patients with AD from the baseline cohort of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Method: Using the ADNI database, fourteen subclasses of lipoproteins as well as a number of lipids and fatty acids and low-molecular metabolites including amino acids, ketone bodies, and glycolysis-related metabolites in blood samples were measured as potential noninvasive markers, and their association with the CSF core biomarkers was statistically investigated controlling for age and gender. Results: A total number of 251 AD subjects were included, among whom 71 subjects were negative for the Apo-E ε4 allele and 150 were positive. There was no significant difference between the two groups regarding cognitive assessments, CSF core biomarkers, and lipoproteins and metabolites except the level of Aß-42 (p < 0.001) and phenylalanine (p = 0.049), which were higher in the negative group. CSF TAU and P-TAU were significantly correlated with medium and small HDL in the negative group, and with extremely large VLDL in the positive group. Our results also indicated significant correlations of metabolites including unsaturated fatty acids, glycerol, and leucine with CSF core biomarkers. Conclusion: Based on our findings, a number of lipoproteins and metabolites were associated with CSF core biomarkers of AD. These correlations showed some differences in Apo-E ε4 positive and negative groups, which reminds the role of Apo-E gene status in the pathophysiology of AD development. However, further research is warranted to explore the exact association of lipoproteins and other metabolites with AD core biomarkers and pathology.

Toll-like receptor 7 regulates cardiovascular diseases.

Cardiovascular disease (CVD) is the major leading cause of morbidity and mortality worldwide. According to the pro-inflammatory nature of CVD, recent studies highlighted the immune system's role in its pathogenesis and development. Toll-like receptors (TLRs) have been identified as dominant innate immune receptors. TLR-7 is an intracellular receptor expressed on endosomes or cytoplasmic reticulum and is responsible for detecting damage-associated molecular patterns, which are remarkable during inflammation and viral infection. In addition to immune cells, TLR-7 is expressed in endothelial cells, vascular smooth muscle cells, and platelets. TLR-7 ligands are single-stranded ribonucleic acid (ssRNA) and short interfering RNA, which can activate the signaling pathway and lead to both inflammatory (e.g., interleukin-1 (IL-1), IL-6, IL-12, tumor necrosis factor- α (TNF-α)) and anti-inflammatory (e.g., IL-10) cytokines release. By growing evidence, it has been proven that TLR-7 activated platelets can increase the risk of thrombus formation by neutrophil aggregation. At the same time, they have a protective role against thrombosis by releasing granulocyte-macrophage colony-stimulating factors. The same two-sided effect was observed between TLR-7 and atherosclerotic plaque formation. Moreover, recent studies explained an association between TLR-7 activation and increased risk of complete heart block, myocarditis, left ventricular remodeling, and rupture. Here we review the rapid progress that has been made in this field, which has improved our understanding of TLR-7 function in CVDs, and discuss the current treatments targeting this receptor.

The potential role of the cardiac MIBG scan in differentiating the drug-induced Parkinsonism from Parkinson's disease.

INTRODUCTION: Considering the difficulties of differentiating Parkinson's disease (PD) from drug-induced Parkinsonism (DIP) in patients receiving antipsychotics, developing robust diagnostic tools is essential. Herein, we used the metaiodobenzylguanidine (MIBG) scan to assess its diagnostic accuracy for this purpose. METHODS: 44 DIP patients and 32 patients with PD as controls were enrolled. All the participants underwent a cardiac 131I-MIBG scan. Statistical analysis was conducted to determine the significance of the results, and accuracy analyses were conducted to calculate the related sensitivity and specificity of the MIBG scan. RESULTS: The mean age of PD and DIP groups were 62.6 ± 5.9 and 51.5 ± 10.8 years, respectively. The mean duration of drug consumption in the DIP group was 52.2 ± 29.4 days (the mean interval between drug initiation and DIP onset was 28.5 ± 20.5). Symptoms relief occurred 40 ± 24.2 days after drug discontinuation. In the PD group, 15.6% showed negative and 84.4% positive results on the MIBG scan. In the DIP group, 86.4% were negative, and the remaining were positive. The difference in MIBG uptake between the two groups was statistically significant (P-value < 0.001). The sensitivity and specificity of the MIBG scan were 84.4% (CI: 84.0-84.8) and 86.36% (CI: 86.0-86.7) for the diagnosis of PD, respectively. CONCLUSION: Our results indicated more positive MIBG scans in the PD group than the DIP. Also, the MIBG scan's sensitivity and specificity in differentiating the PD are acceptable. Future works should assess these findings and the role of the MIBG scan in prognosis assessment of DIP and better allocation of the patients to related disciplines.

How Stable Ischemic Heart Disease Leads to Acute Coronary Syndrome in COVID-19?

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the increased mortality risk of patients with underlying cardiovascular diseases and COVID-19 was raised. Besides, coronavirus itself enhances the incidence of myocardial injury, which suggests a two-sided relation. We aimed to discuss the role of COVID-19 in the progression of stable coronary artery disease (CAD) to acute coronary syndrome (ACS), which might lead to a greater rate of out-of-hospital cardiac arrest and a higher fatality rate of ACS during the pandemic. We briefly reviewed several mechanisms in this regard: Systemic inflammation and cytokine release in critical patients; Plaque rupture and coronary thrombosis; Dysregulation of cytotoxic T-cell lymphocytes; Malignant ventricular arrhythmias. We reinforce applying more attention to COVID-19 patients with stable CAD during follow-up to prevent progression to ACS. These individuals should seriously observe World Health Organization protocols to avoid virus transmission by carriers.

A novel homozygous RAG1 mutation is associated with severe combined immunodeficiency and neurological presentations

Introduction and objectives: Severe combined immunodeficiency (SCID) is a subset of primary immunodeficiency diseases caused by a hereditary deficiency of the adaptive immune system. Mutation in recombination activating gene (RAG) is known as the underlying genetic cause of SCID. RAG protein plays a pivotal role in V(D)J recombination which is the main process to assemble lymphocyte antigen receptors during T- and B-cell development. The patients are characterized by recurrent infections, failure to thrive, chronic diarrhea, and fever, in early infancy. Herein, we present a case of SCID with rare neurological manifestations affected by a mutation in RAG1. Patients and methods: The patient was a 15-month-old infant born to a consanguineous family. She was presented with neurological abnormalities including facial nerve palsy, seizure, and decreased consciousness. Next-generation sequencing (NGS)-based primary immunodeficiency disease (PID)-gene panel screen and Sanger sequencing were performed to identify the genetic mutation. Results: We found a novel homozygous missense mutation in RAG1, c.1210C>T,p.Arg404Trp, which was predicted to be deleterious (combined annotation dependent depletion, CADD score of 27.4). Both parents were heterozygous carriers for this mutation. According to her laboratory data, both T cell and B cell numbers were decreased and the patient was diagnosed as RAG1- SCID. Conclusions: SCID is a pediatric emergency with a variety of manifestations in infants. Therefore, accurate diagnosis importantly in the case of rare manifestations must be considered in these patients. Our findings point toward the importance of genetic assessment for early diagnosis and timely treatment of this disorder (AU)

Cytokine release syndrome: inhibition of pro-inflammatory cytokines as a solution for reducing COVID-19 mortality.

Coronavirus disease (COVID-19) reached pandemic proportions at the beginning of 2020 and continues to be a worldwide concern. End organ damage and acute respiratory distress syndrome are the leading causes of death in severely or critically ill patients. The elevated cytokine levels in severe patients in comparison with mildly affected patients suggest that cytokine release syndrome (CRS) occurs in the severe form of the disease. In this paper, the significant role of pro-inflammatory cytokines, including IL-1, IL-6, and TNF-alpha, and their mechanism of action in the CRS cascade is explained. Potential therapeutic approaches involving anti-IL-6 and anti-TNF-alpha antibodies to fight COVID-19 and reduce mortality rate in severe cases are also discussed.