The prognostic potential of long noncoding RNA XIST in cardiovascular diseases: a review.

There is a significant mortality rate associated with cardiovascular disease despite advances in treatment. long Non-coding RNAs (lncRNAs) play a critical role in many biological processes and their dysregulation is associated with a wide range of diseases in which their downstream pathways are disrupted. A lncRNA X-inactive specific transcript (XIST) is well known as a factor that regulates the physiological process of chromosome dosage compensation for females. According to recent studies, lncRNA XIST is involved in a variety of cellular processes, including apoptosis, proliferation, invasion, metastasis, oxidative stress and inflammation, through molecular networks with microRNAs and their downstream targets in neoplastic and non-neoplastic diseases. Because these cellular processes play a role in the pathogenesis of cardiovascular diseases, we aim to investigate the role that lncRNA XIST plays in this process. Additionally, we wish to determine whether it is a prognostic factor or a potential therapeutic target in these diseases.

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Emerging roles of HOTAIR lncRNA in the pathogenesis and prognosis of cardiovascular diseases.

Highlights HOTAIR, a long noncoding RNA, plays a role in the regulation of proteins involved in the pathogenesis of cardiovascular disease. Furthermore, it has been identified as a biomarker of this type of disease. Several factors and cells contribute to atherosclerosis, a progressive disease. However, the prognosis of HOTAIR in this disease varies depending on the path in which it plays a role. For this condition, there is no single prognosis to consider.

lncRNA TUG1 as potential novel biomarker for prognosis of cardiovascular diseases.

Globally, cardiovascular diseases (CVDs) are among the leading causes of death. In light of the high prevalence and mortality of CVDs, it is imperative to understand the molecules involved in CVD pathogenesis and the signaling pathways that they initiate. This may facilitate the development of more precise and expedient diagnostic techniques, the identification of more effective prognostic molecules and the identification of potential therapeutic targets. Numerous studies have examined the role of lncRNAs, such as TUG1, in CVD pathogenesis in recent years. According to this review article, TUG1 can be considered a biomarker for predicting the prognosis of CVD.

Considering that cardiovascular diseases (CVDs) are very common and can be fatal, we must have a method for assessing heart health and its probability of worsening in order to prevent and treat these diseases. In order to accomplish this, it is possible to look for biomarkers in bodily fluids that are indicative of CVD. The purpose of this article is to examine a molecule called TUG1, which is found in varying levels in patients suffering from CVD. There is an impact of TUG1 on the growth, death and inflammation response of heart cells. The potential application of TUG1 as a biomarker to predict the severity and progression of heart disease is therefore not surprising.

Circular RNAs-mediated angiogenesis in human cancers.

Circular RNAs (circRNAs) as small non-coding RNAs with cell, tissue, or organ-specific expression accomplish a broad array of functions in physiological and pathological processes such as cancer development. Angiogenesis, a complicated multistep process driving a formation of new blood vessels, speeds up tumor progression by supplying nutrients as well as energy. Abnormal expression of circRNAs reported to affect tumor development through impressing angiogenesis. Such impacts are introduced as constant with different tumorigenic features known as "hallmarks of cancer". In addition, deregulated circRNAs show possibilities to prognosis and diagnosis both in the prophecy of prognosis in malignancies and also their prejudice from healthy individuals. In the present review article, we have evaluated the angiogenic impacts and anti-angiogenic managements of circRNAs in human cancers.

Biomarkers of endothelial dysfunction are associated with poor outcome in COVID-19 patients: A systematic review and meta-analysis.

Numerous studies have linked coronavirus disease 2019 (COVID-19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We conducted a systematic review and meta-analysis of the published evidence in this respect. A systematic literature search of PubMed and Scopus databases was performed to find studies investigating biomarkers of endothelial dysfunction in COVID-19 patients. Pooled standardized mean differences and their 95% confidence intervals were calculated for each biomarker using random effect model. 74 studies with 7668 patients were included. In comparison to patients with good outcome, those with poor outcome had higher levels of von Willebrand factor (vWF) (SMD: 0.83, 95% CI: 0.59-1.07, p < 0.00001), vWF:ADAMTS13 (1.23, (0.77-1.7), p < 0.00001), angiopoietin-2 (Ang-2) (1.06 (0.6-1.51), p < 0.0001), E-selectin (1.09 (0.55-1.63), p < 0.0001), P-selectin (0.59 (0.24-0.94), p = 0.001), syndecan-1 (0.99 (0.6-1.37), p < 0.00001), mid-regional pro-adrenomedullin (MR-proADM) (1.52 (1.35-1.68), p < 0.00001), vascular endothelial growth factor (0.27 (0.02-0.53), p = 0.03), soluble fms-like tyrosine kinase-1 (sFLT-1) (1.93 (0.65-3.21), p = 0.03) and lower levels of ADAMTS13 antigen (-0.69 (-0.9 to -0.47) p < 0.00001) and activity (-0.84 (-1.06 to -0.61) p < 0.0000). Plasminogen activator inhibitor-1 and tissue plasminogen activator levels were not different between the two groups (p < 0.05). There were elevated levels of endothelial dysfunction biomarkers in COVID-19 patients with poor outcome, indicating their possible role in disease severity and prognosis. In particular, MR-proADM, vWF, syndecan-1 and sFLT-1 showed a significant association with poor outcome in these patients.

Impact of Obstructive Sleep Apnea Diagnosed Using the STOP-Bang Questionnaire Scale on Postoperative Complications Following Major Cardiac Surgery: A Prospective Observational Cohort Study.

Purpose Obstructive sleep apnea (OSA) is a common and often undiagnosed condition in patients undergoing major surgeries, including cardiac surgery. This disorder is associated with peri- and postoperative problems. This study measured the association between OSA and peri- and postoperative complications in patients undergoing elective cardiac surgery. Methods Candidates for elective cardiac surgery were evaluated for OSA by the STOP-Bang questionnaire before the surgery. We evaluated patients before and after the operation regarding the cardiac, respiratory, and neurologic complications. We divided the participants into high-risk (score of 5-8), intermediate-risk (score of 3-4), and low-risk groups (score of 0-2) based on the STOP-Bang questionnaire. Results Of the 306 patients who underwent cardiac surgery, 173 (56.5%) were in the high-risk group, 100 (32.7%) were in the intermediate-risk group, and 33 (10.8%) were in the low-risk group for OSA. Patients in the high-risk group were significantly older than the other two groups (p value=0.013), had higher BMI (p<0.001), and suffered more from relevant comorbid conditions, including diabetes mellitus, hypertension, and hyperlipidemia (all p-values significant at < 0.05). However, not significant, patients in the high-risk group suffered more from postoperative complications including cardiac, respiratory, and neurological complications. Conclusion OSA is common in patients undergoing cardiac surgery. Our findings indicate that these patients manifest a higher incidence of postoperative complications compared to those with a lower risk of OSA. Because of the limited use of polysomnography, a simple STOP-Bang questionnaire is beneficial to screen patients for the risk of OSA peri-operatively, and patients diagnosed with OSA can get extra care during and after the surgery.

Strategies to inhibit arsenic trioxide-induced cardiotoxicity in acute promyelocytic leukemia.

OBJECTIVE: Arsenic trioxide (ATO) is a drug commonly used for the treatment of acute promyelocytic leukemia (APL). Although ATO has been shown to cause significant improvement in patients, it is associated with serious side effects, which sometimes lead to the patient's death. In this review paper, we examine the reports of ATO-induced cardiotoxicity in APL patients and evaluate the strategies to reduce the incidence of such toxicity. METHODS: The key search terms were "arsenic trioxide," "acute promyelocytic leukemia," "cardiotoxicity," "molecular pathway," and "biomarker." RESULTS: Studies have indicated the involvement of several molecular pathways in ATO-induced cardiotoxicity. These pathways increase the production of reactive oxygen species by interfering with intracellular calcium homeostasis as well as impairing the transfer of calcium into endoplasmic reticulum and mitochondria. On the other hand, increasing or decreasing expressions of some microRNAs (miRs) have been shown to play a role in cardiotoxicity. CONCLUSION: Finally, it can be stated that given the essential role of molecular pathways in cardiotoxicity and considering the fact these pathways impair the regulation of miRs expression, identification of molecular pathways involved in ATO-induced cardiotoxicity aimed at targeting miRs could be a new therapeutic strategy to prevent cardiotoxicity.

T-bet transcription factor in cardiovascular disease: Attenuation or inflammation factor?

T-bet is a major transcription factor increasing inflammatory responses in the immune system. Recently, it has been shown that this factor leads to inflammation in cardiovascular disease (CVD). In this study, we examine the dual role of T-bet in inducing and suppressing inflammatory reactions as well as angiogenesis induction due to inflammatory cytokines in CVD. Relevant literature was identified by a Pubmed search (1992-2018) of English-language papers using the terms "T-bet," "Cardiovascular disease," "Immune response," and "Angiogenesis." Although T-bet causes differentiation of Th1 cells and activation of immune cells such as NK and DC, it suppresses inflammatory responses and replaces damaged vessels with new ones by activating regulatory T-cells and stimulating angiogenesis. It can be stated that T-bet acts as double-edged sword. Therefore, the identification of pathways that can increase the function of T-bet in activating Tregs and inducing angiogenesis might be used as a new therapeutic option in future investigations.

Effect of gemfibrozil on cardiotoxicity induced by doxorubicin in male experimental rats.

Cardiotoxicity is an adverse effect of the anticancer drug doxorubicin (DOX). Gemfibrozil (GEM) is a lipid-lowering drug with a number of biological properties such as anti-inflammatory and antioxidant activities. Therefore, we decided to investigate the effect of GEM on DOX-induced cardiotoxicity in rats. Twenty-eight adult male Wistar rats were divided into four experimental groups as follows: Group I received normal saline (2 ml/kg) orally for 14 days, group II received DOX (2.5 mg/kg; in six injections; accumulative dose: 15 mg/kg) intraperitonially for 14 days, group III received DOX + GEM (100 mg/kg) orally for 14 days concomitantly with DOX administration, and group IV received GEM orally for 14 days. Lipid panel, various biochemical biomarkers, and histological observations were evaluated in serum and heart samples. According to our results, DOX significantly increased the levels of lipid panel (triglycerides, total cholesterol, and low-density lipoproteins cholesterol) as well as markers of cardiac dysfunction (Aspartate aminotransferase, Creatine kinase-muscle/brain, Lactate dehydrogenase and Cardiac Troponin I). Moreover, DOX significantly increased malondialdehyde and nitric oxide levels in cardiac tissue. Furthermore, administration of DOX reduced the level of glutathione as well as the superoxide dismutase, catalase, and Glutathione peroxidase activities. DOX-treated rats showed significantly higher tumor necrosis factor-α and interleukin-1ß. GEM administration significantly attenuated the lipid panel and biochemical biomarkers in DOX-treated rats. Our results were confirmed by histopathological evaluations of the heart. Based on our findings, GEM is a promising cardioprotective agent in patients treated with DOX through mitigative effects on biochemical markers and oxidative stress indices.

Clonal hematopoiesis: Genes and underlying mechanisms in cardiovascular disease development.

The clonal hematopoiesis when occurring without hematologic abnormalities is defined as clonal hematopoiesis of indeterminate potential (CHIP). Aging causes accumulation of somatic mutations, and hematopoietic stem cells (HSCs) can develop clonal expansion of different lineages by these mutations. CHIP has a correlation with cancer and cardiovascular disease (CVD) through acquired mutations in genes. DNMT3A, TET2, ASXL1, and JAK2 genes as well as other genes are the most common somatic mutations causing CHIP and CVD in an older age. Other factors such as cholesterol level, laboratory tests and indexes also affect CVD. In addition, mutations in adenosine triphosphate-binding cassette transporters and also chronic stress in nervous system can result in HSCs proliferation and CVD. However, laboratory tests and indexes are not sensitive for CVD diagnosis. But the therapeutic interventions can be helpful to prevent CVD cases by targeting somatic mutations, chemokine receptors, and growth factors in HSCs. Also, new drugs can control CVD by targeting of cells and their signaling pathways in HSCs. Therefore, more investigations are needed and more questions should be answered for the relationship between CHIP and CVD as a challenging issue in future.

Metformin one in a Million Efficient Medicines for Rheumatoid Arthritis Complications: Inflammation, Osteoblastogenesis, Cardiovascular Disease, Malignancies.

BACKGROUND: Rheumatoid arthritis is a widespread autoimmune disease and inflammation and bone destruction are two main issues in rheumatoid arthritis. OBJECTIVE: To discussing metformin effects on rheumatoid arthritis complications. METHODS: We conducted a narrative literature search including clinical trials, experimental studies on laboratory animals and cell lines. Our search covered Medline, PubMed and Google Scholar databases from 1999 until 2018. We used the terms" Metformin; Rheumatoid arthritis; Cardiovascular disease; Cancer; Osteoblastogenesis. DISCUSSION: Inflammatory pro-cytokines such as Interlukin-6 play important roles in T. helper 17 cell lineage differentiation. Interlukin-6 and Tumor Necrosis Factor-α activate Janus kinase receptors signal through signaling transducer and activator of transcription signaling pathway which plays important role in inflammation, bone destruction and cancer in rheumatoid arthritis patients. Interlukin-6 and Tumor Necrosis Factor-α synergistically activate signaling transducer and activator of transcription and Nuclear Factor-kß pathways and both cytokines increase the chance of cancer development in rheumatoid arthritis patients. Metformin is AMPK activators that can suppress mTOR, STAT3 and HIF-1 so AMPK activation plays important role in suppressing inflammation and osteoclastogenesis and decreasing cancer. CONCLUSION: Metformin effect on AMPK and mTOR pathways gives the capability to change Treg/Th17 balance and decrease Th17 differentiation and inflammation, osteoclastogenesis and cancers in RA patients. Metformin can be useful in protecting bones especially in first stages of RA and it can decrease inflammation, CVD and cancer in RA patients so Metformin beside DAMARs can be useful in increasing RA patients' life quality with less harm and cost.

Strategies to increase cardioprotection through cardioprotective chemokines in chemotherapy-induced cardiotoxicity.

BACKGROUND: Cardiotoxicity is one of the most important side effects of chemotherapy and its management save myocardium from injury and its consequences. AIM: In this review we discuss cardioprotective chemokines and cardioprotective mechanisms and pathways that induce cardioprotection through cardioprotective chemokines. METHOD: We searched English literature articles in Google scholar and PubMed from "1990 to 2018" through using the terms "Cardioprotection; Cardioprotective Chemokine; Chemotherapy Induced Cardiotoxicity; Cardiomyocytes; Cytokine". DISCUSSION: The routine cardioprotective strategies during chemotherapy such as angiotensin-converting enzyme inhibitors and ß-blockers have cardioprotective effects. Cardioprotective mechanisms and strategies can offer the oncologist several methods to protect the cardiac system through using efficient cardioprotective agents. Chemokines such as SDF-1a, IL-6,IL-8,IL-12 and G-CSF are cardioprotective chemokines. Accelerating the cardioprotection through inducing cardioprotective chemokines production can be useful in chemotherapy. CONCLUSION: Stimulating the production of cardioprotective chemokines through the pathways which induce the production of cardioprotective chemokines can work strongly beside the ß-blockers and ACE inhibitors. The ambiguous point in cardioprotective pathways is that JAK2/STAT3 pathway which is linked to IL-6 production pathway, which induce intracellular adhesion molecule-1 in the area of the ischemia in myocardium and this process is not benefit in cardioprotection however IL-6 induce cardiomyocytes regeneration so it enhance our dull vision about IL-6. Finally there are several choices which can increase cardioprotection during the chemotherapy and if we overcome the boundaries in confirming the efficiency of cardioprotective chemokines and the activation of them through using several mechanisms we will break through the difficulties over chemotherapy-induced cardiotoxicity.

Mutations and Common Polymorphisms in ADAMTS13 and vWF Genes Responsible for Increasing Risk of Thrombosis.

BACKGROUND AND OBJECTIVE: ADAMTS13 (A Disintegrin-like and Metalloproteases with Thrombospondin type-1 repeats, member-13) plays an important role in vascular hemostasis by cleaving the von Willebrand Factor (vWF). ADAMTS13 and vWF are involved in the development of ischemic heart disease. In this review paper, we examine the effects of Single Nucleotide Polymorphisms (SNPs) and mutations in the vWF and ADAMTS13 genes and their contribution to the development of thrombosis. METHODS: Relevant English-language literature was searched and retrieved from PubMed search engine (2001-2017). The following keywords were used: "ADAMTS13", "vWF", "Polymorphism", and Thrombosis". RESULTS: SNPs in the ADAMTS13 and vWF genes cause genetic variability and affect the plasma levels of these genes. Moreover, environmental (such as age, smoking, hypertension) and genetic factors (like ABO blood groups) play a role in the development of different polymorphisms in ADAMTS13 and vWF genes. CONCLUSION: The increased or decreased activity of these two genes as a result of genetic changes and the development of thrombosis are a challenging and contradictory matter, and the study of genetic variability in ADAMTS13 and vWF genes may be helpful in the diagnosis of thrombotic disorders.

Cardiovascular Events: A Challenge in JAK2-positive Myeloproliferative Neoplasms.

BACKGROUND: Myeloproliferative neoplasms (MPNs) are chronic blood disorders caused by clonal expansion in one or more myeloid lineages and include essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF) and chronic myeloid leukemia (CML). Cardiovascular events are a main challenge for patients with MPN and can lead to their death. OBJECTIVE: JAK2V617F mutation is observed in Philadelphia-negative MPNs such as ET and PV, increasing the risk of cardiovascular complications in these patients. JAK2 mutation can affect cardiac arteries and veins in ET and PV, which results in thrombosis, ischemia and other cardiovascular events. JAK/STAT signaling pathway plays an important role in heart diseases. In this review, we will survey the cardiovascular events in JAK2-positive MPN patients. METHOD: Relevant English-language literature were searched and retrieved from PubMed search engine (1995-2017). The following keywords were used: "Cardiovascular Events", "JAK2" and "Myeloproliferative Neoplasms". Forty three articles were selected by using the key words. RESULTS: JAK2 phosphorylates the signal transducers and activators of transcription (STAT). Various factors like angiotensin II (ANG II) and cardiotrophin-1 (CT-1) can bind their receptors on myocytes and increase the expression of angiotensinogen (Ao) gene by binding of STAT proteins to these factors in myocytes, causing different cardiovascular complications through autocrine mechanisms. CONCLUSION: JAK2 mutation is observed in patients with thrombosis, ischemia and other cardiovascular complications having abnormal increase in cell count even without definite clinical diagnosis of MPN. Therefore, identification of this mutation in these patients contributes to definite diagnosis of cardiovascular events. Also, cardiovascular complications in MPN patients can be prevented by targeting the factors involved in JAK/STAT signaling pathway.

Pentraxin 3 Is Highly Specific for Predicting Anatomical Complexity of Coronary Artery Stenosis as Determined by the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery Score.

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the hypothesis that pentraxin 3 (PTX3) can have a diagnostic value for predicting anatomical complexity of coronary artery stenosis as measured by the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score. SUBJECTS AND METHODS: We investigated the association of systemic arterial PTX3 with SYNTAX score among 500 patients with ischemic heart disease assigned to medical treatment (251), percutaneous coronary intervention (PCI) (197), or coronary artery bypass graft (CABG) (52). RESULTS: The clinical judgment of the cardiologists was near-perfectly concordant with the SYNTAX score. Mean {99% confidence intervals (CIs)} SYNTAX scores were 5.8 (5.1-6.6), 18.4 (17.1-19.8), and 33.2 (32.8-33.6) in patients assigned to medical therapy, PCI, and CABG, respectively. The AROC (95% CIs) for discriminating between patients with and without a high SYNTAX score (>23) was 0.920 (0.895-0.946) for systemic arterial levels of PTX3. As the systemic arterial level of PTX3 increased, the SYNTAX scores also increased almost in a curvilinear fashion, with the value corresponding to the SYNTAX score of 23 being 0.29 ng · dL(-1). This cutpoint achieved a sensitivity of 0.66 (0.57-0.74), a specificity of 0.94 (0.91-0.96), a positive predictive value of 0.79 (0.70-0.87), and a negative predictive value of 0.89 (0.85-0.92). CONCLUSION: We observed that systemic arterial levels of PTX3 were associated with the SYNTAX score in a curvilinear fashion. The discriminatory power of systemic arterial levels of PTX3 for a high SYNTAX score was excellent. The interesting finding of this study was the near perfect concordance between the decisions made by the cardiologists based on their clinical judgment and the SYNTAX score. The systemic arterial PTX3 level of 0.29 ng · dL(-1) was highly specific for diagnosing complex coronary artery stenosis.

Accidental left circumflex artery to right lung fistula in a suspected case of pulmonary hypertension.

A 56-year-old woman was referred to the cardiology department of the Shahid Modarres hospital. The patient had a history of pulmonary thromboembolism 20 years ago which had been managed by the inferior vena cava filter and since then the patient has been on warfarin. Her chief complaint was chronic dyspnea on exertion (NYHA class II) from several years ago. Right and left heart catheterization was performed for evaluation of pulmonary artery pressure. We found rich collateral formations between LCX as well as RCA and right pulmonary artery, primarily assumed as multiple fistulas. Among patients who have chronic thromboembolic pulmonary hypertension, systemic collateral supply to the pulmonary parenchyma has been previously reported to occur from both bronchial and/or nonbronchial systemic circulations. Our patient had neither signs of heart failure nor myocardial ischemia and, thus, was a candidate for conservative management. The adenosine pulmonary reactivity test was not performed because of low pulmonary pressure which had been estimated to be high.

No Relationship between Serum and Salivary ß2- Microglobulin Levels in A Sample of Adult Diabetic Men with Chronic Kidney Disease without Renal Replacement Therapy.

OBJECTIVE: Β2-microglobulin (ß2M) associated amyloidosis is an inevitable complication of chronic kidney disease (CKD). Testing ß2M in the blood is invasive and expensive. On the other hand, oral fluid is a perfect medium to be explored for public health and disease surveillance. However, it has never been studied if salivary concentration of ß2M reflects its concentration in the serum. The current study; therefore, aimed to examine the relationship between salivary and serum ß2M in a sample of adult diabetic men with CKD. MATERIALS AND METHODS: Among diabetic patients referred to the Nephrology Department of The Golestan Hospital of Ahvaz due to CKD, 40 men not requiring renal replacement therapy were consecutively recruited for this cross-sectional study. Patients were excluded if they had any disease or were using any drugs that might affect the oral mucosa or saliva. The concentration of ß2M was measured in both serum and saliva. The correlation between serum and salivary ß2M was measured by calculating spearman's ρ. RESULTS: The Spearman's ρ for correlation between serum and salivary ß2M was -0.017 (p=0.917), indicating lack of correlation. Serum and salivary creatinine (Spearman's ρ=0.54; p value<0.001) as well as serum and salivary urea nitrogen levels (Spearman's ρ=0.39; p value=0.014) were correlated. CONCLUSION: Salivary ß2M levels poorly agreed with serum ß2M levels, and thus may not be used as a surrogate for serum ß2M in CKD patients who did not require replacement therapy.

Long acting propranolol and HSP-70 rich tumor lysate reduce tumor growth and enhance immune response against fibrosarcoma in Balb/c mice.

BACKGROUND: Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, anti-angiogenic and cytotoxic properties of propranolol, ß-AR blocker, against various cancers. OBJECTIVES: To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma. METHODS: Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxicity activity of the splenocytes, naturally occurring CD4+ CD25high T-reg cells and IFN-γ and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response. RESULTS: A significant increase in the level of IFN-γ in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-γ. Likewise, a decrease in tumor growth in the test group (p<0.01) and a significant increase in CTL activity (p<0.05) was observed. CONCLUSION: HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses.

Bedside-Friendly Prediction for Presence of Post-Myocardial lnfarction Systolic Dysfunction Using Multimarker Panel: Integrating Salivary Diagnostics into Clinical Practice.

BACKGROUND AND OBJECTIVES: We investigated if a combination of plasma or salivary interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-ß), and troponin can improve estimation of the pretest probability of the left ventricular systolic dysfunction (LVSD). SUBJECTS AND METHODS: Eighty patients with newly-diagnosed myocardial infarction (MI) were echocardiographically examined for LVSD (ejection fraction ≤40%). Measurements included traditional MI risk factors, plasma and salivary concentrations of troponin, IL-2, IL-6, TNF-α, and TGF-ß. With the LVSD as the outcome variable, we developed logistic regression models, starting with a basic model incorporating traditional risk factors and consecutively adding salivary and plasma biomarkers. Models were compared using several criteria, including (but not limited to) C statistic (discrimination) and net reclassification improvement index (NRI). RESULTS: APART FROM TROPONIN, PLASMA, AND SALIVARY VALUES OF THE BIOMARKERS WERE CORRELATED: spearman's ρ was 0.19 (p=0.088) for troponin, 0.36 (p=0.001) for IL-2, 0.74 (p<0.001) for IL-6, 0.61 (p<0.001) for TNF-α, and 0.65 (p<0.001) for TGF-ß. The predictive performances of the basic model for estimating the pretest probability of the presence of LVSD considerably improved when cytokines were added (salivary added: C-statistic from 0.77 to 0.82 and NRI 77%; plasma added: C-statistic to 0.80 and NRI 134%). CONCLUSION: Multiple biomarkers added diagnostic value to the standard risk factors for predicting the presence of post-MI LVSD.

Defining the at risk patients for contrast induced nephropathy after coronary angiography; 24-h urine creatinine versus Cockcroft-Gault equation or serum creatinine level.

BACKGROUND: Definitions of chronic kidney disease (CKD) in many catheterization laboratories have relied on the serum creatinine (Scr) rather than glomerular filtration rate (GFR). Regarding that CKD is the primary predisposing factor for contrast induced nephropathy (CIN), we compared the sensitivity of calculated GFR by 24-h Urine creatinine with Cockcroft-Gault (CG) equation and Scr level to define at risk patients for CIN who were undergone coronary angiography (CAG). MATERIALS AND METHODS: Two hundred fifty four subjects who were candidate for CAG and had normal creatinine level were enrolled. Before CAG, GFR was calculated from a 24-h urine collection, CG equation and a single Scr sample regarding to previously described protocol. Contrast volume used for each case <100 ml. CIN was defined as a 0.5 mg/dL or 25% elevation in the Scr. RESULTS: CIN occurred in 10.6%. Baseline GFR, the volume of contrast agent, and diabetes were the independent risk factors for CIN. GFR was less than 60 ml/min/1.73 m2 in 28% and 23.2% of patients regarding to 24-h urine creatinine and CG equation, respectively. In CIN prediction, 24-h urine creatinine estimated GFR had 85.2%, 59.3% and CG equation GFR had 78.9%, 81.1% sensitivity and specificity, respectively. CONCLUSION: Although, GFR estimated by CG equation has less sensitivity than GFR calculated from 24-h creatinine in CIN probability, but it is better than Scr alone and because of cost-effectiveness and convenience using of this method, we suggest at least using CG equation for GFR calculation before CIN, especially in diabetic and/or older than 60 years cases.