Seasonal and Treatment-Related Variation in 25-Hydroxy Vitamin D Concentration in Patients with Rheumatoid Arthritis.

Background/Objectives: 25-hydroxy vitamin D (25-OH-D) is a fat-soluble compound that plays many essential functions, including bone formation, neuromuscular functions, and prevention of osteoporosis and inflammation. Recent data indicate that its metabolites are associated with rheumatoid arthritis (RA) progression and neuropathic pain in RA patients. We aimed to assess the effect of RA pharmacotherapy and seasonal variation on serum levels of 25-OH-D in RA patients who received treatment with methotrexate (MTX) or leflunomide (LEF) for at least one year. Methods: This study is a retrospective analysis of data collected from 101 patients with RA who received treatment for at least one year. All of them have supplemented 25-OH-D (2000 IU daily) for at least one year. Results: We observed a significant seasonal variation in 25-OH-D concentration (p = 0.004). Moreover, there were significant differences (p = 0.03) between LEF (50.63 ± 17.73 ng/mL) and MTX (34.73 ± 14.04 ng/mL) treatment groups, but only for the summer population. A correlation was observed between 25-OH-D and RA duration-once again, in the summer population (the whole group-r = -0.64; treatment subgroups-r = -0.82 for LEF and -0.61 for MTX). Deficiency of 25-OH-D (below 20 ng/mL) was confirmed in 28.7% of patients, while 18.8% had suboptimal 25-OH-D levels (20-30 ng/mL). Conclusions: Our results showed that both RA pharmacotherapy and seasonal variation affect the serum levels of 25-OH-D in patients with active RA.

Circulating miRNA-451a and miRNA-328-3p as Potential Markers of Coronary Artery Aneurysmal Disease.

MicroRNAs (miRNAs) are currently investigated as crucial regulatory factors which may serve as a potential therapeutic target. Reports on the role of miRNA in patients with coronary artery aneurysmal disease (CAAD) are limited. The present analysis aims to confirm the differences in the expression of previously preselected miRNAs in larger study groups and evaluate their usefulness as potential markers of CAAD. The study cohort included 35 consecutive patients with CAAD (Group 1), and two groups of 35 patients matched Group 1 regarding sex and age from the overall cohort of 250 patients (Group 2 and Group 3). Group 2 included patients with angiographically documented coronary artery disease (CAD), while Group 3 enrolled patients with normal coronary arteries (NCA) assessed during coronary angiography. We applied the RT-qPCR method using the custom plates for the RT-qPCR array. We confirmed that the level of five preselected circulating miRNAs was different in patients with CAAD compared to Group 2 and Group 3. We found that miR-451a and miR-328 significantly improved the CAAD prediction. In conclusion, miR-451a is a significant marker of CAAD compared to patients with CAD. In turn, miR-328-3p is a significant marker of CAAD compared to patients with NCA.

Neopterin as a predictive biomarker of postoperative atrial fibrillation following coronary artery bypass grafting.

BACKGROUND: The pathophysiology of postoperative atrial fibrillation (POAF) is multifactorial. Inflammation and increased oxidative stress play a significant role in POAF development. Neopterin, a biomarker of cellular immune response that enhances oxidative stress and increases the cytotoxic potential of activated macrophages and dendritic cells, was recently found as an independent predictive biomarker of non-operative atrial fibrillation. However, as far as we know, neopterin has never been investigated in POAF. AIMS: The study aimed to assess neopterin concentration as a prognostic biomarker of POAF following coronary artery bypass grafting (CABG). METHODS: One hundred one patients (80.2% males, 85% off-pump, 15% on-pump) were included. Blood samples were taken from patients for analysis of serum neopterin and high-sensitive C-reactive protein (hs-CRP) at three time points: (1) before operation (NP0); (2) on the first day after operation (NP1); and (3) between the fifth and eighth day after the procedure (NP5-8). All factors (preoperative, echocardiographic, and surgical), significant in univariate analysis, were included in a multivariable logistic regression analysis. RESULTS: POAF occurred in 30 patients (30%). In the analyzed multivariable logistic regression models, the independent predictors of POAF occurrence were: higher NP0 concentration (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.02-1.38 for continuous and OR, 3.75; 95% CI, 1.39-10.1 for NP0 cut-off >8.7 nmol/l), higher body mass index (OR, 1.15; 95% CI 1.02-1.29), history of pulmonary disease (OR, 6.72; 95% CI 1.57-28), increased diastolic thickness of the interventricular septum (OR, 1.45; 95% CI, 1.14-1.83), and duration of operation (OR, 1.01; 95% CI, 1.03-1.36). CONCLUSIONS: We found that elevated neopterin concentration before CABG may be a predictive biomarker of POAF.

Circulating microRNAs in patients with aneurysmal dilatation of coronary arteries.

To understand the mechanism underlying coronary artery abnormal dilatation (CAAD), the present study identified and compared the expression of circulating microRNAs (miRNAs) in three groups of patients. Group 1 included 20 patients with CAAD, Group 2 included 20 patients with angiographically confirmed coronary artery disease (CAD), and Group 3 included 20 patients with normal coronary arteries (control). miRNAs were isolated from plasma samples and were profiled using PCR arrays and miRCURY LNA Serum/Plasma Focus PCR Panels. The present study demonstrated that the plasma miRNA levels were significantly different in Group 1 compared with in Group 2 and Group 3 (fold change >2 and P<0.05). The comparison of Group 1 with Group 3 identified 21 significantly upregulated and two downregulated miRNAs in patients with CAAD compared with in the control group. Moreover, six upregulated and two downregulated miRNAs were identified in patients with CAD compared with in the controls. The third comparison revealed four upregulated and three downregulated miRNAs in Group 1, when compared with patients with CAD. In conclusion, the present study identified a specific signature of plasma miRNAs, which were upregulated and downregulated in patients with CAAD compared with in patients with CAD and control individuals.

Involvement of Angiogenesis in the Pathogenesis of Coronary Aneurysms.

The present study aimed to evaluate the plasma concentration of pro and antiangiogenic factors and their role in the pathogenesis of coronary artery abnormal dilation (CAAD). We measured the plasma concentration of matrix metalloproteinase-8 (MMP-8), transforming growth factor beta 1 (TGF-ß1), Angiopoietin-2, vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF) using a sandwich ELISA technique in the plasma of patients with coronary artery abnormal dilation (CAAD, Group 1), coronary artery disease (CAD, Group 2), and normal coronary arteries (NCA, Group 3). Patients suffering from CAAD showed significantly higher plasma concentrations of VEGF (p = 0.002) than those from the control group. Both pathological angiogenesis and inflammation appear to be crucial in the pathogenesis of aneurysmal dilatation of the coronary arteries.

Pancreatic Injury after COVID-19 Vaccine-A Case Report.

The COVID-19 pandemic has caused more than 3 million deaths worldwide. Recently developed genetically engineered vaccines are the most critical solution for controlling the pandemic. Clinical trials on a large number of participants confirmed their safety and efficacy. However, with the growing number of vaccinated people, new infrequent adverse effects have been reported, not described in the medicinal product characteristics. We would like to report a case of acute pancreatic injury that occurred shortly after administering Pfizer BioNTech COVID-19 mRNA vaccine (Comirnaty). The report points out the potential need for close monitoring of patients reporting abdominal pain after vaccination (unresponsive to standard oral painkillers) because such symptom can be associated with acute pancreatitis.

Efficacy of coenzyme Q10 in supportive therapy of the cardiovascular diseases and in the prevention of cardiotoxicity caused by chemotherapy.

Cardiovascular diseases are the most common cause of death in Poland and in the world. People with cardiovascular disease or high cardiovascular risk require early detection and pharmacotherapy. New methods of prevention and treatment are needed. Coenzyme Q10 (CoQ10) is an essential component of the human body. CoQ10 plays an important role in the biosynthesis of adenosine-5'-triphosphate (ATP) and has antioxidant activity. More and more evidence indicates that CoQ10 is closely related to cardiovascular disorders. Its supplementation may be beneficial in various chronic and acute disorders. Coenzyme Q10 used in heart failure reduces mortality and improves exercise capacity. CoQ10 can reduce the values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in hypertensive patients. CoQ10 supplementation prevents electrocardiographic (ECG) changes in patients taking doxorubicin and has a positive effect on heart function during anthracycline chemotherapy. The review article was based on available literature found in the Medline database and includes preclinical and clinical research. Further research related to CoQ10 can contribute to significant progress in the prevention and treatment of cardiovascular diseases but may also be the basis for increasing the range of indications for this drug.

Endocan expression correlated with total volume of coronary artery dilation in patients with coronary artery ectasia.

INTRODUCTION: Inflammation and angiogenesis disturbances are considered as factors contributing to the development of coronary artery ectasias (CAE). Endocan (endothelial cell-specific molecule-1 - ESM-1) regulates both inflammatory and angiogenetic processes. However, there are no data about the correlation between endocan level and the severity of CAE measured with total volume of coronary artery dilation. AIM: To assess whether the severity of the inflammatory process measured as endocan concentration correlates with the total volume of CAE. MATERIAL AND METHODS: We selected prospectively a total of 43 consecutive patients with coronary artery ectasia from 2240 patients who underwent coronary angiography in our center. Determination of endocan was performed by using the Human Endothelial cell-specific Molecule 1 (ECSM1/ENDOCAN) ELISA Kit. 3D QCA (three-dimensional quantitative coronary angiography) was used for coronary lesion and aneurysm quantification. The total volume of dilation was defined as the volume of all aneurysms and ectasias of coronary arteries in 1 patient. RESULTS: The mean volume of all aneurysms in 1 patient was 677 ±878.7 mm3. The total aneurysm volume was positively strongly correlated with endocan concentration (Pearson correlation coefficient: 0.811; 2-tailed p < 0.001). CONCLUSIONS: Endocan is a potential marker of vascular wall damage mainly as a result of inflammation in the course of atherosclerosis, but also vascular remodeling as a result of a disturbance of pro- and anti-angiogenic processes. Endocan level reflects the intensity of the above processes and therefore correlates with the severity of CAE, measured as the total volume of dilation.

Photosensitivity reactions in the elderly population: questionnaire-based survey and literature review.

PURPOSE: Older people are at risk of developing adverse drug reactions, including photosensitivity reactions. Therefore, the aim of the study was to assess the use of potentially photosensitizing medications and photoprotection in the elderly population. PATIENTS AND METHODS: Three hundred and fifty-six respondents (223 [63%] women and 133 [37%] men) aged ≥65 years filled in the original questionnaire concerning photosensitivity reactions to drugs. The diagnosis of drug-induced photosensitivity was based on medical history and clinical examination. RESULTS AND CONCLUSION: We found that drugs potentially causing phototoxic/photoallergic reactions comprised more than one fifth of all drugs used by the participants. The most numerous group was patients treated with 3-5 drugs potentially causing phototoxic/photoallergic reactions simultaneously. Of all drugs, ketoprofen was found to cause the highest number of photosensitivity reactions. Cutaneous adverse reactions were also observed for hydrochlorothiazide, atorvastatin, simvastatin, telmisartan, and metformin. Moreover, it was found that the incidence of photosensitivity reactions can be significantly reduced by using proper photoprotection.

Is it possible to prevent chemotherapy-induced heart failure with cardiovascular drugs - the review of the current clinical evidence.

Cardiovascular diseases and cancer are the most common death causes in the USA and Europe. Moreover, many patients suffer from both of these conditions - a situation which may result from cardiotoxicity of anticancer treatment. In order to reduce the severity of this adverse effect, various methods have been proposed, including the usage of new drug forms and less toxic analogs, omitting the combinations of potentially cardiotoxic drugs and introducing potential cardioprotective agents to the therapy. However, prevention of cardiotoxicity still seems to be insufficient. The article reviews the results of current studies on the use of cardiovascular drugs in the prevention of cardiotoxicity. Based on this knowledge, the most promising cardioprotective drugs seem to be carvedilol, nebivolol, enalapril, and candesartan, as they prevent heart remodeling and correct elevated resting heart rate, which directly affects mortality. Alternatively, in case of adverse reactions, statins might be considered.

Prognostic Value of Oxidative Stress Markers in Patients with Pulmonary Arterial or Chronic Thromboembolic Pulmonary Hypertension.

Oxidative stress is regarded to play a crucial role in the pathophysiology of pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). This study evaluated the prognostic value of serum oxidative stress markers (malondialdehyde (MDA), total antioxidant capacity (TAC), catalase activity (CAT), and superoxide activity (SOD)) in patients with PAH and CTEPH (n = 45). During 13 months of follow-up (median 9 months), clinical deterioration occurred in 14 patients (including 2 deaths). On the Cox regression analysis, MDA, TAC, and CAT were associated with clinical deterioration (p = 0.0068, HR = 1.42, 95% CI: 1.10-1.82; p = 0.0038, HR = 0.033, 95% CI: 0.0032-0.33; and p = 0.046, HR = 0.20, 95% CI: 0.04-0.98, respectively). There was no significant difference in SOD (p = 0.53, HR = 0.97, 95% CI: 0.87-1.08). The cut-off value derived from ROC curve analysis was 3.79 µM (p = 0.0048, AUC = 0.76, 95% CI: 0.62-0.91) for MDA, 0.49 mM (p = 0.027, AUC = 0.71, 95% CI: 0.18-0.47) for TAC, and 1.34 U/L (p = 0.029, AUC = 0.71, 95% CI: 0.55-0.86) for CAT. MDA in the group with deterioration was higher (p = 0.0041), while TAC as well as CAT were lower (p = 0.027 and p = 0.028, respectively) when compared to stable patients. Survival without clinical deterioration was significantly longer in patients with lower MDA (p = 0.037, HR = 0.37, 95% CI: 0.12-1.14, log-rank), higher TAC (p = 0.0018, HR = 0.19, 95% CI: 0.06-0.60, log-rank), and higher CAT (p = 0.044, HR = 0.31 95% CI: 0.11-0.88, log-rank). Markers of oxidative stress such as MDA, TAC, and CAT were associated with adverse clinical outcomes in patients with PAH and inoperable or residual CTEPH.

Neopterin as a Biomarker in Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Upregulation of the immune system is regarded to play an important role in the etiopathobiology of pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). To the best of our knowledge, neopterin (NP) has never been investigated in patients with PAH and CTEPH. OBJECTIVES: The aim of the study was to evaluate the concentration of NP in blood in order to examine its impact on outcome and relationship with disease severity in that population. METHODS: Serum concentration of NP was analysed prospectively in 50 patients (36 with PAH and 14 with CTEPH vs. 31 healthy controls) and assessed in relation to clinical parameters and outcome. RESULTS: NP concentration in the PAH and CTEPH groups combined was significantly higher than in the control group (8.68, 6.39-15.03 vs. 5.14, 4.16-5.98 nmol/L, p < 0.0000001). During 9 months of follow-up, clinical deterioration occurred in 18 patients (including 8 deaths), and NP concentration in this group was higher when compared to stable patients (15.6, 8.52-25.13 vs. 7.87, 6.18-9.89, p = 0.002). The cutoff value of NP derived from ROC curve analysis was 15.3 nmol/L (p = 0.002, AUC 0.77, p = 0.0004, HR = 4.35, 95% CI 1.43-13.18, log-rank test). On Cox regression analysis, NP predicted clinical deterioration (p = 0.009, 95% CI 1.01-1.06). NP correlated positively with NT-proBNP (p < 0.001), red blood cell distribution width (p < 0.001), and right atrium area (p = 0.002) and inversely with 6-min walking test (p = 0.002) and peak oxygen consumption (p = 0.001). CONCLUSIONS: NP concentration is increased in patients with PAH and inoperable CTEPH. Elevated NP concentration is associated with adverse clinical outcomes and correlates with clinical parameters.

Baseline and extensions approach to information retrieval of complex medical data: Poznan's approach to the bioCADDIE 2016.

Database URL: https://biocaddie.org/benchmark-data.

Coenzyme Q10 - A new player in the treatment of heart failure?

Coenzyme Q10 is the only endogenously synthesized lipid with a redox function which exhibits broad tissue and intracellular distribution in mammals. Beneficial effects of Coenzyme Q10 supplementation were observed in several age-related diseases including heart failure. CoQ10 (coenzyme Q10) level is significantly decreased in patients with this disease, which correlates with severity of clinical symptoms. Supplementation with various pharmaceutical formulations of CoQ10 improves impaired cardiac function and clinical course of heart failure. Current data from clinical trials indicate that CoQ10 can significantly reduce morbidity and mortality of heart failure patients in addition to guideline recommended pharmacotherapy.

Current approach for detection of sub-clinical left ventricular dysfunction associated with chemotherapy.

The article describes the current knowledge concerning approaches for detection of sub-clinical left ventricular dysfunction associated with chemotherapy. The authors focused on the problem of defining cardiotoxicity as well as diagnostic methods, which may be useful in predicting the occurrence of such complications. Currently, cardiac biomarkers measurement (troponin, NT-proBNP), tissue Doppler-based strain imaging and peak systolic longitudinal strain rate are most useful for detection of early myocardial changes during therapy, whereas speckle tracking echocardiography (STE) and peak systolic global longitudinal strain (GLS) appear to be the best measure. The problem of cardiotoxicity requires close cooperation between oncologists and cardiologists, particularly in light of the growing number of cancer cases.

[Analysis of the problem of addiction in the elderly]. / Analiza problemu uzaleznien w grupie osób w wieku podeszlym.

Demographic changes observed in recent decades around the world lead to the aging of societies at a rapid rate. The increasing number of elder people is a result of extending the average length of human life. Elder people are struggling with many problems--loneli- ness, disability or financial problems. The problem can also be addiction, usually suspected in young people. The aim of the study was to evaluate the prevalence of addiction--smoking, drinking alcohol, use of medicines and drugs, watching television or using the Internet--in the elderly. Additional objective was to assess the problem of sleep disorders and the purchase of OTC drugs, dietary supplements and vitamin preparations in this population. Examined group consisted of 104 people aged over 65 years, of whom only 23 were smokers and 86 were consumers of various alcohols. None of the respondents confirmed any contact with drugs and the use of addiction treatment. Only 4 respondents did not watch any TV programs and 37 did not use the Internet (nor themselves nor with the help of others). 94 respondents used drugs and non-prescription preparations. 57 responders did not experienced sleep disorders.

[Safety of nicotine addiction treatment]. / Bezpieczenstwo terapii uzaleznien od nikotyny.

Not all smoking addicts can succeed in quitting smoking with willpower only. These people may use nicotine replacement therapy (patches, gums, lozenges, sublingual tablets, inhalers), medicines (bupropion, varenicline and cytisine) and psychological aid. Each drug, besides its therapeutic effect, creates the risk of adverse reactions which number and severity is not always accepted by the patient. The aim of the study was to analyze adverse effects of bupropion, varenicline and cytisine formulations reported by patients. From July 2011 to June 2013 Regional Centre for Monitoring Adverse Drug Reactions (Department of Clinical Pharmacology, Department of Cardiology, Poznan University of Medical Sciences) recorded 32 suspected adverse reactions to the use of drugs for the treatment of nicotine addiction (12 after the preparation of cytisine and varenicline, 8 after preparations of bupropion). High determination caused that none of the patients withdrew from the therapy because of adverse effects.

Influence of short-term L-arginine supplementation on carbohydrate balance in rats with ischemia-reperfusion syndrome.

BACKGROUND: There are studies showing stimulative effect of arginine on insulin secretion. This mechanism is not fully explained. The effects of the impact of arginine on carbohydrate balance under the conditions of ischemia and reperfusion remain to be determined. The aim of this study is the evaluation of the influence of short-term L-arginine supplementation on the concentration of glucose and insulin in blood and insulin binding in rat skeletal muscle under the conditions of ischemia and reperfusion. METHODS: The study was conducted on male Wistar rats with average body mass 250 ± 30 g. Animals were divided into four groups: Group I - control, Group II - placebo, Group III - L-arginine 500 mg/kg/24 h for 5 days, Group IV - L-arginine and L-NAME (75 µmol/rat/24 h) for 5 days. Each group was divided into subgroups depending on duration of ischemia and reperfusion. Acute ischemia of hind limb was induced in each group by putting pneumatic tourniquet on the thigh. Blood samples and skeletal muscles were collected from the rats. Plasma concentrations of glucose and insulin were measured. Insulin binding to insulin receptors was determined in skeletal muscle. RESULTS: A clear reduction of insulin binding to receptor was found in the group of animals without ischemia and the group supplemented with L-arginine and subjected to 4-h ischemia and 30- and 120-min reperfusion. A significant increase in insulin level was found in groups of animals with L-arginine and/or L-NAME subjected to 4-h ischemia at all times of reperfusion. Supplementation with L-arginine and/or L-NAME decreased levels of glucose in blood serum of animals undergoing ischemia-reperfusion syndrome compared to the control and placebo groups. CONCLUSION: Under conditions of ischemia-reperfusion, short-term administration of L-arginine causes a decrease in insulin binding capacity of insulin receptors in skeletal muscle, an increase in insulin level and a decrease in the concentration of glucose in blood serum.