ApoA-I and ApoB levels, and ApoB-to-ApoA-I ratio as candidate pre-treatment biomarkers of pathomorphological response to neoadjuvant therapy in gastric and esophago-gastric junction adenocarcinoma.

<b><br>Introduction:</b> Neoadjuvant chemotherapy (NAC) is a part of the current standard of care in a locally advanced gastric adenocarcinoma (GA) and esophagogastric junction adenocarcinoma (EGJA), but only patients with good pathomorphological response (pR) to NAC benefit from prolonged overall survival.</br> <b><br>Aim:</b> The study aims to evaluate ApoA-I and ApoB as candidate pre-treatment biomarkers of pR to NAC in patients with GA and EGJA.</br> <b><br>Materials and methods:</b> Serum samples were collected from 18 patients with GA and 9 with EGJA before the initiation of NAC to determine the ApoA-I and ApoB levels. After NAC tumor regression grade (TRG) was evaluated in resected specimens according to the Mandard's tumor regression grading system and correlated with pre-treatment ApoA-I and ApoB serum concentration, and ApoB-to-ApoA-I serum concentration ratio.</br> <b><br>Results:</b> We found a positive correlation of ApoA-I level and pR (95% CI: -0.863 to -0.467; P < 0.0001), a negative correlation of ApoB level and pR (95% CI: 0.445 to 0.857; P < 0.0001), a negative correlation of ApoB-to-ApoA-I ratio and pR (95% CI: 0.835 to 0.964; P < 0.0001).</br> <b><br>Conclusions:</b> ApoA-I and ApoB levels, and ApoB-to-ApoA-I ratio are candidate pre-treatment predictors of pR to NAC in GA and may help to guide personalized therapy.</br>Our work fits into the dynamically developing trend of personalized treatment. It describes a potentially important rationale for further evaluation of apolipoprotein A-I and apolipoprotein B as predictors of cancer response to neoadjuvant therapy.

SARS-CoV-2 Seroprevalence in Healthcare Workers before the Vaccination in Poland: Evolution from the First to the Second Pandemic Outbreak.

Healthcare workers (HCWs) are on the frontline, struggling with the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To describe recent or past infections, the serological assays enabled the assessment of the immune response developed in coronavirus disease (COVID-19) in the period when testing was hardly available. In this study, we investigated SARS-CoV-2 seroprevalence in HCWs in a Polish teaching hospital and the Regional Occupational Medicine Center after both the first and the second waves. ELISA-based tests for anti-SARS-CoV-2 IgA and IgG were used to determine immune response to SARS-CoV-2 in volunteer HCWs who worked in those institutions in May 2020 (208 participants aged 47.1 ± 12.5, 88% women) and in December 2020 (179 participants aged 45.2 ± 12.4, 86% woman). Risk factors for seropositivity were also assessed using a questionnaire filled out by all participants. We reported a significant increase in seroprevalence after the second wave (22.9%) compared with the first outbreak (2.4%) (OR 12.1; 95%CI 4.6-31.3; p < 0.0001). An association between IgG seroprevalence and severity of infections was noted. Furthermore, we demonstrated that amongst medical personnel, nurses exhibited a proportionally higher SARS-CoV-2 seroprevalence. Moreover, given the high seroprevalence in non-clinical group of HCWs, we suggest that community transmission can play a superior role to workplace exposure.

Polyvalent Mechanical Bacterial Lysate Administration Improves the Clinical Course of Grass Pollen-Induced Allergic Rhinitis in Children: A Randomized Controlled Trial.

BACKGROUND: Recent studies highlight the immunoregulatory potential of bacterial lysates, indicating their potential use in the prevention and treatment of allergic diseases. OBJECTIVE: To investigate the clinical efficacy of polyvalent mechanical bacterial lysates (PMBLs) in children with grass pollen-induced allergic rhinitis. METHODS: Seventy children with seasonal allergic rhinitis were enrolled to this study and were randomly assigned to the PMBL and placebo groups. Severity of seasonal allergic rhinitis symptoms was assessed by the total nasal symptom score, total ocular symptom score, and visual analogue scale. During 3 visits, peak nasal inspiratory flow was measured, and nasal smears for the presence of eosinophils and nasal lavage fluids for the presence of allergen-specific IgE against timothy grass pollen allergens were sampled. RESULTS: A statistically significant decrease in total nasal symptom score (P = .001), total ocular symptom score (P = .04), and visual analogue scale score for nasal and eye symptoms (P < .001 and P < .001, respectively) and an increase in peak nasal inspiratory flow (P = .04) were observed in the PMBL group versus the placebo group. During the grass pollen season, an increase and then a decrease in the number of eosinophils in nasal smears was observed in both groups; however, the number of eosinophils was significantly lower in the PMBL group versus the placebo group. No significant changes in allergen-specific IgE concentrations were observed in the PMBL group, whereas in the placebo group a statistically significant increase in allergen-specific IgE concentration was observed. CONCLUSIONS: Sublingual administration of PMBLs during the grass pollen season offers significant efficacy in alleviating seasonal allergic rhinitis symptoms in children sensitized to grass pollen allergens. PMBLs probably affect mucosal immunity, weakening the response of TH2 cells.

Diagnostic strategies for SARS-CoV-2 infection / Diagnostyka zakazen SARS-CoV-2.

COVID-19 pandemic highlighted the importance of laboratory diagnostics to reduce the spread of SARSCoV-2 and to treat patients with severe coronaviral disease. The situation required a rapid development of molecular and serological tests to enable mass screening, testing of high-risk groups, and establishing epidemiological data. Knowledge of diagnostic methods is continuously evolving, so it is crucial to understand the nature of the tests and to be able to interpret their results. This review discusses the current literature on diagnostic methods, prognostic markers, diagnostic recommendations, choice of the appropriate test, type of biological material, and interpretation of results depending on test sensitivity and disease duration. Also, the percentage of positive results in the selected countries at two distant time points of the epidemic was analyzed. Further development of diagnostic techniques and incorporation of new technologies can provide more accurate and faster tools for control the epidemic.

Myeloperoxidase level and inflammatory markers and lipid and lipoprotein parameters in stable coronary artery disease.

BACKGROUND: Myeloperoxidase (MPO) impairing endothelial functions. We investigated whether increasing concentration of myeloperoxidase (MPO) and inflammatory markers induce progression and incident acute coronary syndrome (ACS) in stable coronary artery disease (SCAD) patients. Therefore, the concentration of MPO, lipids, lipoproteins (apo(apolipoprotein) AI, apoB, lipoprotein associated phospholipase A2 (LpPLA2) level), inflammatory markers (high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) concentration) were examined. METHODS: This study concerned 67 SCAD patients divided into groups: all patients, patients with MPO < 200 ng/ml, MPO 200-300 ng/ml, MPO > 300 ng/ml concentration and 15 controls. ApoAI, apoB and hsCRP levels were examined using the immunonephelometric method, and MPO, LpPLA2, IL-6, TNF-α concentration was performed by using Quantikine ELISA kit R&D Systems. RESULTS: In the all patients, and in group with MPO 200-300 ng/ml TC, LDL-C, nonHDL-C, LpPLA2 concentration and TC/HDL-C, LDL-C/HDL-C ratios were insignificant, and significantly higher concentration of TG, apoB, MPO, inflammatory markers and TG/HDL-C, MPO/apoAI, MPO/HDL-C ratios but HDL-C, apoAI level and HDL-C/apoAI ratio were significantly reduced. In the group of patients with MPO < 200 ng/ml, level of TC, LDL-C, nonHDL-C, apoAI, apoAII, LpPLA2 and MPO and LDL-C/HDL-C ratio were in-significant, HDL-C was decreased but apoB, TG, inflammatory markers, apoB/apoAI, TG/HDL-C, MPO/apoAI, MPO/HDL-C ratio were significantly increased. In the group of patients with MPO > 300 ng/ml concentration of TC, LDL-C, nonHDL-C, apoAII, LpPLA2 and LDL-C/HDL-C ratios were not significant, but HDL-C and apoAI concentrations were significantly decreased. The concentrations of TG, apoB, MPO and inflammatory markers and TG/HDL-C, MPO/apoAI, MPO/HDL-C ratios were significantly increased compared to the controls. The apoAI concentration was significantly decreased and the concentration of MPO and hsCRP as well as MPO/apoAI and MPO/HDL-C ratios were significantly higher as compared to the group of patients with MPO < 200 ng/ml. Spearman's correlation test showed a positive correlation between MPO concentration and MPO/apoAI and MPO/HDL-C ratios in all patients and MPO < 200 ng/ml, MPO 200-300 ng/ml. The patients with MPO > 300 ng/ml showed a positive correlation between the concentration of MPO and the level of hsCRP and IL-6, and a negative correlation between MPO/apoAI ratio and the concentration of HDL-C, apoAI and apoAII. CONCLUSION: The results suggest that moderate dyslipidemia and dyslipoproteinemia deepening of inflammation, and inflammation slowly induce increase MPO concentration which decrease apoAI and HDL-C level and disturb HDLs function. The increasing MPO level and MPO/HDL-C, MPO/apoAI ratios can differentiate the SCAD patients at the risk of acute coronary syndrome (ACAD) and stroke.

γ-amino butyric acid (GABA) level as an overall survival risk factor in breast cancer.

INTRODUCTION: The γ-amino butyric acid (GABA) plays important role in the proliferation and migration of cancer cells. The aim of the study was to evaluate the level of GABA in breast cancer, in relation to clinical and epidemiological data. MATERIAL AND METHODS: The study was conducted on 89 patients with breast cancer in stage I-II. GABA level was assessed using spectrofluorometric method in tumour homogenates. Immunoexpression of E-cadherin was evaluated histologically on paraffin fixed specimens. Overall and disease-free survival was assessed for a 15-year interval period. RESULTS: Median overall survival was significantly longer (127.2 months) in patients with a high level of GABA (>89.3 µg/1), compared with a group with a low level of the amino acid (106.4 months). Disease-free survival was insignificantly different - 99 and 109 months, respectively. A significantly longer overall survival (131.2 months) was seen among patients with a high level of GABA and positive E-cadherin immunoexpression, compared with a group characterized by a low level of GABA and lack of E-cadherin immunorectivity (98.1 months). The co-existence of negative immunoexpression of E-cadherin and low GABA concentration resulted in a six-fold increase in the risk of death (HR=6.03). CONCLUSIONS: GABA has a significant prognostic value in breast cancer. Co-existence of a low level of GABA and loss of E-cadherin immune-expression seems to be a new, independent, and negative prognostic marker of the neoplasm.

Fibroblast growth factor 21 - a key player in cardiovascular disorders?

Fibroblast growth factor 21 (FGF21) is a newly discovered adipokine, synthesized by several organs, mostly by the liver, which was introduced as a potent metabolic regulator and insulin-sensitizing factor. Numerous animal studies have demonstrated that FGF21 improves glucose and lipids metabolism and exerts anti-inflammatory effects. However, data obtained from human studies have shown contradictory results, in which circulating FGF21 levels were often elevated in obesity, dyslipidemia, type 2 diabetes (DM2) and other conditions connected with insulin resistance. This increase in basal FGF21 concentrations observed in patients with obesity and other conditions related to insulin resistance was being explained as a compensatory response to the underlying metabolic disturbances or tissue resistance to FGF21 action. Furthermore, the results of clinical trials have shown that increased FGF21 concentrations were associated with increased cardiovascular (CV) risk and had a prognostic value in CV outcomes. In recent years, it has been reported that FGF21 may exert cardioprotective effects. This mini-review aims to summarize the current state of knowledge about the role of FGF21 in CV disorders, and discuss the molecular mechanism underlying the anti-atherogenic properties of this compound.

Fetuin-A (AHSG) and its usefulness in clinical practice. Review of the literature.

BACKGROUND: Fetuin-A, also called Alpha 2-Heremans Schmid Glycoprotein, is a multifunctional plasma agent what has been proven in animal and human studies. It plays a role as a physiological inhibitor of insulin receptor tyrosine kinase associated with insulin resistance and a negative acute phase reactant. It also regulates bone remodeling and calcium metabolism being an important inhibitor of calcium salt precipitation and vascular calcifications. METHODS: PubMed database was searched for articles from 2002 up to December 2014 to identify the role of fetuin-A in the pathogenesis of selected internal diseases. RESULTS: Due to secretion of fetuin-A mainly by the liver, it may be a marker of liver function and predictor of mortality in patients with cirrhosis and hepatocellular cancer. The associations between high fetuin-A and metabolic syndrome as well as its hepatic manifestation- nonalcoholic fatty liver disease and atherogenic lipid profile have been well proven. However, fetuin-A relation with BMI is not so clear. Contrary to few reports, many authors suggest that fetuin-A may be an independent risk factor for type 2 diabetes and marker of diabetic complications. Close associations of high and low fetuin-A concentrations with cardiovascular diseases and mortality risk have been reported which is explained by differences in analyzed populations, stages of atherosclerosis and calcifications, coexistence of type 2 diabetes or kidney dysfunction and different main pathways of fetuin-A actions in various diseases. CONCLUSIONS: Fetuin-A has a diagnostic potential as a biomarker for liver dysfunction, cardiovascular diseases and disorders associated with metabolic syndrome.

[Reasons for delay in treatment of breast cancer detected due to breast self-examination in women from the Lubelskie region]. / Przyczyny opóznien leczenia chorych na raka piersi wykrytego w trakcie samobadania u kobiet w województwie lubelskim.

OBJECTIVES: A delay in diagnosis and treatment of breast cancer patients is observed despite access to modern diagnostic methods. The aim of the study was to evaluate time between the first symptoms of breast cancer and treatment commencement, as well as to analyze reasons for the delay MATERIALS AND METHODS: The research was conducted on 260 breast cancer patients treated at the Oncology Center in Lublin between 2008 and 2011. 'Patient delay' was defined as the time gap of > 3 months between first symptoms of cancer and the doctor's appointment and 'system delay' as the time gap of > 1 month between the first medical consultation and commencement of treatment. RESULTS: Mean patient delay was 32.2 +/- 63.8 weeks. The main reasons were: disregard of symptoms (51%) and fear of being diagnosed with cancer (48%). Factors which significantly influenced the length of patient delay included: age > 65 years, non-regular gynecologic care, lack of prior cancer screening and lack of family history of breast cancer Mean system delay was 3.1 +/- 2.9 weeks. Tumors < 5 cm in diameter and clinical presentation other than a tumor significantly influenced the system delay CONCLUSIONS: A significant delay in diagnosis and treatment of breast cancer remains to be noted. Delay in seeking medical help was observed in 20% of the patients, whereas the referral was delayed due to system fault in 38% of the cases. Contrary to popular belief, patient delay (mean 32.2 +/- 63.8 weeks) is 10 times longer than system delay (3.1 +/- 2.9 weeks), suggesting an urgent need for further education of the general public and creating more accessible medical care.

Evaluation of prognostic parameters of E-cadherin status in breast cancer treatment.

INTRODUCTION AND OBJECTIVE: Breast cancer is one of the most frequent malignancies in women. Axillary lymph node involvement, tumour size, receptor status, and level of malignancy are the most significant prognostic factors in breast cancer, but insufficient to date. More factors are needed for establishing the prognosis and treatment in these patients. The aim of the presented study was evaluation of E-cadherin expression and its prognostic value among 89 specimens of breast cancer. MATERIALS AND METHODS: 89 formalin-fixed and paraffin-embedded breast cancer specimens were studied for expression of E-cadherin detected by immunohistochemistry. During 10-year observation overall/OS/and disease-free survival/DFS/of patients were assessed. RESULTS: Average of OS and DFS were shorter among patients without expression of E-cadherin in comparison to survival time of patients with expression of E-cadherin. The lack of E-cadherin expression was present more often among patients with distant metastasis. No essential changes were noticed in the level of E-cadherin depending on the size of the tumour, G, presence of metastasis into the lymph nodes, ER, PR and HER-2, hormonal condition and presence of cancerous tissues in lymphatic vessels and the infiltration of lymph nodes capsules. CONCLUSIONS: E-cadherin may play an important role in the prognosis of breast cancer patients.

Evaluation of concentrations of FGF-21 - a new adipocytokine in type 2 diabetes.

INTRODUCTION: Fibroblast growth factor 21 FGF-21 is a newly discovered adipocytokine which may play a vital role in improvement of insulin sensitivity and pathogenesis of type 2 diabetes. The aim of the study was to assess FGF-21 concentrations in the serum of patients with type 2 diabetes, in comparison to a control group, and evaluate the possible relationships between the studied cytokine and selected clinical and biochemical parameters MATERIAL AND METHODS: The study was conducted in 64 patients with type 2 diabetes, 28 women and 36 men aged 47-70 (median age 61.5), with a median duration of diabetes of 8.5 years. In fasting serum samples, concentrations of glucose, insulin, lipids profile parameters, creatinine, C-reactive protein (CRP), fibrinogen, HbA(1c), adiponectin, and FGF-21 were determined. The control group comprised 20 healthy persons matched for age to the study group, with no disturbances in carbohydrate metabolism: 14 women and 8 men. RESULTS: We found significant differences concerning the medians of body mass index (BMI) 32.4 kg/m(2) v. 24.1 kg/m(2), p < 0.001; waist circumference 114 cm v. 81 cm, p < 0.001; HDL cholesterol 42.5 mg/dl v. 62.5 mg/dl, p < 0.001; triglyceride (TG) 152 mg/dl v. 99 mg/dl, p < 0.01 in the studied group, in comparison with the control group, respectively. In patients with diabetes, median FGF-21 concentration was 239.9 pg/ml and was significantly greater in comparison to the control group: 112.6 pg/ml p < 0.01. Median adiponectin concentration in patients with type 2 diabetes was significantly lower in comparison to the control group, 7.5 ng/ml v. 9.95 ng/ml, p < 0.05. Significant correlations between FGF-21 concentrations and adiponectin (r = -0.24, p < 0.05), weight (r = 0.27, p < 0.05), glucose (r = 0.27, p < 0.05), HDL cholesterol (r = -0.26, p < 0.05), TG (r = 0.27, p < 005), and estimated glomerular filtration rate (eGFR) (r = -0.28, p < 0.05) were observed. No significant correlations between FGF-21 and parameters of metabolic control, markers of inflammatory status, and insulin resistance, or the presence of vascular complications of diabetes, were noticed. CONCLUSIONS: On the basis of the conducted studies it can be concluded that the greater FGF-21 concentration observed in the examined group of patients with type 2 diabetes may result from a compensatory reaction to metabolic disturbances or tissue resistance to this cytokine. The negative correlation between FGF-21 and eGFR suggests renal elimination of the examined compound. (Pol J Endocrinol 2010; 61 (1): 50-54).

[Analysis of some risk factors of coronary artery calcification in peritoneal dialysis patients]. / Badanie niektórych czynników ryzyka kalcyfikacji naczyn wiencowych u pacjentów leczonych dializa otrzewnowa.

Cardiovascular disease (CVD) is a major cause of death in peritoneal dialysed patients (PD-pts). Coronary artery calcification (CAC) is likely to affect the development of CVD. Purpose of our study was to evaluate coronary artery calcification and risk factors of this calcification in PD-pts. We studied 62 patients (38 F, 24 M) undergoing peritoneal dialysis (PD). Coronary calcification was examined by ECG-gated multidetector CT (Light Speed Ultra) using Agatson (AG) and volumetric (V) methods. Patients were divided into 3 groups depending on mean value of estimated CAC: group A-no calcification, group B-CAC maximal value 400 mm3, group C-CAC value more than 400 mm3. As risk factors of CAC were evaluated: patients age, sex, dialysis duration, serum concentration of Ca, P, homocysteine CRP and fibrinogen, as well as, CaxP product, intact PTH; presence of diabetes or hypertension. Coronary artery calcification was detected in 68% of patients. In the whole observed population positive correlation between CAC determined by AG and V methods and CRP (r = 0.36, p < 0.05) as well as patients age (r = 0.5, p < 0.01) was observed. There was also positive correlation between CAC and fibrinogen concentration (AG CAC r = 0.58, p < 0.05; V CAC r = 0.72, p < 0.05). When compared group C with the groups A and B cardiovascular complications were in this group more frequent than in the last two: 4 patients from group C died because of cardiovascular complications.

Biventricular versus right ventricular pacing decreases immune activation and augments nitric oxide production in patients with chronic heart failure.

INTRODUCTION: Immune system activation and oxidative stress are involved in the pathogenesis of heart failure (HF). We aimed to test the hypothesis that upgrading from right ventricular pacing (RVp) to biventricular pacing (BiVp) can counteract these phenomena. METHODS: 28 HF patients, with BiVp were switched to RVp for one week, and then returned to BiVp. Immediately prior to, and 48 h after the return to BiVp, left ventricular (LV) systolic function was evaluated by echocardiography, and serum N-terminal pro-brain natriuretic peptide (NTproBNP), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL6), nitric oxide metabolites (NO(x)) and malondialdehyde (MDA) were assayed. RESULTS: LV systolic function significantly improved 48 h after switching from RVp to BiVp: Ao-VTI (p<0.001), SV (p<0.001) and CO (p<0.001), and mitral regurgitation significantly decreased (p=0.003). At the same time, indices of peripheral immune activation decreased: TNF-alpha (p=0.02) and IL6 (p<0.001). MDA decreased (p<0.001), whereas NO(x) increased (p=0.04). NTproBNP and CRP did not change. In addition, in "responders" (i.e. CO increase >10% during BiVp vs. RVp) NTproBNP decreased and NO(x) increased. However, during BiVp, the decreases in TNF-alpha, IL6, and MDA occurred both in responders and in non-responders and were accompanied by a reduction in mitral regurgitation. CONCLUSION: The beneficial effect of BiVp compared to RVp extends beyond improving cardiac haemodynamics and comprises a decrease in immune activation accompanied by an increase in serum NO(x) and decrease in serum MDA.

Citicoline treatment increases retinal dopamine content in rabbits.

Citicoline (exogenous cytidine-5'-diphosphocholine) was reported to enhance dopaminergic neurotransmission in the brain. A few clinical studies showed beneficial effects of this drug on the function of the visual pathway in patients with glaucoma or amblyopia. The present study was aimed at determining whether citicoline could influence retinal catecholamine levels in adult male Albino rabbits. The animals received the drug (50 mg/kg i.p., twice daily) or vehicle for 7 days, and retinal catecholamine concentrations were determined by HPLC. Compared to vehicle-treated controls, citicoline-treated animals displayed a significantly higher retinal dopamine concentration and a tendency toward an increase in adrenaline concentration, while the noradrenaline concentration remained unchanged. It is, therefore, conceivable that citicoline reinforces dopaminergic transmission in the retina.