Detection of anti-infliximab antibodies in Slovak IBD patients and its costs saving effect.

OBJECTIVE: Management chronic inflammatory bowel disease (IBD) patients is associated with diagnosis, targeted treatment and and individual approach. There is a group of patients which loss the response to the biologic treatment caused by insufficient levels of biologics or positive antibodies against these drugs. This study was aimed to determine the prevalence of patients with positive antibodies against the biological treatment and the costs saving probabilities of the antibodies detection during the treatment. STUDY DESIGN: This retrospective study was based on examination of 183 IBD patients' sera (72 with Crohn's disease (CD) and 111 ulcerative colitis (UC)) treated with infiliximab. METHODS: Circulating serum infliximab concentrations and anti-infliximab antibodies (ATI) were quantified by ELISA methods. Costs associated with the treatment were analysed from the data of General Health Insurance Company, Slovakia. RESULTS: The average infliximab concentrations in groups of CD were 2.9 µg/mL, 38.9% of samples had a concentration ≤1 µg/mL. Group with UC had average infliximab levels of 3.19 µg/mL, 32.4% bellow ≤1 µg/mL. Positive ATI levels were detected in 52 patients, in 28 patients with CD (38.8%) and 24 patients with UC (21.6%). The average values of the antibodies were 387.75 U/ml in CD and 391.94 U/ml in UC group. More than 28% IBD patients were positive for ATI. After application of the results to the database of all IBD patients, finishing of the treatment with ATI could lead (after considering the ATI quantification costs) to possible annual savings of more than €2 million in Slovakian health-care system. CONCLUSIONS: Monitoring of infliximab and antibodies against infliximab and anti-TNF-α biologics may help optimize treatment strategies and costs for biological treatment.

Elevated Circulating PCSK9 Concentrations Predict Subclinical Atherosclerotic Changes in Low Risk Obese and Non-Obese Patients.

INTRODUCTION: Many studies have highlighted the important role of PCSK9 in the development of cardiometabolic changes and its possible function as a biomarker of myocardial infarction or ischemic heart disease. This study aimed to determine the relationship between circulating PCSK9 levels and subclinical vascular changes in the group of low risk patients without manifest cardiovascular diseases. METHODS: In this study, 120 healthy patients, free of manifest cardiovascular diseases, diabetes mellitus, and without lipid-lowering therapy, were divided into three groups based on BMI: normal weight (N = 50), overweight (N = 30), and obese (N = 40). Biochemical parameters, including basic lipid and non-lipid ones, were analyzed. PCSK9 levels were measured by ELISA, vascular changes were quantified by carotid ultrasound (carotid artery intima-media thickness, cIMT), and arterial stiffness parameters (pulse wave velocity, PWV; augmentation index, AI; stiffness parameter, ß) were measured by an echo-tracking method. RESULTS: Plasma levels of PCSK9 significantly increased in obese (172.78 ± 51.67 ng/mL) in comparison with overweight (120.14 ± 37.64, p < 0.001) and normal weight groups (114.92 ± 35.87, p < 0.001). Differences between the overweight and normal weight groups were not significant (p = 0.85). The level of PCSK9 significantly correlated with values of BMI (p < 0.001, r = 0.38). In addition to increase in laboratory parameters associated with moderate metabolic changes, significant increase in cIMT and parameters of vascular changes (ß, AI, PWV) were detected in groups with elevated BMI. Significant positive linear correlation of PCSK9 concentrations and cIMT (p < 0.001, r = 0.39), PWV (p < 0.001, r = 0.31), and ß (p < 0.001, r = 0.3) were found. In multivariable regression analysis after adjusting for gender, age, BMI, and LDL, the impact of PCSK9 on cIMT, ß, and PWV remained significant (p = 0.006, 0.03, and 0.002, respectively). CONCLUSION: PCSK9 plasma levels significantly correlated with subclinical vascular changes and their values were significantly elevated in obese subjects. We assume that PCSK9 could be used as a predictor of early vascular involvement, prior to the existence of manifest atherosclerosis. These results also highlight the role of anti-PCSK9 treatment in primary prevention.

Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia.

BACKGROUND: Statins represent a group of drugs that are currently indicated in the primary and secondary prevention of cardiovascular events. Their administration can be associated with side effects and the insufficient reduction of triacylglyceride (TAG) levels. This study aimed to assess the effect of the triple combination of statins with omega-3 fatty acids and coenzyme Q10 (CoQ10) on parameters associated with atherogenesis and statin side effects. METHODS: In this pilot randomized double-blind trial, 105 subjects who met the criteria of combined dislipidemia and elevated TAG levels were randomly divided into three groups. In the control group, unaltered statin therapy was indicated. In the second and third groups, omega-3 PUFA 2.52 g/day (Zennix fa Pleuran) and omega-3 PUFA 2.52 g+CoQ10 200 mg/day (Pharma Nord ApS) were added, res//. At the end of the 3-month period (±1 week), all patients were evaluated. RESULTS: Significant reduction of hepatic enzymes activity, systolic blood preasure, inflammatory markers and TAG levels were detected in both groups in comparison to the control group. Activity of SOD and GPx increased significantly after additive therapy. Coenzyme Q10 addition significantly reduced most of the abovementioned parameters (systolic blood preasure, total cholesterol, LDL, hsCRP, IL-6, SOD) in comparison with the statin+omega-3 PUFA group. The intensity of statin adverse effects were significantly reduced in the group with the addition of CoQ10. CONCLUSIONS: The results of this pilot study suggest the possible beneficial effects of triple combination on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.

Rare Presentation of Left Lower Lobe Pulmonary Artery Dissection.

Background. Pulmonary arterial dissection with chronic pulmonary arterial hypertension as its major cause is a very rare but life-threatening condition. In most cases the main pulmonary trunk is the affected site usually without involvement of its branches. Segmental or lobar pulmonary artery dissection is extremely rare. Case Presentation. We report a unique case of left lower lobe pulmonary artery dissection in a 70-year-old male, with confirmed chronic pulmonary hypertension. To confirm dissection MDCT pulmonary angiography was used. Multiplanar reformation (MPR) images in sagittal, coronal, oblique sagittal, and curved projections were generated. This case report presents morphologic CT features of rare chronic left lobar pulmonary artery dissection associated with chronic pulmonary hypertension at a place of localised pulmonary artery calcification. CT pulmonary angiography excluded signs of thromboembolism and potential motion or flow artefacts. Conclusion. To the best of our knowledge, no case of lower lobe pulmonary artery dissection with flap calcification has been reported yet. CT imaging of the chest is a key diagnostic tool that is able to detect an intimal flap and a false lumen within the pulmonary arterial tree and is preferred in differential diagnosis of rare complications of sustained pulmonary arterial hypertension.

Trehalase as a possible marker of intestinal ischemia--reperfusion injury.

BACKGROUND: Different pathological affections of the small intestine cause corresponding morphological and functional changes. The present study was aimed to assess intestinal trehalase activities during ischemia and following reperfusion, correlate them with the pathological changes and determine whether trehalase could be used as a biochemical marker of the intestinal ischemia, ischemia - reperfusion injury. MATERIAL AND METHODS: Wistar rats, randomly divided into 5 experimental groups (IR) (each n=15), were subjected to one hour mesenteric ischemia followed by 0, 1, 4, 12 and 24 hours of reperfusion. As a control group sham operated animals were used (n=15). The activity of trehalase was determined using an adapted Dahlqwist method. The range of intestinal injury was determined using histological (histopathological injury index and goblet cell quantification) and immunohistochemical (Ki67, InSitu TUNEL) methods. RESULTS: The highest activities of trehalase were recorded in the control group (C=4.42 ± 0.373 µmol/mg/h). The most altered intestinal histology detected in group IR1 was accompanied by the lowest trehalase activity (IR1=0.97 ± 0.209 µmol/mg/h; p < 0.001 C vs. IR1). Improved histological structure in the remaining reperfusion periods correlated with increase in trehalase activity. Almost normal mucosal histological architecture and 72% of the enzymatic activity were restored after 24 hours of reperfusion (IR24=3.20 ± 0.266 µmol/mg/h; p < 0.01 IR1 vs. IR24). CONCLUSION: The correlation between intestinal histology and trehalase activities during intestinal injury has been shown. Trehalase activity is closely associated with the status of the histological architecture of the small intestine.

Intravenous administration of tetramethylpyrazine reduces intestinal ischemia-reperfusion injury in rats.

Intestinal ischemia-reperfusion injury (IIRI) is a life-threatening condition requiring prompt medical intervention. Tetramethylpyrazine (TMP) is a biologically active alkaloid isolated from Ligusticum wallichii. Previously, it was shown that TMP causes vasodilatation and inhibition of platelet aggregation as well as exhibits significant antioxidant effects. Therefore, the aim of the present study was to evaluate possible therapeutic effects of TMP in the prevention of IIRI. Wistar rats (n = 80) were randomly divided into eight experimental groups and subjected to a 1 h occlusion of cranial mesenteric artery followed by 0, 1, 12, and 24 h period of reperfusion. Thirty minutes before the IIRI animals received either TMP (30 mg/kg, i.v.) or identical volume of saline. In addition, a control group of 10 animals was not exposed to IIRI. Intestine morphology was evaluated by using histopathological injury index examination (HII), goblet and Paneth cells quantification as well as by applying immunofluorescent methods such as InSitu TUNEL and caspase-3 positivity assessment. Here we showed that preconditioning with TMP prior IIRI decreases the grade of injury. Significant reduction of HII was detected in TMP pretreated groups after 0, 1, and 12 h of reperfusion where injury reduction up to 75% was found. Lower histopathological damage in preconditioned groups was accompanied with increased number of secretory epithelial cells and decreased number of apoptotic cells. These results demonstrate the protective effect of TMP on the small intestine mucosa, suggesting administration of TMP as a molecule for pharmacological intervention against IIRI.