Phenotype of obesity and gastroesophageal reflux disease in the context of comorbidity in patients with cardiovascular diseases.

The relevance of studying such problems as gastroesophageal reflux disease (GERD) and obesity is caused by their high prevalence in the developed countries of the world. Epidemiological data indicate that obesity is a significant risk factor for developing GERD due to increased intra-abdominal pressure and gastroesophageal gradient, slowing of gastric evacuation and formation of hiatal hernia. Abdominal obesity increases the likelihood of complications of GERD: erosive esophagitis, Barrett's esophagus and adenocarcinoma. This fact is connected with humoral influences: increased production of pro-inflammatory cytokines and leptin, and decreased secretion of adiponectin. Treatment of comorbid patients requires higher dosages and longer courses of antisecretory medicines, and an additional prescription of ursodeoxycholic acid.

Evaluation of the efficacy and safety of the hybrid scheme for eradication therapy of Helicobacter pylori infection.

AIM: The aim is to conduct a comprehensive comparative study of the efficacy and safety of the hybrid scheme of eradication therapy (ET) in patients with peptic ulcer of the stomach or duodenum associated with Helicobacter pylori. MATERIALS AND METHODS: Materials and methods. In a prospective, randomized comparative study, 180 patients were divided into three equal groups of 60 people, depending on the prescribed 10-day ET regimen. Group 1 - the standard triple scheme (omeprazole, amoxicillin and clarithromycin); group 2 - four-component therapy with preparations of bismuth (omeprazole, tetracycline, metronidazole, bismuth tricalium dicitrate); group 3 - hybrid scheme (first 5 days: omeprazole and amoxicillin, the next 5 days: omeprazole, amoxicillin, clarithromycin, metronidazole). The effectiveness of ET was determined with the help of a breath test a month after the end of therapy. Adverse events were recorded by patients in specially developed diaries. Pharmacoeconomic analysis was carried out using the "cost-effectiveness" method with calculation of the CER coefficient. RESULTS: Results and discussion. The effectiveness of standard triple therapy was 73.3% (ITT), 75.9% (PP); four-component therapy with bismuth preparations - 78.3% (ITT), 82.4% (PP); hybrid scheme - 85% (ITT), 91% (PP). Hybrid therapy proved to be significantly more effective than standard triple therapy with a odds ratio (OR) of 3.25; 95% confidence interval (CI) 1.08-9.73 (p=0.043, χ2=4.75, p-level=0.029298). The incidence of adverse events with the use of triple, four-component and hybrid ET regimens was 15; 18.3 and 28.3% respectively. The OR of at least one adverse event in patients receiving a hybrid ET regimen compared with triple therapy was 2.24 (95% CI 0.91-5.53, p=0.0823, χ2=3.14, p-level=0.076394), and compared with the four-component therapy - 1.76 (95% CI 0.74-4.17, p=0.2804, χ2=1.68, p-level=0.194924). According to the results of the pharmacoeconomic analysis, the most profitable from an economic point of view was a hybrid ET scheme with a CER of 20.1. CONCLUSION: The conclusion. Hybrid therapy showed the greatest effectiveness in comparison with the triple and four-component ET regimens, however, the incidence of side effects in patients receiving the hybrid ET scheme was higher, although it remained within the acceptable level for use in clinical practice. Pharmacoeconomic analysis also showed the advisability of designating a hybrid ET scheme. The obtained data allow to draw a conclusion about the necessity of further study of the efficiency and safety of the hybrid ET scheme.

[Clinical significance of heart rhythm variability in patients with gastroesophageal reflux disease].

Cardiac manifestations of gastroesophageal reflux disease (GERD) including retrosternal pain and cardiac rhythm disorders were often mentioned in early publications. However, classification of GERD adopted at the 2005 Montreal congress does not include such conditions. Non-coronarogenic pain in the thoracic cage is recognized to be a typical esophageal syndrome while the reflex spasm of coronary arteries and cardiac rhythm disorders associated with GERD should be regarded as manifestations of comorbidity of GERD and cardiovascular diseases. Arrhythmias occur in 30% of patients with GERD, but relevant therapeutic and preventive modalities are poorly developed. Nor are there reliable predictors of arrhythmias. An important role in their pathogenesis in patients with GERD is played bydisbalance of sympathetic and parasympathetic components of vegetative nervous system (VNS). One of the approaches to studying this issue is the analysis of heart rhythm variability (HRV). We consider basic principles of clinical interpretation of the results of HRV research that allow to evaluate the state of VNS and interaction of its components. Analysis of recent publications gives evidence that many HRV parameters depend not only on the balance between components of VNS as was believed by earlier authors (for the lack of their reciprocal relationship) but also on the activity of these components. Other modulating factors include the heart rate, respiratory pattern, intrathoracic pressure, and diastolic atrial extension. We report the results of HRV assessment in patients with GERD that illustrate heart rhythm rigidity and predominant disorders of activity of the parasympathetic component of VNS especially well apparent in patients with erosive reflux esophagitis. However, other authors demonstrate oppositely directed changes and the involvement of the sympathetic component. A possible cause of this discrepancy is factors other than VNS influencing HRV. It is concluded that analysis of HRV can be used to develop a method for the prevention of GERD-associated arrhythmia. The diagnostic value of such method is limited and requires new algorithms for data interpretation taking account of their multifactorial origin.

[An immune response and an alveolar macrophage phenotype in asthma, gastroesophageal reflux disease and their concurrence].

AIM: To test the hypothesis that an impaired pulmonary immune response in asthma, gastroesophageal reflux disease (GERD) and their concurrence of these diseases is largely determined by disordered alveolar macrophage (AM) reprogramming and to assess the pulmonary immune response and an AM phenotype in patients with asthma, GERD and their concurrence. SUBJECTS AND METHODS: The levels of proinflammatory M1 cytokines, such as IL-1ß, IL-8, IL-12p70, IFN-γ, TNF-α, and TNF-ß, anti-inflammatory M2 cytokines, such as IL-4, IL-5, and IL-10, and bivalent M1/M2 cytokines, such as IL-2 and IL-6, were determined in bronchoalveolar lavage fluid (BALF) and AM culture medium. RESULTS: Serious deformations in the pulmonary immune response were first detected in patients with mixed pathology towards to an anti-inflammatory M2 phenotype. The change in the pulmonary immune response phenotype in GERD towards Ml and in comorbidity towards M2 was coincident with that of the AM phenotype. In asthma, the change in the pulmonary immune response phenotype occurred towards to M2 and that in the intrinsic AM phenotype did towards M1. This phenotype is likely to form a proinflammatory component and to cause an asthma exacerbation. CONCLUSION: Analysis of the spectrum of cytokines in BALF and produced by macrophages in asthma, GERD and their concurrence validated the hypothesis that impaired pulmonary immune responses in these diseases are associated with disordered AM reprogramming. The findings also suggest that therapy for the inflammatory component in these diseases should be performed by taking into account the specificity of the cytokine structure of an immune response and the phenotypic heterogeneity of immune cells.