Gastroesophageal reflux disease: risk factors, current possibilities of diagnosis and treatment optimisation

Gastroesophageal reflux disease (GERD) is one of the most common causes of health care seeking at the primary care level in many countries. At an epidemiological level, GERD has been shown to be associated with a number of risk factors: obesity, tobacco smoking, alcohol abuse, certain patterns of eating behaviour, and the use of several medications. GERD is now regarded as a heterogeneous disease and includes different phenotypes (erosive reflux disease, non-erosive reflux disease, hypersensitive oesophagus, functional heartburn), the proper diagnosis of which improves the effectiveness of therapy in patients with heartburn symptoms. Daily impedance–pH monitoring is known to be an integral part of the diagnostic algorithm for GERD and is a functional diagnostic method to record all types of refluxes entering the oesophagus regardless of pH, to assess their association with symptoms, and to determine whether patients with heartburn symptoms belong to a particular phenotype. Esophageal manometry plays a key role in the evaluation of patients with heartburn symptoms, as it helps to rule out other conditions that may mimic GERD: achalasia cardia and scleroderma esophagus. This technique is used to assess thoracic esophageal motility and sphincter function and in the assessment of patients prior to antireflux surgery or in the refractory course of GERD. The article describes in detail GERD risk factors (triggers of heartburn), as well as diagnostic aspects, taking into account a differentiated approach to patients with heartburn based on daily impedance–pH monitoring data in accordance with the current guidelines and recommendations

Evaluation of the therapeutic efficacy of original and generic meloxicam in the treatment of acute neck pain

Introduction. In the structure of the global burden of diseases, back pain ranks first in the world in the list of causes of disability. Neck pain is one of the most common diseases of the musculoskeletal system. An integral part of the strategy for the treatment of acute neck pain is the use of original nonsteroidal anti-inflammatory drugs (NSAIDs) with high proven effectiveness.Objective. To conduct a comparative analysis of the therapeutic efficacy of the original drug meloxicam (Movalis) and its generic (Amelotex) in the treatment of patients with acute nonspecific musculoskeletal pain of cervical localization.Materials and methods. The article provides an assessment of the therapeutic effectiveness of the original drug meloxicam (Movalis) and its generic (Amelotex) in the treatment of patients with acute neck pain. Comparative analysis of the results of treatment of 108 patients hospitalized in the Branch of the MC JSC “Admiralteyskie Verfi” aged 18 to 60 years (58 men and 50 women) with a diagnosis of acute dorsalgia of cervical localization (M54.2 according to ICD-10). The average age of patients is 42.5 ± 11.1 years.Results. As a result of the clinical and neurological study and statistical processing of the data obtained, it was found that the use of Movalis in the treatment of patients with acute neck pain was more effective compared to the use of generic (Amelotex). In  the  Movalis group, the  level of  pain  intensity and the  index of  disability after treatment was significantly lower than in the Amelotex group at an equivalent dose of 15 mg per day (p < 0.01). The analgesic effect in the group of patients receiving Movalis was longer. There was a significant decrease in sleep disorders associated with pain syndrome in the group (Movalis) compared with patients of the second group (Amelotex). Conclusions. The absence of therapeutic bioequivalence between Movalis and Amelotex revealed in our study determines the relevance of the choice of drugs for the complex therapy of patients of this profile. A multimodal approach to the strategy of treating neck pain, individually patient-oriented, including the use of effective and safe medicines, physical exercises, manual therapy, is optimal.>< 0.01). The analgesic effect in the group of patients receiving Movalis was longer. There was a significant decrease in sleep disorders associated with pain syndrome in the group (Movalis) compared with patients of the second group (Amelotex).Conclusions. The absence of therapeutic bioequivalence between Movalis and Amelotex revealed in our study determines the relevance of the choice of drugs for the complex therapy of patients of this profile. A multimodal approach to the strategy of treating neck pain, individually patient-oriented, including the use of effective and safe medicines, physical exercises, manual therapy, is optimal

Features of the Parameters of 24-Hours pH-Impedance and High-Resolution Esophageal Manometry in Patients with Barrett's Esophagus on Proton Pump Inhibitors

Аim: to identify predictors of insufficient effectiveness of proton pump inhibitors based on the evaluation of the results of 24-hour pH-impedance and high-resolution esophageal manometry in patients with Barrett's esophagus.Materials and methods. 52 patients with histologically confirmed Barrett's esophagus who are on therapy with proton pump inhibitors were examined. All patients underwent daily pH-impedance and high-resolution esophageal manometry.Results. According to daily pH-impedance, group 1 consisted of 37 patients who responded satisfactorily to antisecretory therapy, group 2 of 15 patients who demonstrated insufficient response to acid-suppressive therapy, 11 of whom had no clinical manifestations. The total number of reflux averaged 55 in group 1 and 106 in group 2. The average number of acid reflux in group 1 was 5.68, in group 2 — 48.5. The average number of non-acid reflux prevailed in patients of group 2 and averaged 58, in group 1 the indicator averaged 47. Evaluation of the results of high-resolution esophageal manometry showed that violations of the structure and function of the esophago-gastric junction were detected in 21 patients out of 52. Disorders of the motility of the thoracic esophagus were detected in 31 patients out of 52. When comparing the frequency of motor disorders from the thoracic esophagus in groups 1 and 2, no significant differences were obtained. However, significantly more frequent registration of violations of the structure and/or function of the esophago-gastric junction was found in the group with unsatisfactory effectiveness of proton pump inhibitors.Conclusion. In a number of patients with Barrett's esophagus, there is an insufficient effect of acid-suppressive therapy and at the same time an asymptomatic course of the disease, which may increase the risk of its progression. Predictors of insufficiently successful treatment of patients with Barrett's esophagus may be both insufficient pharmacological effect of proton pump inhibitors themselves, and motility disorders that cause the presence of non-acid reflux, decreased esophageal clearance, which in turn may cause the patient's symptoms to persist and adversely affect the condition of the esophageal mucosa

High resolution manometry and new classification of esophageal motility disorders

Purpose of the review. To present application of Chicago classification criteria of esophageal motility disorders defined in high resolution manometry in clinical practice. Basic provisions. High-resolution manometry is the most exact hi-tech diagnostic method for esophageal motor function disorders according to Chicago classification v3.0. Uniqueness of the method consists in capacity to define integrated quantitative and qualitative metrics of esophageal contractile function and to establish their specific disorders e.g.: change of intrabolus pressure at disorders of esophagogastric junction (EGj) outflow, hypercontractile esophagus, fragmented contractions and weak or failed peristalsis, distal esophageal spasm. Assessment of the type of achalasia subtypes has significant impact on the patients’ treatment choice. According to anatomical location of the lower esophageal sphincter and crural diaphragm several morphological types of gastro-esophageal junction are defined that determine severity of gastroesophageal reflux disease. Multiple rapid swallow responses during esophageal high-resolution manometry reflect esophageal body peristaltic reserve and is a predictor of postoperative complications. Differential diagnosis of belching type became possible at combined application of high-resolution manometry and impedance measurement. Conclusion. High-resolution manometry is a fundamental diagnostic test of esophageal motor function disorders. Clinical application of this method significantly expands diagnostic potential and allows to carry out personalized treatment that increases treatment quality

Особенности репаративного процесса при антиглаукомных операциях (экспериментальное исследование)

The characteristic features of the wound process in the ocular tissues and the effects of drugs that directly affect the formation of connective tissue in the area of intervention are important for understanding and evaluating the prognosis of glaucoma surgery. This experimental study consisted of imitating a glaucoma surgery and evaluating the therapeutic effect of drugs affecting the reparative processes. When assessing the degree of hyperemia in the area of formed filtration blebs as the main prognostic sign of excessive scarring in the postoperative period, its maximum severity was noted with a low tendency to decrease throughout almost the entire follow-up period in the group with the introduction of 5-fluorouracil (5-FU). Morphologically, as the inflammatory process subsided, an increase in the density of fibroblasts was detected in the surgery site, indicating a presence of an active proliferative process. The least amount of local tissue reaction to surgical trauma was noted in the group with 5-FU drug injected in the filtering bleb area in the postoperative period: the absence of inflammatory cells in the stroma, expansion of episcleral vessels and low density of connective tissue cells in the area of surgically formed intraocular fluid outflow pathways. The obtained experimental data indicates a decrease in the activity of scarring processes in the glaucoma surgery site and, consequently, a favorable prognosis of its longterm effectiveness.Особенность раневого процесса в тканях глаза и характер воздействия препаратов, непосредственно влияющих на образование соединительной ткани в области вмешательства важны для понимания и оценки прогноза антиглаукомной операции.Экспериментальное исследование включало имитацию антиглаукомной операции и оценку терапевтического действия препаратов, влияющих на репаративные процессы.При оценке степени гиперемии в области сформированных фильтрационных подушек как основного прогностического признака избыточного рубцевания в послеоперационном периоде была отмечена ее максимальная выраженность с низкой тенденцией к снижению на протяжении практически всего периода наблюдения в контрольной группе без введения 5-фторурацила (5-ФУ). Морфологически по мере стихания воспалительного процесса в зоне вмешательства обнаруживали увеличение плотности фибробластов, свидетельствующее о ходе активного пролиферативного процесса.В группе с введением в послеоперационном периоде препарата 5-ФУ в область фильтрационной подушки отмечена наименьшая местная реакция на операционную травму по сравнению с контрольной группой: отсутствие воспалительных клеток в строме, расширение эписклеральных сосудов и низкая плотность соединительнотканных клеток в зоне хирургически сформированных путей оттока внутриглазной жидкости.Полученные экспериментальные данные свидетельствуют о снижении активности процессов рубцевания в зоне антиглаукомной операции и, следовательно, благоприятном прогнозе ее долгосрочной эффективности

Late pleistocene sedimentation history of the Shirshov Ridge, Bering Sea

The analysis of the lithology, grain-size distribution, clay minerals, and geochemistry of Upper Pleistocene sediments from the submarine Shirshov Ridge (Bering Sea) showed that the main source area was the Yukon–Tanana terrane of Central Alaska. The sedimentary materials were transported by the Yukon River through Beringia up to the shelf break, where they were entrained by a strong northwestward-flowing sea current. The lithological data revealed several pulses of ice-rafted debris deposition, roughly synchronous with Heinrich events, and periods of weaker bottom-current intensity. Based on the geochemical results, we distinguished intervals of an increase in paleoproductivity and extension of the oxygen minimum zone. The results suggest that there were three stages of deposition driven by glacioeustatic sea-level fluctuations and glacial cycles in Alaska

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Radiocarbon ages measured in core PSh63-5159R from the southwest Barents Sea

Environmental changes in the surface and bottom water layers of the Ingøydjupet Basin and history of Atlantic water inflow to the southwestern Barents Sea during the last 16 ka are reconstructed on the base of planktic and benthic foraminiferal assemblages. A multiproxy study of sediment cores PSh-5159R and PSh-5159N, including AMS 14C dating, provides time resolution of about 200 years for the deglaciation period, 100 years for Holocene, and 25-50 years for the last 400 years. Stable polar conditions with sea ice on the surface were typical for the early deglaciation period. Unstable bottom settings and onset of ice rafting marked Oldest Dryas. Cold Atlantic water inflow increased notably during the Boiling-Allerod interstadial nearby the site location and then decreased during the Younger Dryas. Early Holocene was characterized by abrupt warming in the bottom and surface water layers, especially ~9.7-7.6 ka BP. Stable conditions prevailed during Middle Holocene. Remarkable changes in the sea-surface temperature and bottom environments occurred during last 2.5 cal. ka BP