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Introduction. Chronic gastritis is one of the most common problems in gastroenterology and general medical practice. In this study, we tried to analyze the actions of therapists in relation to patients with symptoms of dyspepsia, to assess how different symptom complex affects the choice of therapy and the diagnostics.Aim. Identifying the process of a preliminary diagnosis by symptoms, determining the ability of physicians to differentiate clinical syndromes, and determining the approaches to empirical therapy at first visit and following the “test and treat” strategy aimed at identifying the H. pylori infection.Materials and methods. The study was conducted using the CAWI (Computer-assisted Web Interview) method. Each physician who agreed to participate in the study received a link to take the survey and independently entered the answers to the questions formulated by the researcher. The descriptions of three profiles of adult patients with suspected gastritis diagnosis who applied for the first time were suggested: 1) a patient with a pain syndrome and dyspepsia symptoms; 2) a patient with dyspepsia symptoms; 3) a patient with a pain syndrome.Results. The study involved 205 physicians from 33 cities of Russia. The most commonly assumed diagnosis was gastritis: 50% of responders suggested it for patient 1, 51% – for patient 2, and 40% – for patient 3. Despite the unambiguous description of the delayed motility symptoms in patients 1 and 2, the most commonly assumed diagnoses did not reflect the presence of a problem. At the same time, physicians did not conduct diagnostic tests for H. pylori infection in case of patients 1 and 3 with obvious symptoms of gastritis. In case of infection, physicians suggest prescribing eradication drugs to each patient, and the most popular pharmacological group suggested were PPIs (91%). However, every tenth physician suggested eradication without PPIs.Conclusion. The results of the survey indicate a lack of awareness among therapists about the symptoms of delayed motility. This leads to the symptomatic pharmacotherapy, which does not provide the rupture of pathogenetic mechanisms

Gabrio Bassotti,1 Paolo Usai Satta,2 Massimo Bellini3 1Gastroenterology & Hepatology Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; 2Gastrointestinal Unit, “G. Brotzu” Hospital, Cagliari, Italy; 3Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, ItalyCorrespondence: Gabrio BassottiClinica di Gastroenterologia ed Epatologia, Ospedale Santa Maria della Misericordia, Piazzale Menghini, 1, San Sisto (Perugia), 06156, ItalyEmail gabassot@tin.itAbstract: Chronic idiopathic constipation (CIC) is a common functional bowel disorder characterized by difficult, infrequent, and/or incomplete defecation. It has a great impact on the quality of life and on health care system and represents a heavy economic burden. The diagnosis is based on symptoms, classified by the Rome IV criteria. The aim of this review was to evaluate the current therapeutic guidelines for adult CIC and highlight new emerging treatments. In detail, European, French, Spanish and Korean guidelines have been identified and compared. Osmotic laxatives, and in particular polyethylene glycol, represent the first-line therapeutic approach. Stimulant laxatives are recommended as a second-line therapy. Pelvic floor rehabilitation is recommended in patients with ano-rectal dyssynergia. In patients who fail to improve with pharmacological therapies sacral nerve stimulation is considered as last chance before surgery. Surgical approach has however limited indications in selected cases. Inertia coli refractory to any approach and obstructed defecation are two subtypes which can benefit from surgery. Among emerging agents, prucalopride, a prokinetic agent, is recommended as a second-line treatment in refractory CIC patients. In addition, the secretagogues linaclotide and plecanatide and the bile acid transported inhibitor elobixibat can be effective in patients not responsive to a second-line therapeutic regimen, although they are not worldwide commercially available.Keywords: chronic idiopathic constipation, guidelines, osmotic laxatives, pelvic floor rehabilitation, prokinetics, secretagogues

The review article describes the epidemiology, clinical picture, pathogenesis, approaches to the diagnosis and treatment of chronic gastritis and functional dyspepsia. Chronic gastritis is an unreasonably common diagnosis in our clinical practice, which is diagnosed in patients with disturbing dyspeptic complaints. According to the agreement documents, chronic gastritis is primarily a morphological concept. Chronic gastritis has no pathognomonic clinical signs and should be diagnosed during the histological examination of the gastric mucosa. Functional dyspepsia is a diagnosis that reflects the presence of a certain symptom complex (pain or burning sensation in the epigastrium, a feeling of fullness or early satiety) in the absence of diseases that could explain the symptoms. Secondary dyspepsia is diagnosed in patients with organic diseases of the upper gastrointestinal tract, metabolic or systemic diseases that cause dyspeptic syndrome. In the process of examining a patient with disturbing dyspeptic complaints, it is advisable for the doctor to use the diagnosis “unspecified dyspepsia” – a preliminary diagnosis before laboratory and instrumental examination aimed at identifying the cause of the dyspeptic syndrome. Dyspepsia associated with H. pylori is diagnosed in patients with H. pylori infection. The diagnosis is revised over time and is competent if complaints have been relieved within 6 months after effective H. pylori eradication.The main drugs for the treatment of patients with dyspeptic complaints are proton pump inhibitors and prokinetics. Omeprazole with domperidone sustained release (SR) in a fixed dose combination is characterized by optimal efficacy and a good safety profile in patients with both functional and secondary dyspepsia and ensures a high level of treatment adherence.

The definition of gastritis is based on the histological features of the gastric mucosa. This is not the erythema observed during gastroscopy, and there are no specific clinical manifestations or symptoms that determine it. The modern classification of gastritis is based on time (acute and chronic), histological features, anatomical distribution and the main pathological mechanisms. Acute gastritis will develop into chronic if left untreated. Helicobacter pylori (H. pylori) is the most common cause of gastritis worldwide. However, from 60 to 70% H. pylori-negative subjects with functional dyspepsia or non-erosive gastroesophageal reflux were also found to have gastritis. H. pylori-negative gastritis is considered when a person meets all four of these criteria: negative triple staining of biopsies of the gastric mucosa, no history of treatment of H. pylori. In these patients, the cause of gastritis may be associated with tobacco smoking, alcohol consumption and / or the use of nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids. Other causes of gastritis include autoimmune gastritis associated with antibodies of serum anti-parietal and anti-internal factor; organisms other than H. pylori, such as Mycobacterium avium intracellulare, Herpes simplex and Cytomegalovirus; gastritis caused by acid reflux; Rare causes of gastritis include collagen gastritis, sarcoidosis, eosinophilic gastritis and lymphocytic gastritis. The clinical picture, laboratory studies, gastroscopy, as well as histological and microbiological examination of tissue biopsies are important for the diagnosis of gastritis and its causes. Treatment of gastritis caused by H. pylori leads to the rapid disappearance of polymorphic-nuclear infiltration and a decrease in chronic inflammatory infiltrate with gradual normalization of the mucous membrane. Other types of gastritis should be treated based on their etiology.

Functional dyspepsia is one of the most common functional disorders of the gastrointestinal tract, which resulted from impaired motor skills, visceral hypersensitivity, increased mucosal permeability, disorders of the autonomic nervous system, etc. There is no specific therapy for this disease, which often leads to the irrational use of various groups of drugs. Drug therapy is recommended only during periods of symptoms. The main options of pharmacotherapy include the use of proton pump inhibitors, phytotherapeutic drugs, eradication therapy of Helicobacter pylori. Against the background of possible motor disorders, prokinetics are also one of the possible treatment options, but cisapride has long been withdrawn from sale due to cardiotoxicity, the use of domperidone and metoclopramide is limited due to side effects, especially with long-term therapy, so currently the only prokinetic that can be used in everyday clinical practice is itopride. In refractory cases, tricyclic antidepressants and psychotherapeutic approaches are another effective treatment option.Замедление моторики желудка, или синдром диспепсии, один из самых частых в современной гастроэнтерологии. Симптомы замедленной моторики (диспепсии) встречаются при таких заболеваниях, как гастриты, гастроэзофагеальная рефлюксная болезнь, функциональная диспепсия и др. Функциональная диспепсия является одним из наиболее частых функциональных расстройств желудочно-кишечного тракта, возникающих главным образом в результате замедления моторики, повышения висцеральной гиперчувствительности. В России наиболее часто таким пациентам ставится диагноз хронический гастрит. Зачастую в связи с некорректным интерпретированием симптомов действия врачей могут привести к нерациональному использованию разных групп лекарственных средств. К основным вариантам рациональной фармакотерапии относится применение прокинетических препаратов, ингибиторов протонной помпы. Нарушения моторики основной патогенетический механизм формирования функциональной диспепсии. Прокинетики являются 1-й линией терапии моторных нарушений желудка, однако цизаприд уже давно снят с продажи из-за кардиотоксичности, использование домперидона и метоклопрамида ограничено из-за нежелательных реакций, поэтому в настоящее время единственным прокинетиком, который может использоваться в повседневной клинической практике, является итоприда гидрохлорид. В рефрактерных случаях еще одним эффективным вариантом лечения являются трициклические антидепрессанты и психотерапевтические подходы.

The article presents a clinical case of a 23-year-old patient with an extremely severe congenital form of chronic intestinal pseudoobstruction coupled with a neuromyopathy,colon malrotation, malabsorption, bacterial overgrowth syndrome, cholelithiasis and gastrostasis, which excluded bowel transplantation. Long-term treatment in the intensive care unit with combined, mainly parenteral nutrition for 6 months, using antibiotics, prokinetics, intestinal decompression allowed to achieve partial stabilization of the patients condition and transfer to home treatment with the continuation of adequate complex therapy.Представлено клиническое наблюдение больной 23 лет с крайне тяжелой врожденной формой хронической интестинальной псевдообструкции с нейромиопатией. мальротацией толстой кишки, мальабсорбцией, синдромом избыточного бактериального роста, холелитиазом, гастростазом, исключавшим выполнение трансплантации кишечника. Длительное лечение в отделении интенсивной терапии с комбинированным, преимущественно парентеральным питанием в течение 6 мес, применением антибиотиков, прокинетиков, кишечной декомпрессии позволило добиться частичной стабилизации состояния и перевода пациентки на домашнее лечение с продолжением адекватной комплексной терапии.

Proton pump inhibitors (PPIs) are baseline drugs for induction and maintenance of remission in gastroesophageal reflux disease (GERD). PPIs have proven to be highly effective in healing esophageal mucosal lesions and relieving the symptoms of the disease in most cases. However, according to the literature data, the incidence rate of clinical ineffectiveness of PPIs in the form of partial or complete persistence of current symptoms during administration of standard doses of PPIs ranges from 10 to 40%. Optimization of GERD therapy in PPI refractory patients is a significant challenge. In most cases, experts advise to increase a dose / dosage frequency of PPIs, switch to CYP2C19-independent PPIs (rabeprazole, esomeprazole, dexlansoprazole), add an esophagoprotective or promotility agents to therapy. At the same time, these recommendations have a limited effect in some patients, which opens up opportunities for looking for new solutions related to the optimization of GERD therapy. Today there is growing evidence of the relevance of the role of disruption of the cytoprotective and barrier properties of the esophageal mucosa in the genesis of GERD and the formation of refractoriness. Intercellular contacts ensure the integrity of the barrier function of the esophageal mucosa to protect it from various exogenous intraluminal substances with detergent properties. Acid-peptic attack in patients with GERD leads to alteration of the expression of some tight junction proteins in epithelial cells of the esophageal mucosa. The latter leads to increased mucosal permeability, which facilitates the penetration of hydrogen ions and other substances into the submucosal layer, where they stimulate the terminals of nerve fibers playing a role in the induction and persistence of the symptoms of the disease. The above evidence brought up to date the effectiveness study of the cytoprotective drugs with tropism to the gastrointestinal tract, as part of the combination therapy of GERD.

Background Bacterial translocation is considered the pathophysiological hallmark in the development of spontaneous bacterial peritonitis (SBP). Prokinetics can increase gastrointestinal (GIT) motility, reduce small bowel transit time, decrease bacterial translocation, and the possibility of SBP. The aim of this work was to compare the effectiveness and safety of itopride and norfloxacin versus norfloxacin only in secondary prophylaxis for cirrhotic ascitic patients with spontaneous bacterial peritonitis. Results Regarding the baseline clinical manifestations and laboratory investigations, there was no significant difference between both groups. The incidence of a recurrent SBP in group I, who had received itopride plus norfloxacin, reduced with a significant difference than other group II (P=0.018). The median time for recurrence of SBP was highly longer in group I than group II with a significant difference (P=0.042). Conclusions The combined usage of itopride with norfloxacin in patients with cirrhosis and ascites can decrease the occurrence of a recurrent SBP and significantly improve the survival of patients. Trial registration ClinicalTrials.gov Identifier: NCT04161768.

Chronic intestinal pseudo-obstruction a rare violation of the motor skills of the gastrointestinal complex, similar to mechanical obstruction, but without a mechanical obstacle. The development of chronic intestinal pseudo-obstruction is caused by a disturbance on the part of the smooth muscles and the nervous system of the gastrointestinal system. Common symptoms include constipation, abdominal pain, nausea, vomiting, bloating. Violation of peristalsis leads to food stagnation in the hinges of the small intestine, their dilation, the development of bacterial insemination syndrome. Eating disorders, bacterial contamination syndrome (CDDs) lead to impaired suction syndrome, cahexia. Treatment is aimed at providing adequate nutrition, the use of drugs that activate motor skills, suppress the growth of microbes in the small intestine, the implementation of intestinal decompression. Surgical treatment: resection of the affected segment of the gut. In the refractory course of the disease intestinal transplantation.

A review of current data suggests that the attention to the problem of dyspepsia is huge. The definition of functional dyspepsia was given in the Rome IV criteria, according to which two of its main options are distinguished – epigastric pain syndrome and postprandial distress syndrome. The term “uninvestigated dyspepsia” is important, which means the presence of dyspepsia symptoms in patients who have not performed diagnostic procedures to identify the organic causes of the pathology. The prevalence of uninvestigated dyspepsia in the world is about 21%. The prevalence of functional dyspepsia is significantly lower than the prevalence of uninvestigated dyspepsia and fluctuates around 10%. The risk factors for dyspepsia are usually tobacco smoking, non-steroidal anti-inflammatory drugs and/or aspirin, and Helicobacter pylori infection. The concept of the pathogenesis of functional dyspepsia undergoes significant changes. By analogy with the pathophysiology of irritable bowel syndrome, lesions of the relationship between the modulation of the cerebral cortex and the signal system of the gastroduodenal zone, the association of sluggish immune inflammation in the duodenum with motility and sensory activity of the stomach are most actively studied. The treatment of functional dyspepsia is a complex problem and changes after new ideas about its pathogenesis. Modern meta-analyzes have made it possible to expand the indications for the proton pump inhibitors administration, which can be actively used not only for the treatment of epigastric pain syndrome, but also for postprandial distress syndrome. Along with the required Helicobacter pylori eradication, there are reasons for the use of probiotics and antibiotics for the dyspepsia treatment.

Gastroparesis (Gp) is a chronic disease characterized by a delayed gastric emptying in the absence of mechanical obstruction. Although this condition has been reported in the literature since the mid-1900s, only recently has there been renewed clinical and scientific interest in this disease, which has a potentially great impact on the quality of life. The aim of this review is to explore the pathophysiological, diagnostic and therapeutical aspects of Gp according to the most recent evidence. A comprehensive online search for Gp was carried out using MEDLINE and EMBASE. Gp is the result of neuromuscular abnormalities of the gastric motor function. There is evidence that patients with idiopathic and diabetic Gp may display a reduction in nitrergic inhibitory neurons and in interstitial cells of Cajal and/or telocytes. As regards diagnostic approach, 99-Technetium scintigraphy is currently considered to be the gold standard for Gp. Its limits are a lack of standardization and a mild risk of radiation exposure. The C13 breath testing is a valid and safe alternative method. 13C acid octanoic and the 13C Spirulina platensis recently approved by the Food and Drug Administration are the most commonly used diagnostic kits. The wireless motility capsule is a promising technique, but its use is limited by costs and scarce availability in many countries. Finally, therapeutic strategies are related to the clinical severity of Gp. In mild and moderate Gp, dietary modification and prokinetic agents are generally sufficient. Metoclopramide is the only drug approved by the Food and Drug Administration for Gp. However, other older and new prokinetics and antiemetics can be considered. As a second-line therapy, tricyclic antidepressants and cannabinoids have been proposed. In severe cases the normal nutritional approach can be compromised and artificial nutrition may be needed. In drug-unresponsive Gp patients some alternative strategies (endoscopic, electric stimulation or surgery) are available.

Functional dyspepsia (FD) is one of the dysregulatory lesions of the upper digestive tract. This syndrome has fairly well-defined clinical manifestations that include borderline psychopathological disorders. Its diagnosis becomes a method for ruling out organic gastrointestinal and mental illnesses. Treatment for FD is complex and includes a behavioral component, prokinetics, myotropic spasmolytics, antisecretory drugs, and tricyclic antidepressants. The efficiency of therapy directly depends on a physician's ability to choose an individualized regimen.

Aim . To present the materials of an Expert Council, which was held on September 23, 2019 in Istanbul (Turkey) under the auspices of a World Gastroenterology Organisation congress and the support of the Abbott company. General provisions . During the work of the Expert Council, the role of motility disorders of the stomach and duodenum, intestines, gall bladder and the sphincter of Oddi in the development of functional diseases of the digestive system, such as functional dyspepsia (FD), irritable bowel syndrome (IBS), biliary dyskinesia (BD) was discussed, and the effectiveness of antispasmodics and prokinetics in their treatment was shown. At the same time, the advantages of the mebeverin antispasmodic drug, as well as the high efficiency and safety of the itopride hydrochloride prokinetic drug were noted. It is emphasized that, at the stage of a diagnostic search in the absence of “alarm symptoms” in patients with suspected FD, IBS, and BD, these drugs can be prescribed empirically. Conclusions. When selecting pharmacotherapy for patients with motor impairment, it is extremely important to consider the nature of these disorders. The use of modern medical preparations, which are characterized by a high level of safety and the targeted action towards a specific motility disorder, allows optimal therapy results to be achieved with minimal risks for the patient.

Management of gastroparesis remains challenging, particularly in pediatric patients. Supportive care and pharmacological therapies for symptoms remain the mainstay treatment. Although they are effective for mild and some moderately severe cases, often time they do not work for severe gastroparesis. There are a few prokinetics available, yet the use of these drugs is limited by a lack of persistent efficacy and/or safety concerns. Currently, the only modality for adult patients with severe intractable gastroparesis is surgery, e.g., pyloroplasty and partial gastrectomy, however, this option is generally considered too radical for a growing child. Novel therapeutic approaches, particularly those which are less invasive, are needed. This article explores gastric electrical stimulation (GES), a new therapy for gastroparesis. Unlike others, it neither needs medications nor gastrectomy; rather, it treats through the use of microelectrodes to deliver high-frequency low energy electric stimulation to the pacemaker area of the stomach. Thus, it is tolerated and safe in children. Like in adult patients, GES appears to work in releasing symptoms, improving nutrition, and enhancing the quality of life; it also helps wean off medications and eliminate many needs for hospitalization. Considering the transient nature of gastroparesis in children in many occasions, GES is considered a “bridging” therapy after failed medical interventions and before surgery.

The development of new capsules now allows endoscopic diagnosis in all segments of the gastrointestinal tract and comes with new needs for differentiated preparation regimens. Although the literature is steadily increasing, the results of the conducted trials on preparation are sometimes conflicting. The ingestion of simethicone before gastric and small bowel capsule endoscopy for prevention of air bubbles is established. The value of a lavage before small bowel capsule endoscopy (SBCE) is recommended, although not supported by all studies. Ingestion in the morning before the procedure seems useful for the improvement of mucosa visualization. Lavage after swallowing of the capsule seems to improve image quality, and in some studies also diagnostic yield. Prokinetics has been used with first generation capsules to shorten gastric transit time and increase the rate of complete small bowel visualization. With the massively prolonged battery capacity of the new generation small bowel capsules, prokinetics are only necessary in significantly delayed gastric emptying as documented by a real-time viewer. Lavage is crucial for an effective colon capsule or pan-intestinal capsule endoscopy. Mainly high or low volume polyethylene glycol (PEG) is used. Apart from achieving optimal cleanliness, propulsion of the capsule by ingested boosts is required to obtain a complete passage through the colon within the battery lifetime. Boosts with low volume sodium picosulfate (NaP) or diatrizoate (gastrografin) seem most effective, but potentially have more side effects than PEG. Future research is needed for more patient friendly but effective preparations, especially for colon capsule and pan-intestinal capsule endoscopy.

Functional dyspepsia (FD) is one of the most common gastroenterological diseases. The article presents modern views on the pathogenesis of the disease. It is shown that disorders of motor skills (retardation of voiding function, disturbance of relaxation accommodation) and stomach sensitivity (visceral hypersensitivity to stretching) are considered to be one of the main pathophysiological mechanisms of FD. The authors present a modern algorithm of treatment of patients with FD, based on the clinical recommendations of the Rome Consensus IV revision (2016) and the Russian Gastroenterological Association (2017). The strategy of differentiated use of pharmaceuticals for different variants of FD is considered.

There is overwhelming evidence that functional gastrointestinal disorders (FGIDs) are associated with specific mechanisms that constitute important targets for personalized treatment. There are specific mechanisms in patients presenting with functional upper gastrointestinal symptoms (UGI Sx). Among patients with UGI Sx, approximately equal proportions (25%) of patients have delayed gastric emptying (GE), reduced gastric accommodation (GA), both impaired GE and GA, or neither, presumably due to increased gastric or duodenal sensitivity. Treatments targeted to the underlying pathophysiology utilize prokinetics, gastric relaxants, or central neuromodulators. Similarly, specific mechanisms in patients presenting with functional lower gastrointestinal symptoms, especially with diarrhea or constipation, are recognized, including at least 30% of patients with functional constipation pelvic floor dyssynergia and 5% has colonic inertia (with neural or interstitial cells of Cajal loss in myenteric plexus); 25% of patients with diarrhea-predominant irritable bowel syndrome (IBSD) has evidence of bile acid diarrhea; and, depending on ethnicity, a varying proportion of patients has disaccharidase deficiency, and less often sucrose-isomaltase deficiency. Among patients with predominant pain or bloating, the role of fermentable oligosaccharides, disaccharides, monosaccharides and polyols should be considered. Personalization is applied through pharmacogenomics related to drug pharmacokinetics, specifically the role of CYP2D6, 2C19 and 3A4 in the use of drugs for treatment of patients with FGIDs. Single mutations or multiple genetic variants are relatively rare, with limited impact to date on the understanding or treatment of FGIDs. The role of mucosal gene expression in FGIDs, particularly in IBS-D, is the subject of ongoing research. In summary, the time for personalization of FGIDs, based on deep phenotyping, is here; pharmacogenomics is relevant in the use of central neuromodulators. There is still unclear impact of the role of genetics in the management of FGIDs.

Feed intolerance (FI) is common in cirrhosis patients in intensive care units (ICU). Prokinetics are the first line treatment for FI but their efficacy and safety in critically ill patient with cirrhosis is unknown. We evaluated the role of prokinetics in reversal of FI and clinical outcomes.Consecutive patients admitted in ICU developing new-onset FI, were randomized to receive either intravenous metoclopramide (Gr.A, n = 28), erythromycin (Gr.B, n = 27) or placebo (Gr.C, n = 28). FI was defined with the presence of 3 of 5 variables- absence of bowel sounds, gastric residual volume ≥ 500 ml, vomiting, diarrhoea and bowel distension. Primary end-point was complete resolution of FI (≥ 3 variables resolved) within 24-h and secondary end-points included resolution within 72-h and survival at 7-days.Of the 1030 ICU patients, 201 (19.5%) developed FI and 83 patients were randomized. Baseline parameters between the groups were comparable. Complete resolution at 24-h was higher in Gr.A (7.14%) and B (22.2%) than C (0%, p = 0.017). Overall, 58 (69.9%) patients achieved resolution within 72 h, more with metoclopramide (n = 24, 85.7%) and erythromycin (n = 25, 92.6%) than with placebo (n = 9, 32.1%, p 0.001). The 7-day survival was better in patients who achieved resolution within 72-h (65.5 vs. 36%, p = 0.011) than non-responders. High lactate (OR-3.32, CI-1.45-7.70, p = 0.005), shock at baseline (OR-6.34, CI-1.67-24.1, p = 0.007) and resolution of FI within 72 h (OR-0.11, CI, 0.03-0.51, p = 0.04) predicted 7-day mortality.FI is common in critically-ill cirrhosis patients and non-resolution carries high mortality. Early recognition and treatment with prokinetics is recommended to improve short-term survival.Gastrointestinal dysmotility is common in cirrhosis and higher incidence in critically ill patients. Promotility drugs are the first line of medication especially in ICU patients. In our study, we found that feed intolerance is present in nearly one in five critically ill cirrhosis and is associated with higher mortality. Patients who achieve resolution had an improved short-term survival. Prokinetic medications are safe in critically ill cirrhosis and help in early resolution of feed intolerance. Feed intolerance in critically ill cirrhosis should be recognized as an organ dysfunction and approaches for prevention and early diagnosis of feed intolerance could help in improving the outcomes in critical illness.

Diseases of the gastrointestinal tract (GIT) occupy a significant place in the overall structure of somatic diseases worldwide. Apart from functional diseases (the incidence of functional dyspepsia (FD) in population is 20 %), the following inflammatory and destructive diseases are widespread: gastroesophageal reflux disease (GERD) in up to 40 % of the population, chronic gastritis and chronic duodenitis in 45 — 50 % of the population, peptic ulcer of the stomach and duodenum in 14 — 15 % of the population. Each of these diseases has its own features of etiopathogenesis and approaches to treatment. However, a common pathological factor contributing to the development of these nosologies is a violation of motor‑evacuation function. The administration of drugs for the normalization of peristaltic activity is a component of treatment. The range of existing drugs with prokinetic activity against the gastrointestinal tract is quite large.One of the effective and safe prokinetics registered in October 2020 in Ukraine is the domperidone preparation Doprokin (World Medicine). This drug has a proven effectiveness in the treatment of patients with FD, GERD, chronic gastritis, especially in comorbidity with Diabetes mellitus II (diabetic gastroparesis) and gastroparesis of other etiology. This is a selective dopamine antagonist, that blocks D2‑receptors in the central and peripheral nervous systems. It increases the pressure of the lower esophageal sphincter, esophageal clearance, reduces intragastric pressure, activates peristalsis of the esophagus and antrum of the stomach, increases the frequency, amplitude and duration of contractions of the duodenum, reduces the time of passage of food masses through the small intestine. The indications for domperidone administration include relief of symptoms of nausea, vomiting, heartburn, belching, early satiety, bloating. In contrast to metoclopramide, it almost does not cross the blood‑brain barrier and does not cause unwanted central adverse reactions. Doprokin is over the counter preparation. For adults, the recommended dose is 1 tablet (10 mg) 3 times a day (15 — 30 minutes before the meals). The maximal daily dose is 30 mg, maximal treatment duration should not exceed 1 week., Заболевания органов желудочно‑кишечного тракта занимают значительное место в общей структуре соматических заболеваний во всем мире. Кроме функциональных заболеваний (функциональная диспепсия встречается у 20 % населения), распространены воспалительные и деструктивные (гастроэзофагеальная рефлюксная болезнь — примерно у 40 % населения, хронический гастрит и хронический дуоденит — у 45 — 50 %, язвенная болезнь желудка и двенадцатиперстной кишки — у 14 — 15 %). Эти заболевания отличаются по особенностям этиопатогенеза и подходами к лечению. Общим патологическим фактором, который вызывает развитие упомянутых нозологий, является нарушение моторно‑эвакуаторной функции. Составляющей терапии является назначение препаратов, которые нормализуют перистальтическую активность. Спектр препаратов, обладающих прокинетической активностью в отношении органов желудочно‑кишечного тракта, большой.Одним из эффективных и безопасных прокинетиков в Украине является препарат домперидона «Допрокин» (World Medicine). Это лекарственное средство имеет доказанную эффективность при лечении пациентов с функциональной диспепсией, гастроэзофагеальной рефлюксной болезнью, хроническими гастритами, особенно при коморбидности с сахарным диабетом 2 типа (диабетический гастропарез) и гастропарезами другой этиологии. Это селективный антагонист допамина, который блокирует D2‑рецепторы в центральной и периферической нервной системе. Повышает давление нижнего пищеводного сфинктера, пищеводный клиренс, уменьшает внутрижелудочное давление, активирует перистальтику пищевода и антрального отдела желудка, увеличивает частоту, амплитуду и длительность сокращений двенадцатиперстной кишки, уменьшает время пассажа пищевых масс по тонкой кишке. Показаниями для назначения домперидона является облегчение симптомов тошноты, рвоты, изжоги, отрыжка воздухом, раннее насыщение, вздутие. В отличие от метоклопрамида он почти не проникает через гематоэнцефалический барьер и не вызывает нежелательных центральных побочных реакций. Препарат отпускают без рецепта. Для взрослых рекомендуемая доза — 1 таблетка (10 мг) три раза в сутки (за 15 — 30 мин до еды). Максимальная суточная доза — 30 мг. Максимальная длительность лечения не должна превышать 1 нед., Захворювання органів шлунково‑кишкового тракту посідають значне місце в загальній структурі соматичних захворювань у всьому світі. Найбільшу групу хронічних захворювань органів травлення становлять хвороби органів гастродуоденальної зони. Крім функціональних захворювань (функціональна диспепсія трапляється у 20 % населення), поширені запальні та деструктивні (гастроезофагеальна рефлюксна хвороба — у майже 40 % населення, хронічний гастрит і хронічний дуоденіт — у 45 — 50 %, виразкова хвороба шлунка та дванадцятипалої кишки — у 14 — 15 %). Ці захворювання відрізняються за особливостями етіопатогенезу та підходами до лікування. Спільним патологічним чинником, який спричиняє розвиток зазначених нозологій, є порушення моторно‑евакуаторної функції. Складовою терапії є призначення препаратів, котрі нормалізують перистальтичну активність. Спектр препаратів, які володіють прокінетичною активністю щодо органів шлунково‑кишкового тракту, великий. Одним з ефективних та безпечних прокінетиків в Україні є препарат домперидону «Допрокін» (World Medicine). Цей лікарський засіб має доведену ефективність при лікуванні пацієнтів із функціональною диспепсією, гастроезофагеальною рефлюксною хворобою, хронічними гастритами, особливо при коморбідності із цукровим діабетом 2 типу (діабетичний гастропарез), та гастропарезами іншої етіології. Це селективний антагоніст допаміну, який блокує D2‑рецептори в центральній і периферичній нервовій системі. Препарат підвищує тонус нижнього стравохідного сфінктера, стравохідний кліренс, зменшує внутрішньошлунковий тиск, активує перистальтику стравоходу і антрального відділу шлунка, збільшує частоту, амплітуду і тривалість скорочень дванадцятипалої кишки, зменшує час пасажу харчових мас по тонкій кишці. Показаннями для призначення домперидону є полегшення симптомів нудоти, блювання, печії, відригування повітрям, раннє насичення, здуття. На відміну від метоклопраміду він майже не проникає через гематоенцефалічний бар’єр і не спричиняє небажаних центральних побічних реакцій. Препарат відпускають без рецепта. Для дорослих рекомендована доза — 1 таблетка (10 мг) тричі на добу (за 15 — 30 хв до їди). Максимальна добова доза — 30 мг. Максимальна тривалість лікування не має перевищувати 1 тиж.

Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder characterized by an impairment of coordinated propulsive activity in the gastrointestinal (GI) tract, which clinically mimics mechanical intestinal obstruction. CIPO is the most severe and debilitating form of GI dysmotility. CIPO may be primary or be secondary to pathology at any level of the brain-gut axis as well as systemic disease. The clinical features of CIPO are pleomorphic and largely depend on the site and extent of the segment of the GI tract involved. The diagnostic approach includes the need for investigations to exclude mechanical GI obstruction, screening for causes of secondary CIPO and the identification of the disease phenotype as well as the prompt recognition and treatment of complications such as malnutrition and small intestinal bacterial overgrowth. In managing this disorder, a holistic, multidisciplinary approach is needed with judicious use of pharmacotherapeutic agents. While currently there are no specific therapeutic modalities for CIPO, treatment is largely directed at maintaining adequate nutrition and electrolyte balance and enhancing coordinated GI motility. Surgery should be avoided unless advisable for carefully selected patients and may include stoma formation. This narrative review provides a concise overview of the literature on this rare, severe and complex disorder, and highlights the need and areas for further research to improve both diagnostics and therapeutics.

Background: Recent increase in the non-specific use of prokinetics in clinical practice may alter the etiological profile of hyperprolactinemia and galactorrhea. Hence, we have studied the etiological profile of patients presenting with galactorrhea and characteristics of drug-induced galactorrhea. Materials and Methods: This retrospective study was conducted at a tertiary health care center from South India. Patients who presented with or referred for galactorrhea and/or hyperprolactinemia to the Department of Endocrinology between January 2017 and December 2017 were included in the study. Results: Forty women presented with or referred for galactorrhea to the Department of Endocrinology during the study period. Thirty-two patients had received drugs that are associated with hyperprolactinemia (levosulpiride in 15, domperidone in 13, ranitidine in 2, oral contraceptive pill in 1, and amisulpiride in 1) of whom etiology was proved in 27 patients, whereas in four patients the cause was inconclusive due to lack of follow-up. The patient on amisulpiride was found to have concomitant pituitary microadenoma. Idiopathic galactorrhea (n = 2), idiopathic hyperprolactinemia (n = 2), and prolactinoma (n = 4) accounted for the remaining cases. Six patients with prokinetic-induced galactorrhea had received cabergoline inspite of which hyperprolactinemia and/or galactorrhea persisted and six patients had also undergone pituitary magnetic resonance imaging (MRI) for evaluation of galactorrhea. Conclusions: Prokinetic use is the most common cause of galactorrhea in our study and often was investigated with costly tests and treated with D2 agonists unnecessarily. Hence, there is a need to ensure measures to reduce the non-specific use of prokinetics and increase awareness regarding the occurrence of galactorrhea with prokinetics use, to reduce unnecessary investigations and treatment.

Functional gastrointestinal disorders are currently being considered as the most common pathology of the gastrointestinal tract. Symptoms that may be related to the gastroduodenal region, represent one of the major subgroups among functional gastrointestinal disorders, in which the functional dyspepsia rightly maintains leading positions syndrome. Pathogenetic factors of functional dyspepsia and other functional gastrointestinal disorders, which can be regarded as proven at the moment, are the dysmotility of the gastrointestinal tract, which determines the feasibility of using in the basic treatment of these diseases medications that affect motor function of the gastrointestinal tract and preventing anastaltic contractions of the smooth muscles, which are combined into a group of prokinetic. With comorbidity positions, clinical efficacy and drug safety is a priority itopride hydrochloride prokinetics in treatment of functional dyspepsia and other related functional gastrointestinal disorders.

Aim Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. Main methods To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10 μg, 10 ng/kg ip) immediately after each administrations of haloperidol (0.625, 6.25, 12.5, and 25.0 mg/kg ip), fluphenazine (0.5, 5.0 mg/kg ip), clozapine (1.0, 10.0 mg/kg ip), quetiapine (1.0, 10.0 mg/kg ip), sulpiride (1.6, 16.0 mg/kg ip), metoclopramide (2.5, 25.0 mg/kg ip) or (1.0, 10.0 mg/kg ip). Controls simultaneously received saline (5 ml/kg ip). To assess the ECG presentation before and after neuroleptic/prokinetic medication, the assessment was at 1, 2, 3, 4, 5, 10, 15, 20 and 30 min (first administration) as well as at 30 min, 60 min and 24 h (first administration and subsequent administrations) and the ECG recording started prior to drug administration. Key findings Since very early, a prolonged QTc interval has been continually noted with haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats as a central common effect not seen with domperidone. Consistent counteraction appears with the stable gastric pentadecapeptide BPC 157. Thus, BPC 157 rapidly and permanently counteracts the QTc prolongation induced by neuroleptics and prokinetics. Significance Pentadecapeptide BPC 157 is suited for counteracting a prolonged QT interval.

The adolescence is characterized by high rates of gastroenterological morbidity due to physiological characteristics of the body and social and psychological status of the teenager. Dyspepsia takes the leading position in the structure of functional pathology. Studies have shown the role of family, unhealthy habits and addictions in the development of this disorder. One should also bear in mind that the adolescence is characterized by an increase in organic pathology. There is a close association of the functional dyspepsia and the premorbid background, such as autonomous dysfunction and vertebral abnormalities. The use of cholinolytics, prokinetics, opioid receptor antagonists, antacids and anti-secretory agents seems rational for treatment of dyspepsia. If the above mentioned groups of agents lack efficacy, the second line therapy is proposed, which includes tricyclic antidepressants.

Small intestinal bacterial overgrowth (SIBO) is common in patients with systemic sclerosis (SSc) yet often goes underrecognized in clinical practice. In patients with SSc, untreated SIBO may result in marked morbidity and possible mortality. The pathogenesis of SIBO is multifactorial and relates to immune dysregulation, vasculopathy, and dysmotility. This article reviews various diagnostic approaches and therapeutic options for SIBO. Treatment modalities mainly include prokinetics, probiotics, and antibiotics.

Doina Georgescu,1 Oana Elena Ancusa,1 Liviu Andrei Georgescu,2 Ioana Ionita,3 Daniela Reisz4 1Department of Internal Medicine, 2Department of Urology, 3Department of Hematology, 4Department of Neurology, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania Abstract: Despite the fact that nonmotor symptoms (NMS) like gastrointestinal (GI) complaints are frequently reported in Parkinson’s disease (PD), no therapeutic guidelines are available. This study aimed to manage some lower GI-NMS in a group of patients with PD. A total of 40 patients (17 males, 23 females; mean age 76.05±2.09 years) were randomly selected for this study. Patients were confirmed to have PD (modified Hoehn–Yars scale: 2.075±0.4) who had undergone levodopa or dopamine agonist treatment. In the non-motor symptoms questionnaire (NMS-Quest), regarding GI complaints, the following were recorded: abdominal pain, bloating, and constipation of mild-to-moderate severity. Laboratory studies, abdominal ultrasound, and upper and lower digestive endoscopies were performed to rule out organic issues. All patients increased their water intake to 2 L/d and alimentary fiber to 20–25 g/d. Twenty patients received trimebutine 200 mg three times daily half an hour before meals. The other 20 patients received probiotics (60 mg per-tablet of two lactic bacteria: Lactobacillus acidophilus and Bifidobacterium infantis), 2×/d, 1 hour after meals for 3 months along with the reassessment of GI complaints. Our results demonstrated that there were significant statistical differences in all assessed symptoms in the first group: 1.55±0.51 vs 0.6±0.5 (P

Aim Rikkunshito is a traditional Japanese medicine used for delayed gastric emptying in intensive care units in Japan. This study aimed to investigate whether standard‐ or high‐dose rikkunshito can improve the achievement of enteral calorie target among critically ill adults. Methods This open‐label, single‐center, pilot randomized controlled trial was carried out from March 2018 until December 2018 and enrolled critically ill adult patients requiring enteral nutrition by gastric tube for at least 5 days. Patients were randomized into the control group, the standard‐dose rikkunshito group (2.5 g three times daily), and the high‐dose rikkunshito group (5 g three times daily). Intervention was given for 5 days. The primary outcome measure was the percentage of enteral calorie intake achieved in the target at the fifth day after randomization. Results The cohort comprised 26 patients; of these, 9, 8, and 9 were included in the control group, the standard‐dose group, and the high‐dose group, respectively. Twenty‐one patients (81%) were included in the primary analysis. The percentage of enteral calorie intake achieved in the target at the fifth day was 59% (interquartile range [IQR], 39–63%), 40% (IQR, 26–61%), and 62% (IQR, 17–83%) in the control, the standard‐dose, and the high‐dose groups, respectively (P = 0.42). The number of adverse events did not differ significantly between the groups (control group, 4 [44%]; standard‐dose group, 3 [38%]; and high‐dose group, 4 [44%], P = 1.00). Conclusions Standard‐ or high‐dose rikkunshito did not improve the achievement of enteral calorie target in critically ill adults., Rikkunshito is a traditional Japanese medicine used for delayed gastric emptying in intensive care units in Japan. In this pilot randomized controlled trial, standard‐ or high‐dose rikkunshito did not improve the achievement of enteral calorie target in critically ill adults.

Introduction. Diabetes mellitus (DM) is considered to be one of the most serious problems in internal medicine due to multiple organ lesions and irreversible changes in the functioning of the organism. At present, despite the continuous advancement in medical science pathogenetic mechanisms of the development and progression of gastrointestinal form of autonomic neuropathy, particularly one of its manifestations – diabetic gastroparesis (DG) remains insufficiently studied. Purpose of the study. In the scientific literature there are insufficient data on the clinical efficacy of itopride hydrochloride in patients with impaired motor-evacuation function (MEF) of the stomach. There are no answers to the questions about pathogenetic mechanisms of possible effects of prokinetics on the parameters of glycemic control, the incidence of hypoglycemic events, the progression of gastrointestinal manifestations, etc. Therefore, the objective of the research was to determine therapeutic efficacy of itopride in treatment of gastroparesis considering the state of carbohydrate metabolism in patients with type 2 diabetes mellitus. Materials and research methods. To clarify the relationship between the results of itopride hydrochloride therapy and the dynamics of changes in carbohydrate metabolism were examined 48 patients with type 2 DM. They were divided into two groups. In addition to the standard 6-week course of pathogenetically grounded therapy patients of Group I (n = 24) received itopride hydrochloride at a daily dose of 150 mg (50 mg three times a day 30 min before their main meal). Patients of Group II (the control group) (n = 24) underwent the standard therapy without using medicines affecting MEF of the stomach. The clinical severity of DG was determined using the questionnaire ″Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index″ (PAGI-SYM), which allows the patient to assess the severity of symptoms by himself. According to the survey (D-ABS) the prevalence and intensity of the hypoglycemic episodes were determined. To assess MEF of the stomach all the patients underwent 13C-octanoic acid breath test. Results of the investigation and their discussion. According to the results of additional methods of examination there was a direct correlation between the mean PAGI-SYM scores and the results of 13C-octanoic acid breath test (r = 0.63 ± 0.03, p < 0.001). There was also a strong direct correlation between the state of compensation of carbohydrate metabolism (НbA1C, %) and the degree of slowing of gastrointestinal motility according to the results of 13C-octanoic acid breath test (r = 0.64 ± 0.03, p < 0.001). Thus, the course of DG depends on the effectiveness of glycemic control. Total PAGI-SYM scores indicated the positive effect of treatment which was significantly different in patients of Group I before (14.21 ± 3.28 points – moderate DG) and after the treatment (7.28 ± 0.9 points – mild DG) compared to the control group. The results of 13C-octanoic acid breath test confirmed the effectiveness of a 6-week course of treatment with itopride hydrochloride at a daily dose of 150 mg (50 mg three times a day 30 min before a meal) with recovery of gastrointestinal motility (according to treatment Т ½ – 98.24 ± 3.14 min, in dynamics Т ½ – 68.32 ± 3.55 min; р < 0.05) in patients of Group I. In patients of Group II (the control group) the normalization of MEF of the stomach after the course of treatment was not observed (before treatment Т ½ – 97.23 ± 2.61 min, after treatment Т ½ – 92.12 ± 0.16 min; р >0.05). Conclusions. The effectiveness of using itopride hydrochloride at a daily dose of 150 mg has been proven. It has been established that it contributes to normalizing MEF of the stomach in patients with type 2 DM and signs of DG as well as achieving better compensation of carbohydrate metabolism of both prandial and postprandial glucose levels. The possibility of using prokinetic agents to prevent the labile course of DM should be taken into consideration.

Background and study aims Several studies have demonstrated the superiority of proton-pump inhibitors (PPIs) in resolving erosive gastro-oesophageal reflux disease (GORD). However, this first line of treatment can fail to control symptoms in around 30% of cases, especially in the presence of non-erosive GORD. In situations where the first line of treatment fails, there is a lack of concordance regarding the best strategy to apply. This study presents a systematic review of the trials which have tested second-line treatments after PPI failure. Methods The study was conducted according to the PRISMA statement. The systematic review included medical trials written in English which were published between 2000 and 2016 and were retrieved from PubMed and Scopus using the keywords ‘PPI-resistant gastro-oesophageal reflux’, ‘alginate AND gastro-oesophageal reflux’, ‘hyaluronic acid AND gastro-oesophageal reflux’, ‘prokinetics AND gastro-oesophageal reflux’, ‘sucralfate AND gastro-oesophageal reflux’ and ‘baclofen AND gastro-oesophageal reflux’. Results Ten randomised and non-randomised studies were included, which included 1515 patients of both sexes (mean age = 49.19 years, age range = 18–85, males = 700; 46.2%). Conclusions A personalised choice of the best treatment for PPI-resistant GORD should be based on the results of an upper endoscopy and pH/MII monitoring. For patients in situations where the first line of treatment fails, we encourage the execution of trials for testing double doses of PPIs against alternative medicaments.

Introduction: Gastroesophageal Reflux Disease (GERD) is a common public health problem causing increased economic burden and decreased quality of life. Proton Pump Inhibitor (PPI) and prokinetics are the frequently used medications. The efficacy and safety of combined prokinetic and PPI therapy for GERD remains controversial. Aim: The study was conducted to perform pharmacoeconomic evaluation of Pantoprazole and Pantoprazole plus Domperidone in the management of GERD which helps to provide quality care within limited financial resources. Materials and Methods: This RCT was conducted on 80 patients suffering from GERD. These patients were randomly divided into two groups; Pantoprazole (40 mg once daily) and, Pantoprazole plus Domperidone (40 mg+30 mg once daily), respectively. The clinical outcomes were observed and analysed after two weeks of treatment. Cost-effectiveness ratio for pantoprazole and pantoprazole plus Domperidone was calculated by dividing the cost of treatment by its clinical outcome that is, Frequency Scale for the Symptoms of GERD (FSSG) score. Cost minimization analysis was done in accordance with the cost of both drugs available in market (over the counter) and Hospital pharmacy. All the data was recorded in the entry form and presented as mean±SEM/SD for numerical data, and proportion (%) for the categorical data. In all tests mean values of test groups (A and B) compared with Student's paired t-test. Results: After two weeks of treatment, the total improvement rate was found to be higher in Pantoprazole plus Domperidone group than in Pantoprazole group (improvement score 12.93 vs 11.32 but statistically not significant, p-0.21). But Pantoprazole was found to be more cost effective than Pantoprazole plus Domperidone group (ACER 9.7 vs 11.2). Cost minimisation analysis showed that Pantoprazole is the most economical medicine in hospital pharmacy as well as available in market. Conclusion: Pantoprazole monotherapy is more cost effective than combination of Pantoprazole with Domperidone in GERD patients. Substitution by Pantoprazole alone would be expected to produce cost savings. A combination should be preferred for PPI resistant GERD, patients with nausea and vomiting, in the subgroup of severely symptomatic patients.

Around 40 persons from each 100,000 inhabitants of all ages suffer every year from gastric or duodenal bleeding ulcer. These patients still have high mortality, between 8 and 10%, regardless of constant advancement of the treatment modalities. The patients with bleeding ulcer should be subjected to endoscopy as soon as possible and local hemostasis should be made by mechanical, chemical or thermic methods. While the patient is waiting for endoscopy, an intravenous infusion of a proton pump inhibitor in highdoses should be started, and then continued for 72 hours. Intravenous administration of erythromycin about an hour before endoscopy increases visibility within the stomach and facilitates endoscopic therapy. The intravenous infusion of proton pump inhibitors should be continued by oral administration of the same drugs during the next 7 weeks, and the patient positive to Helicobacter pylori should receive eradication therapy. In order to achieve successful cure and to prevent bleeding relapse it is of utmost importance to make optimal choice, timing and dosing of drugs that accompany endoscopic diagnostics and therapy.

Background Controversies persist regarding the effect of prokinetics for the treatment of functional dyspepsia (FD). This study aimed to assess the comparative efficacy of prokinetic agents for the treatment of FD. Methods Randomized controlled trials (RCTs) of prokinetics for the treatment of FD were identified from core databases. Symptom response rates were extracted and analyzed using odds ratios (ORs). A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS and NetMetaXL. Results In total, 25 RCTs, which included 4473 patients with FD who were treated with 6 different prokinetics or placebo, were identified and analyzed. Metoclopramide showed the best surface under the cumulative ranking curve (SUCRA) probability (92.5%), followed by trimebutine (74.5%) and mosapride (63.3%). However, the therapeutic efficacy of metoclopramide was not significantly different from that of trimebutine (OR:1.32, 95% credible interval: 0.27–6.06), mosapride (OR: 1.99, 95% credible interval: 0.87–4.72), or domperidone (OR: 2.04, 95% credible interval: 0.92–4.60). Metoclopramide showed better efficacy than itopride (OR: 2.79, 95% credible interval: 1.29–6.21) and acotiamide (OR: 3.07, 95% credible interval: 1.43–6.75). Domperidone (SUCRA probability 62.9%) showed better efficacy than itopride (OR: 1.37, 95% credible interval: 1.07–1.77) and acotiamide (OR: 1.51, 95% credible interval: 1.04–2.18). Conclusions Metoclopramide, trimebutine, mosapride, and domperidone showed better efficacy for the treatment of FD than itopride or acotiamide. Considering the adverse events related to metoclopramide or domperidone, the short-term use of these agents or the alternative use of trimebutine or mosapride could be recommended for the symptomatic relief of FD. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0639-0) contains supplementary material, which is available to authorized users.

Introduction: Medical therapy of gastroesophageal reflux disease (GERD) is based on the use of proton pump inhibitors (PPIs) as first choice treatment. Despite their effectiveness, about 20–30% of patients report an inadequate response and alternative drugs are required. Areas covered: This review provides an overview of current pharmacotherapy for treating GERD by showing the results of PPIs, reflux inhibitors, antidepressants and mucosa protective medications. Expert opinion: Medical therapy of GERD does not definitely cure the disease, because even PPIs are not able to change the key factors responsible for it. However, they remain the mainstay of medical treatment, allowing us to alleviate symptoms, heal esophagitis and prevent complications in the majority of cases. Nevertheless, many patients do not respond, because acid does not play any pathogenetic role. Prokinetics and reflux inhibitors have the potential to control motor abnormalities, but the results of clinical trials are inconsistent. Antidepressant drugs are effective in specific subgroups of NERD patients with visceral hypersensitivity, but larger, controlled clinical studies are necessary. Protective drugs or medical devices have been recently adopted to reinforce mucosal resistance and preliminary trials have confirmed their efficacy either combined with or as add-on medication to PPIs in refractory patients.

Intestinal pseudo-obstruction is more commonly known in its chronic form (CIPO), a cluster of rare diseases characterized by gastrointestinal muscle and nerve impairment, so severe to result in a markedly compromised peristalsis mimicking an intestinal occlusion. The management of CIPO requires the cooperation of a group of specialists: the disease has to be confirmed by a number of tests to avoid mistakes in the differential diagnosis. The treatment should be aimed at relieving symptoms arising from gut dysmotility (ideally using prokinetic agents), controlling abdominal pain (possibly with non-opioid antinociceptive drugs) and optimizing nutritional support. Furthermore, a thorough diagnostic work-up is mandatory to avoid unnecessary (potentially harmful) surgery and to select patients with clear indication to intestinal or multivisceral transplantation.

Electrogastrography (EGG) is a non-invasive diagnostic method useful for the registration and analysis of gastric myoelectrical activity. Abnormalities within an electrogastrogram were found to correlate with a number of disorders and symptoms, like functional dyspepsia, diabetic gastroparesis and terminal hepatic or renal failure. The EGG is also a valuable diagnostic method enabling the evaluation of the effect of drugs on gastric myoelectrical activity, which can be intentional, as in the case of prokinetics, or can have an adverse character. Our review focuses on drugs with a proven impact on gastric myoelectrical activity and hence on the electrogastrogram. The paper assembles and discusses the results of investigations dealing with changes in the electrogastrograms evoked by various drugs. Moreover, the mechanisms of the influence on the gastric myoelectrical activity of drugs, curative substances and stimulants are presented.

Motilitone(®) (DA-9701) is a new herbal drug that was launched for the treatment of functional dyspepsia in December 2011 in Korea. The heterogeneous symptom pattern and multiple causes of functional dyspepsia have resulted in multiple drug target strategies for its treatment. DA-9701, a compound consisting of a combination of Corydalis Tuber and Pharbitidis Semen, has being developed for treatment of functional dyspepsia. It has multiple mechanisms of action such as fundus relaxation, visceral analgesia, and prokinetic effects. Furthermore, it was found to significantly enhance meal-induced gastric accommodation and increase gastric compliance in dogs. DA-9701 also showed an analgesic effect in rats with colorectal distension induced visceral hypersensitivity and an antinociceptive effect in beagle dogs with gastric distension-induced nociception. The pharmacological effects of DA-9701 also include conventional effects, such as enhanced gastric emptying and gastrointestinal transit. The safety profi le of DA-9701 is also preferable to that of other treatments.

AIM To define the role of small-bowel transit time in the detection rate of significant small-bowel lesions. METHODS Small-bowel capsule endoscopy records, prospectively collected from 30 participating centers in the Lombardy Registry from October 2011 to December 2013, were included in the study if the clinical indication was obscure gastrointestinal bleeding and the capsule reached the cecum. Based on capsule findings, we created two groups: P2 (significant findings) and P0-1 (normal/negligible findings). Groups were compared for age, gender, small-bowel transit time, type of instrument, modality of capsule performance (outpatients vs inpatients), bowel cleanliness, and center volume. RESULTS We retrieved and scrutinized 1,433 out of 2,295 capsule endoscopy records (62.4%) fulfilling the inclusion criteria. Patients were 67 ± 15 years old, and 815 (57%) were males. In comparison with patients in the P0-1 group, those in the P2 group (n = 776, 54%) were older (P < 0.0001), had a longer small-bowel transit time (P = 0.0015), and were more frequently examined in low-volume centers (P < 0.001). Age and small-bowel transit time were correlated (P < 0.001), with age as the sole independent predictor on multivariable analysis. Findings of the P2 group were artero-venous malformations (54.5%), inflammatory (23.6%) and protruding (10.4%) lesions, and luminal blood (11.5%). CONCLUSION In this selected, prospectively collected cohort of small-bowel capsule endoscopy performed for obscure gastrointestinal bleeding, a longer small-bowel transit time was associated with a higher detection rate of significant lesions, along with age and a low center volume, with age serving as an independent predictor.

Background/Aims: In capsule endoscopy (CE), the capsule does not always reach the cecum within its battery life, which may reduce its diagnostic yield. We evaluated the effect of mosapride citrate, a 5-hydroxytryptamine-4 agonist that increases gastrointestinal motility, on CE completion. Meth- ods: In a retrospective study, we performed univariate and multivariate analyses for 232 CE procedures performed at our hospital. To identify factors that affect CE completion, the following data were systematically collected: gender, age, gastric transit time (GTT), nonsteroidal anti-inflammatory drug administration, previous abdominal surgery, hospitaliza- tion, use of a polyethylene glycol solution, use of mosapride citrate (10 mg), body mass index (BMI), and total recording time. Results: The univariate analysis showed that oral mo- sapride citrate, GTT, and BMI were associated with improved CE completion. Multivariate analyses showed that oral mo- sapride citrate (odds ratio (OR), 1.99; 95% confidence inter - val (CI), 1.01 to 3.91) and GTT (OR, 2.34; 95% CI, 1.13 to 4.87) were significant factors for improving the CE completion. Oral mosapride citrate significantly shortened the GTT and small bowel transit time (SBTT). Conclusions: Oral mosapride ci- trate reduced the GTT and SBTT during CE and improved the CE completion rate. (Gut Liver 2012;6:339-343)

Background: Pharmacotherapy, including prokinetics and proton pump inhibitors for functional dyspepsia (FD) have limited effectiveness, and their safety has been recently questioned. Chinese herbal medicine (CHM) could be considered as an alternative. A systematic review (SR) of SRs was performed to evaluate the potential effectiveness and safety of CHM. Method: We conducted a comprehensive literature search for SRs with meta-analyses in eight international and Chinese databases. Pooled effect estimation from each meta-analysis was extracted. The AMSTAR instrument was used to assess the methodological quality of the included SRs. Results: A total of 14 SRs of mediocre quality assessing various CHMs, alone or in combination with conventional pharmacotherapy, were included. Meta-analyses showed that CHM was more effective than prokinetic agents for the alleviation of global dyspeptic symptoms. Three specific CHM formulae appeared to show superior results in the alleviation of global dyspeptic symptoms, including Si Ni San, modified Xiao Yao San and Xiang Sha Liu Jun Zi decoction. No significant difference in the occurrence of adverse events in using CHM or pharmacotherapy was reported. Conclusion: CHM can be considered as an alternative for the treatment of FD symptoms when prokinetic agents and proton pump inhibitors are contraindicated. Future trial design should focus on measuring changes in individual dyspeptic symptoms and differentiate the effectiveness of different CHM for postprandial distress syndrome and epigastric pain syndrome. A network meta-analysis approach should be used to explore the most promising CHM formula for FD treatment in the future.

Although abdominal bloating is one of the most bothersome symptoms experienced by patients with functional dyspepsia (FD), therapeutic drugs to relieve abdominal bloating have not been established. We investigated the Kampo (Chinese herbal) medicine, Hangekobokuto (Banxia-houpo-tang, HKT) for patients with FD from the standpoint of bowel gas retention. The bowel gas volume calculated from a plain abdominal radiogram (gas volume score, GVS) in FD patients was significantly higher than that in healthy subjects. Two week administration of HKT in the FD patients showed a significant decrease of GVS. Furthermore, gastrointestinal symptoms, especially symptoms of abdominal pain, indigestion and constipation, all of which are closely related to abdominal bloating, improved significantly in FD patients after the administration of HKT. These results suggest that HKT improves abdominal bloating accompanied by the reduction of bowel gas in FD patients.

The use of prokinetics/antiemetics is one of the leading causes of drug-induced parkinsonism (DIP) observed in neurology clinics. Cognitive dysfunction in DIP has recently been recognized, but pathologies related with cognitive dysfunction is unknown. Among our retrospective cohort of 385 consecutive parkinsonian patients enrolled in our parkinsonism registry, 14 patients were identified who satisfied our inclusion criteria: parkinsonism caused by prokinetics/antiemetics, existing T1-weighted 3D volumetric MR images, and normal [18F]-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl) nortropane PET scan images. For the comparison of volumetric MR data, 30 age- and sex-matched healthy individuals were included in this study. Among 14 patients with DIP, 4 patients were diagnosed with dementia, and all other patients had mild cognitive impairment (MCI). Comparisons of MR volumetric data between DIP patients with MCI and controls show that cortical gray matter volumes are reduced bilaterally in DIP (P=0.041) without changes in either total white matter volume or total intracranial volume. Among subcortical structures, the volume of the right hippocampus is reduced in DIP patients compared with controls (P=0.011, uncorrected). In DIP, cortical thickness is reduced in the bilateral lingual (P=0.002), right fusiform (P=0.032) and part of the left lateral occipital gyri (P=0.007). Our results suggests that cognitive dysfunction in DIP caused by prokinetics/antiemetics is common. Structural changes in the brain by 3D MRI may be associated with cognitive decline in DIP. Graphical Abstract

The efficacy of erythromycin was assessed in the treatment of 14 children aged 4 to 13 years with refractory chronic constipation, and presenting megarectum and fecal impaction. A double-blind, placebo- controlled, crossover study was conducted at the Pediatric Gastroenterology Outpatient Clinic of the University Hospital. The patients were randomized to receive placebo for 4 weeks followed by erythromycin estolate, 20 mg kg-1 day-1, divided into four oral doses for another 4 weeks, or vice versa. Patient outcome was assessed according to a clinical score from 12 (most severe clinical condition) to 0 (complete recovery). At enrollment in the study and on the occasion of follow-up medical visits at two-week intervals, patient score and laxative requirements were recorded. During the first 30 days, the mean ± SD clinical score for the erythromycin group (N = 6) decreased from 8.2 ± 2.3 to 2.2 ± 1.0 while the score for the placebo group (N = 8) decreased from 7.8 ± 2.1 to 2.9 ± 2.8. During the second crossover phase, the score for patients on erythromycin ranged from 2.9 ± 2.8 to 2.4 ± 2.1 and the score for the patients on placebo worsened from 2.2 ± 1.0 to 4.3 ± 2.3. There was a significant improvement in score when patients were on erythromycin (P < 0.01). Mean laxative requirement was lower when patients ingested erythromycin (P < 0.05). No erythromycin-related side effects occurred. Erythromycin was useful in this group of severely constipated children. A larger trial is needed to fully ascertain the prokinetic efficacy of this drug as an adjunct in the treatment of severe constipation in children.

The article deals with is one of the most common symptoms, faced by general practitioners or gastroenterologists — functional dyspepsia. Its clinical manifestations are described, attention is paid to the treatment issues. It is emphasized that the primary treatment of functional dyspepsia in most cases is an empirical, based on clinical assessment of predominance of acid-dependent or dysmotor symptoms, for which proton pump inhibitors, prokinetics, or combination drugs containing proton pump inhibitors and prokinetics, such as Omez D or Omez DCR, are administered, respectively., Статья посвящена одному из наиболее частых симптомокомплексов, с которыми приходится сталкиваться врачу общей практики или гастроэнтерологу, — функциональной диспепсии. Изложены ее клинические проявления, уделено внимание вопросам лечения. Подчеркнуто, что первичное лечение функциональной диспепсии в большинстве случаев является эмпирическим, основанным на клинической оценке преобладания кислотозависимых или дисмоторных симптомов, при которых соответственно назначаются ингибиторы протонной помпы, прокинетики или комбинированные препараты, содержащие ингибиторы протонной помпы и прокинетики, например Омез Д или Омез ДСР., Стаття присвячена одному з найбільш частих симптомокомплексів, із якими доводиться стикатися лікарю загальної практики або гастроентерологу, — функціональній диспепсії. Викладені її клінічні прояви, приділено увагу питанням лікування. Підкреслено, що первинне лікування функціональної диспепсії в більшості випадків є емпіричним, заснованим на клінічній оцінці переважання кислотозалежних або дисмоторних симптомів, при яких відповідно призначають інгібітори протонної помпи, прокінетики або комбіновані препарати, що містять інгібітори протонної помпи і прокінетики, наприклад Омез Д або Омез ДСР.

Background:Quality of life (QOL) is impaired in functional dyspepsia (FD). Little is known about the effects of different therapies on the QOL profile in patients with this condition.Objectives:The aims of this study were to measure baseline QOL in patients with FD and to assess changes in QOL over time associated with Helicobacter pylori eradication and prokinetic treatment. The primary and secondary end points were the improvement in QOL 6 weeks and 1 year after successful eradication of the infection or prokinetic therapy.Methods:This 1-year, single-center, prospective, open-label, controlled, parallel-group trial was conducted at the Department of Gastroenterology, Ferencvdros Health Centre, Budapest, Hungary. The Functional Digestive Disorder Quality of Life (FDDQoL) Questionnaire (MAPI Research Institute, Lyon, France) was translated and validated previously in Hungarian. Male and female subjects aged 20 to 60 years were enrolled and classified as H pylori positive (HP+), H pylori negative (HP-) with FD, or healthy (control group). The HP+ patients received pantoprazole 40 mg BID + amoxicillin 1000 mg BID + clarithromycin 500 mg BID for 7 days, followed by on-demand ranitidine (150–300 mg/d) for 1 year. The HP- patients received the prokinetic cisapride 10 mg TID for 1 month, followed by on-demand cisapride (10–20 mg/d) for 1 year. The FDDQoL questionnaire was completed by all 3 groups on enrollment, at 6 weeks, and 1 year.Results:A total of 101 HP+ patients, 98 HP- patients, and 123 healthy controls were included in the study (185 women, 137 men; mean age, 39.0 ears). The mean (SD) baseline QOL scores were significantly lower in the HP+ group (53.3 [9.6]; 95% CI, 54.4-58.2) and the HP- groups (50.0 [9.8]; 95% CI, 58.0–62.0) compared with that in healthy controls (76.2 [8.7]; 95% CI, 74.6–77.8) (both, P < 0.001). Analysis of the short-term domain scores found that the HP+ group had significantly decreased scores in 6 of 8 domains: daily activities (P = 0.005), anxiety level (P = 0.02), diet (P = 0.008), sleep (P < 0.001), discomfort (P = 0.004), and disease control (P = 0.02); the HP- group had significantly decreased scores in 5 of 8 domains: daily activities (P < 0.001), diet (P = 0.004), sleep (P = 0.005), discomfort (P < 0.001), and disease control (P = 0.02). Eradication of the infection was successful in 77/101 (76.2%) of the patients on intent-to-treat analysis and 77/94 (81.9%) on per-protocol analysis. Eradication was associated with an increase in mean (SD) QOL score to 70.8 (10.7) at 6 weeks (95% CI, 63.3–73.2; P < 0.001 vs baseline) and to 75.3 (9.3) at 1 year (95% CI, 73.2–77.5; P= 0.05 vs 6 weeks). In the HP- group, the QOL score increased to 73.3 (9.7) (95% CI, 71.3–75.4; P < 0.001 vs baseline) at 6 weeks of cisapride treatment and to 76.5 (8.5) at 1 year (95% CI, 74.5–78.4; P = 0.06 vs 6 weeks). Most of the impaired domain scores improved significantly after both treatments. The short-term effect size was 1.48 in HP+ and 1.35 in HP− patients. Adverse events (AEs) occurred in 22 (21.8%) patients in the HP+ group (nausea, 8 [7.9%] patients; diarrhea, 5 [5.0%]; loss of appetite, 5 [5.0%]; stomatitis, 5 [5.0%]; abdominal pain, 4 [4.0%]; bloating, 4 [4.0%]; headache, 4 [4.0%]; vomiting, 4 [4.0%]; constipation, 3 [3.0%]; and vaginitis, 3 [3.0%]). In HP− cases, AEs occurred in 9 (9.2%) patients (abdominal cramps, 7 [7.1%]; diarrhea, 4 [4.1%]; and nausea, 3 [3.1%]).Conclusion:In this study in patients with FD and healthy controls, eradication of H pylori infection in infected patients and cisapride treatment in uninfected patients reversed low QOL scores during the 1-year follow-up period.

Gastrointestinal feeding intolerance and critical illness-associated gastric motility dysfunction are common. Although recent guidelines recommend not interrupting gastric feeding when gastric residual volume (GRV) is lower than 500 mL or to completely abandon measurement of GRV, it may seem that the relevance of prokinetics is reduced. In patients at risk for aspiration and in multimodal strategies to enhance feeding performance, however, use of prokinetics is still advocated. Metoclopramide and erythromycin are commonly used promotility agents, although with relevant side effects. Potential targets for new agents and early study results are addressed.