Comparison of pancreatic enzyme abnormalities and protease-activated receptor-2-positive eosinophils in the duodenum of patients with functional dyspepsia-irritable bowel syndrome overlap with functional dyspepsia alone in Asian populations.

BACKGROUND AND AIM: Some patients with functional gastrointestinal disorders exhibit pancreatic dysfunctions and pancreatic enzyme abnormalities. Thus, we aimed to clarify whether significant differences in clinical characteristics, prevalence of pancreatic enzyme abnormalities, duodenal inflammation, and protease-activated receptor 2 (PAR2) expression levels related to hypersensitivity exist between functional dyspepsia (FD) alone and FD-irritable bowel syndrome (IBS) overlap group. METHODS: Ninety-three patients based on the Rome IV criteria, FD alone (n = 44) and FD overlapped with IBS (n = 49) group were enrolled. The patients scored their own clinical symptoms after consuming high-fat meals. Serum trypsin, PLA2, lipase, p-amylase, and elastase-1 levels were measured. PAR2, eotaxin-3, and TRPV4 mRNA levels in duodenum were determined using real-time polymerase chain reaction methods. PRG2- and PAR2 in the duodenum were evaluated using immunostaining. RESULTS: FD score and global GSRS in patients with FD-IBS overlap were significantly higher than FD alone. Although the prevalence of pancreatic enzyme abnormalities in patients with FD alone was significantly (P < 0.01) higher than that in FD-IBS overlap, the ratio of aggravation of clinical symptoms following high-fat intake in patients with FD-IBS overlap was significantly higher (P = 0.007) than that in patients with FD alone. PAR2- and PRG2-double positive cells were localized in the degranulated eosinophils in the duodenum of patients with FD-IBS overlap. The number of PAR2- and PRG2-double positive cells in FD-IBS overlap was significantly (P < 0.01) higher than FD alone. CONCLUSIONS: Pancreatic enzyme abnormalities and PAR2 expression on degranulated eosinophils infiltrations in the duodenum may be associated with the pathophysiology of patients with FD-IBS overlap in Asian populations.

Ultrasonographic assessment of preoperative gastric volume in patients with dyspepsia: a prospective observational study.

BACKGROUND: Patients undergoing gastroenteroscopy during sedation are prone to aspiration, and most patients with dyspepsia have delayed gastric emptying. This study aimed to investigate the feasibility of measuring the gastric antrum cross-sectional area (CSA) to supply a novel clinical diagnostic reference value in patients with dyspepsia. METHODS: Patients with dyspepsia undergoing elective gastroscopy were included. The Perlas qualitative 0-2 grading scale score was determined before the operation. The anteroposterior diameter (D1) and craniocaudal diameter (D2) between gastric antrum serosal surfaces were measured perpendicular to each other in the supine and right lateral decubitus (RLD) positions. CSA values in the supine position and RLD position were determined. Gastric contents were endoscopically suctioned with the volumes measured and noted as actual gastric volume. Multiple regression analysis was used to fit a mathematical model for estimating the gastric volume. Receiver operating characteristic (ROC) curves were constructed to determine the accuracy of RLD CSA to detect gastric volumes of > 0.8 ml/kg. RESULTS: A total of 117 patients were enrolled and divided into a functional dyspepsia (FD) group and an organic dyspepsia group according to gastroscopy findings. For a gastric volume of > 0.8 ml/kg, cut-off values for FD and organic dyspepsia were 6.7 cm2 and 10.0 cm2, respectively. Two new modified mathematical models were derived to predict an estimated gastric volume for FD and organic dyspepsia: volume = 3.93 × RLD CSA - 0.47 × age; and volume = 6.15 × RLD CSA - 0.61 × age. CONCLUSION: We used the cut-off value of the antral area for the fast diagnosis of gastric volumes in patients with dyspepsia, which may assist clinicians in identifying patients at risk of aspiration. TRIAL REGISTRATION: www.chictr.org.cn ( CHICTR-DDD-17010871 ); registered 15 March 2017.

Gastric accommodation: Physiology, diagnostic modalities, clinical relevance, and therapies.

BACKGROUND: Gastric accommodation is an essential gastric motor function which occurs following ingestion of a meal. Impaired gastric fundic accommodation (IFA) is associated with dyspeptic symptoms. Gastric accommodation is mediated by the vagal pathway with several important physiologic factors such as duodenal nutrient feedback playing a significant role. IFA has been described as a pathophysiologic factor in several gastrointestinal disorders including functional dyspepsia, diabetic gastropathy, post-Nissen fundoplication, postsurgical gastrectomy, and rumination syndrome. Modalities for gastric accommodation assessment include gastric barostat, intragastric meal distribution via scintigraphy, drinking tests (eg, water load), SPECT, MRI, 2D and 3D ultrasound, and intragastric high-resolution manometry. Several treatment options including sumatriptan, buspirone, tandospirone, ondansetron, and acotiamide may improve symptoms by increasing post-meal gastric volume. PURPOSE: Our aim is to provide an overview of the physiology, diagnostic modalities, and therapies for IFA. A literature search was conducted on PubMed, Google Scholar, and other sources to identify relevant studies available until December 2020. Gastric accommodation is an important gastric motor function which if impaired, is associated with several upper gastrointestinal disorders. There are an increasing number of gastric accommodation testing modalities; however, each has facets which warrant consideration. Evidence regarding potentially effective therapies for IFA is growing.

Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial.

BACKGROUND: Current treatments for functional dyspepsia have limited efficacy or present safety issues. We aimed to assess spore-forming probiotics in functional dyspepsia as monotherapy or add-on therapy to long-term treatment with proton-pump inhibitors. METHODS: In this single-centre, randomised, double-blind, placebo-controlled pilot trial that took place at University Hospitals Leuven (Leuven, Belgium), adult patients (≥18 years) with functional dyspepsia (as defined by Rome IV criteria, on proton-pump inhibitors or off proton-pump inhibitors) were randomly assigned (1:1) via computer-generated blocked lists, stratified by proton-pump inhibitor status, to receive 8 weeks of treatment with probiotics (Bacillus coagulans MY01 and Bacillus subtilis MY02, 2·5 × 109 colony-forming units per capsule) or placebo consumed twice per day, followed by an open-label extension phase of 8 weeks. Individuals with a history of abdominal surgery, diabetes, coeliac or inflammatory bowel disease, active psychiatric conditions, and use of immunosuppressant drugs, antibiotics, or probiotics in the past 3 months were excluded. All patients and on-site study personnel were masked to treatment allocation in the first 8 weeks. Symptoms, immune activation, and faecal microbiota were assessed and recorded. The primary endpoint was a decrease of at least 0·7 in the postprandial distress syndrome (PDS) score of the Leuven Postprandial Distress Scale in patients with a baseline PDS score of 1 or greater (at least mild symptoms), assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04030780. FINDINGS: Between June 3, 2019, and March 11, 2020, of 93 individuals assessed for eligibility, we included 68 patients with functional dyspepsia (51 [75%] women, mean age 40·1 years [SD 14·4], 34 [50%] on proton-pump inhibitors). We randomly assigned 32 participants to probiotics and 36 to placebo. The proportion of clinical responders was higher with probiotics (12 [48%] of 25) than placebo (six [20%] of 30; relative risk 1·95 [95% CI 1·07-4·11]; p=0·028). The number of patients with adverse events was similar with probiotics (five [16%] of 32) and placebo (12 [33%] of 36). Two serious adverse events occurring during the open-label phase (appendicitis and syncope in two separate patients) were assessed as unlikely to be related to the study product. INTERPRETATION: In this exploratory study, B coagulans MY01 and B subtilis MY02 were efficacious and safe in the treatment of functional dyspepsia. Participants had potentially beneficial immune and microbial changes, which could provide insights into possible underlying mechanisms as future predictors or treatment targets. FUNDING: MY HEALTH.

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. METHODS: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. RESULTS: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.

Nutrient Drinking Test as Biomarker in Functional Dyspepsia.

INTRODUCTION: Functional dyspepsia (FD) is a prevalent condition with multifactorial pathophysiology, including impaired gastric accommodation (GA), hypersensitivity to gastric distention, and delayed gastric emptying. Drink tests (DT) have been proposed as a potential biomarker for the presence and severity of gastric sensorimotor dysfunction. Thus, we aimed to summarize the state of knowledge on different DT and their potential as a biomarker for FD. METHODS: A PubMed and MEDLINE search was conducted for English language articles, reviews, meta-analyses, case series, and randomized controlled trials, including also published meeting abstracts. RESULTS: Several DT have been described in literature (e.g., different type of liquid, number of calories used, pace of drinking, and subject's awareness of the amount of liquid drunk). FD patients ingest significantly less volume in the different variants of the tests. The slow nutrient ("satiety drinking") test (SDT) studies show the most consistent separation between health and FD and correlation with GA. However, sensitivity to distention may be correlated with rapid DT. SDTs were used to evaluate the effect of several pharmacological agents, often showing concordance between their effects on GA and tolerated nutrient volume. This correlation was not found mainly for agents with central actions. DISCUSSION: An SDT is a potential diagnostic biomarker in FD, reflecting GA. Additional studies are required to confirm its role as a predictive biomarker for treatment outcome in FD.

Clinical associations of functional dyspepsia with gastric dysrhythmia on electrogastrography: A comprehensive systematic review and meta-analysis.

BACKGROUND: Functional dyspepsia (FD) is a common gastroduodenal disorder, yet its pathophysiology remains poorly understood. Bioelectrical gastric slow-wave abnormalities are thought to contribute to its multifactorial pathophysiology. Electrogastrography (EGG) has been used to record gastric electrical activity; however, the clinical associations require further evaluation. AIMS: This study aimed to systematically assess the clinical associations of EGG in FD. METHODS: MEDLINE, EMBASE, and CENTRAL databases were systematically searched for articles using EGG in adults with FD. Primary outcomes were percentage normal versus abnormal rhythm (bradygastria, normogastria, and tachygastria). Secondary outcomes were dominant power, dominant frequency, percentage coupling, and the meal responses. RESULTS: 1751 FD patients and 555 controls from 47 studies were included. FD patients spent less time in normogastria while fasted (SMD -0.74; 95%CI -1.22 to -0.25) and postprandially (-0.86; 95%CI -1.35 to -0.37) compared with controls. FD patients also spent more fasted time in bradygastria (0.63; 95%CI 0.33-0.93) and tachygastria (0.45; 95%CI 0.12-0.78%). The power ratio (-0.17; 95%CI -0.83-0.48) and dominant frequency meal-response ratio (0.06; 95%CI -0.08-0.21) were not significantly different to controls. Correlations between EGG metrics and the presence and timing of FD symptoms were inconsistent. EGG methodologies were diverse and variably applied. CONCLUSION: Abnormal gastric slow-wave rhythms are a consistent abnormality present in FD, as defined by EGG and, therefore, likely play a role in pathophysiology. The aberrant electrophysiology identified in FD warrants further investigation, including into underlying mechanisms, associated spatial patterns, and symptom correlations.

Impact of COVID-19 lockdown on symptoms in patients with functional gastrointestinal disorders: Relationship with anxiety and perceived stress.

BACKGROUND: Psychological stress and anxiety, such those generated by forced quarantine, affect gastrointestinal symptoms course in patients with functional gastrointestinal disorders. Thus, our aim was to assess, in a cohort of patients regularly followed up in a devoted outpatient clinic of Southern Italy, the association between their gastrointestinal symptoms changes, stress, and anxiety reported during the Italian lockdown. METHODS: We recruited patients from the outpatient clinic of the University of Salerno, devoted to functional gastrointestinal disorders, selecting only patients for whom an evaluation was available in the last 6 months before the lockdown. Gastrointestinal symptoms were evaluated at each visit through standardized questionnaire and pooled in a database. On 45th days from the beginning of the lockdown, patients were re-assessed by phone with the same questionnaire. Anxiety and stress levels were assessed through a self-administered online questionnaire based on Generalized Anxiety Disorder 7 test and Perceived Stress Scale 10 test. KEY RESULTS: The intensity-frequency scores of several upper gastrointestinal symptoms improved (Wilcoxon test <0.05). Higher anxiety levels had a higher risk of worsening chest pain (OR 1.3 [1.1-1.7]), waterbrash (OR 1.3 [1.0-1.7]), epigastric burning (OR 1.3 [1.0-1.6]), and abdominal pain (OR 1.6 [1.0-2.3]). When compared to the interval preceding the outbreak, half of the patients declared their symptoms remained unchanged, 13.6% worsened, and 36.4% improved. CONCLUSIONS AND INFERENCES: During the COVID-19 quarantine, there was an improvement of the majority of upper gastrointestinal symptoms in our patients, and anxiety seems an important risk of worsening few of them.

Transcutaneous auricular vagal nerve stimulation improves functional dyspepsia by enhancing vagal efferent activity.

This study was designed to investigate whether transcutaneous auricular vagal nerve stimulation (taVNS) would be able to improve major pathophysiologies of functional dyspepsia (FD) in patients with FD. Thirty-six patients with FD (21 F) were studied in two sessions (taVNS and sham-ES). Physiological measurements, including gastric slow waves, gastric accommodation, and autonomic functions, were assessed by the electrogastrogram (EGG), a nutrient drink test and the spectral analysis of heart rate variability derived from the electrocardiogram (ECG), respectively. Thirty-six patients with FD (25 F) were randomized to receive 2-wk taVNS or sham-ES. The dyspeptic symptom scales, anxiety and depression scores, and the same physiological measurements were assessed at the beginning and the end of the 2-wk treatment. In comparison with sham-ES, acute taVNS improved gastric accommodation (P = 0.008), increased the percentage of normal gastric slow waves (%NSW, fasting: P = 0.010; fed: P = 0.007) and vagal activity (fasting: P = 0.056; fed: P = 0.026). In comparison with baseline, 2-wk taVNS but not sham-ES reduced symptoms of dyspepsia (P = 0.010), decreased the scores of anxiety (P = 0.002) and depression (P < 0.001), and improved gastric accommodation (P < 0.001) and the %NSW (fasting: P < 0.05; fed: P < 0.05) by enhancing vagal efferent activity (fasting: P = 0.015; fed: P = 0.048). Compared with the HC, the patients showed increased anxiety (P < 0.001) and depression (P < 0.001), and decreased gastric accommodation (P < 0.001) and %NSW (P < 0.001) as well as decreased vagal activity (fasting: P = 0.047). The noninvasive taVNS has a therapeutic potential for treating nonsevere FD by improving gastric accommodation and gastric pace-making activity via enhancing vagal activity.NEW & NOTEWORTHY Treatment of functional dyspepsia is difficult due to various pathophysiological factors. The proposed method of transcutaneous auricular vagal nerve stimulation improves symptoms of both dyspepsia and depression/anxiety, and gastric functions (accommodation and slow waves), possibly mediated via the enhancement of vagal efferent activity. This noninvasive and easy-to-implement neuromodulation method will be well received by patients and healthcare providers.

Impact of joint hypermobility syndrome on gastric accommodation and nutrient tolerance in functional dyspepsia.

Functional dyspepsia (FD) is defined as the presence of gastroduodenal symptoms in the absence of organic disease that is likely to explain the symptoms. Joint hypermobility (JH) refers to the increased passive or active movement of a joint beyond its normal range and is characteristically present in patients with joint hypermobility syndrome (JHS), which is a hypermobile subtype of Ehlers-Danlos syndrome (EDS). Recent reports have highlighted the co-existence of FD with Ehlers-Danlos syndrome. Our aim was to study the prevalence of JHS in FD compared with healthy subjects and to study the impact of co-existing JHS on gastric motility, nutrient tolerance, and dyspeptic symptoms in FD. METHODS: FD patients filled out a dyspepsia symptom severity score. Intragastric pressure (IGP) was measured with high-resolution manometry (HRM) during the intragastric infusion of nutrition drink (ND, 1.5 Kcal/ml, 60 ml/min) until maximal satiation in healthy subjects and FD. We compared IGP profiles and nutrient tolerance in HS and FD with or without JHS. RESULTS: JHS was present in 54% of FD patients (n = 39, 41.2 ± 2.2 years old) and 7% of healthy subjects (n = 15, 27.3 ± 2.3 years old). IGP drop and nutrient tolerance were lower in non-JHS-FD compared with JHS-FD and HS (AUC JHS-FD: -17.9 ± 2.5 vs. non-JHS-FD: -13.0 ± 3.3 mmHg min, p = 0.2, HS:-19.6 ± 2.9 mmHg min; ND tolerance non-JHS-FD: 671.0 ± 96.0 vs. JHS-FD: 842.7 ± 105.7 Kcal, p = 0.25, HS: 980.0 ± 108.1 Kcal). CONCLUSION: JHS often co-exists with FD. Non-JHS-FD was characterized by decreased accommodation and lower nutrient tolerance characterized compared with JHS-FD. Clinicaltrials.gov, reference number NCT04279990.

Functional Dyspepsia and Gastroparesis in Tertiary Care are Interchangeable Syndromes With Common Clinical and Pathologic Features.

BACKGROUND: The aim of this study was to clarify the pathophysiology of functional dyspepsia (FD), a highly prevalent gastrointestinal syndrome, and its relationship with the better-understood syndrome of gastroparesis. METHODS: Adult patients with chronic upper gastrointestinal symptoms were followed up prospectively for 48 weeks in multi-center registry studies. Patients were classified as having gastroparesis if gastric emptying was delayed; if not, they were labeled as having FD if they met Rome III criteria. Study analysis was conducted using analysis of covariance and regression models. RESULTS: Of 944 patients enrolled during a 12-year period, 720 (76%) were in the gastroparesis group and 224 (24%) in the FD group. Baseline clinical characteristics and severity of upper gastrointestinal symptoms were highly similar. The 48-week clinical outcome was also similar but at this time 42% of patients with an initial diagnosis of gastroparesis were reclassified as FD based on gastric-emptying results at this time point; conversely, 37% of patients with FD were reclassified as having gastroparesis. Change in either direction was not associated with any difference in symptom severity changes. Full-thickness biopsies of the stomach showed loss of interstitial cells of Cajal and CD206+ macrophages in both groups compared with obese controls. CONCLUSIONS: A year after initial classification, patients with FD and gastroparesis, as seen in tertiary referral centers at least, are not distinguishable based on clinical and pathologic features or based on assessment of gastric emptying. Gastric-emptying results are labile and do not reliably capture the pathophysiology of clinical symptoms in either condition. FD and gastroparesis are unified by characteristic pathologic features and should be considered as part of the same spectrum of truly "organic" gastric neuromuscular disorders. CLINICALTRIALS. GOV IDENTIFIER: NCT00398801, NCT01696747.

Vagal gut-brain signaling mediates amygdaloid plasticity, affect, and pain in a functional dyspepsia model.

Functional dyspepsia (FD) is associated with chronic gastrointestinal distress and with anxiety and depression. Here, we hypothesized that aberrant gastric signals, transmitted by the vagus nerve, may alter key brain regions modulating affective and pain behavior. Using a previously validated rat model of FD characterized by gastric hypersensitivity, depression-like behavior, and anxiety-like behavior, we found that vagal activity - in response to gastric distention - was increased in FD rats. The FD phenotype was associated with gastric mast cell hyperplasia and increased expression of corticotrophin-releasing factor (Crh) and decreased brain-derived neurotrophic factor genes in the central amygdala. Subdiaphragmatic vagotomy reversed these changes and restored affective behavior to that of controls. Vagotomy partially attenuated pain responses to gastric distention, which may be mediated by central reflexes in the periaqueductal gray, as determined by local injection of lidocaine. Ketotifen, a mast cell stabilizer, reduced vagal hypersensitivity, normalized affective behavior, and attenuated gastric hyperalgesia. In conclusion, vagal activity, partially driven by gastric mast cells, induces long-lasting changes in Crh signaling in the amygdala that may be responsible for enhanced pain and enhanced anxiety- and depression-like behaviors. Together, these results support a "bottom-up" pathway involving the gut-brain axis in the pathogenesis of both gastric pain and psychiatric comorbidity in FD.

Addition of small-bowel transit scintigraphy to gastric emptying for assessment of patients with upper gastrointestinal symptoms.

BACKGROUND: Dyspeptic symptoms are not well correlated with gastric emptying (GE) results. AIMS: To determine (a) prevalence of delayed SB transit (SBT) in patients undergoing GE scintigraphy for symptoms of gastroparesis; (b) symptoms associated with delayed SBT. METHODS: Patients with symptoms of gastroparesis underwent combined GE and SBT scintigraphy (GES/SBTS). Patients ingested a mixed solid (S)-liquid (L) meal with egg whites labeled with 500 µCi Tc-99 m sulfur colloid and water with 125 µCi In-111 DTPA. Retained S and L gastric activity and percent of L In-111 activity in terminal ileum (TI) and/or cecum/colon at 6 h were determined. Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) assessed symptoms from 0 (none) to 5 (very severe). KEY RESULTS: Of 363 patients, 174 (47.9%) had delayed S GE, 141 (38.8%) delayed L GE, and 70 (19.3%) delayed SBT. Delayed SBT was seen in 24 (6.6%) with normal S GE and 46 (12.7%) with delayed S GE. Patients with isolated delayed SBT had highest symptom scores for postprandial fullness (3.5), stomach fullness (3.4), nausea (3.2), bloating (3.2), compared to isolated delayed S GE who had highest symptom scores for postprandial fullness (3.7), nausea (3.6), stomach fullness (3.4), and early satiety (3.3). CONCLUSIONS & INFERENCES: Delayed SBT occurred in 19.3% of dyspeptic patients using GES/SBTS. While postprandial and stomach fullness were common to both delayed S GE and delayed SBT, early satiety was associated with delayed S GE whereas bloating was associated with delayed SBT. Thus, SBTS can augment GES to help explain some symptoms associated with dyspepsia and suspected gastroparesis.

Functional dyspepsia in children: A study of pathophysiological factors.

BACKGROUND AND AIM: Functional dyspepsia (FD) is common in children, and treatment targeted towards the altered pathophysiology can improve outcome. We evaluated FD children for abnormality of gastric accommodation and emptying, psychological stressors (PS), Helicobacter pylori (HP) infection, and post-infectious FD. METHODS: Diagnosis of FD was based on ROME III criteria. Clinical evaluation including dyspeptic symptom scoring and assessment for PS was performed. Satiety drink test for gastric accommodation, gastroscopy with biopsy for HP infection, and solid meal gastric emptying were performed. Sixty-seven healthy children were enrolled for assessing PS and satiety drink test. RESULTS: Fifty-five FD children (33 boys, age 12 [6-18] years) with symptoms for 4 (2-48) months and dyspeptic score of 5 (1-13) were enrolled. PS were more common in FD than in controls (46/55 vs 9/67; P < 0.001). Median satiety drink volume was 360 mL (180-1320 mL); no patients had satiety drink volume of < 5th centile of healthy children. The frequency (98% vs 85%; P = 0.01) and severity (65 [10-175] vs 50 [5-130]; P < 0.001) of postprandial symptoms were higher in FD than in controls. Of the postprandial symptoms, pain (20.3% vs 0%; P = 0.000) was present only in FD. Delayed gastric emptying was present in 6.5%, HP infection in 11%, and post-infectious FD in 13% cases. Etiological factor was identified in 87% children, with 20% having multiple factors. CONCLUSIONS: Abnormality of gastric sensorimotor function is seen in one-fourth of FD cases. HP infection and post-infectious FD are present in 11% and 13% cases, respectively.

Responses to gastric gas in patients with functional gastrointestinal disorders.

BACKGROUND: Gas-related abdominal symptoms are common in patients with functional gut disorders, but the responses to cope with the large volumes of gas that enter daily into the stomach have not been studied in detail. Our aim was to evaluate transit and tolerance of gastric gas in patients with functional gastrointestinal disorders. METHODS: In eight healthy volunteers and 24 patients with functional gut disorders (eight functional dyspepsia, eight belching disorder, and eight functional bloating) 1500 ml of a gas mixture were infused into the stomach at 25 ml/min. Belching, rectal gas evacuation, and abdominal perception were continuously recorded for 90 minutes. KEY RESULTS: Healthy subjects expelled the infused gas per rectum (1614 ± 73 ml), with a small rise in epigastric perception (score increment 1.0 ± 0.4) and virtually no belching (1 ± 1 belches). Patients with functional dyspepsia had a hypersensitive response to gastric gas, with a significant rise in epigastric perception (score increment 2.5 ± 0.6; P = .045), a transient delay in rectal gas evacuation and similar belching as healthy controls. Patients with belching disorders responded to gastric gas with continuous belches (33 ± 13 belches; P = .002), low epigastric perception, and a small reduction in rectal gas evacuation. Patients with functional bloating exhibited a slow transit response, with reduced rectal gas evacuation (1017 ± 145 ml; P = .002) and abdominal symptoms (score increment 2.5 ± 0.7), but without compensatory belching. CONCLUSIONS AND INFERENCES: Different pathophysiological mechanisms underlay specific adaptive responses to gastric gas in patients with different functional gut disorders. Therapeutic interventions for gas-related abdominal symptoms should be addressed towards these specific pathophysiological disturbances.

Update on Indigestion.

Dyspepsia affects a large percentage of the general population and can lead to lost work productivity and reduced quality of life. Patients with dyspepsia younger than 60 should not routinely undergo endoscopy but instead should pursue Helicobacter pylori test-and-treat approach. For patients 60 and older, endoscopy should be performed. Patients without any identifiable cause for their symptoms are diagnosed with functional dyspepsia. Guideline-based treatment includes H pylori eradication and proton pump inhibitor use. If acid suppression is not adequate, treatment with a tricyclic antidepressant followed by a prokinetic agent and psychological therapy are considered. Complementary therapies are not recommended due to limited evidence.

The rodent model of impaired gastric motility induced by allyl isothiocyanate, a pungent ingredient of wasabi, to evaluate therapeutic agents for functional dyspepsia.

Functional dyspepsia (FD) is thought to be mainly based on gastric motility dysfunction and chronic hypersensitivity, yet FD animal models has been reported a few. We studied to establish the mouse model of impaired gastric motility induced by a pungent ingredient of wasabi allyl isothiocyanate (AITC), which is reliable to evaluate prokinetic agents. Male ddY mice were used. Gastric motility was measured by 13C-acetic acid breath test in conscious mice. AITC (80 mM) was given 60 min before the measurement of motility. Prokinetic agents including itopride (30, 100 mg/kg), mosapride (0.1-1 mg/kg), neostigmine (30 µg/kg), acotiamide (10-100 mg/kg), and daikenchuto (100-1000 mg/kg) were given 40 min before the measurement. AITC impaired gastric motility without mucosal damages, which reverted 24 h after AITC treatment. The decreased motility induced by AITC was restored by prokinetic agents such as itopride, mosapride, neostigmine, and acotiamide. In separate experiment, daikenchuto recovered the decreased motility induced by AITC, although daikenchuto had no effect on motility in normal condition. In conclusion, it is considered that the AITC-induced impaired gastric motility mouse model is useful to develop new prokinetic agents for treatment of FD, and to re-evaluate traditional Japanese herbal medicines.

The clinical efficacy of acupoint sticking combined with massage to treatment functional dyspepsia: A protocol of systematic review and meta-analysis.

BACKGROUND: The objective of this meta-analysis was to summarize and identify the available evidence from studies to estimate the clinical value of acupoint sticking combined with massage (ASM) in the treatment of functional dyspepsia (FD), and provide clinicians with evidence on which to base their clinical decision making. METHODS: This review will include all studies comparing clinical efficacy of ASM in the treatment of FD. The search strategy will be performed in 10 databases. We will not establish any limitations to language and publication status, published from inception to the August 2020. Two reviewers will screen, select studies, extract data, and assess quality independently. Outcome is alleviation of global dyspeptic symptoms, alleviation of individual dyspeptic symptoms, quality-of-life improvement, and safety. The methodological quality including the risk of bias of the included studies will be evaluated. We will carry out statistical analysis using RevMan 5.3 software. RESULTS: This study will summarize current evidence to assess the efficacy and safety of ASM in the treatment of FD. CONCLUSION: The findings of this study will provide helpful evidence for the clinician, and will promote further studies, as well as studying the value of ASM. REGISTRATION NUMBER: INPLASY2020110072 (DOI number: 10.37766/inplasy2020.11.0072).