Organic Gastrointestinal Diseases Research Articles

Symptom profiles compatible with disorders of gut-brain interaction (DGBI) in organic gastrointestinal diseases: A global population-based study.

Patients with organic gastrointestinal (GI) diseases and diabetes mellitus (DM) can have concomitant disorders of gut-brain interaction (DGBI). This study aimed to compare the global prevalence of DGBI-compatible symptom profiles in adults with and without self-reported organic GI diseases or DM. Data were collected in a population-based internet survey in 26 countries, the Rome Foundation Global Epidemiology Study (n=54,127). Individuals were asked if they had been diagnosed by a doctor with gastroesophageal reflux disease, peptic ulcer, coeliac disease, inflammatory bowel disease (IBD), diverticulitis, GI cancer or DM. Individuals not reporting the organic diagnosis of interest were included in the reference group. DGBI-compatible symptom profiles were based on Rome IV diagnostic questions. Odds ratios (ORs [95% confidence interval]) were calculated using mixed logistic regression models. Having one of the investigated organic GI diseases was linked to having any DGBI-compatible symptom profile ranging from OR 1.64 [1.33, 2.02] in GI cancer to OR 3.22 [2.80, 3.69] in IBD. Those associations were stronger than for DM, OR 1.26 [1.18, 1.35]. Strong links between organic GI diseases and DGBI-compatible symptom profiles were seen for corresponding (e.g., IBD and bowel DGBI) and non-corresponding (e.g., IBD and esophageal DGBI) anatomical regions. The strongest link was seen between fecal incontinence and coeliac disease, OR 6.94 [4.95, 9.73]. After adjusting for confounding factors, associations diminished, but persisted. DGBI-compatible symptom profiles are more common in individuals with self-reported organic GI diseases and DM compared to the general population. The presence of these concomitant DGBIs should be considered in the management of organic (GI) diseases.

Epidemiology of functional dyspepsia and gastroparesis as diagnosed in Flemish-Belgian primary care: A registry-based study from the Intego database.

Dyspepsia is a prevalent condition in the general population. Besides organic causes, the differential diagnosis of dyspepsia includes functional dyspepsia (FD) and gastroparesis (GP) which share similar pathophysiological mechanisms and clinical presentation. So far, no study investigated the prevalence of FD and GP in a primary care in Belgium. Data were obtained from Intego, a Flemish-Belgian general practice-based morbidity registration network. From 586,164 patients between 2000 and 2021, we selected patients with ICD-10 code for FD and GP. Patients with organic gastrointestinal diseases were excluded. We determined demographics and comorbidities of FD/GP. For prevalence and incidence calculation, we included those who consulted their general practitioners at least once in the given year. Pair-wise comparison was conducted to access the impact of comorbidities on risk of FD/GP. Between 2011 and 2021, the prevalence of FD/GP ranged from 1.03% to 1.21%. The incidence of FD/GP ranged from 109 to 142 per 100,000 adults. In total 5242 cases of FD/GP were identified. These cases shared commonly coexisting diagnoses of gastroesophageal reflux disease (18.8%), irritable bowel syndrome (17.1%), and chronic constipation (18.7%). Patients with somatization/anxiety/depression had significantly higher risk of FD/GP, compared to the control (OR 1.38, 95% CI 1.19-1.61, p < 0.01). The prevalence (1.03%-1.21%) and incidence (109-142/100,000) of FD/GP in primary care over last decade appear to conflict with epidemiological research in the general population. The discrepancies suggest a potential lack of awareness of FD and GP among physicians and/or patients in Flemish-Belgium.

Functional disorders of the gastrointestinal tract in children of different age groups (a literature review)

In recent years, diseases of the gastrointestinal tract are becoming more common with economic and social impacts. It is believed that in terms of frequency, they rank second both among the adult and pediatric population, second only to respiratory system diseases. Due to significant morphological and physiological changes in individual organs and systems during the period of intensive development of a child, the formation of gastroenterological pathology occurs most often at the age of 5–6 or 9–12 years, that gives rise to various functional disorders of the gastrointestinal tract. There is an opinion that among older children, such functional disorders are often bordering on pathology, prompting pediatricians to an increased interest in their etiology, pathogenesis and current therapy. Aim. To highlight the state of the problem associated with the most frequent functional disorders of the gastrointestinal tract in children at the present stage. According to the recent recommendations, it has been recommended to consider functional changes as disorders of the interaction between the brain and the gastrointestinal tract (disorders of gut-brain interaction).The underlying disorders are abnormal motility, visceral hypersensitivity, the state of the gastrointestinal mucosa and local immune factors, intestinal microflora, activity of the central and autonomic nervous system. Most researchers tend to think about the key role of impaired autonomic regulation of sphincter activity in the pathogenesis of motor-evacuatory dysfunction of the alimentary canal in children, buoyed by the fact that often the lack of gastrointestinal organic lesions in motility disorders indicates their dysregulatory character. Conclusions. Functional disorders of the gastrointestinal tract have an extraordinary brightness of pain syndrome perception (no organic pathology would give such a wide array of symptoms as functional disorders) and a variable pattern of symptoms, so it becomes clear why these diseases impose a major economic burden, and it is this characteristic enables them to be classified as socially significant disorders. This requires a physician at various levels of medical care to provide timely diagnosis, differential diagnosis between organic gastrointestinal diseases, and timely correction of functional disorders.

P421 The faecal biomarker LDN-051 is a novel tool for monitoring disease activity and therapeutic response in Inflammatory Bowel Diseases

Abstract Background Crohn’s disease and ulcerative colitis, two forms of inflammatory bowel disease (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, therefore there is high unmet need to identify novel biomarkers in IBD. Monitoring approaches for IBD are mostly invasive, time-consuming, and expensive. Therefore, a simple, rapid, and non-invasive test, with ability to differentiate IBD from other gastrointestinal conditions and to monitor disease activity, will have important clinical implications. Our previous mucosal cytokine profiling identified that Plasminogen activator inhibitor type 1 (PAI-1) is expressed in IBD patients with active disease, but not in control. Therefore, our aim was to assess the utility of PAI-1 in monitoring disease activity and therapeutic response of IBD patients in different biological samples. Methods Serum, biopsy and faecal samples were collected from 132 IBD patients and 30 controls without IBD. ELISA method was used to define the level of PAI-1 in the mucosa, serum, and faecal samples and the serum CRP levels were also determined. For the mucosal gene expression analysis qRT-PCR was used. The correlation and ROC analyses were applied to observe the relationship between the disease activity and PAI-1 level. Results The applied screening approach detected significant higher expression of PAI-1 in active IBD. We demonstrated that the serum, mucosal and faecal PAI-1 concentration was significantly elevated in IBD patients showing clinical and endoscopic activity. Additionally, in responder patients the initial PAI-1 level decreased significantly upon successful therapy, whereas it remained unchanged in non-responders. We also showed that faecal PAI-1 selectively increases in active IBD patients, but not in other organic gastrointestinal diseases. In addition, the stability analysis of faecal PAI-1 showed that the protein was detectable up to one week at room temperature and 4ºC. The serum, mucosal and faecal PAI-1 level showed positive correlation to the endoscopic activity. ROC curves demonstrated that faecal PAI-1 showed a relatively high power to distinguish between active and control patients. However, the serum CRP level no reflected to the therapeutic response. Conclusion Our results suggest that serum, mucosal and faecal PAI-1 expression reflects to the disease activity in IBD, which could be used to disease monitoring and possibly therapeutic response. The correlation between the faecal PAI-1 level and the endoscopic activity promotes that it could be used as a novel non-invasive disease specific faecal biomarker in the IBD diagnosis.

Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases.

Crohn's disease [CD] and ulcerative colitis [UC] require lifelong treatment and patient monitoring. Current biomarkers have several limitations; therefore, there is an unmet need to identify novel biomarkers in inflammatory bowel disease [IBD]. Previously, the role of plasminogen activator inhibitor 1 [PAI-1] was established in the pathogenesis of IBD and suggested as a potential biomarker. Therefore, we aimed to comprehensively analyse the selectivity of PAI-1 in IBD, its correlation with disease activity, and its potential to predict therapeutic response. Blood, colon biopsy, organoid cultures [OC], and faecal samples were used from active and inactive IBD patients and control subjects. Serpin E1 gene expressions and PAI-1 protein levels and localisation in serum, biopsy, and faecal samples were evaluated by qRT-PCR, ELISA, and immunostaining, respectively. The study population comprised 132 IBD patients [56 CD and 76 UC] and 40 non-IBD patients. We demonstrated that the serum, mucosal, and faecal PAI-1 concentrations are elevated in IBD patients, showing clinical and endoscopic activity. In responders [decrease of eMayo ≥3 in UC; or SES-CD 50% in CD], the initial PAI-1 level decreased significantly upon successful therapy. OCs derived from active IBD patients produced higher concentrations of PAI-1 than the controls, suggesting that epithelial cells could be a source of PAI-1. Moreover, faecal PAI-1 selectively increases in active IBD but not in other organic gastrointestinal diseases. The serum, mucosal, and faecal PAI-1 concentration correlates with disease activity and therapeutic response in IBD, suggesting that PAI-1 could be used as a novel, non-invasive, disease-specific, faecal biomarker in patient follow-up.

Diagnostic value of fecal calprotectin in primary care patients with gastrointestinal symptoms: A retrospective Swedish cohort study.

To investigate the diagnostic accuracy of fecal calprotectin (FC) for inflammatory bowel disease (IBD) and organic gastrointestinal disease (OGID) in primary care. To examine the association with demographic factors, symptoms and concomitant medical therapy. A retrospective analysis of data on all semiquantitative FC tests from individuals ≥18 years conducted in primary care in Östergötland County in 2010. A 5-year follow-up with inclusion of new gastrointestinal diagnoses. A total of 1293 eligible patients were included. IBD was found in 8.8% and other OGID in 30.8% of patients with positive FC. Positive FC was associated with diarrhea, age >60 years, duration <3 months, use of nonsteroidal anti-inflammatory drug (NSAID), and proton pump inhibitor (PPI). Predictors of IBD were positive FC, diarrhea, rectal bleeding, and male sex; predictors of OGID positive FC, age >35 years, abnormal clinical findings, and duration <3 months. FC yielded the highest sensitivity and negative predictive value compared with demographic factors, symptoms, and duration. Use of NSAID and PPI showed a marginal increase in the sensitivity, positive predictive value, and decrease in the specificity of FC. Within 5 years, 4.0% had a new gastrointestinal diagnosis among patients with positive FC (0.6% IBD). FC reliably rules out IBD and contradicts the presence of other OGID in primary care patients. Positive FC test together with other predictors, such as diarrhea, rectal bleeding, short duration, or age >35 years, should encourage a prioritized investigation. Use of NSAID, PPI, and ASA may affect the diagnostic accuracy of FC for IBD and OGID.

Fecal Calprotectin and Organic Gastrointestinal Disease: A Systematic Review.

This review aimed to assess the diagnostic utility of fecal calprotectin (FCP) for identifying organic gastrointestinal disease (OGID) in patients undergoing colonoscopy for gastrointestinal discomfort or active progression of inflammatory bowel disease (IBD). Studies published between January 2013 and December 2022 evaluating the clinical efficacy of FCP for differentiating OGID against functional gastrointestinal disease (FGID) were identified using PubMed, Cochrane, and Scopus databases. Clinical diagnostic studies involving individuals with lower gastrointestinal symptoms; using FCP as a diagnostic biomarker either in primary, secondary, or tertiary healthcare centers conducted either prospectively or retrospectively using stool samples (index test), contrasting FCP with a reference test, such as colonoscopy, or endoscopy, and assessed using enzyme-linked immunosorbent assay were reviewed. The included studies were subjected to the revised Quality Assessment of Diagnostic Accuracy Studies for assessing the methodological quality by two independent authors.An initial literature search yielded 545 articles rendering 417 records after removing the duplicate records. After reading the abstracts and titles, 89 articles were eligible for full-text screening. The qualitative synthesis resulted in 20 articles. The efficient use of FCP for differentiating IBD from irritable bowel syndrome was investigated in 15 studies.Two of the included studies assessed the diagnostic ability of FCP to distinguish OGID from FGID, two studies utilized patients with ulcerative colitis, and one study involved patients with Crohn's disease. Overall study quality was high for 65% of studies,moderate for 25% of studies, and low for 10% of studies. The review outlined the diagnostic accuracy of non-invasive FCP assessment for OGID in various clinical scenarios and in individuals of various ages. FCP is used as a tool for screening and monitoring in clinical practice for determining the need of further comprehensive investigations, thereby reducing the redundant use of invasive techniques.

Physical and psychosocial determinants of quality of life in children with obesity

BackgroundObesity has a negative impact on the physical and psychosocial quality of life of children. As rates of obesity continue to increase, it is important to recognize the widespread effects obesity has on children and their families. MethodsThis clinical investigation evaluated the self-reported quality of life of children with obesity in a weight management program and compared this to a parent/guardian’s perspective of the child’s quality of life using the Pediatric Quality of Life survey 4.0. The quality of life of children with obesity was compared to children with other chronic diseases and healthy children. ResultsAn association was discovered between the guardians’ responses to the Pediatric Quality of Life survey and the child’s age. Guardians with children younger than 11 years reported higher quality of life scores than guardians of children 11 years and older. Race, comorbidities of obesity, insurance type, household structure, and parental education attainment were not significantly associated with a child’s quality of life. Children with obesity had a lower quality of life compared to children who were organ transplant recipients and children with organic gastrointestinal disease. ConclusionsThese results emphasize the need to evaluate and treat the physical and psychosocial components of wellbeing in children with obesity at an early age.

The use of bicarbonate-sulphate-calcium-magnesium and sodium-low drinkable water improves functional gastrointestinal symptoms in patients with non-alcoholic fatty liver disease: A prospective study

Non-alcoholic fatty liver disease is increasingly gaining epidemiological ground in liver diseases. Among the proposed non-pharmacologic interventions, dietary interventions have been widely used. Several patients suffering from it complain of gastrointestinal symptoms unrelated to organic gastrointestinal tract disease. However, the role of drinking water quality modifications in this regard has not been investigated in depth. Patients with upper or lower functional gastrointestinal symptoms were enrolled and divided into groups based on bright liver ultrasound relief's presence (SP) or absence (NSP). These patients were asked to drink bicarbonate-sulphate-calcium-magnesium and sodium-low drinkable water (Fonte Essenziale ®) for six months. Participants were assessed at baseline (T0), at the end of six months of drinking water intake (T6), and after an additional six months of washout (T12) by questionnaires designed to evaluate lower and upper gastrointestinal symptoms (Leeds dyspepsia score, short form) severity and frequency. A total of 61 patients were enrolled. In the SP population, the severity of lower gastrointestinal symptoms improved between T0-T6 (Z:-2.437; ES: 0.312) and worsened after the water washout (Z:-2.492; ES: 0.319). The same was for the Leeds score severity sub score in T0-T6 (Z:-2.850; ES: 0.364) and T6-T12 (Z:-2.921; ES: 0.374). These improvements seem unrelated to the severity of liver steatosis at baseline. Furthermore, no safety issues were recorded while taking the water nor during the six-month follow-up afterwards. Regular six-month intake of 400mL of Fonte Essenziale® water was associated, in the absence of dietary regimen modifications, with an improvement in some qualitative and quantitative features of upper and lower functional gastrointestinal symptoms in both an SP and NSP sample.

A Diagnosis of Irritable Bowel Syndrome Using Rome IV Criteria and Limited Investigations is Durable in Secondary Care

Irritable bowel syndrome (IBS) is a positive diagnosis, made using symptom-based criteria and limited, judicious, investigation. However, this may lead to uncertainty on the part of clinicians regarding potential for a missed diagnosis of organic gastrointestinal disease. Few studies have examined durability of a diagnosis of IBS, and none have used the current gold standard to diagnose IBS, the Rome IV criteria. We collected complete symptom data from 373 well-characterized adults meeting Rome IV criteria for IBS referred to a single UK clinic between September 2016 and March 2020. All patients underwent relatively standardized work-up to exclude relevant organic disease before diagnosis. We followed these individuals up to December 2022, assessing rates of rereferral, reinvestigation, and missed organic gastrointestinal disease. During a mean follow-up of 4.2 years per patient (total follow-up in all patients, 1565 years), 62 (16.6%) patients were rereferred. Of these, 35 (56.5%) were rereferred for IBS and 27 (43.5%) for other gastrointestinal symptoms. Among the 35 rereferred with IBS this was caused by a change in symptoms in only 5 (14.3%). Reinvestigation was undertaken in 21 (60.0%) of 35 rereferred with IBS and 22 (81.5%) of 27 rereferred with other symptoms (P= .12). Only 4 (9.3% of those reinvestigated and 1.1% of the entire cohort) new cases of relevant organic disease, which may have been responsible for IBS symptoms at baseline, were identified (1 case of chronic calcific pancreatitis among those rereferred with IBS and 1 case each of inflammatory bowel disease-unclassified, moderate bile acid diarrhea, and small bowel obstruction among those rereferred with other gastrointestinal symptoms). Despite rereferral for gastrointestinal symptoms among 1 in 6 patients overall, with almost 10% rereferred with ongoing IBS symptoms, and substantial reinvestigation rates, missed organic gastrointestinal disease occurred in only 1%. A diagnosis of Rome IV IBS after limited investigation is safe and durable.

Gastrointestinal Symptoms Profile in Gastroparesis Compared to Other Functional and Organic Gastrointestinal Diseases.

The primary objective was to compare the patient-reported gastrointestinal symptoms profiles of pediatric patients with gastroparesis to pediatric patients with 1 of 7 other functional gastrointestinal disorders and organic gastrointestinal diseases using the Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Scales. The gastrointestinal symptoms profiles of 64 pediatric patients with gastroparesis who manifested abnormal gastric retention based on gastric emptying scintigraphy testing were compared to 582 pediatric patients with 1 of 7 physician-diagnosed gastrointestinal disorders (functional abdominal pain, irritable bowel syndrome, functional dyspepsia, gastroesophageal reflux disease, functional constipation, Crohn disease, ulcerative colitis). The PedsQL Gastrointestinal Symptoms Scales encompass 10 individual multi-item scales which measure stomach pain, stomach discomfort when eating, food and drink limits, trouble swallowing, heartburn and reflux, nausea and vomiting, gas and bloating, constipation, blood in poop, and diarrhea/fecal incontinence, with an overall total gastrointestinal symptoms score. The gastrointestinal symptoms profile analysis identified significantly worse overall total gastrointestinal symptoms scores between pediatric patients with gastroparesis compared to all other gastrointestinal groups except for irritable bowel syndrome (most P s < 0.001), with significant differences for stomach discomfort when eating compared to all 7 other gastrointestinal groups (most P s < 0.001). Nausea and vomiting were significantly worse for gastroparesis compared to all other gastrointestinal groups except for functional dyspepsia (all P s < 0.001). Pediatric patients with gastroparesis self-reported significantly worse overall total gastrointestinal symptoms compared to all other gastrointestinal diagnostic groups except for irritable bowel syndrome, with stomach discomfort when eating and nausea and vomiting symptoms exhibiting the greatest differences compared to most gastrointestinal diagnostic groups.

Prevalence of delayed gastric emptying in patients with gastroparesis-like symptoms.

The European consensus defined gastroparesis as a condition characterised by delayed gastric emptying (GE) in the absence of mechanical obstruction, with a symptom pattern of predominant nausea and/or vomiting and overlapping postprandial distress syndrome (PDS). The distinction between patients with gastroparesis and those with functional dyspepsia (FD), another gastrointestinal condition characterised by predominant PDS or epigastric pain syndrome symptoms, is ongoing. To investigate the extent that symptom patterns may differentiate gastroparesis from FD. This retrospective study included 637 patients from Leuven University Hospital in 2006-2021 who had upper gastrointestinal symptoms, underwent a GE test, and completed the Dyspepsia Symptom Severity (DSS) questionnaire. Patients were identified as with gastroparesis-like symptoms (GPLS; i.e., moderate to severe nausea with moderate to severe PDS) or FD symptoms (not fitting GPLS). We excluded patients aged <18 years, and those with diabetes, organic gastrointestinal disease or a history of abdominal surgeries. Demographic and clinical variables were compared. Among 545 patients, 238 reported GPLS and 307 reported FD symptoms. Those with GPLS had a significantly higher prevalence of delayed GE (half emptying time (T1/2) ≥109 min) and lower body mass index than those with FD (33.2% vs 17.6%, p< 0.01; 19.9 vs 21.2, p< 0.01, respectively). Among GPLS patients, those with delayed GE had higher DSS than those without (13.0 vs 12.0, p< 0.01). In tertiary care patients who reported gastroparesis or FD symptoms, the presence of delayed GE was associated with GPLS. In patients with GPLS, delayed GE was associated with higher symptom severity.

ADMINISTRATION OF OMNI BIOTIC STRESS REPAIR IN CHILDREN'S AGE

our gastrointestinal tract is home to a huge number of beneficial bacteria known as intestinal microflora changed the understanding of many physiological and pathological processes in the human body. Based on these scientific discoveries, the laboratories of the Allergozan Institute in Austria have created the synbiotic combinations "Omnibiotic", which are specific and aimed at specific problems related to human health. Purpose: The aim of the present study is to investigate the effect of the probiotic Omni Biotic Stress Repair in the treatment of functional abdominal pain (FAP) and some organic gastrointestinal diseases in childhood. Material and Methods: A prospective study has been done on children with FAP and PUD. For one year, we monitored 62 children with functional abdominal pain and duodenal ulcer who received Omni Biotic Stress Repair for 3 months. The causes of children's suffering were reported. Results: There are 39 children with functional abdominal pain, 22 of which are girls and 17 boys, and children with peptic ulcer disease – 23/12 boys and 11 girls/. The FAP group received Omni Biotic Stress Repair as self-therapy for three months. We reported very good results in all children. Only four children did not get the desired effect, and they dropped out of the study in the first month. In children with peptic ulcer disease, the probiotic Omni Biotic Stress Repair is added as a satellite therapy to the main treatment. When clinical remission occurred, the patients continued to take only probiotics for 3 months or more. Conclusions: Based on these scientific discoveries, the laboratories of the Allergozan Institute in Austria have created the synbiotic combinations "Omnibiotic", which are specific and aimed at specific problems related to human health.

Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus ongastroparesis.

Background/ObjectivesThe global epidemiology of gastroparesis is unknown. The European UEG and European Society for Neurogastroenterology and motility consensus defines Gastroparesis as a condition characterized by delayed gastric emptying in the absence of mechanical obstruction, with a symptom pattern of nausea and/or vomiting and overlapping postprandial distress syndrome (PDS). Real‐world evidence of this gastroparesis‐like symptom pattern is a crucial step in understanding the epidemiology of gastroparesis.MethodsIn the Rome Foundation Global Epidemiology Study, 54,127 respondents from 26 countries completed the Rome IV Diagnostic Questionnaire and variables associated with disorders of gut‐brain interaction via Internet. We selected subjects with gastroparesis‐like symptoms (GPLS) (nausea and/or vomiting ≥1 day/week and simultaneous PDS). Patients reporting organic gastrointestinal disease, or fulfilling criteria for self‐induced vomiting, cyclic vomiting or cannabinoid hyperemesis syndrome were excluded. We determined prevalence, associated comorbidities, quality of life (QoL) (PROMIS Global‐10), symptoms of anxiety and depression (PHQ‐4), somatic symptoms (PHQ‐12), and healthcare utilization.ResultsThe global prevalence of GPLS was 0.9% overall and 1.3% among diabetic individuals. Subjects with GPLS showed frequent overlapping of epigastric pain syndrome and irritable bowel syndrome. Subjects with GPLS had significantly lower body mass index, QoL, more non‐gastrointestinal somatic complaints, symptoms of anxiety and depression, higher medication usage and doctor visits in the overall and diabetic population, compared to subjects without these symptoms.ConclusionsGPLS are common worldwide and more common in diabetic patients. The symptom complex is associated with multiple aspects of illness and an increased healthcare consumption.

Thermal grill illusion of pain in patients with chronic pain: a clinical marker of central sensitization?

The thermal grill illusion of pain (TGIP) is a paradoxical burning pain sensation elicited by the simultaneous application of innocuous cutaneous warm and cold stimuli with a thermode ("thermal grill") consisting of interlaced heated and cooled bars. Its neurophysiological mechanisms are unclear, but TGIP may have some mechanisms in common with pathological pain, including central sensitization in particular, through the involvement of N-methyl- d -aspartate receptors. However, few studies have investigated TGIP in patients with chronic pain and its clinical relevance is uncertain. We hypothesized that the TGIP would be increased in comparison with controls in patients with fibromyalgia or irritable bowel syndrome, which are regarded as typical "nociplastic" primary pain syndromes related to changes in central pain processing. We compared the sensations elicited by a large range of combinations of temperature differentials between the warm and cold bars of a thermal grill applied to the hand between patients with fibromyalgia (n = 30) or irritable bowel syndrome (n= 30) and controls (n = 30). The percentage of TGIP responses and the intensity and unpleasantness of TGIP were significantly greater in patients than controls. Furthermore, positive correlations were found between TGIP intensity and clinical pain intensity and between TGIP intensity and the cold pain threshold measured on the hand. These results are consistent with our working hypothesis of shared mechanisms between TGIP and clinical pain mechanisms in patients with nociplastic chronic pain syndromes and suggest that TGIP might represent a clinical marker of central sensitization in these patients.

Common polymorphisms of protein tyrosine phosphate non-receptor type 2 gene are not associated with risk of Crohn's disease in Indian.

BACKGROUNDMultiple genetic risk factors for Crohn’s disease (CD) have been identified. However, these observations are not consistent across different populations. The protein tyrosine phosphate non-receptor type 2 (PTPN2) gene plays a role in various aspects of host defense including epithelial barrier function, autophagy, and innate and adaptive immune response. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) have been associated with risk of CD in Western countries. AIMTo evaluate the association of PTPN2 gene polymorphisms with risk of CD in Indian population.METHODSWe conducted a prospective case-control study. Patients with CD were recruited, and their clinical and investigation details were noted. Controls were patients without organic gastrointestinal disease or other comorbid illnesses. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) were assessed. DNA was extracted from peripheral blood samples of cases and controls and target DNA was amplified using specific sets of primers. The amplified fragments were digested with restriction enzymes and the presence of polymorphism was detected by restriction fragment length polymorphism. The frequency of alleles was determined. The frequencies of genotypes and alleles were compared between cases and controls to look for significant differences.RESULTSA total of 108 patients with CD (mean age 37.5 ± 12.7 years, females 42.6%) and 100 controls (mean age 39.9 ± 13.5 years, females 37%) were recruited. For the single nucleotide polymorphism (SNP) rs7234029, the overall frequency of G variant genotype (AG or GG) was noted to be significantly lower in the cases compared to controls (35.2% vs 50%, P = 0.05). For the SNP rs2542151, the overall frequency of G variant genotype (GT or GG) was noted to be similar in cases compared to controls (43.6% vs 47%, P = 0.73). There were no significant differences in minor allele (G) frequency for both polymorphisms between the cases and controls. Both the SNPs had no significant association with age of onset of illness, gender, disease location, disease behaviour, perianal disease, or extraintestinal manifestations of CD.CONCLUSIONUnlike observation form the West, polymorphisms in the PTPN2 gene (rs7234029 and rs2542151) are not associated with an increased risk of developing CD in Indian patients.

Fasting salivary pepsin level as a reliable non-invasive method of screening for laryngopharyngeal reflux in Egyptian patients

BackgroundLaryngopharyngeal reflux (LPR) is caused by the regurgitation of gastric contents above the upper esophageal sphincter. Diagnostic gold standard tests like multichannel intraluminal impedance (MII) and 24-h dual-probe pH-metry are invasive and expensive which limits their accessibility especially in resource-limited settings. Since pepsin is only produced in the stomach, detecting pepsin in the laryngopharynx would make it a specific marker for reflux.Therefore, in this study, we measured fasting salivary pepsin in patients with symptoms suggestive of LPR. We aimed to confirm the role of fasting salivary pepsin as a non-invasive diagnostic tool of LPR, to detect a cut-off value for it in Egyptian patients and to study predictors of changes in its level.MethodsWe conducted a prospective case control study at the gastroenterology clinic in Ain Shams University Hospitals. After testing with esophageal pH-metry, 25 symptomatic patients with confirmed LPR and 25 healthy controls were enrolled in the study. Patients diagnosed with organic upper gastrointestinal disorders, autoimmune diseases, diabetes, malignancy or organ failure were excluded. Patients on PPI were advised to stop 2 weeks before testing. All patients were tested for fasting salivary pepsin levels, esophageal pH-metry, and indirect laryngoscopy in addition to routine laboratory parameters.ResultsOut of the 25 LPR patients, 16% of patients had laryngoscope abnormality in the form of mucosal hyperemia and inflammation, and the average percentage of time pH < 4 in esophageal pH-metry testing was 29.14 ± 39.5%.Comparative study between the 2 groups revealed a significant increase in salivary pepsin in LPR group compared to control group (p < 0.001). By using ROC-curve analysis, salivary pepsin at a cut-off point > 5 ng/ml diagnosed patients with LPR, with fair (77.9%) accuracy, sensitivity = 100% and specificity = 56% (p = 0.0001) while pH-metry (% Time pH < 4) at a cut-off point > 14% diagnosed patients with LPR, with good (87%) accuracy, sensitivity = 80%, and specificity = 100% (p < 0.0001)ConclusionFasting salivary pepsin level at a cut-off value of > 5 ng/ml is a reliable, non-invasive method for detection of LPR especially in resource-limited settings.

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points.IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants.

Irritable bowel syndrome is strongly associated with the primary and idiopathic mast cell disorders.

Mounting evidence supports a mechanistic association between irritable bowel syndrome (IBS) symptoms and mast cell hyperactivity. Yet, association between IBS and mast cell disorders (MCDs) has not been studied. We examined this association using two large databases and verified with manual chart review. The IBM Watson Health Explorys database (Somers, NY), an aggregate of electronic health record (EHR) data from over two dozen US healthcare systems, and Epic's SlicerDicer tool, a self-service tool containing de-identified data from the Epic EHR, were used to identify patients with IBS and MCDs. Patients with organic gastrointestinal disease or diseases associated with secondary mast cell hyperproliferation were excluded. Results were verified with manual chart review from two academic centers. Up to 4% of IBS patients had a comorbid MCD. IBS was strongly associated with all MCDs. The strongest association was between IBS and mast cell activation syndrome (OR 16.3; 95% CI 13.1-20.3). Odds ratios for IBS+urticaria, IBS+idiopathic urticaria, IBS+non-malignant mastocytosis, and IBS+mast cell malignancy ranged from 4.5 to 9.9. Patients from each of these overlap cohorts were predominantly female, and the overlap occurred with all IBS subtypes. Thorough endoscopic evaluation and comorbid mood disorders and migraines are more common in the overlap cohorts than in IBS alone. In a large US database encompassing >53million patients over >20years, patients with IBS are at least 4 times more likely to have a MCD than the general population. Further study of mast cell involvement in the pathogenesis of IBS is warranted.

Gastrointestinal Symptoms and Irritable Bowel Syndrome Are Associated With Female Sex and Smoking in the General Population and With Unemployment in Men.

Background: The influence of daily life exposure on the gastrointestinal tract is not fully understood. This study aimed to examine associations between functional gastrointestinal symptoms and sociodemographic status and lifestyle habits in the general population.Methods: The Malmö Offspring Study (MOS) included 2,648 participants from the general population who had answered a questionnaire about sociodemographic status, lifestyle habits, medical health, and self-reported irritable bowel syndrome (IBS). The visual analog scale for IBS (VAS-IBS) was completed to assess gastrointestinal symptoms the past 2 weeks. Subjects with organic gastrointestinal diseases were excluded. Presence of self-reported IBS and gastrointestinal symptoms the past 2 weeks were used as dependent variables to study the associations with age, sex, body mass index, education, occupation, marital status, smoking, snuff using, alcohol drinking frequency, alcohol amount per drinking occasion, physical activity at work, and physical activity during leisure time, using logistic regression and generalized linear model.Results: Self-reported IBS was associated with gastrointestinal symptoms the past 2 weeks (p < 0.001). There was an association between IBS and female sex (p < 0.001), former smoking (p < 0.001), present smoking (p < 0.001), and an inverse association with drinking 3–4 standard glasses per occasion (p = 0.038). Gastrointestinal symptoms were associated with age 50–59 years (p = 0.009), ≥60 years (p = 0.004), female sex (p < 0.001), studying (p = 0.036), unemployment (p = 0.009), former smoking (p = 0.001), and present smoking (p = 0.012). In men, IBS was associated with middle-age and both IBS and gastrointestinal symptoms were associated with unemployment (p < 0.001 and p = 0.001, respectively). In women, IBS was associated with present smoking (p = 0.022), and gastrointestinal symptoms were associated with former smoking and inversely associated with higher age (p = 0.006) and intermediate physical activity at work (p = 0.008). No associations were found with BMI, education, marital status, or snuff using.Conclusion: Self-reported IBS in the general population shows strongest association with female sex and smoking, whereas gastrointestinal symptoms also are associated with unemployment and inversely associated with higher age. In men, both IBS and gastrointestinal symptoms are associated with unemployment. In women, both IBS and gastrointestinal symptoms are associated with smoking, whereas symptoms are inversely associated with higher age and intermediate physical activity.