Inflammatory Bowel Disease and Neurodegenerative Diseases

A growing body of evidence has demonstrated an intricate association between inflammatory bowel disease (IBD) and neurodegenerative conditions, expanding beyond previous foci of comorbidities between IBD and mood disorders. These new discoveries stem from an improved understanding of the gut-microbiome-brain axis: specifically, the ability of the intestinal microbiota to modulate inflammation and regulate neuromodulatory compounds. Clinical retrospective studies incorporating large sample sizes and population-based cohorts have demonstrated and confirmed the relevance of IBD and chronic neurodegeneration in clinical medicine. In this review, we expound upon the current knowledge on the gut-microbiome-brain axis, highlighting several plausible mechanisms linking IBD with neurodegeneration. We also summarize the known associations between IBD with Parkinson disease, Alzheimer disease, vascular dementia and ischemic stroke, and multiple sclerosis in a clinical context. Finally, we discuss the implications of an improved understanding of the gut-microbiome-brain axis in preventing, diagnosing, and managing neurodegeneration among IBD and non-IBD patients.

Knowledge, Attitude, and Practice Survey of Gastroparesis in Asia by Asian Neurogastroenterology and Motility Association

Background/Aims@#Gastroparesis is identified as a subject that is understudied in Asia. The scientific committee of the Asian Neurogastroenterology and Motility Association performed a Knowledge, Attitude, and Practices survey on gastroparesis among doctors in Asia. @*Methods@#The questionnaire was created and developed through a literature review of current gastroparesis works of literature by the scientific committee of Asian Neurogastroenterology and Motility Association. @*Results@#A total of 490 doctors from across Asia (including Bangladesh, China, Hong Kong, Indonesia, Japan, Malaysia, Myanmar, the Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam) participated in the survey. Gastroparesis is a significant gastrointestinal condition. However, a substantial proportion of respondents was unable to give the correct definition and accurate diagnostic test. The main reason for lack of interest in diagnosing gastroparesis was “the lack of reliable diagnostic tests” (46.8%) or “a lack of effective treatment” (41.5%). Only 41.7% of respondents had access to gastric emptying scintigraphy. Most doctors had never diagnosed gastroparesis at all (25.2%) or diagnosed fewer than 5 patients a year (52.1%). @*Conclusions@#Gastroparesis can be challenging to diagnose due to the lack of instrument, standardized method, and paucity of research data on normative value, risk factors, and treatment studies in Asian patients. Future strategies should concentrate on how to disseminate the latest knowledge of gastroparesis in Asia. In particular, there is an urgent need to estimate the magnitude of the problems in high risk and idiopathic patients as well as a standardized diagnostic procedure in Asia.

Non-pharmacological Approach in the Management of Functional Dyspepsia

Functional dyspepsia (FD) is a common functional gastrointestinal disease which bears a significant burden on society and individuals. Despite the high prevalence of FD, its pathophysiology remains poorly understood and the treatment options are limited and unsatisfactory. In the absence of effective pharmacological treatments for FD, non-pharmacological approaches, including: reassurance, lifestyle modification, psychotherapy, dietary interventions, medical food, acupuncture, and electrical stimulation and modulation are sought after by many physicians and FD patients. In this article, we review clinical studies which investigate nonpharmacological therapies for FD. We will also discuss potential mechanisms involved in the therapeutic effects of these nonpharmacological approaches. Though the evidences to support the routine use of the non-pharmacological management is still lacking, the non-invasive nature and potentially minimal side-effects of these therapies may be attractive in the FD management. In order to confirm the clinical effectiveness of these non-pharmacological approaches, more well-conducted, methodologically rigorous, and large-scaled clinical trials are required.

Second Asian Consensus on Irritable Bowel Syndrome

BACKGROUND/AIMS: There has been major progress in our understanding of the irritable bowel syndrome (IBS), and novel treatment classes have emerged. The Rome IV guidelines were published in 2016 and together with the growing body of Asian data on IBS, we felt it is timely to update the Asian IBS Consensus. METHODS: Key opinion leaders from Asian countries were organized into 4 teams to review 4 themes: symptoms and epidemiology, pathophysiology, diagnosis and investigations, and lifestyle modifications and treatments. The consensus development process was carried out by using a modified Delphi method. RESULTS: Thirty-seven statements were developed. Asian data substantiate the current global viewpoint that IBS is a disorder of gut-brain interaction. Socio-cultural and environmental factors in Asia appear to influence the greater overlap between IBS and upper gastrointestinal symptoms. New classes of treatments comprising low fermentable oligo-, di-, monosacharides, and polyols diet, probiotics, non-absorbable antibiotics, and secretagogues have good evidence base for their efficacy. CONCLUSIONS: Our consensus is that all patients with functional gastrointestinal disorders should be evaluated comprehensively with a view to holistic management. Physicians should be encouraged to take a positive attitude to the treatment outcomes for IBS patients.

Sexual Abuse Is Associated With an Abnormal Psychological Profile and Sleep Difficulty in Patients With Irritable Bowel Syndrome in Taiwan

BACKGROUND/AIMS: Both sexual and physical abuse history have been reported to be associated with irritable bowel syndrome (IBS) in Western countries. The impact of abuse history in IBS patients in Asia remains unclear. We aim to determine the prevalence of abuse history, its associated psychological profiles, and sleep problems among IBS patients in Taiwan. METHODS: In total, 194 Rome III-defined IBS patients were invited to participate. Age- and sex-matched healthy carriers of chronic hepatitis B or hepatitis C without chronic abdominal symptoms were identified as disease-controls. We administered a validated questionnaire to evaluate bowel symptoms, physical/sexual abuse history, anxiety/depression (Hospital Anxiety and Depression Scale [HADS]), and sleep quality. RESULTS: IBS patients had a significantly higher prevalence of sexual abuse history than the disease-control group both before (16.5% vs 6.7%, P < 0.05) and after (16.0% vs 6.6%, P < 0.05) adolescence. These significant differences were mainly observed in women (13.4% vs 3.4%, P < 0.05). No difference was noted in history of physical abuse between the 2 groups. IBS patients with a history of sexual abuse had significantly higher HADS scores and higher frequencies of sleep difficulty than those without. CONCLUSIONS: In Taiwan, sexual abuse history was more prevalent in female IBS patients than controls. Sexual abuse history may contribute to higher anxiety/depression levels and sleep difficulties, which are commonly experienced in IBS patients. In Asia, abuse history should be obtained when approaching IBS patients to facilitate better management.

Development, Translation and Validation of Enhanced Asian Rome III Questionnaires for Diagnosis of Functional Bowel Diseases in Major Asian Languages: A Rome Foundation-Asian Neurogastroenterology and Motility Association Working Team Report

BAome III criteria. METHODS: After EAR3Q was developed by Asian experts by cCKGROUND/AIMS: The development-processes by regional socio-cultural adaptation of an Enhanced Asian Rome III questionnaire (EAR3Q), a cultural adaptation of the Rome III diagnostic questionnaire (R3DQ), and its translation-validation in Asian languages are presented. As English is not the first language for most Asians, translation-validation of EAR3Q is essential. Hence, we aimed to culturally adapt the R3DQ to develop EAR3Q and linguistically validate it to show that the EAR3Q is able to allocate diagnosis according to Ronsensus, it was translated into Chinese, Hindi-Telugu, Indonesian, Korean, and Thai, following Rome Foundation guidelines; these were then validated on native subjects (healthy [n = 60], and patients with irritable bowel syndrome [n = 59], functional dyspepsia [n = 53] and functional constipation [n = 61]) diagnosed by clinicians using Rome III criteria, negative alarm features and investigations. RESULTS: Experts noted words for constipation, bloating, fullness and heartburn, posed difficulty. The English back-translated questionnaires demonstrated concordance with the original EAR3Q. Sensitivity and specificity of the questionnaires were high enough to diagnose respective functional gastrointestinal disorders (gold standard: clinical diagnoses) in most except Korean and Indonesian languages. Questionnaires often uncovered overlapping functional gastrointestinal disorders. Test-retest agreement (kappa) values of the translated questionnaires were high (0.700-1.000) except in Korean (0.300-0.500) and Indonesian (0.100-0.400) languages at the initial and 2-week follow-up visit. CONCLUSIONS: Though Chinese, Hindi and Telugu translations were performed well, Korean and Indonesian versions were not. Questionnaires often uncovered overlapping FGIDs, which were quite common.

Primary Care Management of Chronic Constipation in Asia: The ANMA Chronic Constipation Tool

Chronic constipation (CC) may impact on quality of life. There is substantial patient dissatisfaction; possible reasons are failure to recognize underlying constipation, inappropriate dietary advice and inadequate treatment. The aim of these practical guidelines intended for primary care physicians, and which are based on Asian perspectives, is to provide an approach to CC that is relevant to the existing health-care infrastructure. Physicians should not rely on infrequent bowel movements to diagnose CC as many patients have one or more bowel movement a day. More commonly, patients present with hard stool, straining, incomplete feeling, bloating and other dyspeptic symptoms. Physicians should consider CC in these situations and when patients are found to use laxative containing supplements. In the absence of alarm features physicians may start with a 2-4 week therapeutic trial of available pharmacological agents including osmotic, stimulant and enterokinetic agents. Where safe to do so, physicians should consider regular (as opposed to on demand dosing), combination treatment and continuous treatment for at least 4 weeks. If patients do not achieve satisfactory response, they should be referred to tertiary centers for physiological evaluation of colonic transit and pelvic floor function. Surgical referral is a last resort, which should be considered only after a thorough physiological and psychological evaluation.

Irritable Bowel Syndrome and Migraine: Bystanders or Partners?

Irritable bowel syndrome (IBS) and migraine are distinct clinical disorders. Apart from the characteristics of chronic and recurrent pain in nature, these pain-related disorders apparently share many similarities. For example, IBS is female predominant with community prevalence about 5-10%, whereas that of migraine is 1-3% also showing female predominance. They are often associated with many somatic and psychiatric comorbidities in terms of fibromyaglia, chronic fatigue syndrome, interstitial cystitis, insomnia and depression etc., even the IBS subjects may have coexisted migraine with an estimated odds ratio of 2.66. They similarly reduce the quality of life of victims leading to the social, medical and economic burdens. Their pathogeneses have been somewhat addressed in relation to biopsychosocial dysfunction, heredity, genetic polymorphism, central/visceral hypersensitivity, somatic/cutaneous allodynia, neurolimbic pain network, gonadal hormones and abuses etc. Both disorders are diagnosed according to the symptomatically based criteria. Multidisciplinary managements such as receptor target new drugs, melantonin, antispasmodics, and psychological drugs and measures, complementary and alternatives etc. are recommended to treat them although the used agents may not be necessarily the same. Finally, the prognosis of IBS is pretty good, whereas that of migraine is less fair since suicide attempt and stroke are at risk. In conclusion, both distinct chronic pain disorders to share many similarities among various aspects probably suggest that they may locate within the same spectrum of a pain-centered disorder such as central sensitization syndromes. The true pathogenesis to involve these disorders remains to be clarified in the future.

Silent Gastroesophageal Reflux Disease

No abstract available.

Hiccup: Mystery, Nature and Treatment

Hiccup is the sudden onset of erratic diaphragmatic and intercostal muscle contraction and immediately followed by laryngeal closure. The abrupt air rush into lungs elicits a "hic" sound. Hiccup is usually a self-limited disorder; however, when it is prolonged beyond 48 hours, it is considered persistent whereas episodes longer than 2 months are called intractable. A reflex arc involving peripheral phrenic, vagal and sympathetic pathways and central midbrain modulation is likely responsible for hiccup. Accordingly, any irritant in terms of physical/chemical factors, inflammation, neoplasia invading the arc leads to hiccups. The central causes of hiccup include stroke, space occupying lesions and injury etc, whereas peripheral causes include lesions along the arc such as tumors, myocardial ischemia, herpes infection, gastroesophageal reflux disease and applied instrumentations on human body etc. Besides, various drugs (eg, anti-parkinsonism drugs, anesthetic agents, steroids and chemotherapies etc) are the possible etiology. An effective treatment of persistent hiccup may be established upon the correct diagnosis of lesion responsible for the serious event. The pharmacotherapy of hiccup includes chlorpromazine, gabapentin, baclofen, serotonergic agonists, prokinetics and lidocaine. Non-pharmacological approaches such as nerve blockade, pacing, acupuncture and measures to hold breathing are also successful. Finally, alternative medicines and remedies are convenient to treat hiccups with uncertain effect. In conclusions, hiccup is likely to result from lesions involving the hiccup reflex arc. The lesion may need to be localized correctly for ablative treatment in patients with intractable hiccup. Apart from lesion ablation, drugs acting on reflex arc may be effective, while some other conventional measures may also be tried.

Asian Consensus Report on Functional Dyspepsia

BACKGROUND/AIMS: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared to the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia. METHODS: Consensus team members were selected from Asian experts and consensus development was carried out using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using keypad voting system. A grade of evidence and a strength of recommendation were applied to each statement according to the method of the GRADE Working Group. RESULTS: Twenty-nine consensus statements were finalized, including 7 for definition and diagnosis, 5 for epidemiology, 9 for pathophysiology and 8 for management. Algorithms for diagnosis and management of functional dyspepsia were added. CONCLUSIONS: This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.

Burden of Dyspepsia in Rural and Urban Asia

No abstract available.

The Role of Cholecystokinin 1 Receptor in Prolactin Inhibited Gastric Emptying of Male Rat

BACKGROUND/AIMS: Prolactin (PRL) is essential for the lactating mammals, while cholecystokinin (CCK) does inhibit gastric emptying (GE). Present study attempted to determine whether both peptides interacted on the male rat GE, particularly the role of putative CCK1 receptor. METHODS: Acute hyperprolactinemia of male rats was induced by the intraperitoneal injection of ovine PRL (oPRL) in several divided doses 15 minutes before motility study. Rat chronic hyperprolactinemia was induced by the graft of 2 pituitary glands into the capsule of left kidney, while control rats received cerebral cortex graft only. Motility study was conducted 6 weeks later after graft surgery. Fifteen minutes after the intragastric feeding of radiochromium, rat was sacrificed to measure GE via the distribution of radioactivities within stomach and intestine. Among the CCK1 receptor blocking study using lorglumide, rats were divided to receive the regimens in terms of oPRL-vehicle plus lorglumide-vehicle, oPRL plus lorglumide-vehicle, oPRL-vehicle plus lorglumide and oPRL plus lorglumide. Plasma CCK level was measured using a homemade radioimmunoassay kit. RESULTS: Compared to vehicle treatment, acute hyperprolactinemic rats under highest dose (2.0 mg/kg) of oPRL treatment showed delayed GE (70.6% +/- 3.0% vs 42.1% +/- 6.6%, P < 0.05). Chronic hyperprolactinemic rats under graft surgery also showed inhibited GE (70.5% +/- 1.7% vs 54.5% +/- 4.7%, P < 0.05). Both models finally obtained elevated plasma CCK levels (P < 0.05). Lorglumide itself did not influence GE, however, delayed GE under oPRL treatment was restored following the concomitant lorglumide treatment. CONCLUSIONS: Our study suggests that PRL may delay male rat GE via a mechanism of endogenous CCK activation involving the peripheral CCK1 receptor.

The Evaluation of Otilonium Bromide Treatment in Asian Patients With Irritable Bowel Syndrome

BACKGROUND/AIMS: Antispasmodics including otilonium bromide (OB) are recommended to treat irritable bowel syndrome (IBS). However, reports about OB experience in Asia is sparse. The purpose of present study was to provide the efficacy of OB in treating Asian IBS patients. METHODS: Overall, 117 IBS patients meeting Rome II criteria were enrolled in an 8-week, double-blind, active-controlled and single center trial. Randomized participants received either OB 40 mg or mebeverine 100 mg 3 doses daily. The primary endpoints were to evaluate the net changes of abdominal pain/discomfort frequency score (APDFS) and safety profile, while the secondary endpoints were to assess the changes in abdominal pain/discomfort intensity, flatulence, abdominal bloating, satisfied stool frequency etc. RESULTS: Finally, 49 OB and 52 mebeverine subjects were eligible for efficacy analysis. Compared to baselines in per protocol populations, the reduced APDFSs in OB and mebeverine were 0.55 +/- 1.20 (P = 0.011) and 0.37 +/- 1.11 (P = 0.042), respectively, to show similarly reduced scores. The most reported side effects included dry mouth, nausea and dizziness. Besides, the improved APDFSs at 4th week visit, final alleviations in abdominal pain intensity, flatulence, abdominal bloating and satisfied stool frequency with global assessments filled by both patients and investigators were significantly achieved by both treatments, and OB was not inferior to mebeverine in treating these parameters. CONCLUSIONS: In Orientals, OB is as effective as mebeverine for alleviating IBS symptoms in terms of abdominal pain, flatulence, abdominal bloating etc. However, obvious side effects are also observed. A large-scaled trial and post-marketing surveillance are recommended to confirm its efficacy and safety.

The Current Prevalence of Irritable Bowel Syndrome in Asia

Irritable bowel syndrome (IBS) has been one of the commonly presented gastrointestinal disorders. It is of interest how commonly it presents in the society. Western studies indicated that most population-based IBS prevalences range 10%-15%. It is believed that IBS is prevalent in both East and West countries without a significant prevalence difference. Most recently, the Asia IBS prevalence has a higher trend in the affluent cities compared to South Asia. Since many Asia IBS prevalence studies have been published in the recent decade, we could compare the IBS prevalence data divided by various criteria in looking whether they were also comparable to this of West community. Summarized together, most Asia community IBS prevalences based on various criteria are usually within the range 1%-10% and are apparently lower than these of selected populations. Within the same population, the prevalence orders are first higher based on Manning criteria, then followed by Rome I criteria and finally reported in Rome II criteria. Overall, the median value of Asia IBS prevalences defined by various criteria ranges 6.5%-10.1%. With regard to gender difference, female predominance is usually found but not uniquely existed. For the IBS subtypes, the proportions of diarrhea predominant-IBS distribute widely from 0.8% to 74.0%, while constipation predominant-IBS proportion ranges 12%-77%. In conclusions, current Asia IBS prevalence is at least equal to the Western countries. Female predominant prevalence in Asia is common but not uniquely existed, while the proportions of IBS subtypes are too variable to find a rule.