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Pankaj Garg’s story is an interesting one and is a source of inspiration for all physicians and budding innovators. He started his career as a community doctor about two decades back in the year 2001, then changed gears in between to become an avid researcher and innovator. He progressed to become a leading international figure in his field. Garg has exemplified three important points. First, with proper temperament, it is possible to achieve academic excellence and conduct research even in a primary care setting. Second, every specialist should fulfill the role of a family physician as well. While pursuing any specialty, the role of a “general physician” should never be ignored. Third, innovation is a state of mind, and big institutions and well-equipped laboratories with costly gadgets are not a prerequisite to it. This is clearly exemplified by Pankaj Garg’s story that it is possible to excel in research, academics, and clinical work at the global level without any research budget, big institute tag, or the help of government or non-government organizations. Garg has more than 175 publications in high-impact journals. He has 30 innovations to his name, in and outside his field of expertise, all of which have been published in international journals. The innovations include new operative procedures, successful non-operative management, the discovery of new anatomical spaces, new concepts in disease understanding and management, and finding non-operative treatment for diseases for which surgery is routinely performed. It is impressive that seven of his innovations are popularly known by his name - Garg classification, Garg space, Garg protocol, Garg cardinal principles, Garg scoring system, Garg phenomenon, and Garg incontinence scores. Due to 30 innovations done single-handedly, Garg has been certified as a “doctor with maximum innovations” by several record books. Due to his ability to think “out-of-the-box” and his immense contribution to advancements in the field of proctology, he is recognized as a global icon in his field. Garg is a master teacher. He has taught surgical skills and the art of scientific paper writing to hundreds of surgeons and doctors. In spite of limited resources at his disposal, Garg goes out of his way to help poor people. He performs about 30–40% of operations free of cost. He has successfully treated patients from 41 countries and several patients from royal families of the Gulf who offered him lucrative money to move to the Middle East. However, Garg flatly refused all offers because his priority was to serve his country and countrymen first. Hence, a simple doctor working in a small city was never discouraged by the lack of resources, and the fear of working alone in a small set-up and without any help from the government has carved out a tale that can motivate professionals in any corner of the world. Dr. Garg’s story provides immense inspiration to every practicing physician in the country to innovate whether he/she is practicing in a primary healthcare center or a rural area. [ABSTRACT FROM AUTHOR]

Introduction: Symptomatic uncomplicated diverticular disease (SUDD) is a clinical condition included in the spectrum of symptomatic diverticular disease. The symptom profile associated with SUDD is highly heterogeneous, as there are currently discordant definitions, that encompass many clinical scenarios. Areas covered: We conducted a narrative review to assess the symptom profile and diagnostic criteria of SUDD based on the available evidence. A thorough literature search was performed on PubMed following the SANRA scale. Abdominal pain, regardless of its duration and location, emerges as the cardinal symptom of SUDD, suggesting that it should be central to its diagnosis. Although abdominal bloating and changes in bowel habits are commonly reported, they do not appear to be specifically attributable to SUDD. Other issues considered are the possible overlap with irritable bowel syndrome and the identification of a subcategory of SUDD patients with chronic symptoms following an episode of acute diverticulitis. Expert opinion: The future agenda should include the development of shared diagnostic criteria for SUDD, including well-defined inclusion and exclusion clinical features and symptom patterns. [ABSTRACT FROM AUTHOR]

Purpose: Hemorrhoids (HEM) are the most common perianal disease, but current observational studies have yielded inconsistent results in investigating the risk factors. Our further exploration of the risk factors will help prevent the disease. Patients and Methods: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis using publicly available genome-wide association studies (GWAS) statistics from multiple consortia. The inverse-variance weighted (IVW) method was used for the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression, and Cochrane's Q value, to detect and correct the effects of horizontal pleiotropy. Results: Genetically determined constipation (OR = 0.97, 95% CI: 0.91– 1.03, P = 0.28) and diarrhea (OR = 1.00, 95% CI: 0.99– 1.01, P = 0.90) did not have a causal effect on HEM but stool frequency (OR = 1.28, 95% CI: 1.05– 1.55, P = 0.01), waist-to-hip ratio adjusted for BMI (OR = 1.11, 95% CI: 1.06– 1.64, P = 1.59× 10-5), and order Burkholderiales (OR = 1.09, 95% CI = 1.04– 1.14, p = 1.63× 10-4) had a causal effect on. Furthermore, we found a significant causal effect of constipation on HEM in the reverse MR analysis (OR = 1.21, 95% CI: 1.13– 1.28, P = 3.72× 10-9). The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates, as indicated by the sensitivity analysis. Conclusion: Our MR analysis reveals a causal association between stool frequency and waist-to-hip ratio with HEM, despite variations in results reported by observational studies. Unexpectedly, we found a relationship between the order Burkholderiales in the gut flora and HEM, although the mechanism is unclear. [ABSTRACT FROM AUTHOR]

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID), whose prevalence has widely increased in pediatric population during the past two decades. The exact pathophysiological mechanism underlying IBS is still uncertain, thus resulting in challenging diagnosis and management. Experts from 4 Italian Societies participated in a Delphi consensus, searching medical literature and voting process on 22 statements on both diagnosis and management of IBS in children. Recommendations and levels of evidence were evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was reached for all statements. These guidelines suggest a positive diagnostic strategy within a symptom-based approach, comprehensive of psychological comorbidities assessment, alarm signs and symptoms' exclusion, testing for celiac disease and, under specific circumstances, fecal calprotectin and C-reactive protein. Consensus also suggests to rule out constipation in case of therapeutic failure. Conversely, routine stool testing for enteric pathogens, testing for food allergy/intolerance or small intestinal bacterial overgrowth are not recommended. Colonoscopy is recommended only in patients with alarm features. Regarding treatment, the consensus strongly suggests a dietary approach, psychologically directed therapies and, in specific conditions, gut-brain neuromodulators, under specialist supervision. Conditional recommendation was provided for both probiotics and specific fibers supplementation. Polyethylene glycol achieved consensus recommendation for specific subtypes of IBS. Secretagogues and 5-HT4 agonists are not recommended in children with IBS-C. Certain complementary alternative therapies, antispasmodics and, in specific IBS subtypes, loperamide and rifaximin could be considered. [ABSTRACT FROM AUTHOR]

Background: Constipation is characterized by symptoms of straining, hard stool, difficult evacuation, and infrequent bowel movements. Online surveys provide valuable information about patients' perspectives, symptoms, management, treatment satisfaction, and risk factors. Methods: This survey explored subject experiences involving 20 gastrointestinal (GI) conditions. In total, 20,099 respondents in seven countries with varied cultural and socioeconomic backgrounds participated. Post hoc analysis of 'self-reported constipation' and related symptoms experienced within the past 6 months and the last episode of constipation provided data on prevalence, demographics, frequency and duration of episodes and related symptoms, impact on quality of life (QoL), management with or without laxatives, and resulting treatment satisfaction. Results: In total, 10,425 subjects reported constipation within 6 months and 2637 at the last episode. Prevalence was highest in females and younger adults. Most subjects reported various coexisting GI symptoms. Almost 80% of 6865 episodes reported by 5337 subjects occurred every 2–3 months to every 2–3 weeks. A higher frequency of constipation correlated with a greater impact on QoL. On a 10-point scale, the mean impact was 6.4. More than 90% of respondents had episodes ranging from 1 day to 1 week. More than 90% took action; 16% used laxatives, of whom 80.3% were satisfied. Conclusion: Constipation, a highly prevalent disorder, spans cultures and socioeconomic classes. Its chronic recurrence has a significant impact on QoL, resulting in symptom self-management in >90% of subjects. Significantly higher satisfaction rates in subjects treated with than without laxatives reflect subjects' reports that self-reported constipation can be treated effectively with laxatives. [ABSTRACT FROM AUTHOR]

Disorders of Gut-Brain Interactions (DGBI) are a common clinical problem in children and pose significant challenges to the attending pediatrician. Radiological investigations are commonly ordered to evaluate these children. This review focuses on the current best practice of using radiological investigations in DGBIs and how novel radiological investigations could revolutionize the assessment and therapeutic approach of DGBI in children. We believe imaging in DGBI is still in its early stages, but it has the potential to revolutionize how we diagnose and treat children with DGBI. As the understanding of the gut-brain axis continues to grow, we can expect to see the disappearance of conventional imaging techniques and the emergence of more sophisticated imaging techniques with less radiation exposure in the future which provide more clinically meaningful information regarding the gut-brain axis and its influence on intestinal function. Some of the novel imaging modalities will be able to broaden our horizon of understanding DGBI in children providing more useful therapeutic options to minimize their suffering. [ABSTRACT FROM AUTHOR]

Japan is becoming a superaged society, and nutrition therapy for the elderly population is very important. Elderly individuals often have multiple diseases and are prone to malnutrition. Furthermore, functional constipation, diarrhoea, faecal incontinence, etc., may occur despite no organic abnormality of digestive tract function. Due to these disabilities, the resulting malnutrition, and the slow recovery, it is often difficult for elderly individuals to reintegrate into society. Secondary or incorrect nutritional management increases complications, decreases physical function and worsens the prognosis. Previous statistical research suggests that in-hospital mortality is significantly higher among hospitalised patients aged ≥65 years who ingest less than half of their caloric needs. Therefore, appropriate nutritional management from an early stage is essential for elderly individuals. Moreover, functional excretion disorders, dementia, and sarcopenia (muscle-wasting disease) are attracting attention as pathological conditions unique to elderly individuals, and it is essential to undergo rehabilitation early with nutritional management. Being elderly does not preclude nutritional management, and it is necessary to reconsider appropriate nutritional therapy even in the terminal stage and in advanced physical and mental illnesses. This review explores the relationship between dietary intake and FGIDs, with a focus on elderly adults. [ABSTRACT FROM AUTHOR]

Constipation is a major complications of diabetes mellitus. With the accelerating prevalence of diabetes worldwide and an aging population, there is considerable research interest regarding the altered function and structure of the gastrointestinal tract in diabetic patients. Despite current advances in hyperglycemic treatment strategies, the specific pathogenesis of diabetic constipation remains unknown. Patients with constipation, may be reluctant to eat regularly, which may worsen glycemic control and thus worsen symptoms associated with underlying diabetic bowel disease. This paper presents a review of the complex relationship between diabetes and constipation, exploring the morphological alterations and biomechanical remodeling associated with intestinal motility dysfunction, as well as alterations in intestinal neurons, cellular signaling pathways, and oxidative stress. Further studies focusing on new targets that may play a role in the pathogenesis of diabetic constipation may, provide new ideas for the development of novel therapies to treat or even prevent diabetic constipation. [Display omitted] • DM-induced myopathic effects, colonic neuropathy, and mucosal absorption can lead to changes in colonic sensory and motor responses. • DM alters the intestinal flora, impairs local neurotransmitters and hormone release. • Constipation in DM are associated with intracellular signaling pathways in enterocytes. • DM increases oxidative stress, impairs the contractile and diastolic responses of colonic circular muscle strips. [ABSTRACT FROM AUTHOR]

This study evaluates the onset, magnitude, and consistency of improvement of opioid-induced constipation (OIC) symptoms with naloxegol treatment.Methods: This was a pooled analysis of two Phase 3, double-blind, randomized, placebo-controlled studies (KODIAC-04/05, NCT01309841/NCT01323790) in patients with chronic non-cancer pain and OIC treated with naloxegol 25mg or 12.5mg daily. This analysis assessed improvements in response rates, frequency of spontaneous bowel movement (SBM) and complete SBMs (CSBM), OIC constipation symptoms (straining, stool consistency), time to first post-dose SBM and CSBM, and onset of adverse events over the 12-week period.Subjects: The population of 1337 subjects had a mean age of 52 years and mean duration of opioid use of 3.6 years at baseline. Mean SBM frequency was 1.4/week.Results: Naloxegol 25mg and 12.5mg demonstrated significantly higher response rates vs placebo (PBO) [41.9% (P < 0.001), 37.8% (P = 0.008), 29.4% respectively]. Rapid (within 1 week) and sustained (over 12 weeks) symptom improvement was significantly greater for naloxegol vs PBO (P < 0.05). Both doses showed statistically significant and clinically meaningful improvements in straining, stool consistency, number of SBMs and CSBMs/wk. Significantly shorter times to first post-dose SBM and CSBM were observed with naloxegol vs PBO (SBM HR: 25mg = 1.90, 12.5mg= 1.60; CSBM HR: 25mg = 1.42, 12.5mg = 1.36; P < 0.001 for each regimen). Adverse events occurred more frequently in the naloxegol 25mg group and were most frequently reported during the first week.Conclusion: In patients with chronic non-cancer pain, naloxegol 25mg and 12.5mg demonstrated significantly higher response rates and rapid and sustained improvements in OIC symptoms compared with PBO. [ABSTRACT FROM AUTHOR]

Background: The Rome IV criteria have been established as an international standard for diagnosing disorders of gut–brain interaction. In this study, we aimed to examine the upper gastrointestinal (GI) endoscopic findings and symptoms of subjects with functional constipation (FC) and irritable bowel syndrome (IBS) of individuals undergoing a medical check-up. Methods: A total of 13,729 subjects underwent a medical check-up at Osaka City University-affiliated clinic, MedCity21, between April 2018 and March 2019. Among the 5,840 subjects who underwent screening upper GI endoscopy and completed a questionnaire based on the Rome IV criteria, 5,402 subjects were consecutively enrolled after excluding subjects with a large amount of gastric residue (n = 6), those who had previously undergone partial or total gastrectomy (n = 40), or those with daily use of low-dose aspirin (n = 82), nonsteroidal anti-inflammatory drugs (n = 63), or acid secretion inhibitors (n = 308). Results: Robust Poisson regression analyses adjusted for age, sex, Helicobacter pylori infection status, alcohol intake, and smoking habits showed a significant association between FC and corpus erosion (adjusted prevalence ratio [aPR], 2.93; 95% confidence interval [CI], 1.51–5.67; p < 0.01) and red streaks (aPR, 3.83; 95% CI, 2.53–5.79; p < 0.01), whereas IBS was significantly associated with erosive gastritis (aPR, 8.46; 95% CI, 4.89–14.67; p < 0.01) and duodenitis (aPR, 7.28; 95% CI, 3.64–14.59; p < 0.01). Red streaks tended to be associated with IBS (aPR, 1.96; 95% CI, 1.00–3.83; p = 0.05). Subjects with IBS were the most to complain of both upper and lower GI symptoms and psychological symptoms, followed by those with FC and controls. IBS subjects with erosive gastritis or duodenitis had significantly more complaints of stomachache and feeling stressed than those without erosive gastritis or duodenitis (54.5% vs. 18.8%; p = 0.03 and 66.7% vs. 25.0%; p = 0.01). Conclusions: Subjects with FC and IBS had a variety of upper GI and psychological symptoms. In the upper GI endoscopic findings, corpus erosion and red streaks were associated with FC, and erosive gastritis, duodenitis, and possibly red streaks were associated with IBS. [ABSTRACT FROM AUTHOR]

Aims Gastrointestinal disorders, including constipation and fecal incontinence, are common in type 2 diabetes mellitus (T2DM) and may derive from diabetic autonomic neuropathy, severe intestinal bacterial overgrowth, or a dysfunctional anorectal sphincter. The present study aims to characterize the correlation between these conditions. Methods Patients with T2DM, prediabetes, and normal glucose tolerance (NGT) were included. The anorectal function was assessed with high-resolution anorectal manometry. Patients were screened for autonomic neuropathy by measuring olfactory, sweat, and erectile dysfunction as well as heart rate variability. Constipation and fecal (in-)continence were evaluated using validated questionnaires. Breath tests were used to assess severe intestinal bacterial overgrowth. Results We included 59 participants (32 (54.2%) with T2DM, 9 (15.3%) with prediabetes, and 18 (30.5%) NGT). The presence of autonomic neuropathy, severe bacterial overgrowth, and symptoms of constipation and incontinence were comparable. HbA1c was correlated with an increased anorectal resting sphincter pressure (r =0.31, P =0.019) and constipation symptoms (r =0.30, P =0.031). In patients with a long-standing diagnosis of T2DM, significantly higher values for maximum anorectal resting pressure (Δ=+27.81±7.84 mmHg, P =0.0015) and baseline pressure (Δ=20.50±9.74 mmHg, P =0.046) were found compared with NGT, but not with prediabetes. Conclusions Long-standing T2DM increases anorectal sphincter activity, and constipation symptoms are associated with higher HbA1c levels. The lack of an association of symptoms with autonomic neuropathy suggests glucotoxicity as the primary mechanism. [ABSTRACT FROM AUTHOR]

Background and Aim: The aim of this study was to determine the frequency, characteristics, and associations of functional gastrointestinal disorders (FGIDs) among healthcare professionals. Methods: A qualitative survey was conducted among the staff at a tertiary Australian hospital between January 2017 and June 2018. Rome III criteria (excluding endoscopic) were used to define FGID. Multivariable logistic regression was used to explore associations. Results: Of the 274 respondents (17% doctors, 66% nurses, 17% others; 77% female), 54% had experienced GI symptoms ≥3 times per week and 23% were diagnosed with FGIDs (2% IBS, 19% FD, 2% both). GI symptoms were more common in females (58% vs. 38%), Caucasians versus Asians (59% vs. 35%), respondents who were easily (67% vs. 40%) or often stressed (58% vs. 37%), and had irregular working hours (62% vs. 46%, each P < 0.05). Independent predictors of GI symptoms included being easily stressed (OR 2.7) and female sex (OR 2.4), while Asian ethnicity was protective (OR 0.42, each P < 0.05). FGIDs were more prevalent in respondents who often felt stressed (27% vs. 10%), felt easily stressed (29% vs. 17%), and in nurses compared to others (27% vs. 16%; each P < 0.05). The only independent predictor of FGID was being often stressed (OR 4.1, P = 0.011). Conclusions: FGIDs and GI symptoms are prevalent among hospital workers. Stress, female sex, irregular working hours, and non‐Asian ethnicity appeared to be associated with GI symptoms and FGIDs. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disease with no effective treatment. Altered microbiota composition seems implicated in disease etiology and therefore fecal microbial transplantation (FMT) has emerged as a possible treatment therapy. To clarify the clinical parameters impacting FMT efficacy, we conducted a systematic review with subgroup analysis. Methods: A literature search was performed identifying randomized controlled trials (RCTs) comparing FMT with placebo in IBS adult patients (8-week follow-up) with a reported improvement in global IBS symptoms. Results: Seven RCTs (489 participants) met the eligibility requirements. Although FMT seems not to be effective in global improvement of IBS symptoms, subgroup analysis shows that FMT through gastroscopy or nasojejunal tube are effective IBS treatments (RR 3.03; 95% CI 1.94–4.73; I2 = 10%, p < 0.00001). When considering non-oral ingestion routes, IBS patients with constipation symptoms are more likely to benefit from FMT administration (p = 0.003 for the difference between IBS subtypes regarding constipation). Fresh fecal transplant and bowel preparation seem also to have impact on FMT efficacy (p = 0.03 and p = 0.01, respectively). Conclusion: Our meta-analysis revealed a set of critical steps that could affect the efficacy of FMT as clinical procedure to treat IBS, nevertheless more RCTs are needed. [ABSTRACT FROM AUTHOR]

Aim: The study aimed primarily to compare the transverse rectal diameter in children with functional constipation (FC) and children without constipation in different age groups, and between cases of constipation at baseline and after treatment. Secondary aim was to determine factors that could affect the transverse rectal diameter. Methods: A controlled prospective study, including a total of 100 children between the ages of 2 and 11 years, who were divided into 50 patients suffering from constipation according to Rome IV criteria and 50 age‐ and sex‐matched controls. Transverse rectal diameter was measured at presentation, and after 3 months of laxative therapy and behavioural modification. Results: Initial rectal diameter was significantly different between cases (3.55 cm (interquartile range, IQR), 3.2–4) and controls (2.3 cm (IQR, 1.8–2.5)), P value < 0.001, and it was also significantly different between those above and below 4 years, so a separate cut‐off point for diagnosis of constipation was suggested being >3 cm for the former and >2.5 cm for the latter. After 3 months of follow‐up, rectal diameter significantly reduced to become 2.6 (IQR, 2‐2.8), P value < 0.001. Duration of symptoms positively correlated with rectal diameter. Conclusions: Ultrasound measurement of rectal diameter is an important tool to diagnose and follow‐up functional constipation in children. Different values of rectal diameter are found between those above and below 4 years of age. [ABSTRACT FROM AUTHOR]

Disorders of gut–brain interaction (DBGI), also known as functional gastrointestinal disorders, are common in individuals with eating disorders, and may precede or perpetuate disordered eating. Understanding the pathophysiology of common gastrointestinal symptoms in DGBI can be important for the care of many patients with eating disorders. In this review, we summarize the literature to date on the complex relationship between DBGI and eating disorders and provide guidance on the assessment and management of the most common symptoms of DBGI by anatomic region: esophageal symptoms (globus and functional dysphagia), gastroduodenal symptoms (functional dyspepsia and nausea), and bowel symptoms (abdominal pain, bloating and constipation). Plain English Summary: Disorders of gut–brain interaction, also known as functional gastrointestinal disorders, are common in individuals with eating disorders and can cause symptoms that affect all parts of the gastrointestinal system. In this review, we describe common symptoms of disorders of gut–brain interaction and recommendations for their assessment and management. [ABSTRACT FROM AUTHOR]

Linaclotide is a 14-amino acid residue peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation (IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Here we show a new method for the synthesis of linaclotide through the completely selective formation of three disulfide bonds in satisfactory overall yields via mild oxidation reactions of the solid phase and liquid phase, using 4-methoxytrityl (Mmt), diphenylmethyl (Dpm) and 2-nitrobenzyl (O-NBn) protecting groups of cysteine as substrate, respectively. [ABSTRACT FROM AUTHOR]

Objectives: Functional constipation (FC), or chronic idiopathic constipation, is one of the most common chronic disorders with no specific cause. Although FC is not associated with the progress of severe disease or additional mortality, it significantly decreases the patients' quality of life. While several medications are available to treat constipation, there is no adequate treatment response in most cases. Herbal remedies are one of the most widely used options for FC. Materials and Methods: In this double-blind controlled trial, all patients, researchers, and analysts were unaware of the ingredients contained in the drugs, as well as the assigned groups. We recruited a total of 90 elderly patients diagnosed with FC according to the Rome IV diagnostic criteria for irritable bowel syndrome (IBS). Patients were divided into two equal groups (n=45 in each) receiving fig-walnut syrup and lactulose syrup. Then, CBC-FBS-TSH-CR-NA-K-CA tests were taken from all patients, and the developed syrups (walnut-fig or lactulose) were prescribed to patients (15 cc half an hour before bedtime). Results: While 43 (95.6%) patients responded to treatment in the intervention group, 41 (91.1%) patients responded to treatment in the conventional treatment group. There was no statistically significant difference between the two groups in terms of response to treatment (P = 0.677). Conclusions: The results showed that the oral syrups developed in this study improved FC in the elderly and had no side effects. [ABSTRACT FROM AUTHOR]

Background: Functional constipation (FC) and irritable bowel syndrome constipation type (IBS‐C) share many similarities, and it remains unknown whether they are distinct entities or part of the same spectrum of disease. Magnetic resonance imaging (MRI) allows quantification of intraluminal fecal volume. We hypothesized that colonic volumes of patients with FC would be larger than those of patients with IBS‐C, and that both patient groups would have larger colonic volumes than healthy controls (HC). Methods: Based on validated questionnaires, three groups of participants were classified into FC (n = 13), IBS‐C (n = 10), and HC (n = 19). The colonic volume of each subject was determined by MRI. Stool consistency was described by the Bristol stool scale and colonic transit times were assessed with radiopaque makers. Key Results: Overall, total colonic volumes were different in the three groups, HC (median 629 ml, interquartile range (IQR)(562–868)), FC (864 ml, IQR(742–940)), and IBS‐C (520 ml IQR(489–593)) (p = 0.001). Patients with IBS‐C had lower colonic volumes than patients with FC (p = 0.001) and HC (p = 0.019), but there was no difference between FC and HC (p = 0.10). Stool consistency was similar in the two patient groups, but patients with FC had longer colonic transit time than those with IBS‐C (117.6 h versus 43.2 h, p = 0.019). Conclusion: Patients with IBS‐C have lower total colonic volumes and shorter colonic transit times than patients with FC. Future studies are needed to confirm that colonic volume allows objective distinction between the two conditions. [ABSTRACT FROM AUTHOR]

Background and Aims: Fecal microbiota transfer (FMT) is a potential treatment for irritable bowel syndrome (IBS). Several randomized trials have tested FMT effects using different routes of administration, doses, and sample sizes. We aim to assess the overall efficacy of FMT for IBS patients and the safety of the intervention. Methods: We systematically searched four databases for randomized control trials that studied the efficacy and safety of FMT in IBS patients. Results: We included 8 randomized trials (472 patients) that compared FMT with placebo in IBS patients. Pooled results showed no statistically significant difference between FMT and control groups in the overall change in IBS symptom severity (IBS‐SSS) at 1 month (p = 0.94), 3/4 months (p = 0.82), and at the end of trials (p = 0.67). No significant difference in the total number of respondents between the FMT and control groups (risk ratios = 1.84, [95% confidence interval (CI) = 0.82–2.65], p = 0.19). Although the oral route of administration showed a significant difference in the number of respondents (p = 0.004), there was no statistically significant difference in the IBS‐SSS when subgrouping the oral route of administration (mean difference = 47.57, [95% CI = −8.74–103.87], p = 0.10). Conclusion: FMT is not an effective treatment to relieve all the symptoms of IBS. Even in the groups that showed relatively significant improvement after FMT, the effect was proven to wear off over time and the re‐administration carries a low success rate. Future research should consider different bacterial‐based interventions such as probiotics or specific antibiotics. [ABSTRACT FROM AUTHOR]

Background: The healthcare burden of pediatric functional gastrointestinal pain disorders (FGIDs) is unclear. Our study aimed to characterize the burden of these hospitalizations in the United States (US). Methods: We utilized the US National Inpatient Sample from 2002 to 2018 to capture pediatric hospitalizations (ages 4 to 18 years old) with a primary discharge diagnosis of abdominal pain, constipation, irritable bowel syndrome, dyspepsia, abdominal migraine, cyclic vomiting syndrome, or fecal incontinence. We calculated the FGID hospitalization prevalence rate, length of stay (LOS), and inflation‐adjusted costs annually and assessed for statistically significant trend changes using joinpoint analyses. Key Results: 22.3 million pediatric hospitalizations were captured, and 1 in 64 pediatric hospitalizations were attributed to a primary FGID hospitalization. The overall FGID hospitalization prevalence rate initially remained stable but decreased significantly from 2013 to 2018. Constipation and abdominal pain hospitalization rates, respectively, increased and decreased significantly over time. Constipation hospitalizations were more prevalent for younger non‐Hispanic Blacks and Hispanics. FGID hospitalization rates stratified by sex were similar. Mean LOS was 2.3 days; average LOS increased significantly from 2002 to 2013 and then stabilized. FGID hospitalization costs averaged $6,216 per admission and increased significantly for all FGIDs except dyspepsia. Endoscopic procedures were the most common interventions. Conclusions & Inferences: FGID hospitalization prevalence rates decreased recently, possibly due to national healthcare policy implementation. Nonetheless, constipation admissions increased. LOS was stable in recent years but associated costs‐per‐hospitalization were increasing over time, probably due to endoscopic procedures. More studies are needed to explain these prevalence and cost trends. [ABSTRACT FROM AUTHOR]

Background: Nocebo effects occurring in patients receiving placebo frequently impact on adverse events reported in randomized controlled trials (RCTs) in irritable bowel syndrome (IBS). Therefore, we conducted a systematic review and meta‐analysis to assess the proportion of patients randomized to placebo or active drug experiencing any adverse event in trials of licensed drugs for IBS with constipation (IBS‐C) or diarrhea (IBS‐D), and to estimate the risk of developing adverse events among patients randomized to placebo. Methods: We searched MEDLINE, EMBASE CLASSIC and EMBASE, and the Cochrane central register of controlled trials (through June 2021) to identify RCTs comparing licensed drugs with placebo in adults with IBS‐C or IBS‐D. We generated Forest plots of pooled adverse event rates in both active drug and placebo arms and pooled risk differences (RDs) with 95% confidence intervals (CIs). Key results: There were 21 RCTs of licensed drugs versus placebo in IBS‐C (5953 patients placebo) and 17 in IBS‐D (3854 patients placebo). Overall, 34.9% and 46.9% of placebo patients in IBS‐C and IBS‐D trials, respectively, developed at least one adverse event, with a statistically significantly higher risk of any adverse event and withdrawal due to an adverse event with active drug. In IBS‐C and IBS‐D trials, rates of each individual adverse event were generally higher with active drug. However, in IBS‐C trials, only diarrhea or headache was significantly more common with active drug (RD 0.066 (95% CI 0.043–0.088) and RD 0.011 (95% CI 0.002–0.021), respectively), and in IBS‐D trials only constipation, nausea, or abdominal pain (RD 0.096 (95% CI 0.054–0.138), 0.014 (95% CI 0.002–0.027), and 0.018 (95% CI 0.002–0.034), respectively). Conclusions & Inferences: Patients with IBS randomized to placebo have a high risk of reporting adverse events, which might relate to both nocebo and non‐nocebo factors. Although patients' expectations and psychosocial factors may be involved, further understanding of the mechanisms are important to control or optimize these effects in RCTs, as well as in clinical practice. [ABSTRACT FROM AUTHOR]

Although functional gastrointestinal disorders (FGIDs) are very common in pediatric patients, there is a scarcity of published epidemiologic data, characteristics, and management patterns from Saudi Arabia, which is the 2nd largest Arabic country in terms of area and the 6th largest Arabic country in terms of population, with 10% of its population aged <5 years. Functional constipation (FC) is an FGID that has shown a rising prevalence among Saudi infants and children in the last few years, which urges us to update our clinical practices. Nine pediatric consultants attended two advisory board meetings to discuss and address current challenges, provide solutions, and reach a Saudi national consensus for the management of pediatric constipation. The pediatric consultants agreed that pediatricians should pay attention to any alarming signs (red flags) found during history taking or physical examinations. They also agreed that the Rome IV criteria are the gold standard for the diagnosis of pediatric FC. Different therapeutic options are available for pediatric patients with FC. Dietary treatment is recommended for infants with constipation for up to six months of age. When non-pharmacological interventions fail to improve FC symptoms, pharmacological treatment with laxatives is indicated. First, the treatment is aimed at disimpaction to remove fecal masses. This is achieved by administering a high dose of oral polyethylene glycol (PEG) or lactulose for a few days. Subsequently, maintenance therapy with PEG should be initiated to prevent the re-accumulation of feces. In addition to PEG, several other options may be used, such as Mg-rich formulas or stimulant laxatives. However, rectal enemas and suppositories are usually reserved for cases that require acute pain relief. In contrast, infant formulas that contain prebiotics or probiotics have not been shown to be effective in infant constipation, while the use of partially hydrolyzed formula is inconclusive. These clinical practice recommendations are intended to be adopted by pediatricians and primary care physicians across Saudi Arabia. [ABSTRACT FROM AUTHOR]

(1) Background: Irritable bowel syndrome (IBS) is a common disease, with multiple pathophysiological mechanisms involved. A single treatment for all the patients with IBS is not possible. Prebiotics may have a beneficial effect on IBS patients with constipation. (2) Methods: A randomized cross-over case-control study was conducted, including patients with IBS and constipation (IBS-C), who were randomized into two groups receiving a specific constipation diet with or without a food supplement containing inulin, choline and silymarin (Stoptoxin®, Fiterman Pharma, Iasi, Romania). Patients were evaluated at baseline, after four and eight weeks, using a questionnaire to assess IBS symptoms. (3) Results: 51 IBS-C patients were included, of which 47 patients finished the trial (33 women, mean age 52.82 years). Adding Stoptoxin® to a diet for constipation brought extra benefits. Abdominal pain severity improved by 68.3% after the diet and Stoptoxin® (p = 0.004) and abdominal bloating severity parameter improved by 34.8% (p = 0.040). The stool number per week and the stool consistency according to the Bristol scale were improved, but without statistical significance between groups (p > 0.05). (4) Conclusions: The combination of inulin, choline and silymarin associated with a specific-constipation diet had obvious clinical beneficial effects on IBS-C patients in terms of bowel movement, abdominal pain and bloating. [ABSTRACT FROM AUTHOR]

Background: Abdominal pain is a bothersome and lifestyle limiting symptom in patients with functional bowel disorders. It is associated with decreased quality of life in affected individuals, as well as significant annual healthcare expenditure. Knowledge of specific factors that predict improvement in abdominal pain in those with functional bowel disorders is thus far limited. Methods: Consecutive patients presenting for outpatient care at a major academic medical center between October 2017 and March 2020 completed an electronic symptom survey prior to initial clinic visit, and again after 3 months. The Rome IV questionnaires for functional dyspepsia, irritable bowel syndrome, functional constipation, and functional diarrhea were all included. Additionally, all subjects completed the Patient Reported Outcomes Measurement Information System Anxiety, Depression, and sleep disturbance questionnaires. Patients with a diagnosis of a Rome IV functional gastrointestinal disorder without any organic cause for symptoms were identified based on both chart review as well as survey response data. Univariable and multivariable analysis was used to assess predictors of improved abdominal pain after 3 months. Key Results: 180 patients with a mean age of 45.3 years were included in the final analysis. 78.3% of patients were female, and 77.2% met Rome IV criteria for irritable bowel syndrome. On multivariable analysis, improvement in constipation and diarrhea were both independent predictors of improved abdominal pain after 3 months. Conclusions and Inferences: Improvement in constipation and diarrhea both predicted improvement in abdominal pain, suggesting that addressing these factors is central to the management of abdominal pain in functional gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

Background/Aims To assess the effects and safety of DA-9701 (Motilitone) in patients with constipation-type irritable bowel syndrome (IBS-C) which frequently accompany functional dyspepsia (FD). Methods FD and IBS-C were diagnosed based on the Rome III criteria. Randomized subjects were administered 30 mg of DA-9701 or placebo 3 times a day for 4 weeks. The study endpoints were evaluated the percentage of responders in the overall symptom evaluation of IBS-C and FD. Results Thirty IBS-C patients and 30 placebos were prospectively enrolled. The proportion of responders with improvement in overall symptoms of IBS-C was 53.33% in the DA-9701 group and 40.00% in the placebo group (P = 0.301). Compared to the placebo group, the decrease of abdominal pain score in the DA-9701 group was significantly higher at week 3 in the DA-9701 group (0.96 ± 0.77 vs 0.55 ± 0.79, P = 0.042) but no significance at week 4. There was no significant difference in total IBS quality of life score at week 4 between the 2 groups (P = 0.897). Among patients with IBS-C accompanied by FD, the proportion of responders in the DA-9701 group was 50.00% (15/30), which was higher than 31.03% (9/29) of the placebo group (P = 0.138). Conclusions DA-9701 showed trend of treatment efficacy in patients with IBS-C and FD overlap including overall improvement, and safety, compared to placebo but without significance probably due to small numbers. It is suggested the need for a large-scale clinical trial to confirm this preliminary effect of DA-9701. [ABSTRACT FROM AUTHOR]

Background: Functional constipation (FC), a functional bowel disorder with symptoms of constipation, has considerable impact on quality of life. As data regarding its prevalence and epidemiology are lacking, this study aimed to evaluate the prevalence, population composition, lifestyle, quality of life, and clinical characteristics of these individuals by comparing people with and without FC. These parameters were also compared among individuals with strong and weak awareness of constipation. Methods: An internet survey was conducted among 10,000 individuals aged 20–69 years from the general Japanese population; they were registered with an internet survey company. The following data were obtained: age, sex, educational history, occupation, residence, history of other diseases, lifestyle (including smoking/drinking habits using the Japanese Health Practice Index, medication use, symptoms of constipation according to the Rome III criteria, stool types according to the Bristol stool scale, and use of laxatives, including the place of purchase and cost per month or acceptable cost per month. The 8-item Short Form Health Survey Questionnaire was also used; FC was diagnosed based on Rome III criteria. All respondents were classified according to their awareness of constipation (i.e. strong or weak), and their characteristic features were compared. Results: The data of 3000 respondents were evaluated; 262 (8.7%) had FC, which was common among older adults, women, and homemakers. FC was associated with changes in the frequency of bowel movement, sensation of incomplete or scanty evacuation, and the use of manual maneuvers; these are consequential clinical symptoms of FC. These individuals frequently skipped breakfast, had insufficient sleep, had more severe constipation, and had purchased laxatives in pharmacies or online more often than those without FC. A strong awareness of constipation was significantly more prevalent among women and homemakers. A history of anemia and cardiovascular disease was significantly more frequent in the strong awareness group, whereas a history of hypertension was more frequent in the weak awareness group. Conclusions: Appropriate and comprehensive management should be provided for FC, based on the understanding of its characteristic features and considering the symptoms and lifestyle. [ABSTRACT FROM AUTHOR]

Functional gastrointestinal disorders (FGIDs), such as irritable bowel syndrome, functional constipation, and functional dyspepsia, have had a high prevalence over the past few years. Recent evidence suggests that functional foods and bioactive compounds, such as probiotics and phytochemicals, may have a positive effect in treating the symptoms of the above diseases. In this systematic review study, 32 published studies were selected with the use of comprehensive scientific databases, according to PRISMA guidelines, with emphasis on recent interventional studies that reflect the effect of probiotics and selected phytochemicals on the improvement of FGID symptoms. The bioactive compounds in the selected studies were administered to patients either in capsule form or in enriched food products (yogurt, juice, etc.). According to the results, there is a correlation between the consumption of probiotics and phytochemicals, such as polyphenols, and the relief of symptoms in selected gastrointestinal disorders. Enriching foods that are regularly consumed by the population, such as fruit juices, yogurt, and cheese, with ingredients that may have a positive effect on gastrointestinal disorders, could be a possible novel goal for the management of these diseases. However, further evidence is required for the role of probiotics and phytochemicals in FGIDs to be fully understood. [ABSTRACT FROM AUTHOR]

Background: Early adverse life events (EALs) and post‐traumatic stress disorder (PTSD) are associated with irritable bowel syndrome (IBS). Disordered defecation (DD) presents with symptoms of IBS or functional constipation (FC) and is associated with psychological distress. However, the role of trauma and stress in chronic constipation is poorly defined. We aimed to examine EALS, PTSD, and psychological symptoms in patients with constipation and suspected DD. Methods: We conducted a survey study among adults with constipation who completed anorectal manometry (ARM) and balloon expulsion testing (BET). Data were collected on socio‐demographics, EALs, PTSD, bowel symptoms, quality of life, and anxiety and depression. We performed comparisons between individuals with normal versus abnormal ARM or BET, subgroup analysis by detailed ARM and BET findings, and latent class analysis using individual EAL domains. Key Results: Among 712 eligible patients, 69 completed the study. EALs and provisional PTSD were present in 75.4% and 27.5%, respectively; rates did not differ between those with normal versus abnormal ARM or BET. Normal testing was associated with higher rates of specific EAL domains (emotional abuse and mental illness), higher depression scores, and poorer mental component scores in both primary and subgroup comparisons (all p < 0.05). Normal testing was associated with a lower likelihood of high‐EAL latent class (p = 0.01) membership. Presence of IBS or FC did not influence associations. Conclusions & Inferences: Early adverse life events and PTSD are prevalent in patients with constipation and suspected DD. Those with normal ARM and BET have higher rates of prior emotional abuse and poorer mental health. [ABSTRACT FROM AUTHOR]

Introduction: The cause of constipation is multifactorial and common problem for patients on hemodialysis. A lack of strong evidence on suitable treatment strategies means there is an unorganized approach to selecting therapies, which can exacerbate constipation or worsen symptoms. Clinicians and patients would benefit from a content and face validated treatment algorithm for treating constipation. In this study, our objective was to develop and content and face validate a constipation treatment toolkit for patients on hemodialysis, consisting of treatment algorithm, and patient information tools (pamphlet and video). Methods: Literature searches were performed to develop an initial toolkit using Lynn's method for developing content‐valid clinical tools. Content and face validity were evaluated as per Lynn's method for determining content validity; the algorithm was evaluated by Canadian nephrology clinicians, while patient information tools were evaluated by clinicians and patients. Components were rated on a Likert scale for content relevance and on a 5‐point scale for face validity. After each round, the content validity index (CVI) score was calculated and revisions were made based on feedback. Findings: A total of 23 clinicians and 15 patients were interviewed across three validation rounds. After three rounds, the treatment algorithm achieved content (overall CVI = 0.93) and face (91% agreement) validity. Our patient information tools achieved content and face validity (pamphlet overall CVI = 0.99, 85.5% agreement; video overall CVI = 0.99, 90.5% agreement). Discussion: A treatment algorithm and patient information toolkit for the treatment of constipation in patients on hemodialysis were content and face validated via expert review. Further research will be needed to ascertain the effectiveness and implementation of this toolkit. [ABSTRACT FROM AUTHOR]

Wei Chang An (WCA) is a commercial prescription developed for the coordination of gastrointestinal movement. To investigate the role of WCA in the regulation of diarrhoea and constipation in rats. The diarrhoea and constipation models were prepared by gavage of Folium senna and diphenoxylate hydrochloride. Rats were randomized equally (n = 6) into the normal group given saline daily, the positive group given Pinaverium Bromide (13.5 mg/kg) or Sennoside A (0.1 mg/kg) and three WCA-treated groups (22, 44, and 88 mg/kg) by gavage daily for 7 consecutive days. The effects of WCA were assessed by a series of faecal symptoms and histopathology. Gastrointestinal parameters were determined by ELISA. The effect of WCA on gastrointestinal tissues was evaluated by strip assay. Expression of ROCK-1 and MLCK was measured by RT-PCR and Western blotting. Data from Bristol stool form scale, diarrhoea index, visceral sensitivity, defaecation time, and intestinal propulsive rate showed that WCA protected rats against diarrhoea and constipation (p < 0.01). The up-regulation of Substance P and 5-hydroxytryptamine in diarrhoea rats and down-regulation of Substance P and vasoactive intestinal polypeptide in constipation rats were inhibited by WCA (p < 0.05). WCA stimulated the gastrointestinal strip contractions but inhibited ACh-induced contractions (p < 0.01). The decreased ROCK-1 and MLCK expression in diarrhoea rats and increased in constipation rats were suppressed by WCA (p < 0.01). WCA has both antidiarrhea and anti-constipation effects, suggesting its bidirectional role in gastrointestinal modulation, and providing evidence of WCA for irritable bowel syndrome treatment. [ABSTRACT FROM AUTHOR]

Chronic idiopathic constipation (CIC) is a common functional bowel disorder characterized by difficult, infrequent, and/or incomplete defecation. It has a great impact on the quality of life and on health care system and represents a heavy economic burden. The diagnosis is based on symptoms, classified by the Rome IV criteria. The aim of this review was to evaluate the current therapeutic guidelines for adult CIC and highlight new emerging treatments. In detail, European, French, Spanish and Korean guidelines have been identified and compared. Osmotic laxatives, and in particular polyethylene glycol, represent the first-line therapeutic approach. Stimulant laxatives are recommended as a second-line therapy. Pelvic floor rehabilitation is recommended in patients with ano-rectal dyssynergia. In patients who fail to improve with pharmacological therapies sacral nerve stimulation is considered as last chance before surgery. Surgical approach has however limited indications in selected cases. Inertia coli refractory to any approach and obstructed defecation are two subtypes which can benefit from surgery. Among emerging agents, prucalopride, a prokinetic agent, is recommended as a second-line treatment in refractory CIC patients. In addition, the secretagogues linaclotide and plecanatide and the bile acid transported inhibitor elobixibat can be effective in patients not responsive to a second-line therapeutic regimen, although they are not worldwide commercially available. [ABSTRACT FROM AUTHOR]

Aim: There is a requirement for a reliable serologic marker that can be used for the diagnosis of Irritable Bowel Syndrome (IBS). The aim of our study was to research whether serum levels of Alpha-galactosidase (AG) is associated with IBS and to assess quality of life (QOL) of IBS patients. Materials and Methods: 110 adult patients who were diagnosed with IBS were evaluated. 90 patients and 25 healthy volunteers were included. Patients were classified into subtypes: IBS-Diarrhea (IBS-D), IBS-Constipation (IBS-C), IBS-Mixed (IBS-M), and 30 patients were enrolled for each group. We administered the Short Form 36 (SF-36) to participants to evaluate QOL. Serum AG levels of participants was determined. Results: The mean AG levels of IBS-C and control group were significantly lower than the other groups (p<0.05). The SF-36 questionnaire scores, except for the vitality and mental health domains, were higher significantly in the control group compared to IBS patients (p<0.05). The mean scores of IBS subtypes were similar. In addition, the mean physical functioning score of the control group was higher in comparison with the IBS-D group significantly (p<0.05). Conclusion: Our study has shown that IBS impairs QOL in patients. In addition, we suggest that future studies needed for the role of AG deficiency in IBS patients. [ABSTRACT FROM AUTHOR]

Chronic constipation (CC) is a gastrointestinal disorder that adversely affects the quality of life. MicroRNAs are involved in the pathogenesis of functional gastrointestinal disorders. This study aims to investigate the molecular mechanism of microRNA-128 in CC. Here, we successfully constructed a murine model of CC based on morphine and rhubarb. The expression of stem cell factor (SCF) and neuron-specific enolase (NSE) was low in the models. Using miRNA array and bioinformatic analysis, we predicted and confirmed the expression of miR-128 and its downstream target genes in CC model. Compared with the control group, CC group showed a significant downregulation of miR-128 and upregulation of p38α and macrophage colony-stimulating factors (M-CSFs). Moreover, we observed elevated inflammatory cytokine and decreased anti-inflammatory cytokine levels in colonic tissues. Furthermore, coculture assays indicated that regulating expression of miR-128 in colonic epithelial cells induced the secretion of IL-6 and TNF-α by macrophages. In conclusion, our study demonstrated that miR-128 regulated the p38α/M-CSF signaling pathway to promote chronic inflammatory responses and changes in the immune microenvironment of the colon, thereby offering potential insights into the pathogenesis of CC and therapeutic targets for its treatment. [ABSTRACT FROM AUTHOR]

Background: Chronic constipation can have one or more of many etiologies, and a diagnosis based on symptoms is not sufficient as a basis for treatment, in particular surgery. Aim: To investigate the cause of chronic constipation in a patient with complete absence of spontaneous bowel movements. Methods: High-resolution colonic manometry was performed to assess motor functions of the colon, rectum, the sphincter of O'Beirne and the anal sphincters. Results: Normal colonic motor patterns were observed, even at baseline, but a prominent high-pressure zone at the rectosigmoid junction, the sphincter of O'Beirne, was consistently present. In response to high-amplitude propagating pressure waves (HAPWs) that were not consciously perceived, the sphincter and the anal sphincters would not relax and paradoxically contract, identified as autonomous dyssynergia. Rectal bisacodyl evoked marked HAPW activity with complete relaxation of the sphincter of O'Beirne and the anal sphincters, indicating that all neural pathways to generate the coloanal reflex were intact but had low sensitivity to physiological stimuli. A retrograde propagating cyclic motor pattern initiated at the sphincter of O'Beirne, likely contributing to failure of content to move into the rectum. Conclusions: Chronic constipation without the presence of spontaneous bowel movements can be associated with normal colonic motor patterns but a highly exaggerated pressure at the rectosigmoid junction: the sphincter of O'Beirne, and failure of this sphincter and the anal sphincters to relax associated with propulsive motor patterns. The sphincter of O'Beirne can be an important part of the pathophysiology of chronic constipation. [ABSTRACT FROM AUTHOR]