Significant Gastrointestinal Symptoms Research Articles

A high prevalence of chronic gastrointestinal symptoms in adults with cystic fibrosis is detected using tools already validated in other GI disorders.

People with cystic fibrosis (CF) report a variety of gastrointestinal (GI) symptoms, independent of pancreatic enzyme insufficiency (PEI), reminiscent of other chronic GI disorders. There are currently no accepted or validated assessment tools and neither the range, frequency nor severity of GI symptoms has been systematically described in CF. We present results of a cross-sectional study using established tools and compare them to current measures of quality of life (QOL). Consecutive patients attending specialist CF appointments were asked to complete questionnaires including the GI Symptom Rating Scale (GSRS); Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) and Cystic Fibrosis Questionnaire (CFQ-R). Questionnaire terminology was altered to replace references to 'IBS' with 'GI symptoms'. In total, 107 patients were recruited (mean age, 27.8 ± 9.6 years; 60 female), and 94 (88%) had PEI. Body mass index was 22.1 ± 3.6 kg/m2, forced expiratory volume in one second was 59 + 27.7% predicted. Fifty-three (49.5%) were p.Phe508del homozygous. Overall 69/107 (65%) reported significant GI symptoms independent of PEI or adherence to pancreatic enzyme replacement therapy (PERT), with the four most frequent being attributable to the lower GI tract: bloating/distension, flatulence, abdominal pain and borborygmi (gurgling). There was no numerical correlation between any CFQ-R domain (particularly Digestion domain) and GSRS or SSS. This is the first systematic study measuring GI symptoms in CF using validated GI tools. Symptoms are not related to PERT or genotype and appear to be captured well by the GSRS. Further research will study longitudinal changes with treatment, and therapeutic trials in CF may use these tools to demonstrate a positive impact on 'non-respiratory' symptoms and QOL.

Lack of Associations Between Dietary Intake and Gastrointestinal Symptoms in Autism Spectrum Disorder.

Background: Many individuals with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but their etiology is currently unknown. Dietary interventions are common in children and adolescents with ASD, including diets with increased omega-3 fatty acids or diets free of gluten and/or casein, which may also impact GI symptoms and nutrition. However, little is known about the relationship between nutritional intake and GI symptomatology in ASD. The objective of this study was to assess the relationships between GI symptoms, omega-3 intake, micronutrients, and macronutrients in children with ASD. Methods: A total of 120 children diagnosed with ASD participated in this multisite study. A food frequency questionnaire was completed by the patient’s caretaker. The USDA Food Composition Database was utilized to provide nutritional data for the food items consumed by each participant. GI symptomatology was assessed using a validated questionnaire on pediatric gastrointestinal symptoms. Results: There were no significant associations between GI symptoms and the amount of omega-3 fatty acids and/or other micro- and macronutrients contained in the diet. Conclusions: This study suggests that dietary variations do not appear to drive GI symptoms, nor do GI symptoms drive dietary variations in those with ASD, although causation cannot be determined with this observational assessment. Furthermore, there may be other factors associated with lower GI tract symptoms in ASD, such as increased stress response.

Abstract 2708: Potent CAB CTLA4 antibody to reduce immune side effects and toxicities associated with single-agent and combination cancer immuno therapies

Abstract CTLA4 is a receptor on T cells that acts as a brake on their activation during immune responses, and when blocked can stimulate cancer immune-surveillance. The use of anti-CTLA4 antibodies to unleash T cells has demonstrable anti-tumor efficacy in animal models and in certain patients in the clinic. However, blockade of CTLA4 as a single agent and in combination with chemotherapy, targeted, and other immunomodulatory therapies has been limited clinically in part due to systemic immune-response related toxicities. In addition, there is increasing concern that systemic immune activation may lead to sustained autoimmune-related disease in survivors. The Conditionally Active Biologics (CAB) technology generates antibodies that reversibly bind to target antigen in the context of diseased tissues, but not normal tissues, by taking advantage of the unique cancer microenvironment that is produced largely because of glycolytic tumor metabolism including the Warburg effect. Using our CAB technology, we have identified anti-CTLA4 Abs that reversibly bind human CTLA4 and enhance T cell response to bacterial super-antigen under in vitro tumor microenvironment, but not in normal tissue conditions. CAB-CTLA4 Abs have anti-tumor efficacy equal to that of ipilimumab analog, including tumor regression, against MC38 colorectal tumor in a syngeneic human CTLA4 knock-in mouse model. Interestingly, CAB CTLA4 antibodies modulate the activity and numbers of infiltrating T cell subsets within the tumor microenvironment, but unlike ipilimumab analog, the CAB CTLA antibodies do not increase CD4 effector T Cells in periphery, suggesting less systemic immune toxicities impacting normal tissues. Repeated co-administration of either CAB CTLA4 or ipilimumab analog in combination with an anti-PD-1 (nivolumab analog) into monkeys for four weeks was performed to access the peripheral systemic and normal tissue effects of combination treatments. Combination treatment with ipilimumab and nivolumab analogs (I+N) resulted in increases in T cell proliferation markers in peripheral blood cells, while the CAB CTLA4 plus nivolumab analog had normal immunophenotypic patterns. All animals in the I+N treated groups had significant gastrointestinal symptoms (diarrhea, loose stools) that presented early, were sustained throughout the treatment period and were associated with substantial mononuclear infiltration within the intestinal wall. In sharp contrast, the CAB-CTLA4 plus nivolumab treated groups showed no significant GI symptomology nor histopathology. These data indicate that our CAB CTLA4 molecule may have a superior safety profile when used in combination with PD-1 inhibitors and allow increased dosing levels to achieve superior efficacy to current anti CTLA4 therapy as a single agent or in combination with other anti-cancer therapies including immuno-oncology agents. Citation Format: Leslie Sharp, Cathy Chang, Gerhard Frey, Haizhen Liu, Charles Xing, Jing Wang, Marlena Walls, Christina Wheeler, Yong Ben, William J. Boyle, Jay M. Short. Potent CAB CTLA4 antibody to reduce immune side effects and toxicities associated with single-agent and combination cancer immuno therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2708.

Preoperative Nutrition Status and Postoperative Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex surgery to treat peritoneal surface malignancy (PSM). PSM and gastrointestinal (GI) resection from CRS can lead to significant GI symptoms and malnutrition. There is limited research into the nutrition status of this patient group and the impact of malnutrition on morbidity. This study aims to determine if preoperative malnutrition, assessed using the Subjective Global Assessment (SGA), is associated with postoperative morbidity and increased length of stay (LOS) in patients undergoing CRS/HIPEC for PSM. This study prospectively assessed the nutritional status of patients undergoing CRS/HIPEC using a validated nutrition assessment tool. Preoperative clinical symptoms, Peritoneal Cancer Index (PCI), intraoperative blood transfusions, operative time, GI resections, postoperative morbidity, and LOS, as well as pre- and postoperative nutritional interventions, were recorded. The impact of preoperative nutritional status was assessed in relation to postoperative complications and hospital LOS. The study included 102 participants; 34 patients (33%) were classified as malnourished (SGA = B or C). Preoperative weight loss (15% vs. 74%; p ≤ 0.001) and the presence of clinical symptoms (18% vs. 47%; p = 0.002) were significantly higher in malnourished patients. While PCI, intraoperative blood transfusions, and GI resections were independent predictors of morbidity, malnutrition was significantly associated with infectious complications and LOS. For each grade of worsening malnutrition, LOS increased by an average of 7.65 days. Preoperative malnutrition is prevalent in patients undergoing CRS/HIPEC and postoperative morbidity is common. Malnutrition is linked to LOS and plays a role in postoperative outcomes such as infection. Clear pre- and postoperative nutrition pathways are needed to optimize nutrition support and postoperative recovery.

Bone sclerosis as the initial manifestation of gastric cancer without significant gastrointestinal symptoms: a case report

患者因腰背阵发性钝痛1个月就诊，检查显示骨密度升高，未治疗。入院前5d症状加重，无明显胃肠道症状，进一步检查确诊为胃癌（印戒细胞癌）。提示临床中对腰背疼痛伴骨密度升高的患者应提防恶性肿瘤骨转移的可能。.

SUN-515 A Case report of Severe Persistent Hypocalcaemia due to Functional Hypoparathyroidism

Introduction: Severe Hypocalcaemia is generally seen in clinical practice in patients following thyroid or parathyroid surgery .We report a case of severe hypocalcaemia with unusual presentation and etiology with challenging management. Case report: A 49 year old gentleman presented to hospital with unexpected, unintentional severe weight loss (20kg over 2 months), vomiting, diarrhoea, muscle cramps and pins & needles in both hands. His past medical history included beta thalassemia trait. He had a recent bereavement in his family and therefore had attributed his symptoms to the grieving process. He had no significant or relevant family history of note.Physical examination revealed positive Chvostek and Trousseau’s signs. His initial biochemistry showed corrected calcium of 0.86 (Normal range:2.20-2.60 mmol/l), Magnesium 0.58 (Normal range:0.7-1.0mmol/l), K+:3.3(Normal range:3.5-5.3mmol/l),Parathyroid hormone(PTH) suppressed at 0.7(Normal range:1.1-4.7pmol/l) and 25 OH Vitamin D 25(Normal range:50-250nmol/l).ECG showed long QTc.He wasn’t taking any proton pump inhibitor. He was started on intravenous magnesium infusion (6g of MgSO4 in 500 ml Normal saline), Calcium Gluconate infusion (100ml of 10% Ca. Gluconate in 1000mls of Normal saline at 50-100 ml/hr), Calcium carbonate tablets and Cholecalciferol 20,000 units daily(for 10 days). His corrected calcium gradually improved and he noticed immediate resolution of his symptoms. His CT chest,Abdomen,Pelvis did not show any evidence of malignancy and Gastroscopy showed mild erosive gastritis.He was reviewed by Gastroenterology but no other cause for significant weight loss and gastrointestinal symptoms was found. He was thought to be having Severe Hypocalcaemia due to Functional Hypoparathyroidism caused by Magnesium and Vitamin D deficiency. He was discharged on oral calcium and cholecalciferol tablets. He represented to hospital a month later with corr. Ca+ of 1.57mmol/l. Vitamin D had improved to 90nmol/l, however, PTH was still suppressed at 0.8pmol/l.His calcium carbonate tablets were increased to daily dose of 3g per day and he was also started on 1-alfacalcidol 250 nanograms BD. Subsequent review in ambulatory clinic revealed that he was still hypocalcaemic at 1.75mmol/l. His 1-alfacalcidol was increased to 500 nanograms BD. He continues to be on this treatment, has gained weight and is asymptomatic. Conclusion: Although calcium abnormalities are commonly treated on medical wards, it is very rare to see such severe hypocalcaemia in the absence of any significant pathology. Understanding the physiology of calcium homeostasis is vital to guide appropriate management, especially in situations of clinical emergency which can be very challenging, as we have highlighted in our case.

Advanced Biventricular Heart Failure Leading to the Formation of a Gastric Bezoar: The Implications of Heart Failure on the Gastrointestinal Tract

While dyspnea or increasing peripheral edema come to mind when thinking of worsening heart failure (HF), seemingly unrelated symptoms such as nausea or bloating can indicate exacerbation. We highlight the significant gastrointestinal (GI) symptoms that result from HF, with emphasis on impaired gastric and intestinal motility. A 43 year-old man with cardiomyopathy (CM) presented with worsening abdominal pain, distention and nausea for 4 months. Physical exam showed jugular venous distention, peripheral edema, diminished breath sounds and a murmur. The abdomen was soft, mildly distended and tender. Labs showed B-type natriuretic peptide of 1374pg/ml. Blood gas showed a lactic acid of 3.2mmol/L. Platelet count was 66K/UL and international normalized ratio was 2.3. Total bilirubin was 4.0mg/dl with direct of 1.9mg/dl; aspartate aminotransferase of 98IU/L, alanine aminotransferase of 121IU/L and an alkaline phosphatase of 87IU/L. Computerized tomography showed wall thickening of the stomach, ascites, diffuse anasarca and thickening in the sigmoid colon. Echocardiogram showed an ejection fraction of 21-25% and global CM. Upper endoscopy revealed a gastric bezoar. The patient was given a can of Pepsi Cola and kept nil per os for repeat endoscopy, which showed resolution of the bezoar. Cardiac catheterization showed normal coronaries and reduced cardiac output (CO). Gastric emptying study confirmed gastroparesis. We look at the pathophysiology of HF and its effect on the structure and function of the GI tract. The small and large intestine display bowel wall edema with increased wall thickness leading to impaired nutrition of the enterocytes resulting in decreased absorptive function of the bowel. In the sigmoid colon, increased thickness correlates with increased concentrations of C-reactive protein and leukocytes. The intestine is one of the most perfused organs at rest, receiving 25% of the CO. At maximal exercise, gut perfusion drops to 4% of the CO. Increased sympathetic stimulation causes vessel constriction and decreased bowel perfusion. Small changes in CO lead to significant ischemia causing decreased motility and absorption and increased bowel wall permeability. Hepatic congestion from blood backup into the liver results in delayed gastric emptying, slowed gut motility, increased bowel permeability and bacterial translocation. Presented case demonstrates pathophysiology of frequently seen but often underappreciated GI manifestations of heart failure.2631_A Figure 1. CT scan of the abdomen showing wall thickening of the cardia of the stomach2631_B Figure 2. Gastric Bezoar2631_C Figure 3. Body or the stomach, on second EGD, 24 hours after can of Pepsi Cola

Continuing Medical Education Questions: April 2018: ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts

LEARNING OBJECTIVES After this activity, the participant will identify patients appropriate for pancreatic cyst surveillance and choose pancreatic cyst surveillance intervals based on imaging characteristics. QUESTIONS: 1. A thin 68-year-old woman underwent an abdominal ultrasound to evaluate kidney size during an evaluation of her recently diagnosed chronic kidney disease. A pancreatic tail cyst was incidentally identified. She reports no fever, abdominal pain, nausea, vomiting, or weight loss. Her past medical history is notable for gastroesophageal reflux disease. Her only medication is oral esomeprozole 40 mg daily as needed. There is no history of pancreatitis or significant alcohol consumption. On exam, she is afebrile, blood pressure is 108/70 mm Hg, pulse rate is 84/min, and respirations are 14/min. Her abdomen is soft and nontender. The remainder of her exam is normal. Abdominal ultrasound revealed normal kidneys without hydronephrosis. The pancreas was notable for a 1.8 cm pancreatic tailcyst. No further characteristics of the cyst are reported. Which of the following imaging modalities is recommended to further characterize this pancreatic cyst? A. Computed tomography (CT) of the abdomen with intravenous and oral contrast B. Endoscopic ultrasound with fine needle aspiration (EUS-FNA) C. Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) D. Positron emission tomography/computed tomography (PET/CT) 2. A 76-year-old woman with a history of lower extremity claudication is referred for further evaluation of a pancreatic cyst identified on a recent CT angiogram. She has no significant gastrointestinal symptoms. She has multiple medical problems including insulin-dependent diabetes mellitus type II with subsequent end-stage renal disease, coronary artery disease requiring 2 coronary artery stents following a myocardial infarction, peripheral vascular disease, and a transient ischemic attack 6 months ago. She quit cigarettes 5 years ago and does not drink alcohol. On physical exam, she appears chronically ill, with a blood pressure of 148/96 mm Hg. Her abdominal exam is normal. Her peripheral pulses are weak. Laboratory testing reveals hemoglobin of 10.1 g/dL, alkaline phosphatase 125 U/L, and total bilirubin 0.8 mg/dL. Recent abdominal CT reveals a 2.1-cm pancreatic body cyst directly adjacent to a mildly dilated 4-mm pancreatic duct. There is no mention of mural nodules, cyst septation, or chronic pancreatitis. The splenic artery is densely calcified as are many other intra-abdominal arteries. Which of the following is the best next step in evaluation of this pancreatic cyst? A. MRI with MRCP B. CT of the abdomen with intravenous and oral contrast C. Referral to multidisciplinary pancreatic group D. No further evaluation is required 3. Five years ago, a 72-year-old woman was found to have a 1.8-cm pancreatic head cyst on chest CT imaging performed for lung cancer screening due to smoking history. Based on these findings, annual MRI scanning was performed for 5 years and there has been no subsequent change in cyst size or characteristics. She has no current gastrointestinal or systemic symptoms. She no longer smokes and does not drink alcohol. On physical exam, her blood pressure of 118/72 mm Hg. Her physical examination, laboratory values, and Ca 19-9 are normal. The most recent follow-up abdominal MRI reveals a 1.8-cm pancreatic head cyst. There is no evidence for mural nodularity and the pancreatic duct size is normal. There is no associated mass. Based on this guideline, which of the following would be the most appropriate recommendation for surveillance of this cyst? A. Repeat MRI with MRCP in 2 years. B. Repeat MRI with MRCP in 1 year. C. Discontinue pancreatic cyst surveillance as the cyst characteristics are unchanged. D. Order PET/CT and, if negative, discontinue surveillance.

Systemic Scleroderma and Colonic Volvulus

Introduction: Patients with scleroderma may have significant gastrointestinal symptoms due to intestinal dysmotility and pseudo-obstruction. Abnormal bowel motility is a risk factor for volvulus, a lifethreatening condition with a similar presentation as pseudo-obstruction. The literature shows the rare occurrence of colonic volvulus in scleroderma. The aims of this study were to examine the occurrence of colonic volvulus in scleroderma and its associated clinical features. Methods: Patients with documented ICD-9 or ICD-10 codes for both scleroderma and colonic volvulus were identified from the electronic and archived medical records using institutional software between July 1950 and January 2017. Records eligible were limited to patients between the ages of 18 and 99 at time of diagnosis. This data was combined with similar patients from the medical literature using PubMed. Results: From our database, 8 patients were identified with concomitant scleroderma and colonic volvulus. In combination with the 8 cases from the literature, a total of 16 patients were analyzed. The mean age at diagnosis of volvulus was 54.3 (SD +/-15.5) and the mean disease duration from onset of scleroderma diagnosis to colonic volvulus was 16.1 years (SD +/-12.3). There were 11 females and 5 males, with most having limited disease versus diffuse (81.3% vs. 18.7%, respectively). The most frequent associated disease was universally Raynaud's phenomenon (n=16), followed by interstitial lung disease (n=6). As for chronic GI symptoms, half the patients had documented gastroesophageal reflux disease (GERD), and 37.5% had chronic constipation. The most common site for initial volvulus was sigmoid (50%), followed by cecum (25%), and the majority required surgery for successful final treatment of volvulus (81.3%). While half the patients had a good outcome, 37.5% had poor outcomes including 2 deaths. Conclusion: While scleroderma with colonic volvulus is a rare occurrence, it is critical to consider this diagnosis in scleroderma patients presenting with symptoms of pseudo-obstruction because it is lifethreatening and requires surgery. The misdiagnosis of pseudo-obstruction in a patient with colonic volvulus can be catastrophic.

Diabetes and the Stomach.

Longstanding diabetes mellitus (both type 1 and type 2) can impair gastric motor function and cause significant upper gastrointestinal symptoms which significantly degrade quality of life, cause nutritional deficits, and degrade healthcare resource use. The most commonly considered gut complication of diabetes, diabetic gastroparesis, is a syndrome of delayed gastric emptying in the absence of mechanical obstruction which leads to symptoms of nausea, vomiting, postprandial fullness, early satiation, bloating, and upper abdominal pain. Gastroparesis also can lead to loss of glycemic control. A diagnosis of gastroparesis is made by documenting delayed gastric emptying and excluding mechanical obstruction. Gastric emptying scintigraphy is the most commonly utilized test for the diagnosis of gastroparesis but novel tests of gastric function have recently been introduced including the gastric emptying breath test and wireless motility capsule. Management most often is aimed at controlling symptoms, which includes dietary modification, optimization of glycemic control, and medication therapy with prokinetics, antiemetics, and neuromodulatory agents. Endoscopic and/or surgical therapies may be considered for refractory cases of gastroparesis. Recent research has provided new insights into the pathophysiology of this disease and is characterizing potential benefits of novel therapeutic agents which show promise in the treatment of this condition. This article will review the pathophysiology, new insights into disease mechanism, and treatment options for diabetic gastroparesis.

Successful outcome following pneumonectomy in a teenage boy with cystic fibrosis: a case report

BackgroundCystic fibrosis lung disease is generally a diffuse process however rarely one lung may become particularly damaged through chronic collapse and consolidation resulting in end-stage bronchiectasis with relative sparing of the contralateral lung. This clinical situation is sometimes referred to as “destroyed lung”. Lung resection surgery is seldom indicated in cystic fibrosis and the associated medical literature is relatively sparse.Case presentationA 14 year old boy was referred to our centre for lung transplantation assessment. He had a chronic history of complete collapse and consolidation of his entire right lung. This was causing severe morbidity in terms of a continuous requirement for intravenous antibiotics over the last year, poor exercise tolerance with forced expiratory volume in 1 s of 35–40% predicted and need for home tuition. He also had significant nutritional problems and gastrointestinal symptoms following a Nissen’s fundoplication operation a year earlier. His nutritional status was firstly improved by the institution of jejunal feeding, which also greatly improved his distressing symptoms of nausea and wretching. After thorough multidisciplinary assessment the therapeutic option of performing a right pneumonectomy was considered due to relative sparing of the left lung, which demonstrated only mild bronchiectasis on computed tomography scan. This was performed uneventfully with a smooth peri-operative course. Targeted antimicrobials were used to treat the multiresistant organisms colonising his airways. Subsequently his quality of life, nutritional status and lung function all improved significantly and requirement for lung transplantation has been delayed.ConclusionsWe report a successful outcome following pneumonectomy in a teenage boy with cystic fibrosis referred to our centre for lung transplantation assessment with chronic unilateral collapse and consolidation of his right lung. We believe that improvement of nutritional status pre-operatively and targeted antimicrobial therapy, all contributed to the smooth peri-operative course. Pneumonectomy can be a feasible option in this clinical situation in cystic fibrosis but the associated risks must be considered carefully on a case-by-case basis.

Gastrointestinal symptoms predictors of health-related quality of life in pediatric patients with functional gastrointestinal disorders.

To investigate the patient-reported multidimensional gastrointestinal symptoms predictors of generic health-related quality of life (HRQOL) in pediatric patients with functional gastrointestinal disorders (FGIDs). The Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms Scales and PedsQL™ 4.0 Generic Core Scales were completed in a 9-site study by 259 pediatric patients with functional constipation, functional abdominal pain (FAP), or irritable bowel syndrome (IBS). Gastrointestinal Symptoms Scales measuring 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 were identified as clinically important symptom differentiators from healthy controls based on prior findings, and subsequently tested for bivariate and multivariate linear associations with overall HRQOL. Gastrointestinal symptoms were differentially associated with decreased HRQOL in bivariate analyses for the three FGIDs. In predictive models utilizing hierarchical multiple regression analyses controlling for age, gender, and race/ethnicity, gastrointestinal symptoms differentially accounted for an additional 47, 40, and 60% of the variance in patient-reported HRQOL for functional constipation, FAP, and IBS, respectively, reflecting large effect sizes. Significant individual gastrointestinal symptoms predictors were identified after controlling for the other gastrointestinal symptoms in the FGID-specific predictive models. Gastrointestinal symptoms represent potentially modifiable predictors of generic HRQOL in pediatric patients with FGIDs. Identifying the condition-specific gastrointestinal symptoms that are the most important predictors from the patient perspective facilitates a patient-centered approach to targeted interventions designed to ameliorate impaired overall HRQOL.

Post-Fecal Microbiota Transplantation (FMT) Constipation and Abdominal Distention Due to Methane-Predominant Bacterial Overgrowth Contracted from the Donor

FMT is becoming increasingly used in patients with severe, recurrent and/or relapsing Clostridium difficile infections (CDI). Despite durable benefits associated complications are poorly defined. Up to 10% of patients develop bloating and constipation after FMT (Lee CH 2014); however, causality is not established as most patients undergoing FMT are ill and suffer from significant gastrointestinal (GI) symptoms. Excessive methane production (>10 ppm) is present in up to 25% of the general population and can lead to constipation and bloating. (Chang 2015) Here we report a 21 year-old female with history of recurrent sinusitis due to IgA deficiency requiring multiple courses of antibiotics and no prior GI-related complaints. She contracted CDI in Jan 2014, which persisted despite treatment with vancomycin and metronidazole. In July 2014, she underwent FMT via colonoscopy from her stepbrother. Despite eradication of CDI, she developed significant post-prandial bloating, distention, fatigue and constipation without rectal bleeding or constitutional symptoms. Her physical exam was without focal abnormalities. Laboratory evaluation showed normal IgG and IgM levels, but undetectable IgA and IgE titres. ANA was slightly elevated at 1:80, however CRP, anti-CCP, anti-tTG, C3, C4, LFTs, lipase CBC, and electrolytes were normal. Anti-vinculin and anti-CdtB antibodies were negative, as were stool for C. difficile, elastase, calprotectin and O&P. EGD and ileocolonoscopy were normal with normal gastric and duodenal biopsies. Capsule endoscopy and CT of the abdomen were normal. Antidepressants, low FODMAPs diet, peppermint, over-the-counter laxatives, linaclotide, lubiprostone and prucalopride proved to be minimally effective. Breath testing performed in Oct 2014 showed normal hydrogen levels, but significantly elevated methane peaking at 51 ppm (Figure 1). On further testing, FMT donor was also found to be an excessive methane producer, with a methane level of 35 ppm. The patient was treated with 14 days of rifaximin 550 mg TID and neomycin 500 mg BID leading to eradication of excessive methane production to 0 ppm and resolution of her GI symptoms. CDI has not recurred as of June 2016. This is the first report of methane-predominant bacterial overgrowth contracted from the FMT donor as a potential cause of post-FMT IBS-like symptoms such as bloating and constipation. Screening of FMT donors for excessive methane production may prevent such complications.Figure 1

Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder

Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is currently unknown. Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically-developing individuals, particularly stress-responsive cytokines including tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Acute and chronic stress is associated with the onset and exacerbation of GI symptoms in those without ASD. The present study examined whether GI symptoms in ASD were associated with increases in cortisol, a stress-associated endocrine marker, and TNF-α and IL-6 in response to stress. As hypothesized, a greater amount of lower GI tract symptoms were significantly associated with post-stress cortisol concentration. The relationship between cortisol response to stress and GI functioning was greater for children who had a history of regressive autism. Exploratory analyses revealed significant correlations between cortisol response, intelligence, and inappropriate speech. In contrast, symptoms of the lower GI tract were not associated with levels of TNF-α or IL-6. Significant correlations were found, however, between TNF-α and IL-6 and irritability, socialization, and intelligence. These findings suggest that individuals with ASD and symptoms of the lower GI tract may have an increased response to stress, but this effect is not associated with concomitant changes in TNF-α and IL-6. The relationship between cortisol stress response and lower GI tract symptoms in children with regressive autism, as well as the relationships between cortisol, IL-6, and intelligence in ASD, warrant further investigation.

Malabsorption, Orocecal Transit Time and Small Intestinal Bacterial Overgrowth in Type 2 Diabetic Patients: A Connection.

Type 2 diabetes mellitus consists of dysfunctions characterized by hyperglycemia and resulting from combination of resistance to insulin action and inadequate insulin secretion. Most of diabetic patients report significant gastrointestinal symptoms. Entire GI tract can be affected by diabetes from oral cavity to large bowel and anorectal region. Proteins, carbohydrates, fats, and most fluids are absorbed in small intestine. Malabsorption may occurs when proper absorption of nutrients does not take place due to bacterial overgrowth or altered gut motility. The present study was planned to measure various malabsorption parameters in type 2 diabetic patients. 175 patients and 175 age and sex matched healthy controls attending Endocrinology Clinic in PGI, Chandigarh were enrolled. Lactose intolerance was measured by using non-invasive lactose hydrogen breath test. Urinary d-xylose and fecal fat were estimated using standard methods. Orocecal transit time and small intestinal bacterial overgrowth were measured using non-invasive lactulose and glucose breath test respectively. Out of 175 diabetic patients enrolled, 87 were males while among 175 healthy subjects 88 were males. SIBO was observed in 14.8% type 2 diabetic patients and in 2.8% of controls. There was statistically significant increase (p<0.002) in OCTT in type 2 diabetic patients compared with controls. OCTT was observed to be more delayed (p<0.003) in patients who were found to have SIBO than in patients without SIBO. Lactose intolerance was observed in 60% diabetic patients and 39.4% in controls. Urinary d-xylose levels were also lower in case of diabetic patients but no significant difference was found in 72h fecal fat excretion among diabetic patients and controls. Urinary d-xylose and lactose intolerance in SIBO positive type 2 diabetic patients was more severe as compared to SIBO negative diabetic patients. From this study we can conclude that delayed OCTT may have led to SIBO which may have instigated the process of malabsorption among type 2 diabetic patients.

Histopathological features of gastrointestinal mucosal biopsies in children with juvenile idiopathic arthritis.

The association between inflammatory bowel disease and joint involvement is well established. There is a paucity of data describing histopathological features of the gut in relation to juvenile idiopathic arthritis (JIA). We retrospectively identified 33 (21 male) children aged 3-16 y with JIA (11 with oligoarthritis, 5 with polyarthritis, 8 with systemic onset arthritis, 8 with enthesitis-related arthritis (ERA), and 1 with psoriatic arthritis) with significant gastrointestinal (GI) symptoms who underwent upper and/or lower endoscopy. The histopathological findings were reviewed in addition to presence of autoantibodies and concomitant treatment. The most common GI indications for endoscopy were persistent abdominal pain (14/33 (42%)) and diarrhea (10/33 (30%)). Of the 33 children, 28 (85%) had gut mucosal inflammation, mostly affecting the colon (80%). Active inflammation of the gut was found in 5 of 28 (17%) children, and 15 of 28 (53%) children showed mild nonspecific inflammation. Eight patients (27%) had predominantly an eosinophilic infiltrate. Twenty-six patients had previously received treatment for JIA. There was a negative association with the use of immunomodulators and the presence of eosinophil inflammation. The majority of children with JIA and GI symptoms have histological evidence of mild nonspecific inflammation, but some having active colitis and prominent eosinophil infiltrate.

Histologic Features of Intestinal Thrombotic Microangiopathy in Pediatric and Young Adult Patients after Hematopoietic Stem Cell Transplantation

High-risk transplantation-associated thrombotic microangiopathy (TMA) can present with multisystem involvement and is associated with a poor outcome after hematopoietic stem cell transplantation (HSCT), with < 20% 1-year survival. TMA may involve the intestinal vasculature and can present with bleeding and ischemic colitis. There are no established pathologic criteria for the diagnosis of intestinal TMA (iTMA). The goal of our study was to identify histologic features of iTMA and describe associated clinical features. We evaluated endoscopic samples from 50 consecutive HSCT patients for 8 histopathologic signs of iTMA and compared findings in 3 clinical groups based on the presence or absence of systemic high-risk TMA (hrTMA) and the presence or absence of clinically staged intestinal graft-versus-host disease (iGVHD): TMA/iGVHD, no TMA/iGVHD, and no TMA/no iGVHD. Thirty percent of the study subjects had a clinical diagnosis of systemic hrTMA. On histology, loss of glands, intraluminal schistocytes, intraluminal fibrin, intraluminal microthrombi, endothelial cell separation, and total denudation of mucosa were significantly more common in the hrTMA group (P < .05). Intravascular thrombi were seen exclusively in patients with hrTMA. Mucosal hemorrhages and endothelial cell swelling were more common in hrTMA patients but this difference did not reach statistical significance. Patients with hrTMA were more likely to experience significant abdominal pain and gastrointestinal bleeding requiring multiple blood transfusions (P < .05). Our study shows that HSCT patients with systemic hrTMA can have significant bowel vascular injury that can be identified using defined histologic criteria. Recognition of these histologic signs in post-transplantation patients with significant gastrointestinal symptoms may guide clinical decisions.

Five cases of recurrent meningitis associated with chronic strongyloidiasis.

Although meningitis secondary to chronic strongyloidiasis is a rare complication, it is associated with a high mortality rate. Recurrent meningitis can occur if the underlying parasitic infection is left untreated. We report five cases of recurrent meningitis related to chronic strongyloidiasis that were associated with human T-lymphotropic virus type 1 (HTLV-1) infection. Common causative organisms are Escherichia coli, Streptococcus bovis, and Klebsiella pneumonia. One patient died during the second episode of meningitis. Three patients showed significant gastrointestinal and respiratory symptoms before developing headache and fever. In four cases, patients developed multiple recurrences even with the treatment of thiabendazol. Ivermectin seems to be a better agent compared with thiabendazol to achieve eradication of strongyloidiasis.

Consuming foods with added oligofructose improves stool frequency: a randomised trial in healthy young adults.

The impact of oligofructose (OF) intake on stool frequency has not been clearly substantiated, while significant gastrointestinal (GI) symptoms have been reported in some individuals. The aim of the present study was to determine the effects of OF on stool frequency and GI symptoms in healthy adults. In an 8-week, randomised, double-blind, parallel-arm study, ninety-eight participants were provided with 16g OF in yogurt and snack bars (twenty male and thirty female) or matching control foods (seventeen male and thirty-one female), to incorporate, by replacement, into their usual diets. Participants completed a daily online questionnaire recording stool frequency and rating four symptoms: bloating, flatulence, abdominal cramping and noise, each on a Likert scale from '0' for none (no symptoms) to '6' for very severe, with a maximum symptom intensity score of 24 (sum of severities from all four symptoms). Online 24h dietary recalls were completed during pre-baseline and weeks 4, 6 and 8 to determine fibre intake. When provided with OF foods, fibre intake increased to 24·3 (sem 0·5) g/d from pre-baseline (12·1 (sem 0·5) g/d; P<0·001). Stool frequency increased with OF from 1·3 (sem 0·2) to 1·8 (sem 0·2) stools per d in males and 1·0 (sem 0·1) to 1·4 (sem 0·1) stools per d in females during intervention weeks compared with pre-baseline (P<0·05),but did not change for control participants (males: 1·6 (sem 0·2) to 1·8 (sem 0·2); females: 1·3 (sem 0·1) to 1·4 (sem 0·1)). Flatulence was the most commonly reported symptom. Mean GI symptom intensity score was higher for the OF group (3·2 (sem 0·3)) v. control (1·7 (sem 0·1)) (P<0·01), with few participants reporting above moderate symptoms. No change in symptom intensity occurred over time. Consuming yogurt and snack bars with 16g OF improves regularity in young healthy adults. However, GI symptoms, resulting from an increase in oligofructose intake, may not diminish with time.

Gastrointestinal Complications in Patients with Chronic Kidney Disease—A 5-Year Retrospective Study from a Tertiary Referral Center

Background: Gastrointestinal complications are frequent in patients with renal disease and are responsible for substantial morbidity and mortality among these patients in developing countries. Many times, these patients are subjected to endoscopic evaluation and mucosal biopsies are taken for definitive diagnosis. This study explores the various upper and lower nonneoplastic gastrointestinal complications in patients with chronic kidney disease (CKD) and the role of endoscopic mucosal biopsies in the management of these patients. Methods: Sixty-three patients with CKD, who were referred to endoscopic evaluation and biopsy due to significant gastrointestinal symptoms between January 2007 and December 2011 form the study group. Patients were divided into two groups: group 1 and group 2. Group 1 consisted of patients with CKD stages 1–5 and group 2 consisted of renal allograft recipients. All biopsies were reviewed by an experienced pathologist. Clinical data were collected from patient’s medical records. Results: There were 38 patients in group 1 and 25 patients in group 2. Twenty-nine out of 38 patients in group 1 presented with upper gastrointestinal (GI) symptoms and underwent esophagogastroduodenoscopy (OGD) evaluation, which showed erosive gastritis as the most common biopsy finding followed by ulcerative esophagitis and duodenitis. These patients were also found to be susceptible to develop ischemic colitis due to hypotensive episodes during dialysis, which are likely to occur during the initial stages of dialysis. The most frequent symptom in group 2 was chronic diarrhea (13 out of 25 patients) for which a colonoscopic examination was done which revealed various infection and drug-related colitis, mycophenolate mofetil (MMF) being a major culprit. Conclusion: CKD patients with high urea level are prone to develop upper GI symptoms and mostly show erosive gastritis, ulcerative esophagitis, and duodenitis on biopsy. On the contrary, renal allograft recipients mostly develop opportunistic infections and drug-related toxicity in the colon. MMF-related GI toxicity is an underrecognized entity and further prospective studies are required for its better understanding.