Gastrointestinal Comorbidities Research Articles

Acetylcholinesterase Inhibitors: Beneficial Effects on Comorbidities in Patients With Alzheimer's Disease.

Elderly patients with Alzheimer's disease (AD) and other dementias are at high risk of polypharmacy and excessive polypharmacy for common coexisting medical conditions. Polypharmacy increases the risk of drug-drug and drug-disease interactions in these patients who may not be able to communicate early symptoms of adverse drug events. Three acetylcholinesterase inhibitors (ACHEIs) have been approved for AD: donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). They are also used off-label for other causes of dementia such as Lewy body and vascular dementia. We here report evidence from the literature that ACHEI treatment, prescribed for cognitive impairment, can reduce the load of medications in patients with AD by also addressing cardiovascular, gastrointestinal, and other comorbidities. Using one drug to address multiple symptoms can reduce costs and improve medication compliance.

Self-stool banking as a source for fecal microbiota transplantation: A pilot study

Background: Fecal microbiota transplantation is a promising therapeutic alternative for refractory Clostridium difficile infection. Self-stool donation can overcome challenges with donor screening and eliminate risks of blood borne pathogen exposure. We assessed the feasibility of a fecal banking protocol. A secondary objective was to identify perceptions around fecal banking. Methods: Admitted medicine patients were screened over 15 months. Patients with gastrointestinal comorbidities or factors affecting intestinal microbiota were excluded. Participants completed a survey and could opt to bank a sample. Processing occurred during defined lab hours. Feasibility was assessed on process and resource indicators. Success was defined as 50% consent rate. Results: A total of 4,675 patients were screened; 60% were excluded, primarily because of antibiotic exposure (1,343, 48%). A total of 537 patients were surveyed, of whom 73% consented to fecal banking. The primary reason for declining was that fecal banking was considered ‘too gross’ (34%). Of 72 samples provided, 27 were successfully banked. Lack of a bowel movement was the primary reason for not banking (54%), and inadequate quantity was the top reason for rejecting a collected sample (63%). Average processing time was 58 minutes (range 22–640 min). The majority of participants reported a preference for using their own stool (82%), and 87.5% (n=64) were willing to bank again. Conclusion: A self-donor fecal banking protocol is feasible. Scalability of this process is addressed through dedicated resources for collecting and processing samples from larger cohorts. Formal evaluation of the efficacy and microbiome integrity of samples is required.

The coexistence of psychiatric and gastrointestinal problems in children with restrictive eating in a nationwide Swedish twin study

BackgroundRestrictive eating problems are rare in children but overrepresented in those with neurodevelopmental problems. Comorbidities decrease wellbeing in affected individuals but research in the area is relatively scarce. This study describes phenotypes, regarding psychiatric and gastrointestinal comorbidities, in children with restrictive eating problems.MethodsA parental telephone interview was conducted in 9- or 12-year old twins (n = 19,130) in the Child and Adolescent Twin Study in Sweden. Cases of restrictive eating problems and comorbid problems were established using the Autism, Tics-AD/HD and other Comorbidities inventory, parental reports of comorbidity as well as data from a national patient register. In restrictive eating problem cases, presence of psychiatric and gastrointestinal comorbidity was mapped individually in probands and their co-twin. Two-tailed Mann–Whitney U tests were used to test differences in the mean number of coexisting disorders between boys and girls. Odds ratios were used to compare prevalence figures between individuals with or without restrictive eating problems, and Fisher exact test was used to establish significance.ResultsPrevalence of restrictive eating problems was 0.6% (concordant in 15% monozygotic and 3% of dizygotic twins). The presence of restrictive eating problems drastically increased odds of all psychiatric problems, especially autism spectrum disorder in both sexes (odds ratio = 11.9 in boys, odds ratio = 10.1 in girls), obsessive-compulsive disorder in boys (odds ratio = 11.6) and oppositional defiant disorder in girls (odds ratio = 9.22). Comorbid gastrointestinal problems, such as lactose intolerance (odds ratio = 4.43) and constipation (odds ratio = 2.91), were the most frequent in girls. Boy co-twins to a proband with restrictive eating problems generally had more psychiatric problems than girl co-twins and more girl co-twins had neither somatic nor any psychiatric problems at all.ConclusionsIn children with restrictive eating problems odds of all coexisting psychiatric problems and gastrointestinal problems are significantly increased. The study shows the importance of considering comorbidities in clinical assessment of children with restrictive eating problems.

Distinct projection targets define subpopulations of mouse brainstem vagal neurons that express the autism-associated MET receptor tyrosine kinase.

Detailed anatomical tracing and mapping of the viscerotopic organization of the vagal motor nuclei has provided insight into autonomic function in health and disease. To further define specific cellular identities, we paired information based on visceral connectivity with a cell-type specific marker of a subpopulation of neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (nAmb) that express the autism-associated MET receptor tyrosine kinase. As gastrointestinal disturbances are common in children with autism spectrum disorder (ASD), we sought to define the relationship between MET-expressing (MET+) neurons in the DMV and nAmb, and the gastrointestinal tract. Using wholemount tissue staining and clearing, or retrograde tracing in a METEGFP transgenic mouse, we identify three novel subpopulations of EGFP+ vagal brainstem neurons: (a) EGFP+ neurons in the nAmb projecting to the esophagus or laryngeal muscles, (b) EGFP+ neurons in the medial DMV projecting to the stomach, and (b) EGFP+ neurons in the lateral DMV projecting to the cecum and/or proximal colon. Expression of the MET ligand, hepatocyte growth factor (HGF), by tissues innervated by vagal motor neurons during fetal development reveal potential sites of HGF-MET interaction. Furthermore, similar cellular expression patterns of MET in the brainstem of both the mouse and nonhuman primate suggests that MET expression at these sites is evolutionarily conserved. Together, the data suggest that MET+ neurons in the brainstem vagal motor nuclei are anatomically positioned to regulate distinct portions of the gastrointestinal tract, with implications for the pathophysiology of gastrointestinal comorbidities of ASD.

Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis.

The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastrointestinal tract communicates with the central nervous system through the gut-brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signaling mediators and the immune system. Together, these systems create a highly integrated molecular communication network that link systemic imbalances with the development of neurodegeneration including insulin regulation, fat metabolism, oxidative markers and immune signaling. Age is a common factor in the development of neurodegenerative disease and probiotics prevent many harmful effects of aging such as decreased neurotransmitter levels, chronic inflammation, oxidative stress and apoptosis-all factors that are proven aggravators of neurodegenerative disease. Indeed patients with Parkinson's and Alzheimer's diseases have a high rate of gastrointestinal comorbidities and it has be proposed by some the management of the gut microbiota may prevent or alleviate the symptoms of these chronic diseases.

Gastrointestinal complications induced by sevelamer crystals.

BackgroundSevelamer is a phosphate binder widely used in chronic kidney disease (CKD) patients. Sevelamer, as well as other resin-based binders, can crystallize leading to the formation of concretions. Sevelamer crystals (SC) have been associated with gastrointestinal (GI) mucosal injury. We describe three new cases of GI lesions associated with SC and review previously reported cases.MethodsWe describe three new cases of GI lesions associated with SC and review previously reported cases.ResultsWe found 16 previously reported cases of SC-induced GI lesions. The mean patient age was 61 years (interquartile range 51.5–71.75), 62.5% were females and 10 patients were diabetic. In 13 cases, SC was found inside the GI mucosa. Six patients had history of major abdominal surgery. GI bleeding was the most common clinical symptom (n = 7), with three patients presenting with acute abdomen requiring surgical intervention. Although, SC-induced lesions were observed in all GI segments, intestine was involved in 81% of the cases. Endoscopic examination revealed mainly erosions and ulcerations (n = 7) and pseudoinflammatory polyps (n = 5). No association between sevelamer doses and the severity of GI lesions was found. However, diabetics patients seemed to develop GI lesions with smaller doses of sevelamer as compared with non-diabetic patients, in spite of their fewer GI comorbidities.ConclusionsSC-induced GI lesions should be considered in CKD patients treated with sevelamer who present GI symptoms, especially lower GI bleeding, once other causes have been ruled out. Diabetics seem more prone to develop SC- associated GI lesions. Sevelamer therapy should be avoided if possible in patients with a history of major abdominal surgery or chronic constipation, because of the high risk of serious GI complications.

Tu1075 - Management of Constipation in Secondary Care. Is Everyone Singing from the Same HYMN Sheet?

Introduction Chronic constipation is a common problem within the general population and can have a negative impact on quality of life. Patients referred to secondary care with this symptom often undergo a colonoscopy, which is often normal. There are American Gastroenterological Association (AGA) and NICE guidelines on the investigation and management of constipation. We hypothesised that there is variability in how patients with constipation are assessed and managed, and that patients with chronic constipation are often discharged following a normal colonoscopy without a clear diagnosis or plan. Our aim was to observe current practice in the management of patients with symptoms of constipation and a normal colonoscopy. Method This was a single centre, retrospective study of patients with constipation who had a normal colonoscopy within a large London District General Hospital. Data was collected from patients with constipation and a normal colonoscopy using the ‘Unisoft GI reporting tool’ and electronic patient records. Data was collected on 50 patients and scrutinised for subgroup analysis to include demographic data, investigations performed, type of clinic, diagnosis in clinic and further management. Results Mean age 51. Female 74%. In terms of further investigations 28% had imaging, 32% had a thyroid function test, 20% had a calcium blood test, 16% had a colon transit study and 6% had anorectal manometry. 10% of patients had biofeedback therapy. 58% of patients were discharged or never followed up following a normal colonoscopy. Of those that were followed up, 38% had other diagnosis or gastrointestinal co-morbidities unrelated to the constipation. 70% of patients had no clear diagnosis documented in relation to their constipation. 44% of patients had no clear documented management plan for their constipation. 64% of patients were under the care of surgical specialties. Conclusion There is clear variability in how patients with chronic constipation are assessed and managed in secondary care. The majority of patients are discharged following a normal colonoscopy back to the GP without further investigations of potentially reversible causes of their symptoms (only a third had TFTs checked, only 20% had calcium assessment) and no clear diagnosis or long-term management plan. In this study only a small number of patients in secondary care have investigations to categorise the subgroup of constipation disorders (only 16% had colon transit study) into normal transit, slow transit and defecation disorder by way of colon transit study. We conclude that more awareness and implementation of guidelines such as those from AGA in assessment and management of constipation is required. We also conclude that the assessment and management of constipation in secondary care is substandard. Disclosure of Interest None Declared

Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab

Pertuzumab disrupts heterodimerization between human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), HER3, and HER4. Thus, pertuzumab could result in adverse events similar to those observed with EGFR antagonists, such as diarrhea. We report the incidence and severity of diarrhea observed with pertuzumab in the CLEOPATRA, NeoSphere, and TRYPHAENA studies. Patients (n = 1443) had metastatic [CLEOPATRA (n = 804)] or early-stage breast cancer [NeoSphere (n = 416) and TRYPHAENA (n = 223)]. The incidence and severity of diarrhea were analyzed by treatment received. The incidence of febrile neutropenia concurrent with diarrhea and the effect of pre-existing gastrointestinal comorbidities were also evaluated. Subgroup analyses were carried out using CLEOPATRA data. The incidence of all-grade diarrhea across studies was generally greater for pertuzumab-based treatment, ranging from 28% to 72% (grade 1, 21%-54%; grade 2, 8%-37%; grade 3, 0%-12%; grade 4, 0%). Incidence was highest during the first pertuzumab-containing cycle, decreasing with subsequent cycles. Dose delays or discontinuations due to diarrhea were infrequent, ranging from 0% to 8%. Among pertuzumab-treated patients with diarrhea, 47%-67% received pharmacological intervention, most commonly with loperamide. Overlap between diarrhea and febrile neutropenia was uncommon, ranging from 0% to 11%. No relationship was observed between pre-existing gastrointestinal comorbidities and diarrhea. In CLEOPATRA, patients ≥65 years treated with pertuzumab had a higher incidence of grade 3 diarrhea than patients <65 years (19% versus 8%). All-grade diarrhea occurred at greater frequency among pertuzumab-treated Asian versus white patients with metastatic breast cancer (74% versus 63%); the corresponding rates in the control arm were 53% and 45%, respectively. In both the metastatic and early-stage breast cancer settings, diarrhea was common but manageable for all pertuzumab-containing regimens. Diarrheal episodes were mainly low grade and occurred most often during the first treatment cycle. Diarrheal-related drug delays or discontinuations were uncommon. NCT00567190 (CLEOPATRA), NCT00545688 (NeoSphere), NCT00976989 (TRYPHAENA).

Analysis of Morbidity, Readmission, and Reoperation After Craniosynostosis Repair in Children.

The impact of specific patient comorbidities on outcomes in craniosynostosis surgical repair is not well defined. The aim of this retrospective review was to evaluate the short-term 30-day reoperation rate, unplanned readmission rate, and overall morbidity of craniosynostosis surgical repair using the 2012 through 2014 American College of Surgeons National Surgical Quality Improvement Program-Pediatrics (ACS NSQIP-Pediatric) database. Overall morbidity included pneumonia, wound occurrence, shock/sepsis, venous thromboembolism, cardiac complication, renal and urinary complications, or nerve injury. The authors identified patients undergoing craniosynostosis repair by CPT code resulting in 2,037 patients. A univariate and multivariate analysis was performed to identify risk factors for reoperation, readmission, and morbidity. The reoperation rate was 2.4%, the overall morbidity rate was 2.8%, and readmission rate was 3.4%.Regression analysis identified age, high American Society of Anesthesiologists (ASA) classification, and history of either neurologic or pulmonary disorders as associated with unplanned reoperations within 30 days. High ASA classification also demonstrated significant correlation with unplanned 30-day readmission, and a history of neurologic disorders was associated with overall morbidity. The most common reason for readmission was wound complications (n = 15) followed by respiratory complications (n = 7). Gender, gastrointestinal comorbidities, blood disorders, cardiac risk factors, and prior operation within 30 days did not show significant association with any outcome. Craniosynostosis surgical repair is safe and associated with low complication and readmission rates. Careful patient selection and preoperative optimization of these factors should be sought to reduce detrimental outcomes.

Suspicion of respiratory tract infection with multidrug-resistant Enterobacteriaceae: epidemiology and risk factors from a Paediatric Intensive Care Unit

BackgroundMultidrug-resistant (MDR) infections are a serious concern for children admitted to the Paediatric Intensive Care Unit (PICU). Tracheal colonization with MDR Enterobacteriaceae predisposes to respiratory infection, but underlying risk factors are poorly understood. This study aims to determine the incidence of children with suspected infection during mechanical ventilation and analyses risk factors for the finding of MDR Enterobacteriaceae in tracheal aspirates.MethodsA retrospective single-centre analysis of Enterobacteriaceae isolates from the lower respiratory tract of ventilated PICU patients from 2005 to 2014 was performed. Resistance status was determined and clinical records were reviewed for potential risk factors. A classification and regression tree (CRT) to predict risk factors for infection with MDR Enterobacteriaceae was employed. The model was validated by simple and multivariable logistic regression.ResultsOne hundred sixty-seven Enterobacteriaceae isolates in 123 children were identified. The most frequent isolates were Enterobacter spp., Klebsiella spp. and E.coli. Among these, 116 (69%) isolates were susceptible and 51 (31%) were MDR. In the CRT analysis, antibiotic exposure for ≥ 7 days and presence of gastrointestinal comorbidity were the most relevant predictors for an MDR isolate. Antibiotic exposure for ≥ 7 days was confirmed as a significant risk factor for infection with MDR Enterobacteriaceae by a multivariable logistic regression model.ConclusionsThis study shows that critically-ill children with tracheal Enterobacteriaceae infection are at risk of carrying MDR isolates. Prior use of antibiotics for ≥ 7 days significantly increased the risk of finding MDR organisms in ventilated PICU patients with suspected infection. Our results imply that early identification of patients at risk, rapid microbiological diagnostics and tailored antibiotic therapy are essential to improve management of critically ill children infected with Enterobacteriaceae.

Incidence and outcomes of hospitalized patients with gastrointestinal malignancies and Clostridium difficile infection: A nationwide analysis.

704 Background: Inpatients with gastrointestinal (GI) malignancies are at a high risk for Clostridium difficile infection (CDI) but the impact of CDI on outcomes in these patients needs elucidation. We analyzed the incidence of CDI and its impact on outcomes in GI cancer patients using the National Hospital Discharge Survey (NHDS) database from 2001 - 2010. Methods: NHDS collects clinical information on patients dismissed from non-Federal short-stay United States hospitals. Demographics, diagnoses (GI malignancies, CDI and comorbidities), length of stay (LOS), and dismissal information were abstracted using ICD-9 diagnosis and procedure codes. Weighted analyses were performed using SAS version 9.4. Results: Of an estimated 317.9 million unique hospitalizations; 4.6 million had a diagnosis of a GI malignancy (1.4%); median age 68 years, 46.1% female. CDI was more common in patients with GI malignancies compared to patients with no GI malignancy (1.05% vs 0.69%, aOR 1.16, 95% CI 1.15- 1.17, p &lt; 0.0001). There was a significant increase in CDI incidence in GI cancer patients over the 10-year study period (72.7 in 2001-2002 to 109.1 in 2009-2010, per 10,000 discharges, p &lt; 0001). In multivariable analysis, compared to GI cancer patients without CDI, GI cancer patients with CDI had a longer mean LOS (3.94 more days, 95% CI 3.31-4.56) and dismissal to a care facility (adjusted OR, 1.75; 95% CI, 1.71-1.79), but lower all-cause in-hospital mortality (adjusted OR, 0.76; 95% CI, 0.74-0.79), all p &lt; 0.0001 Conclusions: In this national database of hospitalized patients, an increasing incidence of CDI in patients with GI malignancies was noted over the study period. CDI prolonged hospitalization, and was associated with increased dismissal to a care-facility. Lower rates of in-hospital mortality may represent early diagnosis due to vigilance or a milder form of CDI. Despite increased attention over the last few decades, CDI remained a serious infection in GI cancer patients, and merits appropriate prevention, management and follow-up.

Functional Bowel Disorders Are Associated with a Central Immune Activation.

Background Subjects with depression and unexplained neurological symptoms have a high prevalence of gastrointestinal comorbidity probably related to the brain-gut communication. This study explored associations between functional gastrointestinal disorders (FGID) and inflammatory markers in subjects with these disorders. Methods The FGID, including irritable bowel syndrome (IBS), were classified according to the Rome III criteria, and degree of symptoms was assessed with IBS symptom severity score (IBS-SSS). A range of interleukins (IL), chemokines and growth factors, tryptophan, and kynurenine were analysed in serum and the cerebrospinal fluid (CSF), and short-chain fatty acids (SCFA) were analysed in the faeces. The results are reported as partial correlation (pc) and p values. Results Sixty-six subjects were included. IBS was associated with high levels of tryptophan (p = 0.048) and kynurenine (p = 0.019) and low level of IL-10 (p = 0.047) in the CSF. IBS-SSS was associated with high tumor necrosis factor and low IL-10 in the CSF; pc = 0.341 and p = 0.009 and pc = −0.299 and p = 0.023, respectively. Propionic minus butyric acid in faeces was negatively associated with IL-10 in the CSF (pc = −0.416, p = 0.005). Conclusions FGID were associated with a proinflammatory immune activation in the central nervous system and a disturbed tryptophan metabolism that could have been mediated by the faecal microbiota.

Community-acquired Pseudomonas aeruginosa bloodstream infection: a classification that should not falsely reassure the clinician.

Pseudomonas aeruginosa bloodstream infection (BSI) is predominantly acquired in the hospital setting. Community-onset infection is less common. Differences in epidemiology, clinical features, microbiological factors and BSI outcomes led to the separation of bacterial community-onset BSI into the categories of healthcare-associated infection (HCAI) and community-acquired infection (CAI). Community-acquired P. aeruginosa BSI epidemiology is not well defined in the literature. In addition, it is also not clear if the same factors separate CAI and HCAI BSI caused by P. aeruginosa alone. A retrospective multicentre cohort study was performed looking at P. aeruginosa BSI from January 2008 to January 2011. Strict definitions for HCAI and CAI were applied. Extensive epidemiological, clinical and outcome data were obtained. Thirty-four CAI episodes and 156 HCAI episodes were analysed. The CAI group could be characterised into seven distinct categories based on comorbidities and clinically suspected source of infection. A pre-morbidly healthy group could not be identified. On multivariate analysis, the presence of a rheumatological or a gastrointestinal comorbidity were significantly associated with CAI. There was no significant difference in length of stay or rates of mortality between HCAI or CAI. The clinician should not be falsely reassured regarding outcome by the diagnosis of a community-acquired P. aeruginosa BSI.

Adverse events associated with interactions with dietary and herbal supplements among inpatients.

Dietary and herbal supplements (DHS) are commonly used among inpatients and may cause interactions with drugs or other DHS. This study explored whether adverse events were actually associated with such interactions and examined specific characteristics among inpatient DHS users prone to such adverse events. This was a cross-sectional study of 947 patients hospitalized in 12 departments of a tertiary academic medical centre in Haifa, Israel. It evaluated the rate of DHS use among inpatients, the potential for interactions, and actual adverse events during hospitalization associated with DHS use. It also assessed whether DHS consumption was documented in patients' medical files. Statistical analysis was used to delineate DHS users at risk for adverse events associated with interactions with conventional drugs or other DHS. In 17 (3.7%) of the 458 DHS users, an adverse event may have been caused by DHS-drug-DHS interactions. According to the Drug Interaction Probability Scale, 14 interactions 'probably' caused the adverse events, and 11 'possibly' caused them. Interactions occurred more frequently in older patients (P=0.025, 95% CI: 2.26-19.7), patients born outside Israel (P=0.025, 95% CI: 0.03-0.42), those with ophthalmologic (P=0.032, 95% CI: 0.02-0.37) or gastrointestinal (P=0.008, 95% CI: 0.05-0.46) comorbidities, and those using higher numbers of DHS (P<0.0001, 95% CI: 0.52-2.48) or drugs (P=0.027, 95% CI: 0.23-3.77). Approximately one in 55 hospitalizations in this study may have been caused by adverse events associated with DHS-drug-DHS interactions. To minimize the actual occurrence of adverse events, medical staff education regarding DHS should be improved.

Gastrointestinal comorbidities which complicate the treatment of anorexia nervosa

ABSTRACTPatients with anorexia nervosa often voice a multitude of symptoms in regards to their gastrointestinal tract. These complaints can complicate the treatment of their eating disorder as they distract attention from the important goal of weight restoration. Moreover, the restricting of certain food groups also makes the task of weight restoration substantially more difficult, or may result in binging. Therefore a working knowledge of common gastrointestinal comorbidities, such as celiac disease, irritable bowel syndrome, inflammatory bowel disease, and gastroparesis, is useful when treating a patient who has anorexia nervosa.

Probiotic normalization of Candida albicans in schizophrenia: A randomized, placebo-controlled, longitudinal pilot study

The molecules and pathways of the gut-brain axis represent new targets for developing methods to diagnose and treat psychiatric disorders. Manipulation of the gut microbiome with probiotics may be a therapeutic strategy with the potential to relieve gastrointestinal (GI) comorbidities and improve psychiatric symptoms. Candida albicans and Saccharomyces cerevisiae, commensal yeast species, can be imbalanced in the unhealthy human microbiome, and these fungal exposures were previously found elevated in schizophrenia. In a longitudinal, double-blind, placebo-controlled, pilot investigation of 56 outpatients with schizophrenia, we examined the impact of probiotic treatment on yeast antibody levels, and the relationship between treatment and antibody levels on bowel discomfort and psychiatric symptoms. We found that probiotic treatment significantly reduced C. albicans antibodies over the 14-week study period in males, but not in females. Antibody levels of S. cerevisiae were not altered in either treatment group. The highest levels of bowel discomfort over time occurred in C. albicans-seropositive males receiving the placebo. We observed trends towards improvement in positive psychiatric symptoms in males treated with probiotics who were seronegative for C. albicans. Results from this pilot study hint at an association of C. albicans seropositivity with worse positive psychiatric symptoms, which was confirmed in a larger cohort of 384 males with schizophrenia. In conclusion, the administration of probiotics may help normalize C. albicans antibody levels and C. albicans-associated gut discomfort in many male individuals. Studies with larger sample sizes are warranted to address the role of probiotics in correcting C. albicans-associated psychiatric symptoms.

Doxycycline-Induced Esophageal Ulcers among Deployed U.S. Service Members: A Case Series

Introduction: Over the past 15 years, members of the U.S Armed Forces have experienced higher rates and duration of deployments to malaria endemic areas in Central Asia. Doxycycline remains the preferred form of chemoprophylaxis for troops deployed to this region. Although the propensity of doxycycline to cause esophageal injury is well known and preventable, it continues to account for one of the most substantial gastrointestinal co-morbidities of our ongoing presence overseas. Methods: This case series retrospectively examines 5 cases of doxycycline-induced esophageal ulcers that presented to a Role III Combat Hospital in Afghanistan during a 2 month span between February and April 2016. Data reviewed includes demographics, comorbidities, presenting symptoms, endoscopic characteristics, exacerbating factors, and outcomes. Results: Our study includes 5 patients between the ages of 25-44, one of which was female. There was no history of gastrointestinal or systemic disease. Odynophagia was the presenting symptom in four patients, and substernal chest pressure in one. Mean duration of symptoms prior to presentation was 6.8 days (range 2-12 days). Two of the five patients reported weight loss (5-7 lbs) due to odynophagia. On endoscopy, two patients had 1-2cm classic kissing ulcers. The remaining cases had severe ulceration with >80% circumferential distribution. All lesions were noted between 21-33 cm from the incisors. All patients endorsed taking doxycycline with < 6 oz. of fluid and three out of five reported taking doxycycline prior to bedtime. No standardized counseling was reported for medication administration or side effects. No other risk factors for esophageal ulceration were found in any case. All patients received supportive therapy and were returned to duty on atovaquone/proguanil as alternate prophylaxis. Discussion The use of doxycycline as anti-malarial prophylaxis and its associated risk of esophageal injury presents a unique challenge in the deployed setting. Thousands of healthy service members are taking this medication daily, with evidence of poor administration precautions and late presentations in the course of injury. This is complicated by lack of standardized counseling, suboptimal alternatives to doxycycline, and limited availability of diagnostic endoscopy. Given the anticipated need for our continued U.S. military presence in the region, these root causes must be addressed to reduce the disease burden on our troops and mission.Figure 1Figure 2Figure 3

Abstract # 1787 Unique immune profiles in children with autism who experience gastrointestinal co-morbidity

Children with an autism spectrum disorder (ASD) are 6–8 times more likely to have persistent gastrointestinal (GI) symptoms. In addition, intestinal and peripheral inflammation, altered microbiome profiles, and impaired intestinal permeability have also been observed in children with ASD who exhibit GI issues. To further assess immune dysfunction and relationship to behavior in children with ASD and GI co-morbidities, we analyzed samples from children placed into the following study groups based on responses from standardized GI questionnaires: children with ASD who experience GI symptoms (ASDGI), children with ASD without a history of GI symptoms (ASDNoGI), or typically developing (TD) children. Cytokine analysis of supernatants collected from stimulated peripheral blood mononuclear cells, revealed elevated innate immune responses from ASDNoGI including increased levels of IL-1alpha, IL-1beta and TNFalpha after stimulation with Toll-Like receptor (TLR)-4 ligands compared to TD. The ASDGI group produced increased levels of mucosa-relevant cytokines IL-5, IL-15 and IL-17 compared to ASDNoGI following TLR-4 stimulation. Interestingly, the production of regulatory cytokine, TGFbeta1, was decreased across all stimulatory conditions in ASDGI compared to either ASDNoGI or TD groups. Furthermore, ASDGI scored worse on the Aberrant Behaviors Checklist than ASDNoGI. Overall, data from this study found evidence of reduced regulatory cytokines and increased mucosa-related cytokines in ASDGI which suggest that children with ASD and GI symptoms have an imbalance between regulatory and inflammatory pathways.

Gastrointestinal comorbidities in patients with psoriatic arthritis.

Comorbidities associated with psoriatic arthritis (PsA) include cardiovascular diseases, diabetes mellitus, and obesity. This study evaluated the association between PsA and common gastrointestinal (GI) diseases. A retrospective study was performed in Israel's largest health care provider database between 2002 and 2013. 3161 PsA patients were matched for age and sex with 31610 randomly selected patients. We searched these patients' records for the presence of peptic ulcer disease (PUD), reflux esophagitis, Crohn's disease, ulcerative colitis, irritable bowel syndrome (IBS) and celiac disease. T-test was used to compare continuous variables and a Chi-square test was used for categorical variables. Multivariate logistic regression models were used to assess the association between PsA and GI comorbidities. PsA was associated with Crohn's disease (OR 2.4, 95%CI: 1.75-3.32, p<0.0001), ulcerative colitis (OR 2.1, 95%CI: 1.33-3.26, p=0.001), reflux esophagitis (OR 1.6, 95%CI: 1.44-1.78, p<0.0001), PUD (OR 1.5, 95%CI: 1.31-1.63, p<0.0001) and IBS (OR 1.4, 95%CI: 1.01-1.86, p=0.045). After controlling for known risk factors, the association remained significant between PsA and Crohn's disease (OR 2.2, 95%CI: 1.59-3.03, p<0.0001), ulcerative colitis (OR 1.9, 95%CI: 1.21-3.00, p=0.005), reflux esophagitis (OR 1.5, 95%CI: 1.31-1.63, p<0.0001), and PUD (OR 1.3, 95%CI: 1.12-1.47, p<0.0001). No significant association was found between PsA and celiac disease. In the current study PsA was associated with gastrointestinal morbidities including Crohn's disease, ulcerative colitis, PUD and IBS. Physicians treating patients with PsA should be aware of these associations.

Symptoms and patient factors associated with longer time to diagnosis for colorectal cancer: results from a prospective cohort study.

Background:The objective of this study is to investigate symptoms, clinical factors and socio-demographic factors associated with colorectal cancer (CRC) diagnosis and time to diagnosis.Methods:Prospective cohort study of participants referred for suspicion of CRC in two English regions. Data were collected using a patient questionnaire, primary care and hospital records. Descriptive and regression analyses examined associations between symptoms and patient factors with total diagnostic interval (TDI), patient interval (PI), health system interval (HSI) and stage.Results:A total of 2677 (22%) participants responded; after exclusions, 2507 remained. Participants were diagnosed with CRC (6.1%, 56% late stage), other cancers (2.0%) or no cancer (91.9%). Half the cohort had a solitary first symptom (1332, 53.1%); multiple first symptoms were common. In this referred population, rectal bleeding was the only initial symptom more frequent among cancer than non-cancer cases (34.2% vs 23.9%, P=0.004). There was no evidence of differences in TDI, PI or HSI for those with cancer vs non-cancer diagnoses (median TDI CRC 124 vs non-cancer 138 days, P=0.142). First symptoms associated with shorter TDIs were rectal bleeding, change in bowel habit, ‘feeling different' and fatigue/tiredness. Anxiety, depression and gastro-intestinal co-morbidities were associated with longer HSIs and TDIs. Symptom duration-dependent effects were found for rectal bleeding and change in bowel habit.Conclusions:Doctors and patients respond less promptly to some symptoms of CRC than others. Healthcare professionals should be vigilant to the possibility of CRC in patients with relevant symptoms and mental health or gastro-intestinal comorbidities.