Celiac Crisis in an Adult Patient: Case Report and Review of the Literature

We report a case of celiac crisis in a previously healthy 51-year-old female presenting with a month’s history of diarrhea, cachexia and an abnormal metabolic panel.The patient’s diarrhea resolved after initiation of a gluten free diet and she gained 4 kilograms during hospitalization. Celiac crisis is a very rare presentation of celiac disease in adults but nonetheless should be considered in patients with marked metabolic derangements in the setting of osmotic diarrhea.

Enteroendocrine Dysfunction in Two Saudi Sisters

Proprotein convertase (PC) deficiency is a rare autosomal recessive disorder caused by mutations in proprotein convertase subtilisin/kexin type 1 (PCSK1). It is characterized by severe malabsorptive early-onset diarrhea, obesity, and systemic endocrinopathies. Only few cases have been reported in the literature; we have add two female sisters with some difference in clinical progress. Herein, we describe two sisters with congenital osmotic diarrhea diagnosed with PC1/3 deficiency, causing malabsorptive diarrhea and enteroendocrine dysfunction, who presented with chronic enteropathy with hypernatremia but with different expressivity. PC1/3 deficiency presents with symptoms and signs that mimic glucose-galactose malabsorption. Because of the clinical paucity and heterogeneity of congenital enteropathies, whole-exome sequencing may be of great help towards early diagnosis and effective treatment.

Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis

WNT2B is a member of the Wnt family, a group of signal transduction proteins involved in embryologic development and stem cell renewal and maintenance. We recently reported homozygous nonsense variants in WNT2B in three individuals with severe, neonatal-onset diarrhea, and intestinal failure. Here we present a fourth case, from a separate family, with neonatal diarrhea associated with novel compound heterozygous WNT2B variants. One of the two variants was a frameshift variant (c.423del [p.Phe141fs]), while the other was a missense change (c.722 G > A [p.G241D]) that we predict through homology modeling to be deleterious, disrupting post-translational acylation. This patient presented as a neonate with severe diet-induced (osmotic) diarrhea and growth failure resulting in dependence on parenteral nutrition. Her gastrointestinal histology revealed abnormal cellular architecture particularly in the stomach and colon, including oxyntic atrophy, abnormal distribution of enteroendocrine cells, and a paucity of colonic crypt glands. In addition to her gastrointestinal findings, she had bilateral corneal clouding and atypical genital development later identified as a testicular 46,XX difference/disorder of sexual development. Upon review of the previously reported cases, two others also had anterior segment ocular anomalies though none had atypical genital development. This growing case series suggests that variants in WNT2B are associated with an oculo-intestinal (and possibly gonadal) syndrome, due to the protein’s putative involvement in multiple developmental and stem cell maintenance pathways.

Stool Reducing Sugars and Stool pH Are Poor Screening Tests for Intestinal Disaccharidase Deficiencies in Children

Background Tests for stool reducing sugars and stool pH are ordered for children with osmotic diarrhea to screen for carbohydrate malabsorption. Methods We compared the results of the two screening tests, stool reducing sugars and stool pH, with a more definitive result from an intestinal tissue disaccharidase activity assay ordered for pediatric patients (<18 years old). Overall, 159 patients had results for tissue disaccharidase and stool reducing sugars, but only 115 had additional results of stool pH. Forty-six of the 159 patients had mild, moderate, or severe disaccharidase deficiencies. The sensitivity and specificity of the screening tests were calculated for individual disaccharidase deficiencies. In addition, trends of abnormal tissue disaccharidase, stool reducing sugars, and stool pH results were examined in different age groups. Results The sensitivities for stool reducing sugars and stool pH were 9% to 28% and specificities were 74% to 81% for individual disaccharidase deficiencies. Infants (0 years of age) had the highest percentage of abnormal results across all three tests; however, the positive predicative values were 54% and 50% for stool reducing sugars and stool pH, respectively. Conclusions The screening tests, stool reducing sugars and stool pH, had low sensitivity compared with results of measured tissue disaccharidase activity in pediatric patients. Infants had the highest percentage of abnormal results for all three tests, but the screening tests still performed poorly in that age group. This study suggests that stool reducing sugars and stool pH should not be used as screening tests for carbohydrate malabsorption due to disaccharidase deficiencies in pediatric patients.

A99 IMPACT OF OSMOTIC PERTURBATIONS ON THE GUT MICROBIOTA AND HOST HEALTH

Background Osmotic diarrhea is a prevalent condition concurrent with diverse pathologies such as Crohn’s disease and is due to unabsorbed solutes in the gastrointestinal contents inhibiting normal water absorption. Osmotic laxatives such as polyethylene glycol (PEG) take advantage of this process to counteract constipation. However, short-term PEG treatment impacts the gut microbial community, and in humanized and conventional mice leads to disappearance of the abundant and prevalent bacterial family S24-7, while increasing the relative abundance of a related family, Bacteroidaceae. Excitingly, despite community re-equilibration over weeks, S24-7 is capable of superseding other bacterial members and reach its original levels when reintroduced into the environment. My central hypothesis is that the depletion of S24-7 during osmotic diarrhea is due to its deficiency of stress response pathways required to counteract increased osmolality. However, in the absence of this stress, S24-7 is capable of exploiting a unique interaction with the immune system to successfully recolonize. Aims To shed light on this, I will pursue the following two aims: Aim 1: Compare the growth, survival and expression profiles of S24-7 and B. thetaiotaomicron in a bi-colonized gnotobiotic mouse model before, during and after osmotic perturbation to identify candidate genes involved in response to osmotic perturbation. Aim 2: Identify changes in S24-7 gene expression during recolonization and evaluate the host immune response. Methods Gnotobiotic mice were first colonized with S24-7 and then B. thetaiotaomicron, treated with PEG for 6 days and monitored during recovery and recolonization for 20 days. Fecal pellets were used to quantify bacterial abundances via qPCR and bacterial gene expression analysis through metatranscriptomics. Mouse serum was used for ELISA immunoassays to compare adaptive immune responses through serum IgG as well as to quantify glycine betaine levels. Results During PEG treatment S24-7 became undetectable and recolonized to pre-treatment levels during recovery. Using genomic and metagenomic annotation we have identified that S24-7 isolates do not possess the glycine betaine transport system, which is present in B. thetaiotaomicron (Figure 1). B. thetaiotaomicron reduced host serum glycine betaine levels, unlike S24-7. In S24-7 mono-colonized mice, S24-7 specific serum IgG was not detectable. However, once mice were co-colonized with B. thetaiotaomicron, both S24-7 and B. thetaiotaomicron specific IgG is detected, identifying an interesting relationship between S24-7 and the adaptive immune system that may shed light on its unique recolonization. Conclusions By studying S24-7 sensitivity to osmotic stress and its robust colonization abilities we are shedding light on the mechanisms of microbiota response to perturbations that are commonly experienced by the human gut. Funding Agencies None

Etomidate and Propofol: Which Would be Safe from the Hemodynamic Viewpoint in Colonoscopy Exams?

Most patients who undergo colonoscopy are over 55 years old, with comorbidities and who use cardio-depressant drugs. In addition, exam preparation includes the use of osmotic diuretics, causing osmotic diarrhea leading many patients to some degree of dehydration. Considering all these factors and knowing that the drug selected for sedation also acts by depressing the cardiovascular system, this study proposes to evaluate the action of two hypnotic drugs (etomidate and propofol) routinely used for sedation..

Pathogenetic aspects of exicosis associated with acute intestinal infections in early age (review)

Острые кишечные инфекции остаются одной самых актуальных проблем педиатрии в связи с высоким уровнем заболеваемости, развитием тяжелых форм и летальности, особенно у детей первых пяти лет жизни. В большинстве случаев тяжесть заболевания обусловлена развитием эксикоза, в основе которого лежат потери электролитов и жидкости в следствии эметического и диарейного синдромов. Однако существуют различия в механизмах формирования дегидратации в зависимости от вида инфекционного агента. Так при дегидратации, вызванной вирусами, в основе лежит механизм нарушения абсорбции, причиной которого являются дистрофические изменения в энтероцитах и уменьшение количества клеток, способных адсорбировать жидкость из кишечника. Повышение осмотического давления в процессе нарушенной ферментации нерасщепленных дисахаридов приводит к перемещению воды в просвет кишечника и объясняет появление осмотической диареи и, как следствие, тяжелой дегидратации при отсутствии своевременной коррекции данного патологического состояния. При внедрении бактериальных кишечных патогенов, происходит воздействие различных энтеротоксинов на мембранные комплексы. В частности, стимулируется выработка медиаторов воспаления, повышается уровень внутриклеточного циклического аденозинмонофосфата или циклического гуанозинмонофосфата или происходит нарушение проницаемости слизистой оболочки кишечника под влиянием специфических белков инвазивных патогенов и в целом изменение активности нормального процесса обмена ионов. В статье так же рассмотрены альтернативные механизмы развития диареи при участии энтероэндокринно-нейронных рефлексов, а также описаны типы дегидратации с детализацией водно-электролитных нарушений и современные подходы к регидратационной терапии. Знание и понимание особенностей патогенеза, диагностики типа дегидратации необходимо практикующему врачу для выбора тактики патогенетической терапии острых кишечных инфекций у детей. Acute intestinal infections are one of the most urgent challenges in pediatrics due to a high morbidity, development of severe forms and mortality, especially in children under five years. In most cases, severity of the disease is due to development of exicosis induced by loss of electrolytes and fluids as a result of emetic and diarrheal syndromes. However, the mechanisms of dehydration differ depending on the type of infectious agent. Thus, dehydration caused by viruses is due to the mechanism of absorption disorders induced by dystrophic changes in enterocytes and reduced number of cells that could absorb fluid from the intestine. The increase in osmotic pressure under disturbed fermentation of unsplit disaccharides results in translocation of water into the intestinal lumen, which explains the development of osmotic diarrhea and ensuing severe dehydration in the absence of timely correction of this pathological condition. After invasion of bacterial intestinal pathogens, various enterotoxins impact membrane complexes. Specifically, production of inflammatory mediators is stimulated, levels of intracellular cyclic adenosine monophosphate or cyclic guanosine monophosphate increase, or specific proteins of invading pathogens affect the permeability of intestinal mucosa and, eventually, change the activity of normal ion exchange process. The article also addresses alternative mechanisms of diarrhea involving enteroendocrine-neural reflexes and focuses on types of dehydration with a detailed description of water-electrolyte disorders and modern approaches to rehydration therapy. Knowledge and understanding of the pathogenetic and diagnostic features specific for a dehydration type are necessary for practitioners to choose the tactics for pathogenetic therapy of children’s acute intestinal infections. The aim of this review was to summarize modern aspects of the pathogenesis of exicosis syndrome in acute intestinal infections in young children.

Biological Activities of Lactose-Derived Prebiotics and Symbiotic with Probiotics on Gastrointestinal System

Lactose-derived prebiotics provide wide ranges of gastrointestinal comforts. In this review article, the probable biochemical mechanisms through which lactose-derived prebiotics offer positive gastrointestinal health are reported along with the up-to-date results of clinical investigations; this might be the first review article of its kind, to the best of our knowledge. Lactose-derived prebiotics have unique biological and functional values, and they are confirmed as ‘safe’ by the Food and Drug Administration federal agency. Medical practitioners frequently recommend them as therapeutics as a pure form or combined with dairy-based products (yoghurt, milk and infant formulas) or fruit juices. The biological activities of lactose-derived prebiotics are expressed in the presence of gut microflora, mainly probiotics (Lactobacillus spp. in the small intestine and Bifidobacterium spp. in the large intestine). Clinical investigations reveal that galacto-oligosaccharide reduces the risks of several types of diarrhea (traveler’s diarrhea, osmotic diarrhea and Clostridium difficile associated relapsing diarrhea). Lactulose and lactosucrose prevent inflammatory bowel diseases (Crohn’s disease and ulcerative colitis). Lactulose and lactitol reduce the risk of hepatic encephalopathy. Furthermore, lactulose, galacto-oligosaccharide and lactitol prevent constipation in individuals of all ages. It is expected that the present review article will receive great attention from medical practitioners and food technologists.

The interesting case of a woman who gets eating satisfaction through a gastrostomy tube

Aim of this study is to show how people are getting accustomed to alternative ways of eating in cases of illness and eating disability. Case report presentation: A 60-year-old woman was admitted in the Intensive Care Unit due to an acute upper airway obstruction. The woman was tracheostomized before entering the ICU and presented a large goiter and thus she was operated two days later and a thyroidectomy was executed. Post-operatively, it was diagnosed that a tracheo-esophageal fistula was present and the patient was obliged to live with a gastrostomy for months. During the first attempts for eating via a nasogastric tube at first and later via a gastrostomy, she had various problems with enteric nutrition, most prominent of which was osmotic diarrhea. The patient asked soon to stop eating enteral nutrition and preferred to eat food of her choice according to her appetite. She insisted that she was able to receive eating satisfaction, even by eating through a gastrostomy, because her bowels gave to her a positive feedback with the form of abdominal comfort after lunches. She said that the only food that would not harm her was real food and she chose food on her own with the help of her sister. This woman never presented any kind of psychiatric disorder in the past, neither she lost her courage inside hospital, although she was forced to live with a tracheostomy and a gastrostomy for more than 6 months.Disclosure of interestThe authors have not supplied their declaration of competing interest.