Outcome associated with EPCAM founder mutation c.499dup in Qatar.

Tufting enteropathy (TE) is a rare autosomal recessive congenital enteropathy that usually requires long-term parenteral nutrition (PN). In the Arabic Peninsula, four distinct EPCAM mutations have been identified to cause TE. As consanguineous marriages are socially favored, pre-marital and pre-conception testing has become a critical disease prevention strategy. This study aimed to identify the pathogenic EPCAM mutations causing TE in Qatari families and determine possible genotype-phenotype correlations. Twenty-two TE patients from seven multiplex families with TE were identified. Blood samples were collected from patients and first-degree relatives. Exons of the gene were amplified and sequenced. Retrospective chart review and/or family interviews were conducted to determine phenotypic characteristics of the disease. Sequence analysis revealed a single, previously described c.499dup mutation in exon 5 of all families tested, suggesting a founder effect. Of the 18 patients whose full clinical information was available, three patients (17%) were off PN with a good quality of life, without intestinal transplantation, and one (6%) was receiving partial PN. Our patients with TE were severely stunted compared to a similar group of patients receiving long-term PN for short bowel syndrome, suggesting that this could possibly be due to TE rather than secondary to inadequate nutrition. Our study identified the EPCAM mutation c.499dup as the genetic defect causing TE in all the participant Qatari families. This finding should facilitate early diagnosis of TE and genetic counseling. Furthermore, it should aid in the prevention of TE through pre-marital screening, antenatal diagnosis, and pre-implantation genetic diagnosis.

Growth and Nutrition in Cystic Fibrosis.

Optimal nutrition support has been integral in the management of cystic fibrosis (CF) since the disease was initially described. Nutritional status has a clear relationship with disease outcomes, and malnutrition in CF is typically a result of chronic negative energy balance secondary to malabsorption. As the mechanisms underlying the pathology of CF and its implications on nutrient absorption and energy expenditure have been elucidated, nutrition support has become increasingly sophisticated. Comprehensive nutrition monitoring and treatment guidelines from professional and advocacy organizations have unified the approach to nutrition optimization around the world. Newborn screening allows for early nutrition intervention and improvement in short- and long-term growth and other clinical outcomes. The nutrition support goal in CF care includes achieving optimal nutritional status to support growth and pubertal development in children, maintenance of optimal nutritional status in adult life, and optimizing fat soluble vitamin and essential fatty acid status. The mainstay of this approach is a high calorie, high-fat diet, exceeding age, and sex energy intake recommendations for healthy individuals. For patients with exocrine pancreatic insufficiency, enzyme replacement therapy is required to improve fat and calorie absorption. Enzyme dosing varies by age and dietary fat intake. Multiple potential impediments to absorption, including decreased motility, altered gut luminal bile salt and microbiota composition, and enteric inflammation must be considered. Fat soluble vitamin supplementation is required in patients with pancreatic insufficiency. In this report, nutrition support across the age and disease spectrum is discussed, with a focus on the relationships among nutritional status, growth, and disease outcomes.

The influence of bariatric surgery on oral drug bioavailability in patients with obesity: A systematic review.

Anatomical changes in the gastrointestinal tract and subsequent weight loss may influence drug disposition and thus drug dosing following bariatric surgery. This review systematically examines the effects of bariatric surgery on drug pharmacokinetics, focusing especially on the mechanisms involved in restricting oral bioavailability. Studies with a longitudinal before-after design investigating the pharmacokinetics of at least one drug were reviewed. The need for dose adjustment following bariatric surgery was examined, as well as the potential for extrapolation to other drugs subjected to coinciding pharmacokinetic mechanisms. A total of 22 original articles and 32 different drugs were assessed. The majority of available data is based on Roux-en-Y gastric bypass (RYGBP) (18 of 22 studies), and hence, the overall interpretation is more or less limited to RYGBP. In the case of the majority of studied drugs, an increased absorption rate was observed early after RYGBP. The effect on systemic exposure allows for a low degree of extrapolation, including between drugs subjected to the same major metabolic and transporter pathways. On the basis of current understanding, predicting the pharmacokinetic change for a specific drug following RYGBP is challenging. Close monitoring of each individual drug is therefore recommended in the early postsurgical phase. Future studies should focus on the long-term effects of bariatric surgery on drug disposition, and they should also aim to disentangle the effects of the surgery itself and the subsequent weight loss.

Cumulative Inflammation Could Be a Risk Factor for Intestinal Failure in Crohn's Disease.

BACKGROUND: Intestinal failure is the most critical complication of Crohn's disease. Intestinal failure requires home parenteral nutrition, which worsens the quality of life of the patients and sometimes causes life-threatening complications. AIMS: The purpose of this study was to investigate the incidence and risk factors for intestinal failure in Crohn's disease. METHODS: We performed a retrospective analysis of Crohn's disease patients (162 cases) at Osaka University Hospital between January 2000 and December 2017. Kaplan-Meier analysis was used to investigate the cumulative incidence of intestinal failure. To identify the risk factors of intestinal failure, patient characteristics were analyzed by multivariate analysis, including disease classification, surgical history, medical treatment other than surgery, and cumulative inflammation was calculated using the average C-reactive protein value and disease duration. RESULTS: The cumulative incidence of intestinal failure 5, 10, and 15 years after Crohn's disease diagnosis was 2.6%, 3.4%, and 8.6%, respectively. Multivariate analysis identified the following as independent risk factors for intestinal failure in Crohn's disease: residual small intestinal length < 200 cm (odds ratio 7.51, 95% confidence interval 2.14-29.96), non-use of anti-tumor necrosis factor-alpha therapy (3.34, 1.22-10.74), and cumulative inflammation (1.01, 1.001-1.038). We created a new predictive nomogram consisting of these risk factors. CONCLUSIONS: Intestinal failure occasionally occurred during long-term treatment of Crohn's disease. Cumulative inflammation for the first time, in addition to short residual small intestinal length and non-use of anti-tumor necrosis factor-alpha therapy, was shown to be potential risk factors for intestinal failure in Crohn's disease.

Off-Label Teduglutide Therapy in Non-intestinal Failure Patients with Chronic Malabsorption.

BACKGROUND: Teduglutide, a glucagon-like peptide 2 analog, has demonstrated efficacy in treating adult patients with short bowel syndrome (SBS) and dependence on parenteral nutrition (PN), but its role in chronic malabsorptive states that do not necessitate PN remains uncertain. AIMS: To evaluate teduglutide use beyond its approved indications and to discuss the results of this adjunctive treatment in patients resistant to established therapy. RESULTS: This series reports four patients treated with teduglutide off-label. The first case had Crohn's disease (CD) with persistent colocutaneous fistulae that demonstrated complete closure after 8 months of teduglutide therapy. The second case involved a PN-dependent CD patient with persistent fistulae and intra-abdominal abscesses who weaned off PN and had a significant improvement in her nutritional status after 3 months of teduglutide therapy. The third case had CD complicated by severe malnutrition and previous PN-associated line infections, but by 9 months of teduglutide therapy, she gained 5 kg and no longer required re-initiation of PN. The fourth case had a high-output diverting ileostomy with resultant impaired healing of a stage IV decubitus ulcer, and after 2 months of therapy, the patient's pre-albumin increased by 250% and the ulcer had decreased by 40% in size. CONCLUSION: The use of teduglutide might be broadened to include patients with functional SBS not meeting strict criteria for intestinal failure. Further studies should evaluate the efficacy of teduglutide in patients who may require short-term small intestine rehabilitation or who have chronically impaired absorptive capacity not yet requiring PN.

Short article: Frequency, pathophysiology, and clinical classification of intestinal failure type II and III at a tertiary referral center.

OBJECTIVE: Intestinal failure (IF) is a complex disease that is gaining significance and attention throughout the world. In Mexico, there are no available data on this condition. The aim of this study was to determine the frequency and characteristics of patients with IF type II and III hospitalized at a tertiary referral center in our country. PATIENTS AND METHODS: A cross-sectional study was carried out from August 2016 to July 2017. Adult patients hospitalized in noncritical areas with a recent diagnosis of IF type II or III according to the European Society for Clinical Nutrition and Metabolism classification were included. Demographic, anthropometric, nutritional therapy, biochemical, and clinical characteristics were registered. Nutritional risk was determined by the Nutritional Risk Score 2002. RESULTS: During the study, 4144 patients were admitted to noncritical areas; 21 (5/1000) of these patients were included. The mean age of the patients was 51±18.8 years, and the mean BMI was 17.6±5.5 kg/m. Fifteen (71.5%) patients were diagnosed with IF type II and six (28.5%) with IF type III. The primary diagnosis was surgical complications in seven (33.3%) of the cases and the principal pathophysiological mechanism was short bowel syndrome in nine (42.8%) patients. The most frequent (37%) clinical classification was D2: more than 20 kcal/kg/day and 1001-2000 ml/day and parenteral nutrition and PN2: 1001-2000 ml/day (52.3%) based on the modified European Society for Clinical Nutrition and Metabolism clinical classification. CONCLUSION: In this study, a high frequency of IF was found; surgical complications and short bowel syndrome were the main mechanisms involved, and D2 was the most frequent clinical category.

Renal lithiasis and inflammatory bowel diseases, an update on pediatric population.

BACKGROUND AND AIM OF THE WORK: Historical studies have demonstrated that the prevalence of symptomatic nephrolithiasis is higher in patients with inflammatory bowel disease (IBD), compared to general population. The aim of the review was to analyze literature data in order to identify the main risk conditions described in literature and the proposed treatment. METHODS: A research on the databases PubMed, Medline, Embase and Google Scholar was performed by using the keywords "renal calculi/lithiasis/stones" and "inflammatory bowel diseases". A research on textbooks of reference for Pediatric Nephrology was also performed, with focus on secondary forms of nephrolithiasis. RESULTS: Historical studies have demonstrated that the prevalence of symptomatic nephrolithiasis is higher in patients with inflammatory bowel disease (IBD), compared to general population, typically in patients who underwent extensive small bowel resection or in those with persistent severe small bowel inflammation. In IBD, kidney stones may arise from chronic inflammation, changes in intestinal absorption due to inflammation, surgery or intestinal malabsorption. Kidney stones are more closely associated with Crohn's Disease (CD) than Ulcerative Colitis (UC) in adult patients for multiple reasons: mainly for malabsorption, but in UC intestinal resection may be an additional risk. Nephrolithiasis is often under-diagnosed and might be a rare but noticeable extra-intestinal presentation of pediatric IBD. Secondary enteric hyperoxaluria the main risk factor of UL in IBD, this has been mainly studied in CD, whether in UC has not been completely explained. In the long course of CD recurrent urolithiasis and calcium-oxalate deposition may cause severe chronic interstitial nephritis and, as a consequence, chronic kidney disease. ESRD and systemic oxalosis often develop early, especially in those patients with multiple bowel resections. Even if we consider that many additional factors are present in IBD as hypomagnesuria, acidosis, hypocitraturia, and others, the secondary hyperoxaluria seems to finally have a central role. Some medications as parenteral vitamin D, long-term and high dose steroid treatment, sulfasalazine are reported as additional risk factors. Hydration status may also play an important role in this process. Intestinal surgery is a widely described independent risk factor. Patients with ileostomy post bowel resection may have relative dehydration from liquid stool, which, added to the acidic pH from bicarbonate loss, is responsible for this process. In this acidic pH, the urinary citrate level excretion reduces. The stones most commonly seen in these patients contain uric acid or are mixed. In addition, the risk of calcium containing stones also increases with ileostomy. The treatment of UL in IBD involves correction of the basic gastrointestinal tract inflammation, restricted dietary oxalate intake, and, at times, increased calcium intake. Citrate therapy that increases both urine pH and urinary citrate could also provide an additional therapeutic benefit. Finally, patients with IBD in a pediatric study had less urologic intervention for their calculosis compared with pediatric patients without IBD.

Intestinal fructose malabsorption is associated with increased lactulose fermentation in the intestinal lumen / Má absorção intestinal de frutose associa-se com maior fermentação de lactulose na luz intestinal

Abstract Objective: To study fructose malabsorption in children and adolescents with abdominal pain associated with functional gastrointestinal disorders. As an additional objective, the association between intestinal fructose malabsorption and food intake, including the estimated fructose consumption, weight, height, and lactulose fermentability were also studied. Methods: The study included 31 patients with abdominal pain (11 with functional dyspepsia, 10 with irritable bowel syndrome, and 10 with functional abdominal pain). The hydrogen breath test was used to investigate fructose malabsorption and lactulose fermentation in the intestinal lumen. Food consumption was assessed by food registry. Weight and height were measured. Results: Fructose malabsorption was characterized in 21 (67.7%) patients (nine with irritable bowel syndrome, seven with functional abdominal pain, and five with functional dyspepsia). Intolerance after fructose administration was observed in six (28.6%) of the 21 patients with fructose malabsorption. Fructose malabsorption was associated with higher (p < 0.05) hydrogen production after lactulose ingestion, higher (p < 0.05) energy and carbohydrate consumption, and higher (p < 0.05) body mass index z-score value for age. Median estimates of daily fructose intake by patients with and without fructose malabsorption were, respectively, 16.1 and 10.5 g/day (p = 0.087). Conclusion: Fructose malabsorption is associated with increased lactulose fermentability in the intestinal lumen. Body mass index was higher in patients with fructose malabsorption.

Resumo Objetivo: Pesquisar a má absorção de frutose em crianças e adolescentes com dor abdominal associada com distúrbios funcionais gastrintestinais. Como objetivo adicional, estudou-se a relação entre a má absorção intestinal de frutose e a ingestão alimentar, inclusive a estimativa de consumo de frutose, o peso e a estatura dos pacientes e a capacidade de fermentação de lactulose. Métodos: Foram incluídos 31 pacientes com dor abdominal (11 com dispepsia funcional, 10 com síndrome do intestino irritável e 10 com dor abdominal funcional). O teste de hidrogênio no ar expirado foi usado para pesquisar a má absorção de frutose e a fermentação de lactulose na luz intestinal. O consumo alimentar foi avaliado por registro alimentar. Foram mensurados também o peso e a estatura dos pacientes. Resultados: Má absorção de frutose foi caracterizada em 21 (67,7%) pacientes (nove com síndrome do intestino irritável, sete com dor abdominal funcional e cinco com dispepsia funcional). Intolerância após administração de frutose foi observada em seis (28,6%) dos 21 pacientes com má absorção de frutose. Má absorção de frutose associou-se com maior produção de hidrogênio após ingestão de lactulose (p < 0,05), maior consumo de energia e carboidratos (p < 0,05) e maior valor de escore z de IMC para a idade (p < 0,05). As medianas da estimativa de ingestão diária de frutose pelos pacientes com e sem má absorção de frutose foram, respectivamente, 16,1 e 10,5 g/dia (p = 0,087). Conclusão: Má absorção de frutose associa-se com maior capacidade de fermentação de lactulose na luz intestinal. O índice de massa corporal foi maior nos pacientes com má absorção de frutose.

Ten years of follow-up of bilio-intestinal bypass: is malabsorption necessary for long-term metabolic results?

BACKGROUND: Bilio-intestinal bypass (BIBP) is an uncommon bariatric procedure. In 1999, a prospective trial was started at our institution to evaluate the effectiveness of BIBP. Trial was interrupted in 2006 due to high rate of complications. The aim of the present paper was to retrospectively review 10-year outcomes of BIBP. METHODS: Retrospective review of bariatric database was performed to find patients that had undergone BIBP from 1999 to 2006. Data collected were as follows: age, gender, body weight, body mass index (BMI), percentage of excess weight loss (%EWL), remission from weight-related diseases, complications, and deaths at 1,3, 5, 7, and 10 years. Quality of life was evaluated using "BAROS" questionnaire. RESULTS: From May 1999 to September 2006, 86 patients underwent BIBP. The mean age was 34.9 ± 22.4 years, and the initial weight and BMI were 141.2 ± 40.4 kg and 49.8 ± 15.5 kg/m2, respectively. After 10 years, the mean %EWL and BMI were 72.6 ± 18.7 and 31.2 ± 5.6 kg/m2. Almost all patients had diarrhea after surgery. Bloating syndrome occurred in 24% of patients, 48% had nephrolithiasis, and 20.9% had cholelithiasis. Remission from diabetes and hypertension was obtained in 75% and 80% of patients. Mortality was 3.2% and reoperation rate was 14.5%. CONCLUSIONS: Malabsorption plays a determinant role to obtain a long-lasting treatment for obese patients. However, BIBP is not recommendable due to high rate of complications and metabolic disorders.

Obeticholic acid for severe bile acid diarrhea with intestinal failure: A case report and review of the literature.

Bile acid diarrhea results from excessive amounts of bile acids entering the colon due to hepatic overexcretion of bile acids or bile acid malabsorption in the terminal ileum. The main therapies include bile acid sequestrants, such as colestyramine and colesevelam, which may be given in combination with the opioid receptor agonist loperamide. Some patients are refractory to conventional treatments. We report the use of the farnesoid X receptor agonist obeticholic acid in a patient with refractory bile acid diarrhea and subsequent intestinal failure. A 32-year-old woman with quiescent colonic Crohn's disease and a normal terminal ileum had been diagnosed with severe bile acid malabsorption and complained of watery diarrhea and fatigue. The diarrhea resulted in hypokalemia and sodium depletion that made her dependent on twice weekly intravenous fluid and electrolyte infusions. Conventional therapies with colestyramine, colesevelam, and loperamide had no effect. Second-line antisecretory therapies with pantoprazole, liraglutide, and octreotide also failed. Third-line treatment with obeticholic acid reduced the number of stools from an average of 13 to an average of 7 per 24 h and improved the patient's quality of life. The fluid and electrolyte balances normalized. The effect was sustained during follow-up for 6 mo with treatment at a daily dosage of 25 mg. The diarrhea worsened shortly after cessation of obeticholic acid. This case report supports the initial report that obeticholic acid may reduce bile acid production and improve symptoms in patients with bile acid diarrhea.

Use of an In-line Digestive Cartridge With Enteral Nutrition Improves the Weight Trajectory of 2 Children With Cystic Fibrosis Complicated by Another Medical Diagnosis.

This clinical observation describes the enteral nutrition (EN) management of 2 toddlers at high nutrition risk due to cystic fibrosis (CF), exocrine pancreatic insufficiency, and comorbid medical conditions. The first case report describes a boy with severe malabsorption after intestinal resection. The second case report reviews a boy with CF and neuroblastoma. When pancreatic enzyme replacement therapy with EN was not effective or appropriate, use of an in-line digestive cartridge was initiated. While using the digestive cartridge, both children showed improvements in their anthropometric measures. This observation reviews the nutrition management throughout their clinical course and describes the use of a digestive cartridge with EN.

Metabolic markers of protein maldigestion after a 15N test meal in minipigs with pancreatic exocrine insufficiency.

The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is little documented, partly due to methodological barriers. We aimed to validate biomarkers of protein malabsorption using a 15N test meal in a minipig model of PEI. Six pancreatic duct-ligated minipigs were used as a model of PEI and four nonoperated animals as a control. All animals were equipped with an ileocecal reentrant cannula. Minipigs were given a test meal containing [15N]casein. The PEI animals repeated the test three times, in the absence of any pancreatic enzymes, or after pancreatic substitution at two levels [ A or B: 7,500 or 75,000 (lipase) and 388 or 3881 (protease) FIP U]. Ileal chyme, urine, and blood were collected postprandially. Nitrogen and 15N were measured in digestive and metabolic pools. We obtained a gradient of ileal protein digestibility from 29 ± 11% in PEI to 89 ± 6% in the controls and a dose- dependent response of enzymes. Insulin and gastric inhibitory polypeptide secretions were decreased by PEI, an effect that was counteracted with the enzymes at level B. The total recovery of 15N in urinary urea and plasma proteins was 14 ± 5.1% in the control group and decreased to 5.5 ± 2.1% by PEI. It was dose dependently restored by the treatment. Both 15N recovery in plasma and urine were correlated to protein digestibility. We confirm that the 15N transfer in those pools is a sensitive marker of protein malabsorption. Nevertheless, an optimization of the test meal conditions would be necessary in the view of implementing a clinical test. NEW & NOTEWORTHY We designed an intervention study to create a gradient of ileal protein digestibility in minipigs with pancreatic exocrine insufficiency and to validate reliable metabolic markers using a 15N oral meal test. 15N recovery in plasma proteins and to a higher extent in urine was sensitive to protein malabsorption. This test is minimally invasive and could be used to reveal protein malabsorption in patients.

Incidence and predictive factors for positive 75SeHCAT test: improving the diagnosis of bile acid diarrhoea.

AIMS: To determine the value of 75SeHCAT retention in determining bile acid diarrhoea (BAD), treatment response and predictors of a positive result. METHODS: Retrospective casenote review of consecutive patients undergoing 75SeHCAT from 2008 to 2014, including gender, age, history, clinical, and laboratory parameters. This included diseases associated with Type 1 BAD (ileal resection, Crohn's disease) and Type 3 BAD. Chi-squared test and logistic regression determined factors predictive of BAD. Subjective response to treatment with bile acid sequestrants (BAS) was analysed with respect to the 75SeHCAT result. RESULTS: Of 387 patients, 154 (39.7%) were male and average age was 50 years. Ninety-five patients (24.5%) were investigated for Type 1 BAD, 86 (22.2%) for Type 3, and 206 patients (53.2%) for Type 2 or idiopathic BAD. There was a large increase in the number performed with time but no difference in percentage positive tests. One hundred and seventy-nine patients (46.2%) had BAD. Positive result was commonest in possible Type 1 and they had most severe BAD. Ninety-nine patients had severe BAD (<5% 75SeHCAT retention), 47 moderate BAD (5% to <10% retention), and 33 mild BAD (10% to <15% retention). Predictors of a positive 75SeHCAT were right hemicolectomy (OR 4.88), cholecystectomy (OR 2.44), and Crohn's (OR 1.86). A positive 75SeHCAT predicted a good or partial response to BAS of 66.7% (mild), 78.6% (moderate), or 75.9% (severe BAD). CONCLUSION: 75SeHCAT test use increased in 2008-2014, with high positive results throughout. Ileal resection, Crohn's, and cholecystectomy independently predict BAD. 75SeHCAT predicted response to BAS.

Impairment of Small Intestinal Function in Ulcerative Colitis: Role of Enteric Innervation.

Small intestinal dysfunction has been described in patients with ulcerative colitis and in experimental animal models of colitis. This is demonstrated by a decrease in fluid, electrolyte, amino acid, fat and carbohydrate absorption as well as by deranged intestinal motility. Histopathological changes in the small intestines in colitis have not been consistently demonstrated, but there is evidence of structural and biochemical alterations as shown by increased intestinal permeability and a decrease in the expression of multiple brush border membrane enzymes such as disaccharidases and aminopetidases, in both humans and experimental animals. The pathophysiology of this dysfunction has not been elucidated, but it is thought to include alterations in neural circuitry such as increased neuronal excitability, neuronal damage and changes of neuropeptidergic innervation and receptors as well as an increase in local production of pro-inflammatory cytokines and alterations in the production of some neurohumoral mediators. In the following, we provide an update on the advancement of clinical and scientific contributions to elucidate the underlying mechanisms of the alteration of the functions of apparently intact small intestinal segments, induced by ulcerative colitis.

Cystic Fibrosis and the Nervous System.

Cystic fibrosis (CF) is a life-shortening autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an anion channel that conducts bicarbonate and chloride across cell membranes. Although defective anion transport across epithelial cells is accepted as the basic defect in CF, many of the features observed in people with CF and organs affected by CF are modulated by the nervous system. This is of interest because CFTR expression has been reported in both the peripheral and central nervous systems, and it is well known that the transport of anions, such as chloride, greatly modulates neuronal excitability. Thus it is predicted that in CF, lack of CFTR in the nervous system affects neuronal function. Consistent with this prediction, several nervous system abnormalities and nervous system disorders have been described in people with CF and in animal models of CF. The goal of this special feature article is to highlight the expression and function of CFTR in the nervous system. Special emphasis is placed on nervous system abnormalities described in people with CF and in animal models of CF. Finally, features of CF that may be modulated by or attributed to faulty nervous system function are discussed.

[Fructose and fructose intolerance]. / A fruktóz és a fruktózintolerancia.

Although fructose was discovered in 1794, it was realised in recent decades only that its malabsorption can lead to intestinal symptoms while its excessive consumption induces metabolic disturbances. Fructose is a monosaccharide found naturally in most fruits and vegetables. Dietary intake of fructose has gradually increased in the past decades, especially because of the consumption of high fructose corn syrup. With its 16.4 kg/year consumption, Hungary ranks secondly after the United States. Fructose is absorbed in the small intestine by facilitated transport mediated by glucose transporter proteins-2 and -5, and arrives in the liver cells. Here it is transformed enzymatically into fructose-1-phosphate and then, fructose-1,5-diphosphate, which splits further into glyceraldehyde and dihydroxyacetone-phosphate, entering the process of glycolysis, triglyceride and uric acid production. The prevalence of fructose intolerance varies strongly, depending on the method used. The leading symptoms of fructose intolerance are similar, but less severe than those of lactose intolerance. Multiple secondary symptoms can also occur. A symptom-based diagnosis of fructose intolerance is possible, but the gold standard is the H2 breath test, though this is less accurate than in lactose testing. Measuring fructosaemia is costly, cumbersome and not widely used. Fructose intolerance increases intestinal motility and sensitivity, promotes biofilm formation and contributes to the development of gastrooesophageal reflux. Long-term use of fructose fosters the development of dental caries and non-alcoholic steatohepatitis. Its role in carcinogenesis is presently investigated. The cornerstone of dietary management for fructose intolerance is the individual reduction of fructose intake and the FODMAP diet, led by a trained dietetician. The newly introduced xylose-isomerase is efficient in reducing the symptoms of fructose intolerance. Orv. Hetil., 2016, 157(43), 1708-1716.

[Malabsorption is a leading clinical sign of small bowel disease]. / Narushenie vsasyvaniya - vedushchii klinicheskii priznak bolezni tonkoi kishki.

The paper presents a variety of clinical manifestations of malabsorption syndrome (MAS) in celiac disease, collagenous sprue, Whipple's disease, Crohn's disease, intestinal lymphangiectasia, amyloidosis, common variable immune deficiency, and treatment of short bowel syndrome. It shows the specific features of the pathophysiology, diagnosis, and treatment of MAS in small bowel diseases.

Nuclear transit study in children with chronic faecal soiling after Hirschsprung disease (HSCR) surgery has revealed a group with rapid proximal colonic treatment and possible adverse reactions to food.

BACKGROUND/PURPOSE: Long-term problems with faecal incontinence occur in up to 50 % of patients after pull-through for Hirschsprung disease (HSCR). The cause often remains unknown, leading to empirical treatments. Using nuclear transit study, we found some patients surprisingly had rapid proximal colonic transit, suspicious of occult diarrhoea. We aimed to assess whether these patients had unrecognized adverse reactions to food. METHODS: Patients (n = 10, all males, 9.6 year; 4.25-15.5 years) with persistent faecal incontinence following pull-through for HSCR referred to the senior author and after exclusion of anatomical defects, underwent nuclear transit studies. Most (8) subsequently underwent breath hydrogen tests for sugar malabsorption and were tested for adverse reactions to food. Exclusion diets for protein allergens, lactose or fructose were then trialed. RESULTS: Of the 10 patients with rapid intestinal transit proven on nuclear transit study, breath hydrogen tests for fructose and/or lactose malabsorption were done in 8, and were positive in 7/8 patients. Exclusion diets contributed to either resolution or improvement in faecal incontinence in 9/10 patients. CONCLUSIONS: Rapid transit in the proximal, ganglionated colon may be present in children with faecal incontinence following pull-through for HSCR, possibly secondary to adverse reactions to food. This study suggests that children with post-operative soiling may benefit from a transit study and hydrogen breath tests to diagnose adverse reactions to food caused by sugar malabsorption.

ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis.

BACKGROUND: Malnutrition is both a frequent feature and a comorbidity of cystic fibrosis (CF), with nutritional status strongly associated with pulmonary function and survival. Nutritional management is therefore standard of care in CF patients. ESPEN, ESPGHAN and ECFS recommended guidelines to cover nutritional management of patients with CF. METHODS: The guidelines were developed by an international multidisciplinary working group in accordance with officially accepted standards. The GRADE system was used for determining grades of evidence and strength of recommendation. Statements were discussed, submitted to Delphi rounds, reviewed by ESPGHAN and ECFS and accepted in an online survey among ESPEN members. RESULTS: The Working Group recommends that initiation of nutritional management should begin as early as possible after diagnosis, with subsequent regular follow up and patient/family education. Exclusive breast feeding is recommended but if not possible a regular formula is to be used. Energy intake should be adapted to achieve normal weight and height for age. When indicated, pancreatic enzyme and fat soluble vitamin treatment should be introduced early and monitored regularly. Pancreatic sufficient patients should have an annual assessment including fecal pancreatic elastase measurement. Sodium supplementation is recommended and a urinary sodium:creatinine ratio should be measured, corresponding to the fractional excretion of sodium. If iron deficiency is suspected, the underlying inflammation should be addressed. Glucose tolerance testing should be introduced at 10 years of age. Bone mineral density examination should be performed from age 8-10 years. Oral nutritional supplements followed by polymeric enteral tube feeding are recommended when growth or nutritional status is impaired. Zinc supplementation may be considered according to the clinical situation. Further studies are required before essential fatty acids, anti-osteoporotic agents, growth hormone, appetite stimulants and probiotics can be recommended. CONCLUSION: Nutritional care and support should be an integral part of management of CF. Obtaining a normal growth pattern in children and maintaining an adequate nutritional status in adults are major goals of multidisciplinary cystic fibrosis centers.