Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue.

The question about recommending pure, noncontaminated oats as part of the gluten-free diet of patients with celiac disease remains controversial. This might be due to gluten cross contamination and to the possible immunogenicity of some oat cultivars. In view of this controversy, a review of the scientific literature was conducted to highlight the latest findings published between 2008 and 2014 to examine the current knowledge on oats safety and celiac disease in Europe and North America. Results showed that regular oats consumed in Canada are largely contaminated. Overall, the consumption of pure oats has been generally considered to be safe for adults and children. However, it appears that some oat cultivars may trigger an immune response in sensitive individuals. Therefore, further long-term studies on the impact of consumption of oats identifying the cultivar(s) constitute an important step forward for drawing final recommendations. Furthermore, a closer and more accurate monitoring of the dietary intake of noncontaminated oats would be paramount to better determine what its actual contribution in the gluten-free diet of adults and children with celiac disease are in order to draw sound recommendations on the safety of pure oats as part of the gluten-free diet.

Short bowel syndrome in infants: the critical role of luminal nutrients in a management program.

Short bowel syndrome develops when the remnant mass of functioning enterocytes following massive resections cannot support growth or maintain fluid-electrolyte balance and requires parenteral nutrition. Resection itself stimulates the intestine's inherent ability to adapt morphologically and functionally. The capacity to change is very much related to the high turnover rate of enterocytes and is mediated by several signals; these signals are mediated in large part by enteral nutrition. Early initiation of enteral feeding, close clinical monitoring, and ongoing assessment of intestinal adaptation are key to the prevention of irreversible intestinal failure. The length of the functional small bowel remnant is the most important variable affecting outcome. The major objective of intestinal rehabilitation programs is to achieve early oral nutritional autonomy while maintaining normal growth and nutrition status and minimizing total parenteral nutrition related comorbidities such as chronic progressive liver disease. Remarkable progress has been made in terms of survivability and quality of life, especially in the context of coordinated multidisciplinary programs, but much work remains to be done.

Malnutrition in hospitalized children: prevalence, impact, and management.

PURPOSE: Malnutrition in hospitalized children has been reported since the late 1970s. The prevalence of acute and chronic malnutrition was examined in hospitalized patients in a general pediatric unit, and the impact and management of malnutrition were assessed. METHODS: The nutritional risk score (NRS) and nutritional status (NS) (weight, height, body mass index, and skinfold thickness) of children aged zero to 18 years were assessed upon hospital admission. Growth and energy intake were monitored every three days until discharge. RESULTS: A total of 173 children (median age three years, 88 girls) participated; 79.8% had a moderate to severe NRS and 13.3% were acutely and/or chronically malnourished. A high NRS was associated with a longer hospital stay in children older than three years (P<0.05), while a poor NS (weight for height percentile) was correlated with prolonged hospitalization in children aged three years or younger (P<0.05). Although weight did not change during hospitalization, a decrease in skinfolds was documented (n=43, P<0.05). Patients with a high NRS had lower energy intake than those not at risk. However, children with abnormal NS received 92.5% of recommended energy intake. CONCLUSIONS: This study suggests that all children admitted to hospital should have an evaluation of their NRS and NS, so that they can receive appropriate nutrition interventions provided by a multidisciplinary nutrition team.

Humoral immune mechanism of liver injury in giant cell hepatitis with autoimmune hemolytic anemia.

BACKGROUND AND AIMS: Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is presumed to be an autoimmune disease, but the mechanism of liver injury is unknown. We proposed that in CGH-AHA, the humoral limb of autoimmunity is the dominant force driving progressive liver injury. METHODS: We studied 6 cases of GCH-AHA and 6 cases of autoimmune hepatitis (AIH) with early childhood onset (3 type 1 and 3 type 2). Liver biopsies were graded for portal and periportal inflammation and for giant cells. Immunohistochemistry characterized cellular inflammation and complement involvement in injury by showing C5b-9 complex in hepatocytes. RESULTS: Clinical and biochemical features at presentation were generally similar; however, the absence of autoantibodies and the presence of Coombs positivity did distinguish GCH-AHA from early-onset AIH. Liver biopsy pathology in CGH-AHA showed giant cells and little inflammation, whereas AIH showed the opposite. C5b-9 staining showed high-grade complement-mediated pan-lobular hepatocyte injury in all of the cases with GCH-AHA, whereas little C5b-9 was seen in hepatocytes in cases with AIH. Inflammation in GCH-AHA comprised mainly lobular macrophages and neutrophils, whereas portal and periportal T-cell and B-cell inflammation characterized cases with AIH. Most cases with AIH responded to therapy with prednisone and azathioprine, whereas most cases with GCH-AHA responded only to rituximab. CONCLUSIONS: Widespread complement-mediated hepatocyte injury and typical C3a and C5a complement-driven liver inflammation along with Coombs-positive hemolytic anemia in GCH-AHA provide convincing evidence that systemic B-cell autoimmunity plays a central pathologic mechanism in the disease. Our findings support B-cell-directed immunotherapy as a first-line treatment of GCH-AHA.

Clinical problem-solving: Short bowel syndrome in an infant.

The present case report describes the clinical problems encountered over a five-month period in an infant born with jejunal atresia, extensive midgut volvulus and a microcolon. After an initial surgical resection, the patient had no remaining ileum and his ileocecal valve was also removed. The patient had 35 cm of jejunum, which was successfully lengthened to 60 cm using enteral nutrition and two bowel-lengthening procedures (serial transverse enteropathy procedures). Bouts of cholestatic liver disease, sepsis and small bowel bacterial overgrowth were vigorously treated. The patient was discharged at 5.5 months of age and is now 40 months of age. He is at the 50th percentile for both height and weight, and is developing normally. The outcome for infants with short bowel syndrome has improved significantly in the past few years due to intestinal rehabilitation programs, which integrate nutritional, surgical and pharmacological approaches tailored to individual needs.

Le présent rapport de cas décrit les problèmes cliniques observés pendant une période de cinq mois chez un nourrisson né avec une atrésie jéjunale, un volvulus étendu de l'intestin moyen et un microcôlon. Après une résection chirurgicale initiale, le patient n'avait plus d'iléon et de valve iléocæcale. Il lui restait 40 cm de jéjunum, lequel a pu être allongé à 60 cm grâce à une alimentation entérale et à deux interventions d'allongement intestinal (interventions entéropathiques transverses sérielles). Les épisodes de cholestase intrahépatique, de septicémie et de prolifération bactérienne dans l'intestin grêle ont fait l'objet d'un traitement énergique. Le patient a obtenu son congé à 5,5 mois et en a maintenant 40. Il se situe au 50e percentile sur le plan de la taille et du poids et se développe normalement. Les issues des nourrissons présentant un syndrome de l'intestin court se sont considérablement améliorées ces dernières années, grâce à des programmes de réadaptation intestinale qui intègrent des approches nutritionnelles, chirurgicales et pharmacologiques adaptées à leurs besoins.

Guidelines for the diagnosis and management of chylomicron retention disease based on a review of the literature and the experience of two centers.

Familial hypocholesterolemia, namely abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease (CRD), are rare genetic diseases that cause malnutrition, failure to thrive, growth failure and vitamin E deficiency, as well as other complications. Recently, the gene implicated in CRD was identified. The diagnosis is often delayed because symptoms are nonspecific. Treatment and follow-up remain poorly defined.The aim of this paper is to provide guidelines for the diagnosis, treatment and follow-up of children with CRD based on a literature overview and two pediatric centers 'experience.The diagnosis is based on a history of chronic diarrhea with fat malabsorption and abnormal lipid profile. Upper endoscopy and histology reveal fat-laden enterocytes whereas vitamin E deficiency is invariably present. Creatine kinase (CK) is usually elevated and hepatic steatosis is common. Genotyping identifies the Sar1b gene mutation.Treatment should be aimed at preventing potential complications. Vomiting, diarrhea and abdominal distension improve on a low-long chain fat diet. Failure to thrive is one of the most common initial clinical findings. Neurological and ophthalmologic complications in CRD are less severe than in other types of familial hypocholesterolemia. However, the vitamin E deficiency status plays a pivotal role in preventing neurological complications. Essential fatty acid (EFA) deficiency is especially severe early in life. Recently, increased CK levels and cardiomyopathy have been described in addition to muscular manifestations. Poor mineralization and delayed bone maturation do occur. A moderate degree of macrovesicular steatosis is common, but no cases of steatohepatitis cirrhosis. Besides a low-long chain fat diet made up uniquely of polyunsaturated fatty acids, treatment includes fat-soluble vitamin supplements and large amounts of vitamin E. Despite fat malabsorption and the absence of postprandial chylomicrons, the oral route can prevent neurological complications even though serum levels of vitamin E remain chronically low. Dietary counseling is needed not only to monitor fat intake and improve symptoms, but also to maintain sufficient caloric and EFA intake. Despite a better understanding of the pathogenesis of CRD, the diagnosis and management of the disease remain a challenge for clinicians. The clinical guidelines proposed will helpfully lead to an earlier diagnosis and the prevention of complications.

Chylomicron retention disease: a long term study of two cohorts.

Lipoprotein assembly is critical for the intestinal absorption of dietary lipids and of fat-soluble vitamins. Through their inhibition of chylomicron secretion, mutations of the Sar1B gene coding for Sar1 GTPase are associated with chylomicron retention disease (CRD). The aim of this study was to describe the phenotypic expression of CRD in two clinically and genetically well characterized cohorts, and to compare their long term evolution. The study in 7 children from France (X age 11.3+/-1.7 years) and 9 from Quebec, Canada (X age 12+/-2.5 years) involved data collection from medical records for growth evaluation, neurological and ophthalmological status as well as bone density over an average follow-up period of 4.9 years for the French cohort and of 10.6 years for the Canadian one. All CRD patients presented within the first few months of life with diarrhea and failure to thrive. Severe hypocholesterolemia coupled with normal triglycerides was associated with low LDL and HDL-cholesterol, as well as with low apolipoproteins A-I and B. Varying degrees of essential fatty acid and of vitamin E deficiency were observed. The earlier diagnosis in the Canadian cohort (1.3+/-0.04 years) than in the French one (6.3+/-1.3 years) was unrelated with the severity of presenting symptoms. The fact that the disease had more impact on growth and bone density in the latter group may be related to delayed diagnosis of the disease. Vitamin E deficiency led to functional neurological and ophthalmic changes in a small number of patients but only one developed areflexia. Finally, genotype-phenotype correlation is not obvious in our cohort with CRD; even if, the Canadian subjects with the allele 409G>A had a more severe degree (P<0.001) of hypocholesterolemia than the other patients, many clinical data are inconsistent with a hypothetical genotype-phenotype correlation. This study provides new insights on the phenotypic expression of CRD over time and emphasizes the need to screen the lipid profile of infants with chronic diarrhea and failure to thrive.

Anderson or chylomicron retention disease: molecular impact of five mutations in the SAR1B gene on the structure and the functionality of Sar1b protein.

Anderson disease (and/or chylomicron retention disease-CMRD) is a rare, autosomic recessive disorder characterized by chronic diarrhea, failure to thrive, and hypocholesterolemia in childhood. The specific molecular defect was identified in 2003 and consists of mutations in the SAR1B gene which encodes for intracellular Sar1b protein. To date, only 8 mutations in six families have been described. We report here 15 new cases of CMRD among 8 families from France and Canada. We identified three unique homozygous mutations of SAR1B gene in French families originated from Turkey, Algeria and Portugal: a stop codon in exon 6 (c.364G>T, p.Glu122X), a whole deletion of exon 2 (c. 1-4482_58+1406 del 5946 ins15bp) and a missense mutation in exon 7 (c.554G>T, p.Gly185Val). The 2 missense mutations found in the 5 French-Canadian families had already been described in the eight previously published mutations: c.409G>A (p.Asp137Asn) and c.537T>A (p.Ser179Arg). In an attempt to explain the functional impairment of mutated proteins, computational analysis and sequence alignment were performed. The nonsense mutation and the whole deletion of exon 2 produced truncated proteins, the missense mutations probably non-functional proteins. All the affected children presented with similar phenotype at onset; the absence of phenotype-genotype correlation was discussed. A determination of the specific mutation in Anderson disease or CMRD is required to ensure diagnosis and allow prompt therapeutic intervention in these children.

[Teasing out the various factors associated with the digestive and absorptive phases of intestinal transport]. / Avancées dans la dissection fonctionnelle du transport intestinal des lipides.

The small bowel has traditionally been considered a simple organ for the transport of food-stuffs. Although the function of nutrient delivery is vital, the digestive and absorptive phases of fat were poorly understood until the past two decades. Moreover, the small bowel was not thought to have any modulating transport properties nor a role in the genesis of chronic diseases such as atherosclerosis. Given its enormous capacity to transform nutrients and to synthesize atherogenic proteins and gastro-intestinal peptides, the intestinal epithelium plays a key role in a number of metabolic pathways. The aim of the brief review is to provide an update on recent advances in our understanding of the absorption of dietary lipids with emphasis on the role and contribution of key proteins to malabsorptive syndromes as well as hyperlipidemic syndromes and eventually to atherosclerosis.

Short-chain fatty acids: ready for prime time?

The concept of colonic health has become a major target for the development of functional foods such as probiotics, prebiotics, and synbiotics. These bioactive agents have a profound effect on the composition of the microflora, as well as on the physiology of the colon, and display distinct health benefits. Dietary carbohydrates escaping digestion/absorption in the small bowel and prebiotics undergo fermentation in the colon and give rise to short-chain fatty acids (SCFA). As the main anions of the colon and the major source of energy for colonocytes, SCFA are rapidly absorbed by nonionic diffusion mostly but also by active transport mediated by a sodium-coupled transporter, thereby fostering the absorption of sodium and water. SCFA in general and butyrate in particular enhance the growth of lactobacilli and bifidobacteria and play a central role on the physiology and metabolism of the colon. The effect of prebiotics on cell proliferation, differentiation, apoptosis, mucin production, immune function, mineral absorption, lipid metabolism, and gastrointestinal (GI) peptides has been well documented experimentally. These effects seem to be largely mediated by SCFA, but evidence from human studies remains inconsistent. The food industry is making a leap of faith in their efforts to commercialize prebiotics and exploit potential health benefits. The future lies with the design of studies to further explore basic mechanisms, and gene expression in particular, but emphasis should be placed on human intervention trials.

Abnormal intracellular lipid processing contributes to fat malabsorption in cystic fibrosis patients.

A common feature of cystic fibrosis (CF) is the functional derangement of the exocrine pancreas, which affects output of pancreatic lipase. This condition results in severe dietary malabsorption due to the poor hydrolysis of triacylglycerol (TG) in the lumen of the small intestine. Despite the benefits of pancreatic enzyme supplements, patients with CF present with persistent intestinal fat malabsorption. The aim of the present investigation was to determine whether defects in the intracellular phase of lipid transport occur in this pathophysiology in addition to the known disturbed digestive processes. Our hypothesis was tested by incubating intestinal biopsies from six CF and six healthy subjects with radiolabeled lipid and protein precursors. Lipid esterification and secretion were markedly decreased by 22-31% and 38-42%, respectively, in CF samples, as noted by the low incorporation of [(14)C]palmitic acid into TGs, phospholipids, and cholesteryl esters in patients' duodenal explants and culture media compared with controls (100%). Accordingly, the output of TG-rich lipoproteins was substantially reduced (P < 0.05), and a similar trend was observed for high-density lipoproteins. Because intestinal lipoprotein assembly/secretion shows an absolute requirement for apolipoprotein (apo) B-48, radioactive labeling experiments were performed; these experiments demonstrated a significantly (P < 0.05) diminished synthesis of apoB-48 (40%) and apoA-I (30%). Given the critical role of microsomal triglyceride transfer protein in the formation of apoB-containing lipoproteins, its activity was determined and not found to be altered in CF intestinal tissue. Together, these results suggest that CF malabsorption may also be caused by defects in mucosal mechanisms leading to abnormal lipoprotein delivery into the blood circulation.

New lipids in enteral feeding.

PURPOSE OF REVIEW: Lipid sources for enteral nutrition continue to be an exciting area of investigation. It is timely to review recent developments which have largely contributed to thrust enteral feeding into a new era. RECENT FINDINGS: Although much more research needs to be done, there is a better understanding of the competitive relationships between n-6/n-3 fatty acids in conditions of metabolic and immune stress as well as in autoimmune and degenerative diseases. Although structured lipids are more completely absorbed and cleared, other more important clinical benefits need to be documented before they can be considered cost-effective. Immune enhancing formulas are the subject of controversy and some have been shown to be more effective than others. Enteral formulations with short-chain fatty acids are promising but more experimental work on the normal, and the sick colon is needed. Finally, there are a few isolated studies suggesting that enteral feeding with liposomes and with lipolytic products may have advantages when the digestive phase needs to be circumvented. The era of nutrigenomics, in which the effect of specific lipids on genes and proteins is being explored, is with us. We can look forward to nutrigenetics when the effect of genetic variation on the interaction between diet and disease will guide our practice. SUMMARY: Clinicians already have access to lipid sources and formulations which allow them to individualize enteral feeding programs. More clinical and technological research needs to be carried out, however, before products can be tailored to produce optimal effects in specific conditions.

Surveillance for cystic fibrosis-associated hepatobiliary disease: early ultrasound changes and predisposing factors.

OBJECTIVE: To investigate routine ultrasonography (US) as an early marker and to identify risk factors for the development of cirrhosis and portal hypertension (PHT) in cystic fibrosis (CF). STUDY DESIGN: A cohort of 106 children with CF aged 5.9+/-2.3 years were followed for 10.4+/-0.2 years in a CF clinic. RESULTS: At enrollment, the US was normal, but biochemical and/or clinical disease was present in 10%. By the end of the study, 19 had developed US changes, eight with evidence of PHT. At the time of the initial US change, only 36.4% of those had, at the end of the study, either a heterogeneous or a nodular parenchyma, and only 50% of those with PHT had biochemical and/or clinical disease. Of the 30 patients treated with ursodeoxycholic acid for biochemical and/or clinical disease with (n=15) and without (n=15) associated US changes, PHT developed in six of the former and two of the latter. Univariate analysis and logistic regression showed that children with more severe disease in terms of forced expiratory volume in one second were at somewhat greater risk (P<.06) of PHT developing. CONCLUSION: US was an early marker of liver disease and more severe CF disease, a predictor of progressive liver disease. A controlled trial should be done to assess isolated US-detected disease as an indication for UDCA.

Training the gastroenterologist of the future: a different mix of knowledge, skills and attitudes is needed.

In the United States, the declining interest of residents in gastroenterology is thought to be the result of the specialty being too procedure driven and not intellectually challenging. It is clear that the growth of technology and excessive demands for procedures have forced the curtailing of clinic time, erosion of clinical skills, distraction from scholarly pursuits and a decrease in the intellectual content of our training programs. In order to attract the 'best and the brightest' and to better prepare gastroenterologists for the future, trainees will require more knowledge and experience in nutrition, genetics and the evaluative sciences. Furthermore, they need to realize that the main responsibility of clinicians is problem solving. This can be learned only through personal clinical experience and teaching by clinicians with good analytical and intuitive skills. Quality care requires the integration of the needs, means and preferences of patients with evidence-based medical practice. Finally, new physicians should be imbued with the concept that an empathic relationship with patients is crucial for the accurate collection of information and plays an important therapeutic role.

Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders.

Dietary fat is an important source of nutrition. Here we identify eight mutations in SARA2 that are associated with three severe disorders of fat malabsorption. The Sar1 family of proteins initiates the intracellular transport of proteins in COPII (coat protein)-coated vesicles. Our data suggest that chylomicrons, which vastly exceed the size of typical COPII vesicles, are selectively recruited by the COPII machinery for transport through the secretory pathways of the cell.

Effect of an organized lipid matrix on lipid absorption and clinical outcomes in patients with cystic fibrosis.

OBJECTIVES: To compare the absorption of a lysophosphatidylcholine, monoglyceride, and fatty acid matrix (organized lipid matrix, OLM) with that of a triacylglycerol (TG)-based fat meal in patients with cystic fibrosis (CF). STUDY DESIGN: Five adolescents with CF and 3 control patients were given fat meals supplemented with retinyl palmitate of either OLM or TG at a 2-week interval. In a clinical trial, 73 patients with CF were randomly assigned to nutritional supplements containing either OLM or TG for a 1-year double-blind trial followed by a 6-month observation period. RESULTS: The peak increases and areas under the curve for TG and retinyl palmitate after the fat meal were 10-fold higher after OLM than after the TG fat load and did not differ from values obtained in control patients. OLM led to better clinical outcomes in terms of energy intake from the diet, weight-for-age Z score, essential fatty acid status, vitamin E, and retinol binding protein. Height-for-age Z score and FEV(1) only reached statistical significance at the end of the 6-month observation period. CONCLUSIONS: These results suggest that OLM is a readily absorbable source of fat and energy in CF and is an effective nutritional supplement.