No-biopsy strategy for coeliac disease is applicable in adult patients: a 'real-world' Scottish experience.

Objective: Emergency interim guidance from the British Society for Gastroenterology (BSG) states that a no-biopsy strategy is possible to diagnose coeliac disease (CD) in adults with elevated transglutaminase IgA antibody (TGA-IgA) levels. We aimed to determine if the suggested TGA-IgA ≥10× ULN is safe and robust in making the diagnosis in adult patients in Scotland. We also aimed to establish if any important co-diagnoses would be missed if no biopsy was performed. Method: All positive coeliac serology results for patients aged >15 years in Scotland in 2016 (Grampian 2019) were accessed. Data were collected on demographics, TGA-IgA titres, D1 sampling, histology and macroscopic findings at upper and lower gastrointestinal (GI) endoscopy. Results: 1037/1429 patients with positive serology proceeded to biopsy, of which 796/1037 (76.8%) were diagnosed as CD. A total of 320/322 (99.37%) patients with TGA-IgA ≥10× ULN were diagnosed as CD giving the cut-off a positive predictive value of 99.38%. No significant co-pathology was found at endoscopy in these patients. Conclusion: Our results show that a no-biopsy strategy using a cut-off of TGA-IgA ≥10× ULN is safe to diagnose CD and that no important pathology would be missed. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition 2020 and BSG COVID-19 interim guidelines are applicable to adult patients in Scotland.

Enteroinsular axis response to carbohydrates and fasting in healthy newborn foals.

BACKGROUND: The enteroinsular axis (EIA) comprises intestinal factors (incretins) that stimulate insulin release after PO ingestion of nutrients. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the main incretins. The EIA has not been investigated in healthy neonatal foals but should be important because energy demands are high in healthy foals and dysregulation is frequent in sick foals. OBJECTIVES AND HYPOTHESIS: To evaluate the EIA response to carbohydrates or fasting in newborn foals. We hypothesized that incretin secretion would be higher after PO versus IV carbohydrate administration or fasting. ANIMALS: Thirty-six healthy Standardbred foals ≤4 days of age. METHODS: Prospective study. Blood was collected before and after a PO glucose test (OGT; 300, 500, 1000 mg/kg), an IV glucose test (IVGT; 300, 500, 1000 mg/kg), a PO lactose test (OLT; 1000 mg/kg), and fasting. Foals were muzzled for 240 minutes. Blood was collected over 210 minutes glucose, insulin, GIP, and GLP-1 concentrations were measured. RESULTS: Only PO lactose caused a significant increase in blood glucose concentration (P < .05). All IV glucose doses induced hyperglycemia and hyperinsulinemia. Concentrations of GIP and GLP-1 decreased until foals nursed (P < .05), at which time rapid increases in glucose, insulin, GIP, and GLP-1 concentrations occurred (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Healthy newborn foals have a functional EIA that is more responsive to milk and lactose than glucose. Non-carbohydrate factors in mare's milk may be important for EIA activity. Constant exposure of intestinal cells to nutrients to maintain EIA activity could be relevant to management of sick foals. Foals can be fasted for 4 hours without experiencing hypoglycemia.

Double outlet right ventricle with subpulmonary ventricular septal defect (Taussig-Bing anomaly) and other complex congenital cardiac malformations in an American Quarter Horse foal.

A 4-week-old American Quarter Horse colt presented with a recent history of diarrhea and decreased activity level. On initial physical examination, the animal was bright and alert and major findings were limited to a loud systolic heart murmur radiating widely over both sides of the thorax. While in the hospital, the clinical condition of the foal warranted further imaging to determine the cause and extent of cardiac disease. A variety of congenital cardiac malformations were identified during echocardiographic examination and autopsy, including a double outlet right ventricle and a subpulmonary interventricular septal defect (Taussig-Bing anomaly), ventricular inversion with atrioventricular discordance, tricuspid valve atresia, a septum primum interatrial septal defect, mitral valve dysplasia with a cleft in the septal mitral valve cusp, aortic, and subaortic stenosis, tubular hypoplasia of the ascending aorta and the aortic arch, a patent ductus arteriosus, an aberrant circumflex coronary artery, and aberrant left and right subclavian arteries. Echocardiographic and postmortem findings of the cardiac defects in this foal are presented and discussed.

Cis elements of the villin gene control expression in restricted domains of the vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine.

Villin, an actin bundling protein found in the apical brush border of absorptive tissues, is one of the first structural genes to be transcriptionally activated in the embryonic intestinal endoderm. In the adult, villin is broadly expressed in every cell of the intestinal epithelium on both the vertical axis (crypt to villus tip) and the horizontal axis (duodenum through colon) of the intestine. Here, we document that a 12.4-kilobase region of the mouse villin gene drives high level expression of two different reporter genes (LacZ and Cre recombinase) within the entire intestinal epithelium of transgenic mice. Deletion of a portion of this transgene results in reduction of beta-galactosidase activity in restricted domains of the small intestine (duodenum) and large intestine (cecum). In addition, expression is reduced in the crypt compartment throughout the intestine. Thus, the global expression pattern of villin in the intestine is apparently the consequence of an amalgam of distinct and individual domain-specific control processes. That is, expression of villin in the duodenum and cecum requires different regulatory sequences than the rest of the intestine, and the expression of villin in crypts is regulated by different circuitry than expression of villin on villus tips.

Villin: A marker for development of the epithelial pyloric border.

In the adult gastrointestinal tract, the morphologic borders between esophagus and stomach and between stomach and small intestine are literally one cell thick. The patterning mechanisms that underlie the development of these sharp regional divisions from a once continuous endodermal tube are still obscure. In the embryonic endoderm of the developing gut, region-specific expression of certain genes (e.g., intestine-specific expression of the actin bundling protein villin) can be detected as early as 9.0 days post coitum, although the morphologic differentiation of the gut epithelium proper does not begin until 4 to 5 days later. By using a mouse model in which a beta-galactosidase marker has been inserted into the endogenous villin locus, we examined the development of the stomach/intestinal (pyloric) border during gut organogenesis. The data indicate that the border is not sharp from the outset. Rather, the initial border region is characterized by a decreasing gradient of villin/beta-galactosidase expression that extends into the distal stomach. A sharp epithelial border of villin/beta-galactosidase expression appears abruptly at day 16 and is further refined over the next 3 weeks to form the distinct one-cell-thick border characteristic of the adult. These results indicate that an important previously unrecognized patterning event occurs in the gut epithelium at 16 days; this event may define an epithelial compartment boundary between the stomach and the intestine. The villin/beta-galactosidase mouse model characterized here provides an excellent substrate with which to further dissect the mechanisms involved in this patterning process.