No abstract

In an analysis of a large cohort of subjects with IBD, we found a significant association between symptoms of depression or anxiety and clinical recurrence. Patients with IBD should therefore be screened for clinically relevant levels of depression and anxiety and referred to psychologists or psychiatrists for further evaluation and treatment.

We compared the intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with Crohn's disease and resections of the small bowel. Patients were subgrouped into those with small (less than 100 cm), intermediate (100-300 cm), and large (greater than 300 cm) resections. [3H]cholecalciferol or [3H]25-hydroxycholecalciferol were given orally and serial blood samples were taken for measurement of plasma radiolabeled vitamin. Absorption of both forms of the vitamin decreased with extent of resection but 25-hydroxycholecalciferol absorption was always greater than that of cholecalciferol. When compared with normal control subjects, 25-hydroxycholecalciferol absorption in these patients was better maintained than that of cholecalciferol. These data indicate that vitamin D malabsorption reflects the extent of distal small-bowel resection in Crohn's disease. Treatment with oral cholecalciferol is sufficient in those with small or moderate resections but oral 25-hydroxycholecalciferol supplementation may be preferred in those with a severe short-bowel syndrome.

Ingestion of protein is known to increase urinary calcium excretion. By studying the effect of intravenous amino acid infusion on calcium excretion, the variables of diets and intestinal absorption are avoided. Five patients on total parenteral nutrition with otherwise constant nutrient infusions containing 240 mg of calcium were randomized to two different levels of amino acid infusion. On 1 g/kg ideal body weight amino acid infusion, two patients excreted more than 240 mg of calcium in the urine, while on 2 g/kg ideal body weight amino acid infusion all five patients lost more calcium in urine than was infused. Mean urinary calcium excretion was increased from 287 to 455 mg/day. On the higher amino acid dose, mean glomerular filtration rate increased from 102 to 143 ml/min. There was no effect of amino acid dose on serum calcium, ionized calcium, parathyroid hormone, and 25 (OH) vitamin D. Calcium excretion corrected for the glomerular filtration rate was increased at the higher amino acid dose, indicating a decrease in renal calcium reabsorption. Daily urinary excretion of sulfate, ammonia, and titratable acidity were increased during the high amino acid infusion. Hypercalciuria induced by high levels of amino acid infusion during total parenteral nutrition may contribute to the development of metabolic bone disease.

No abstract

We compared the absorption of cholecalciferol and 25-hydroxycholecalciferol in normal subjects and in patients with mild and severe cholestatic liver disease. 3H-cholecalciferol and 3H-25-hydroxycholecalciferol were given orally and serial blood samples were drawn for measurement of the serum level of radiolabeled vitamin. Absorption of 25-hydroxycholecalciferol peaked earlier and was greater than absorption of cholecalciferol at all times in all three groups. Patients with mild cholestasis (normal bilirubin and fecal fat excretion) absorbed both forms of the vitamin normally. Those with severe cholestasis (jaundice and steatorrhea) had minimal absorption of cholecalciferol but relatively preserved absorption of 25-hydroxycholecalciferol. Absorption of cholecalciferol and 25-hydroxycholecalciferol was inversely related to fecal fat excretion. The superior absorption of 25-hydroxycholecalciferol may partly explain its greater efficacy in oral treatment of vitamin D deficiency in patients with severe cholestasis.

Metabolic bone disease is common in patients with cholestatic liver disease. The importance of vitamin D status and calcium malabsorption in the pathogenesis of bone disease in these patients remains undefined. We have measured intestinal calcium absorption in relation to vitamin D status in 14 patients with chronic cholestatic liver disease including 11 with primary biliary cirrhosis. Fractional calcium absorption was determined from radioactive counts in the right forearm after separate oral and intravenous doses of 47CaCl2 in the fasting state. Eight of 14 patients (57%) had a decreased calcium absorption compared to controls. A significant correlation was observed between serum 25-hydroxyvitamin D levels and fractional calcium absorption (r = 0.623, p less than 0.02). Treatment with oral 25-hydroxyvitamin D3 in three patients with low serum 25-hydroxyvitamin D levels resulted in correction of serum 25-hydroxyvitamin D levels and improvement in fractional calcium absorption. No correlation was found between serum 1,25-dihydroxyvitamin D levels and fractional calcium absorption (r = 0.221). Calcium malabsorption was common in this series of patients, and serum 25-hydroxyvitamin D levels were useful in predicting fractional calcium absorption. Treatment with oral 25-hydroxyvitamin D3 was accompanied by improved calcium absorption.

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exomesequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10 −10 ), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10 −10 ). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.