Objective To determine if bone mineral content (BMC) and density (BMD) of infants and children with parenteral nutrition (PN)-dependent intestinal failure (IF) is lower than healthy controls, and investigate potential causes of lower BMC and BMD. Methods We performed a cross-sectional study comparing infants and children with PN-dependent IF with duos of age, sex, and race matched controls. Lumbar spine BMC and BMD were measured by dual energy x-ray absorptiometry, and serum cytokines, aluminum, IGF-1, insulin-like growth factor-binding protein (IGF-BP)-3, parathyroid hormone, 25(OH) vitamin D, and 1,25(OH)2 vitamin D were measured. Generalized estimating equation models accounting for matching were used for comparisons. Results BMC was 15% and BMD was 12% lower in IF participants than controls (p≤0.004). Group differences were attenuated to 3% and 7% and were not statistically significant (p=0.40 and p=0.07) when adjusted for length and weight; length- and weight-for-age were lower in IF than control participants (12.5% vs. 63%; 29.5% vs. 54%, p≤0.03). IF participants had higher serum aluminum (23 vs. 7 mcg/L, p<0.0001), IGF-1 (97 vs. 64 ng/mL, p=0.04), and 25(OH) vitamin D concentrations (40 vs. 30 ng/mL, p=0.0005), and lower IGF-BP3 (1418 vs. 1812 ng/mL, p<0.0001) and parathyroid hormone concentrations (51 vs. 98 pg/mL, p=0.0002) than controls. There was no difference in serum cytokine concentrations (p≥0.09). Conclusions Growth retardation is a significant problem for PN-dependent IF patients. Additional investigation is needed to elucidate the cause and its impact on bone mass and density, especially the role of IGF-1 resistance and aluminum toxicity.

Vanishing bile duct syndrome (VBDS) is a rare disorder characterized by loss of interlobular bile ducts and progressive worsening cholestasis. The acute presentation of this disease is typically associated with a drug hypersensitivity and Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN). The mainstay of treatment has been ursodeoxycholic acid with mixed results from immunosuppressive regimens. Anti–tumor necrosis factor-α and plasmapheresis have been speculated to be of potential benefit. It is hoped that early identification and intervention in VBDS secondary to Stevens-Johnson syndrome/TEN with continued reporting will lead to better regimens and outcomes. Our case report details the first reported use of infliximab and plasmapheresis, in addition to steroids, in a patient with VBDS secondary to TEN, as well as a literature review that supports a mechanism for why these modalities could be effective treatments. Unfortunately, our patient died, and the use of these therapies had an unclear benefit on his liver and skin disease. We hope that additional work can be published to confirm or refute their utility in the treatment of these diseases.

Previous studies have shown that the bisphosphonates (BP) vary in their damaging effect on the gastric mucosa, and endoscopy scores (erosions or erosions plus ulcers) after 1 and 2 weeks use of BP were significantly lower in H. pylori-positive versus -negative subjects. The mechanism of this damaging effect of BP and the interaction with H. pylori is unknown. As part of a separately reported study of the incidence of gastric damage after 2 weeks of treatment of healthy female postmenopausal volunteers with risedronate (5 mg/day) or alendronate (10 mg/day), gastric aspirates were taken at the time of the baseline esophagogastroduodenoscopy (EGD), and again at 1 and 2 weeks after daily intake of a BP At the time of the third EGD, when the volunteers had been on risedronate or alendronate for 2 weeks, antral biopsies were taken from normal-appearing mucosa. Gastric juice and antral biopsies were assessed for their concentration of the cytokines interleukin-la (IL-1alpha), IL-8, IL-13, and epidermal growth factor (EGF). H. pylori, the use of BP, and development of gastric mucosal lesions had no effect on gastric mucosal concentrations of IL-1alpha, IL-13, or EGF. In contrast, the concentration of IL-8 in antral mucosal biopsies of volunteers given BP for 2 weeks was higher in the presence than in the absence of an H. pylori infection and was increased further in those who develop lesions associated with the use of BP. There was no correlation between gastric mucosal and gastric juice concentrations of IL-8. Gastric juice concentrations of IL-8 and EGF were not affected by H. pylori status, the use of BP, or the development of lesions. However, gastric juice concentrations of IL-1alpha were numerically lower in those who were negative for H. pylori with no mucosal lesions (Hp-L-), intermediate in those who were H. pylori-negative with lesions (Hp-L+), and highest in those who were positive for H. pylori and had lesions (Hp+L+). The gastric juice concentration of IL-13 was threefold higher in the absence than in the presence of H. pylori, and the relative abundance of IL-13 was: Hp-L- >Hp-L+ >Hp+L(-1) >Hp+L+. The prostaglandin E2 concentration in gastric antral biopsies was similar in the four groups and was unchanged with the in vitro biopsy incubation with celecoxib. We speculate that the higher gastric endoscopy scores observed with the use of BP in H. pylori negative as compared with H. pylori positive individuals is due to their lower mucosal concentration of IL-8 as well as the lower gastric juice concentration of IL-1alpha and higher concentration of IL-13.