Growth hormone to improve short bowel syndrome intestinal autonomy: a pediatric randomized open-label clinical trial

Background: The ability of growth hormone (GH) to promote the weaning‐off of parenteral nutrition (PN) in short bowel syndrome (SBS) is unclear. No randomized controlled study is available in children. This study was undertaken to determine if GH could enhance the weaning off of PN in PN‐dependent children with SBS. Methods: A prospective randomized open‐label multicenter study was performed in 14 patients (mean age, 9 ± 1.4 years) with SBS (average small bowel length, 33 cm) and long‐term PN dependency (8 years) on an unrestricted diet. A standardized PN decrease with and without GH (0.14 mg/kg/d) was conducted. The patients were randomized to either a GH group (4 months of GH) or a control (CTR) group (4 months without GH, followed by 4 months with GH). Blood tests and a nutrition assessment of enteral and parenteral intakes were performed. Groups were compared with the Wilcoxon test. Results: Treatment with GH did not improve the weaning off of PN (decrease in PN caloric intake of 32.5% ± 9.6% in the GH group vs 35.2% ± 8.7% in the CTR group, nonsignificant). In the CTR group, GH treatment induced an additional but not statistically significant decrease of 8.8% ± 12.4% in daily calories. Parenteral needs returned to near basal rates 6 months after GH discontinuation (GH: 77.6% ± 10.6% vs CTR: 73.2% ± 7.4%). Weight decreased slightly in both groups. No biological parameters varied significantly. Conclusions: GH did not improve the weaning off of PN in PN‐dependent children with SBS.     

Maintenance of parenteral nutrition volume reduction, without weight loss, after stopping teduglutide in a subset of patients with short bowel syndrome

Background: Teduglutide was discontinued after being tested for ≥ 24 weeks in patients with parenteral nutrition (PN) ‐dependent short bowel syndrome in a clinical trial for efficacy to reduce PN volume. This study was describes change in body mass index (BMI) and PN volume over 12 months in patients who stopped drug after the clinical trial. Methods: Prescribed PN volume, weight, and complications were reported. Patients with stable (NEUT, n = 15) or decreased (DEC, n = 7) PN volume by 12 months after stopping drug (NEUT/DEC, n = 22) were compared to those who had increased PN volume (INC, n = 15). With drug response defined by ≥20% reduction from pre‐drug PN volume to end of drug therapy, 12 INC and 13 NEUT/DEC patients were drug responders. Results: Eleven of 20 eligible sites reported data for 39 of 53 eligible study participants, with follow‐up data for 37. INC patients had shorter colon and less frequently had colon in continuity than NEUT/DEC. BMI was decreased at 3, 6, and 12 months relative to the first off‐drug visit in INC patients (P = .001), but not in NEUT/DEC patients. Change in BMI off‐drug was predicted by colon and small bowel length, baseline BMI, and on‐drug change in PN volume (adjusted R2 = 0.708). Conclusions: Gastrointestinal anatomy, baseline BMI, and PN volume reduction on‐drug predicted change in BMI off‐drug. Whether this response would be maintained for a longer time or in the context of a challenging clinical situation has not been evaluated.     

Bone marrow oxalosis with pancytopenia in a patient with short bowel syndrome: Report of a case and review of the literature

Systemic oxalosis is a condition in which calcium oxalate crystals deposit into various bodily tissues. Although this may occur as the result of a rare primary syndrome in which an error of glyoxylate metabolism causes an overproduction of oxalate, it is more often seen as a secondary process characterized by increased enteric oxalate absorption. Here, we describe a patient with short bowel syndrome on long-term parenteral nutrition support who developed a unique manifestation of systemic oxalosis, leading to deposition of oxalate crystals within the bone marrow contributing to pancytopenia. In this report, in addition to reviewing the literature on this presumably rare manifestation of oxalosis, we also discuss its pathogenesis in the setting of short bowel syndrome and its management, including prevention.     

Enteral feeding induces early intestinal adaptation in a parenterally fed neonatal piglet model of short bowel syndrome

Background: Successful small intestinal (SI) adaptation following surgical resection is essential for optimizing newborn growth and development, but the potential for adaptation is unknown. The authors developed an SI resection model in neonatal piglets supported by intravenous and enteral nutrition. Methods: Piglets (n = 33, 12–13 days old) were randomized to 80% SI resection with parenteral nutrition feeding (R‐PN), 80% SI resection with PN + enteral feeding (R‐EN), or sham SI transection with PN + enteral feeding (sham‐EN). In resected pigs, the distal 100 cm of ileum (residual SI) and 30 cm of proximal SI were left intact. All pigs received parenteral nutrition postsurgery. Enteral nutrition piglets received continuous gastric infusion of elemental diet from day 3 (40:60 parenteral nutrition:enteral nutrition). Piglets were killed 4, 6, or 10 days postsurgery. Results: By 10 days, R‐EN piglets had longer residual SI than R‐PN and sham‐EN pigs (P < .05). At days 6 and 10, R‐EN piglets had greater weight per length of intact SI (P < .05) and isolated mucosa (P < .05) compared to other groups. Greater gut weight in R‐EN piglets was facilitated by a greater cellular proliferation index (P < .01) by 4 days compared to other groups and greater overall ornithine decarboxylase activity vs R‐PN piglets (P < .05). Conclusions: This new model demonstrated profound SI adaptation, initiated early postsurgery by polyamine synthesis and crypt cell proliferation and only in response to enteral feeding. These changes translated to greater gut mass and length within days, likely improving functional capacity long term.     

Macronutrient absorption characteristics in humans with short bowel syndrome and jejunocolonic anastomosis: starch is the most important carbohydrate substrate, although pectin supplementation may modestly enhance short chain fatty acid production and fluid absorption

Background: Diet may play an important role in the management of patients with short bowel syndrome who have colon in continuity. However, macronutrient absorption has not been well characterized, and the most appropriate dietary constituents have not been well defined. Objective: To define carbohydrate absorption characteristics in patients with short bowel syndrome and determine the potential role of pectin as a dietary substrate. Methods: The authors studied the effect of a custom pectin‐based supplement in 6 subjects (3 male/3 female) aged 29–67 years with jejunocolonic anastomosis, 4 of whom required long‐term parental nutrition. Small intestinal absorption capacity, macronutrient and fluid balance, gastrointestinal transit time, and energy consumption were measured. Results: Data showed that 53% nitrogen, 50% fat, and 32% total energy were malabsorbed. In contrast, the majority (92%) of total carbohydrate was utilized. Fecal short‐chain fatty acids (SCFAs) were increased, an indication of increased fermentation. Although only 4% of starch was recovered in stool, it is indicative of considerable starch malabsorption, thus providing the main carbohydrate substrate, for colonic bacterial fermentation. In contrast, nonstarch polysaccharide was a relatively minor fermentation substrate with only 49% utilized. Eighty percent of the pectin was fermented. Supplementation was associated with increased total SCFAs, acetate, and propionate excretion. There was a trend observed toward greater fluid absorption (?5.9% ± 54.4% to 26.9% ± 25.2%) following pectin supplementation. Nonsignificant increases in gastric emptying time and orocolonic transit time were observed. Conclusion: Despite malabsorption, starch is the primary carbohydrate substrate for colonic bacterial fermentation in patients with short bowel syndrome, although soluble fiber intake also enhances colonic SCFA production.     

Serum vitamins in adult patients with short bowel syndrome receiving intermittent parenteral nutrition

Background: Short bowel syndrome (SBS) occurs after massive intestinal resection, and parenteral nutrition (PN) therapy may be necessary even after a period of adaptation. The purpose of this study was to determine the vitamin status in adults with SBS receiving intermittent PN. Methods: The study was conducted on hospitalized adults with SBS who were receiving intermittent PN therapy (n = 8). Nine healthy volunteers, paired by age and sex, served as controls. Food ingestion, anthropometry, plasma folic acid, and vitamins B₁₂, C, A, D, E, and K were evaluated. Results: The levels of vitamins A, D, and B₁₂ in both groups were similar. SBS patients presented higher values of folic acid (21.3 ± 4.4 vs 14.4 ± 5.2, P = .01) and lower values of vitamin C (0.9 ± 0.4 vs 1.2 ± 0.3 mg/dL, P = .03), α‐tocopherol (16.3 ± 3.4 vs 24.1 ± 2.7 µmol/L, P < .001), and phylloquinone (0.6 ± 0.2 vs 1.0 ± 0.5 nmol/L, P < .03). Eight‐seven percent of patients had vitamin D deficiency, and all patients presented with serum vitamin E levels below reference values. Conclusions: Despite all efforts to offer all the nutrients mentioned above, SBS patients had lower serum levels of vitamins C, E, and K, similar to those observed in patients on home PN. These findings suggest that the administered vitamins were not sufficient for the intermittent PN scheme and that individual adjustments are needed depending on the patient's vitamin status.