Histo-blood group antigen profile of Australian Aboriginal children and seropositivity following oral rotavirus vaccination.

BACKGROUND: Histo-blood group antigens (HBGAs) may influence immune responses to rotavirus vaccination. METHODS: HBGA phenotyping was determined by detection of antigens A, B, H and Lewis a and b in saliva using enzyme-linked immunosorbent assay. Secretor status was confirmed by lectin antigen assay if A, B and H antigens were negative or borderline (OD ± 0.1 of threshold of detection). PCR-RFLP analysis was used to identify the FUT2 'G428A' mutation in a subset. Rotavirus seropositivity was defined as serum anti-rotavirus IgA ≥ 20 AU/mL. RESULTS: Of 156 children, 119 (76 %) were secretors, 129 (83 %) were Lewis antigen positive, and 105 (67 %) were rotavirus IgA seropositive. Eighty-seven of 119 (73 %) secretors were rotavirus seropositive, versus 4/9 (44 %) weak secretors and 13/27 (48 %) non-secretors. CONCLUSIONS: Most Australian Aboriginal children were secretor and Lewis antigen positive. Non-secretor children were less likely to be seropositive to rotavirus antibodies following vaccination, but this phenotype was less common. HBGA status is unlikely to fully explain underperformance of rotavirus vaccines among Australian Aboriginal children.

Recent insights into trace element deficiencies: causes, recognition and correction.

PURPOSE OF REVIEW: Trace elements are vital components involved in major body functions. Cases of trace elements deficiencies are increasingly encountered in clinical practice, although often underrecognized. This review gives a thorough insight into the newest findings on clinical situations associated with trace elements deficiencies in children and adults, their recognition and management. RECENT FINDINGS: Trace elements deficiencies are frequently found in various conditions, most commonly in burns, bariatric surgery, intestinal failure, renal replacement therapy, oncology, critical illness and cardiac surgery. The main trace elements involved are selenium, zinc, copper and iron. Trace elements deficiencies are associated with increased risk of morbidity and mortality. Recognition of clinical signs of trace elements deficiencies can be challenging. Although trace elements supplementation is indisputable in many circumstances, it is still debatable in other situations such as sepsis and cardiac surgery. SUMMARY: Recent findings on trace elements deficiencies could have important implications on health outcomes. Trace elements delivery is a core component of nutritional care. Front-line clinicians should be aware of at-risk clinical situations to provide correct and timely intervention. Future research should be directed towards investigating the potential benefits of antioxidant trace elements supplementation in children in whom studies are scarce, especially in critical conditions such as burns, sepsis and cardiac surgery.

Nutritional challenges in children with primary immunodeficiencies undergoing hematopoietic stem cell transplant.

Nutritional profile and management of patients with primary immunodeficiencies (PID) undergoing hematopoietic stem cell transplant (HSCT) has not been described in the literature. We aim to report the nutritional challenges and practices peculiar to this population before and after HSCT and suggest clinical pathways for their management. We conducted a single-centre retrospective study. Inclusion criteria were children aged less than 20 years with a diagnosis of PID who have undergone HSCT at the Royal Children's Hospital Melbourne since April 2014 with a minimal follow-up of 1 year. Nutritional parameters were collected in the pre-transplant period, at conditioning, and at 1, 3, 6 and 12 months post-HSCT. Descriptive analysis were used. Between April 2014 and December 2018, 27 children received 31 HSCT. Before transplant, 33% had a weight and/or height ≤ -2 standard deviations (SD). Forty percent required nutritional support before transplant: 33% had enteral nutrition (EN) while 7% required long-term parenteral nutrition (PN) due to intestinal failure. After transplant, although most children were started on EN, 82% required PN with a mean duration of 67 days. Mean time to full oral diet was 154 days. Pre-transplant mean weight and height were -0.57 SD and -0.88 SD respectively. After a decrease in anthropometric parameters the first 3 months post-transplant, progressive catch up was noticeable for weight (-0.27 SD) with no catch up for height at 1 year (-0.93 SD). Our work highlights the nutritional challenges and specificities of children with PID in the peri-transplant period. An approach to nutrition assessment and management in the pre- and post-transplant period is proposed.

Farnesoid X Receptor Agonist Treatment Alters Bile Acid Metabolism but Exacerbates Liver Damage in a Piglet Model of Short-Bowel Syndrome.

BACKGROUND & AIMS: Options for the prevention of short-bowel syndrome-associated liver disease (SBS-ALDs) are limited and often ineffective. The farnesoid X receptor (FXR) is a newly emerging pharmaceutical target and FXR agonists have been shown to ameliorate cholestasis and metabolic disorders. The aim of this study was to assess the efficacy of obeticholic acid (OCA) treatment in preventing SBS-ALDs. METHODS: Piglets underwent 75% small-bowel resection (SBS) or sham surgery (sham) and were assigned to either a daily dose of OCA (2.4 mg/kg/day) or were untreated. Clinical measures included weight gain and stool studies. Histologic features were assessed. Ultraperformance liquid chromatography tandem mass spectrometry was used to determine bile acid composition in end point bile and portal serum samples. Gene expression of key FXR targets was assessed in intestinal and hepatic tissues via quantitative polymerase chain reaction. RESULTS: OCA-treated SBS piglets showed decreased stool fat and altered liver histology when compared with nontreated SBS piglets. OCA prevented SBS-associated taurine depletion, however, further analysis of bile and portal serum samples indicated that OCA did not prevent SBS-associated alterations in bile acid composition. The expression of FXR target genes involved in bile acid transport and synthesis increased within the liver of SBS piglets after OCA administration whereas, paradoxically, intestinal expression of FXR target genes were decreased by OCA administration. CONCLUSIONS: Administration of OCA in SBS reduced fat malabsorption and altered bile acid composition, but did not prevent the development of SBS-ALDs. We postulate that extensive small resection impacts the ability of the remnant intestine to respond to FXR activation.

Australian Rotavirus Surveillance Program: Annual Report, 2016.

This report from the Australian Rotavirus Surveillance Program (ARSP) and collaborating laboratories Australia-wide, describes the rotavirus genotypes identified in children and adults with acute gastroenteritis during the period 1 January to 31 December 2016. During this period, 949 faecal specimens were referred for rotavirus G and P genotype analysis, of which 230 were confirmed as positive for wildtype rotavirus, and 184 were identified as rotavirus vaccine-like. Genotype analysis of the 230 samples from both children and adults revealed that G2P[4] was the dominant genotype in this reporting period nationally, identified in 29% of samples, followed by equine-like G3P[8] and G12P[8] (19% and 15% respectively). Genotype distribution remained distinct between States using RotaTeq® and Rotarix® vaccines. In RotaTeq ® States, G12P[8] strains were more common, while G2P[4] and equine-like G3P[8] genotypes were more common in Rotarix® States and Territories. This report highlights the continued dominance of G12P[8] strains in RotaTeq® States and co-dominance of G2P[4] and equine-like G3P[8] in States and Territories using Rotarix®.

Changes in the colon microbiota and intestinal cytokine gene expression following minimal intestinal surgery.

AIM: To investigate the impact of minor abdominal surgery on the caecal microbial population and on markers of gut inflammation. METHODS: Four week old piglets were randomly allocated to a no-surgery "control" group (n = 6) or a "transection surgery" group (n = 5). During the transection surgery procedure, a conventional midline incision of the lower abdominal wall was made and the small intestine was transected at a site 225 cm proximal to the ileocaecal valve, a 2 cm segment was removed and the intestine was re-anastomosed. Piglets received a polymeric infant formula diet throughout the study period and were sacrificed at two weeks post-surgery. Clinical outcomes including weight, stool consistency and presence of stool fat globules were monitored. High throughput DNA sequencing of colonic content was used to detect surgery-related disturbances in microbial composition at phylum, family and genus level. Diversity and richness estimates were calculated for the control and minor surgery groups. As disturbances in the gut microbial community are linked to inflammation we compared the gene expression of key inflammatory cytokines (TNF, IL1B, IL18, IL12, IL8, IL6 and IL10) in ileum, terminal ileum and colon mucosal extracts obtained from control and abdominal surgery groups at two weeks post-surgery. RESULTS: Changes in the relative abundance of bacterial species at family and genus level were confined to bacterial members of the Proteobacteria and Bacteroidetes phyla. Family level compositional shifts included a reduction in the relative abundance of Enterobacteriaceae (22.95 ± 5.27 vs 2.07 ± 0.72, P < 0.01), Bacteroidaceae (2.54 ± 0.56 vs 0.86 ± 0.43, P < 0.05) and Rhodospirillaceae (0.40 ± 0.14 vs 0.00 ± 0.00, P < 0.05) following transection surgery. Similarly, at the genus level, changes associated with transection surgery were restricted to members of the Proteobacteria and Bacteroidetes phyla and included decreased relative abundance of Enterobacteriaceae (29.20 ± 6.74 vs 2.88 ± 1.08, P < 0.01), Alistipes (4.82 ± 1.73 vs 0.18 ± 0.13, P < 0.05) and Thalassospira (0.53 ± 0.19 vs 0.00 ± 0.00, P < 0.05). Surgery-associated microbial dysbiosis was accompanied by increased gene expression of markers of inflammation. Within the ileum IL6 expression was decreased (4.46 ± 1.60 vs 0.24 ± 0.06, P < 0.05) following transection surgery. In the terminal ileum, gene expression of TNF was decreased (1.51 ± 0.13 vs 0.80 ± 0.16, P < 0.01) and IL18 (1.21 ± 0.18 vs 2.13 ± 0.24, P < 0.01), IL12 (1.04 ± 0.16 vs 1.82 ± 0.32, P < 0.05) and IL10 (1.04 ± 0.06 vs 1.43 ± 0.09, P < 0.01) gene expression increased following transection surgery. Within the colon, IL12 (0.72 ± 0.13 vs 1.78 ± 0.28, P < 0.01) and IL10 (0.98 ± 0.02 vs 1.95 ± 0.14, P < 0.01) gene expression were increased following transection surgery. CONCLUSION: This study suggests that minor abdominal surgery in infants, results in long-term alteration of the colonic microbial composition and persistent gastrointestinal inflammation.

Intussusception in Australia: epidemiology prior to the introduction of rotavirus vaccine.

OBJECTIVES: To describe the incidence rate and clinical outcomes of intussusception in Australia in children aged <24 months prior to the use of rotavirus vaccines in Australia, and to explore associations between patient characteristics and outcomes in children with intussusception. METHODS: This study used Australian national hospital discharge data on intussusception from July 2000 to June 2006 for children aged <24 months and data from the Australian Bureau of Statistics (ABS) as a proxy for population numbers to estimate incidence. Logistic regression was used to examine associations between patient characteristics (age, sex, ethnicity) and outcomes (length of hospital stay >2 days and the need for surgical intervention). RESULTS: The overall incidence rate of intussusception was 5.4 per 10,000 child-years in children under 24 months (95%CI 5.17-5.70). There was a declining rate over the study period (p<0.001). Age at time of intussusception was strongly associated with length of hospital stay and surgery. CONCLUSIONS: This study provides an estimate of the pre-rotavirus vaccine incidence of intussusception across Australia, which is important for monitoring the occurrence of intussusceptions post the introduction of rotavirus vaccine.

Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome.

BACKGROUND AND OBJECTIVES: Following small bowel resection (SBR), the luminal environment is altered, which contributes to clinical manifestations of short bowel syndrome (SBS) including malabsorption, mucosal inflammation and bacterial overgrowth. However, the impact of SBR on the colon has not been well-defined. The aims of this study were to characterize the colonic microbiota following SBR and to assess the impact of SBR on mucosal inflammation in the colon. RESULTS: Analysis of the colonic microbiota demonstrated that there was a significant level of dysbiosis both two and six weeks post-SBR, particularly in the phylum Firmicutes, coupled with a decrease in overall bacterial diversity in the colon. This decrease in diversity was associated with an increase in colonic inflammation six weeks post-surgery. METHODS: Female (4-week old) piglets (5-6/group) received a 75% SBR, a transection (sham) or no surgery. Compositional analysis of the colonic microbiota was performed by high-throughput sequencing, two- and six-weeks post-surgery. The gene expression of the pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF)-α in the colonic mucosa was assessed by qRT-PCR and the number of macrophages and percentage inducible nitric oxide synthase (iNOS) staining in the colonic epithelium were quantified by immunohistochemistry. CONCLUSIONS: SBR significantly decreased the diversity of the colonic microbiota and this was associated with an increase in colonic mucosal inflammation. This study supports the hypothesis that SBR has a significant impact on the colon and that this may play an important role in defining clinical outcome.

Optimizing immunization in pediatric special risk groups.

This article analyzes the current recommended practices and evidence in the immunization of pediatric 'special risk groups'. Special risk group patients are at higher risk of vaccine-preventable diseases and hence require additional strategies to maximize protection against these diseases. The special risk groups include those with an underlying chronic disease, some of whom are on immunosuppressive therapy to treat that condition. The article uses four special risk groups (acute lymphoblastic leukemia; preterm birth; juvenile idiopathic arthritis; and inflammatory bowel disease), to highlight the management considerations and potential vaccination strategies. The risks, benefits and timing of vaccination in the setting of immunosuppression require detailed discussion with treating clinicians, in particular the use of live-attenuated vaccines. The immunogenicity of vaccines in these special risk groups helps provide the evidence base for their immunization guidelines. Protection can include 'cocooning' (i.e., ensuring appropriate immunizations within the immediate family; e.g., varicella, influenza and pertussis vaccination). Improving timeliness and minimizing missed opportunities to vaccinate individuals with these special risk conditions will also optimize protection from vaccine-preventable diseases.

Morphological and functional changes in the colon after massive small bowel resection.

PURPOSE: Anecdotal evidence suggests that the colon plays an important role after small bowel resection (SBR). However, colonic changes have not previously been studied. The aim of this study was to characterize morphological and functional changes within the colon after SBR and elucidate the influence of diet complexity on adaptation. METHOD: In study 1, 4-week-old piglets underwent a 75% SBR or sham operation and were studied at 2, 4, and 6 weeks postoperation to allow analysis of early and late adaptation responses. Piglets received a polymeric infant formula (PIF). In study 2, SBR piglets received an elemental diet and were studied at 6 weeks postoperation and compared with SBR + PIF piglets from study 1. For both studies, immunohistochemistry was used to quantitate intestinal cell types. Changes in functional proteins were measured by Western blot, enteroendocrine/peptide YY (PYY), enterocyte/liver fatty acid binding protein (L-FABP), and goblet cells/trefoil factor 3 (TFF3). RESULTS: In study 1, early and late adaptation-related changes were observed after SBR. Early adaptation included increased numbers of enterocytes (P = .0001), whereas late adaptation included increased proliferative cell numbers (P = .02). Enteroendocrine, goblet, and apoptotic cells numbers were significantly elevated in the resected group at all time-points studied (P < .05). Functional changes included increased levels of L-FABP (P = .04) and PYY (P = .03). There was no change in TFF3 expression. In study 2, feeding with an elemental diet resulted in suboptimal adaptation as evidenced by reduced rate of weight gain and significant reductions in total cell numbers (P = .0001), proliferative (P = .0001) and apoptotic cells (P = .04), enteroendocrine cells (P = .001), and PYY expression (P .004). CONCLUSION: These findings indicate that significant morphological and functional changes occur in the colon after massive SBR and that these occur as early and late adaptation responses. Elemental diet was associated with suboptimal adaptation suggesting an effect of diet complexity on colonic adaptation.

Tolerability and safety of olive oil-based lipid emulsion in critically ill neonates: a blinded randomized trial.

OBJECTIVE: We assessed the safety and tolerability of an olive oil-based lipid emulsion compared with a soybean-based lipid emulsion in critically ill neonates. METHODS: A double-blinded, randomized study was conducted in critically ill neonates requiring parenteral nutrition in the first week of life. Infants were randomized to receive a lipid emulsion based on olive oil (OO; ClinOleic) or soybean oil (SO; Intralipid) for a minimum of 5 d. Plasma phospholipid fatty acids, F(2)-isoprostanes, liver function, and clinical outcome were assessed after 5 d of therapy. RESULTS: Seventy-eight neonates (men gestational age 37 wk, range 26-41 wk) received OO (n = 39) or SO (n = 39). Both emulsions were well tolerated with no adverse events observed. At day 5, plasma phospholipid oleic acid (C18:1omega-9) levels increased in infants receiving OO compared with lower levels in infants receiving SO (mean percentage +/- SD 33.1 +/- 6.4 for OO versus 18.6 +/- 2.4 for SO; mean difference -14.7 mmol/L, 95% confidence interval -17.5 to -11.9). The increase in plasma phospholipid linoleic acid levels was attenuated in infants receiving OO (mean percentage +/- SD 12.6 +/- 3.0 for OO versus 23.7 +/- 6.9 for SO; adjusted mean 11.4 mmol/L, 95% confidence interval 8.1-14.8). No differences were observed in plasma F(2)-isoprostane levels according to the type of lipid emulsion received. CONCLUSION: The OO-based emulsion (ClinOleic) was well tolerated in critically ill neonates. Differences in plasma phospholipids at day 5 reflected the fatty acid composition of the administered emulsion. No significant differences in plasma F(2)-isoprostane levels were detected after 5 d of lipid administration.

Accuracy of ultrasonography for the diagnosis of intussusception in infants in Vietnam.

BACKGROUND: Intussusception (IS) is the most common cause of acute bowel obstruction in infants and young children. Ultrasonography is being increasingly used as the primary investigation for the diagnosis of IS and to guide air or hydrostatic enema reduction. However the accuracy of ultrasonography outside tertiary care settings in developed countries has not been assessed, particularly in Asia where the incidence of IS based on sonographic diagnosis has been reported as the highest in the world. OBJECTIVE: The aim of this study was to evaluate the accuracy of ultrasonography in the diagnosis of acute IS in infants less than 2 years of age in a paediatric hospital in Vietnam. MATERIALS AND METHODS: A prospective study was conducted at the National Hospital for Paediatrics, Hanoi, Vietnam, over a 14-month period recruiting patients <2 years of age with IS. Abdominal ultrasonography was performed on each patient and the accuracy of the diagnosis was evaluated against the final diagnosis provided by air enema and/or surgery. RESULTS: A total of 640 infants <2 years of age presented with clinical symptoms and signs of IS. The diagnosis was confirmed in 533 patients via air enema or surgery. Abdominal ultrasonography was 97.5% (466/478) sensitive and 99% (106/107) specific in the detection of IS. CONCLUSION: Ultrasonography is an accurate, safe and valuable clinical tool in the diagnosis of IS. The use of ultrasonography as a primary investigation for patients with suspected IS prevents unnecessary radiological or surgical procedures being performed, and reduces radiation exposure while maintaining a high level of diagnostic accuracy. These results validate the use of ultrasonography for the diagnosis of IS in a developing country setting.

Risk factors for intussusception in infants in Vietnam and Australia: adenovirus implicated, but not rotavirus.

OBJECTIVE: This study aimed to investigate risk factors for the development of intussusception in infants in a developing country with a suspected high incidence and in a developed country with a low incidence. STUDY DESIGN: A prospective case-control study of infants <2 years of age with idiopathic intussusception confirmed by air enema or surgery was conducted at the National Hospital of Paediatrics (NHP), Vietnam (n = 533) and the Royal Children's Hospital (RCH), Australia (n = 51). Diagnosis was validated in a subset (84% NHP; 67% RCH) by an independent blinded radiologist. Risk factor assessment was performed using a standardized questionnaire. Stool specimens were assayed for bacterial, viral, and parasitic agents. RESULTS: The incidence of intussusception in Vietnam was 302/100,000 in infants <1 year of age (95% CI: 258-352), substantially higher than in Australia (71/100,000). A strong association with adenovirus infection was observed at both sites (cases positive at NHP: 34%, OR 8.2; cases positive at RCH: 40%, OR 44). No association was identified between intussusception and rotavirus, other enteric pathogens, oral polio vaccine, feeding practices, or living conditions. CONCLUSIONS: The incidence of intussusception in infants was markedly higher in Vietnam than in Australia. A strong association between adenovirus infection and intussusception was identified at both sites suggesting that adenovirus may play a role in the etiology of intussusception.

Validation of clinical case definition of acute intussusception in infants in Viet Nam and Australia.

OBJECTIVE: To test the sensitivity and specificity of a clinical case definition of acute intussusception in infants to assist health-care workers in settings where diagnostic facilities are not available. METHODS: Prospective studies were conducted at a major paediatric hospital in Viet Nam (the National Hospital of Pediatrics, Hanoi) from November 2002 to December 2003 and in Australia (the Royal Children's Hospital, Melbourne) from March 2002 to March 2004 using a clinical case definition of intussusception. Diagnosis of intussusception was confirmed by air enema or surgery and validated in a subset of participants by an independent clinician who was blinded to the participant's status. Sensitivity of the definition was evaluated in 584 infants aged<2 years with suspected intussusception (533 infants in Hanoi; 51 in Melbourne). Specificity was evaluated in 638 infants aged<2 years presenting with clinical features consistent with intussusception but for whom another diagnosis was established (234 infants in Hanoi; 404 in Melbourne). FINDINGS: In both locations the definition used was sensitive (96% sensitivity in Hanoi; 98% in Melbourne) and specific (95% specificity in Hanoi; 87% in Melbourne) for intussusception among infants with sufficient data to allow classification (449/533 in Hanoi; 50/51 in Melbourne). Reanalysis of patients with missing data suggests that modifying minor criteria would increase the applicability of the definition while maintaining good sensitivity (96-97%) and specificity (83-89%). CONCLUSION: The clinical case definition was sensitive and specific for the diagnosis of acute intussusception in infants in both a developing country and a developed country but minor modifications would enable it to be used more widely.

Energy metabolism in infants with congenital heart disease.

Failure to thrive is common in children with congenital heart disease and influences the metabolic response to injury and outcome after corrective cardiac surgery. Energy imbalance is a major contributing factor. However, the published literature is difficult to interpret as studies generally involve small patient numbers with a diverse range of types and severity of cardiac lesions and genetic and/or prenatal factors. The age and time of corrective surgery affects the potential for nutritional recovery. Although the immediate postoperative period is characterized by a hypermetabolic state, low total and resting energy expenditure are reported within 24 h of surgery. After 5 d, resting energy expenditure returns to preoperative levels. Significant improvements in weight and growth occur within months after corrective surgery. However, limited postoperative recovery in nutritional status and growth occurs in infants with a low birth weight, intellectual deficit, or residual malformation. Further studies are needed to inform the timing of corrective cardiac surgery to maximize nutritional outcomes and to identify those infants who may benefit from aggressive preoperative nutrition support.

Intussusception: trends in clinical presentation and management.

BACKGROUND: The association of a rotavirus vaccine and intussusception has renewed interest in understanding the incidence, clinical presentation and outcome of intussusception. METHODS: A retrospective chart review of all patients diagnosed with intussusception at Royal Children's Hospital, Melbourne over a 6.5-year period (1 January 1995-30 June 2001) was conducted using patients identified by a medical record database (ICD-9-CM code 560.0 1993-1997; ICD-10-CM code 56.1 1998-2001). Patient profile, clinical presentation, diagnosis methods, treatment and outcome were analyzed and compared to data previously reported on children with intussusception at the same hospital during 1962-1968. RESULTS: The hospitalization rate for primary idiopathic intussusception increased marginally from 0.19 to 0.27 per 1000 live births during the period 1962-1968 to 1995-2001. Most patients (80%) were <12 months of age (median age 7 months, range 2-72 months). The combination of abdominal pain, lethargy and vomiting was reported in 78% of infants. Air enema confirmed the diagnosis of intussusception in 186 of 191 cases (97%) and air reduction was successful in most cases (82%). Factors associated with increased risk of intestinal resection included abdominal distension (32%), bowel obstruction on abdominal X-ray (27%) and hypovolemic shock (40%). No mortality was observed in the present study. CONCLUSIONS: Over the past 40 years at Royal Children's Hospital, Melbourne the hospitalization rate due to primary idiopathic intussusception has marginally increased from 0.19 to 0.27 per 1000 live births. Diagnosis and treatment using air enema has been highly successful, resulting in a reduction in patients requiring surgery and reduced hospital stays.

New growth factor therapies aimed at improving intestinal adaptation in short bowel syndrome.

Short bowel syndrome (SBS) is used to describe a condition of malabsorption and malnutrition resulting from the loss of absorptive area following massive small bowel resection. The key to improved clinical outcome after massive small bowel resection is the ability of the residual bowel to adapt. Although still in experimental stages, a major goal in the management of SBS may be the augmented use of growth factors to promote increased adaptation. A number of growth factors have been implicated in promoting the adaptation process. The best-described growth factors are reviewed: glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF), and growth hormone (GH). This article reviews the ability of recombinant GLP-2, EGF and GH to modulate structural and functional aspects of intestinal adaptation following small bowel resection. Although these growth factors have shown promise, small sample size, inconsistent measurement parameters and uncontrolled study designs have hampered the acquisition of strong data advocating the use of growth factor treatment for SBS. Multicenter trials using well-defined outcome measures to assess clinical efficacy are needed to direct the clinical indications, timing and duration of therapy and assess potential risks associated with growth factor therapies.

Energy metabolism in infants with cystic fibrosis.

OBJECTIVE: To determine whether a defect in energy metabolism exists in infants with cystic fibrosis (CF). DESIGN: Unselected, newly-diagnosed subjects with CF (n = 46) and 24 healthy infants aged <20 weeks had measurements of resting energy expenditure (REE), total energy expenditure (TEE) (n = 25), and body composition. Metabolizable energy intake (MEI) was calculated. Genotype, energy intake, and pancreatic status was determined in all subjects with CF, and 24 underwent bronchial lavage. RESULTS: At diagnosis, infants with CF detected by newborn screening had significant anthropometric deficits (mean [SD] z-weight = 0.5 [1.0], z-length = 0.7 [1.3]) associated with pancreatic insufficiency. Their REE, TEE, or MEI (absolute measurements, per unit body weight or fat-free mass) were not increased. No relationship between REE, TEE, or MEI and Delta F(508) genotype, and no proportional differences in individual components of MEI between subjects with CF and controls, or between subjects with CF who were homozygotes or compound heterozygotes for Delta F(508) were observed. REE and TEE were not correlated with bronchial infection or inflammation. CONCLUSION: Growth impairment during the first weeks of life in infants with CF is associated with pancreatic insufficiency. However, there is no evidence for a defect of energy metabolism related to Delta F(508), and in infants with CF, minimal lung disease is unaccompanied by increased energy expenditure.