Plasma proteomics reveals markers of metabolic stress in HIV infected children with severe acute malnutrition.

HIV infection affects up to 30% of children presenting with severe acute malnutrition (SAM) in Africa and is associated with increased mortality. Children with SAM are treated similarly regardless of HIV status, although mechanisms of nutritional recovery in HIV and/or SAM are not well understood. We performed a secondary analysis of a clinical trial and plasma proteomics data among children with complicated SAM in Kenya and Malawi. Compared to children with SAM without HIV (n = 113), HIV-infected children (n = 54) had evidence (false discovery rate (FDR) corrected p < 0.05) of metabolic stress, including enriched pathways related to inflammation and lipid metabolism. Moreover, we observed reduced plasma levels of zinc-α-2-glycoprotein, butyrylcholinesterase, and increased levels of complement C2 resembling findings in metabolic syndrome, diabetes and other non-communicable diseases. HIV was also associated (FDR corrected p < 0.05) with higher plasma levels of inflammatory chemokines. Considering evidence of biomarkers of metabolic stress, it is of potential concern that our current treatment strategy for SAM regardless of HIV status involves a high-fat therapeutic diet. The results of this study suggest a need for clinical trials of therapeutic foods that meet the specific metabolic needs of children with HIV and SAM.

No role for increased rectal compliance in pediatric functional constipation.

BACKGROUND & AIMS: Increased rectal compliance has been proposed to contribute to pediatric functional constipation (FC). We evaluated the clinical relevance of increased rectal compliance and assessed whether regular use of enemas improves rectal compliance in children with FC. METHODS: A prospective longitudinal study was conducted on children (8-18 years old) with FC. Pressure-controlled rectal distensions were performed at baseline and at 1 year. Rectal compliance was categorized into 3 groups: normal, moderately increased, or severely increased. Patients were randomly assigned to groups given conventional therapy or rectal enemas and conventional therapy. Clinical success was defined as >or=3 spontaneous defecations per week and fecal incontinence <1 per week. RESULTS: Baseline measurements were performed in 101 children (11.0 +/- 2.1 years); rectal compliance was normal in 36%, moderately increased in 40%, and severely increased in 24%. Patients with severely increased rectal compliance had lower defecation frequency (P = .03), more fecal incontinence (P = .04), and more rectal fecal impaction (P < .001). After 1 year, success values were similar between groups: 42% normal, 41% moderately increased, and 40% with severely increased compliance. Barostat studies performed after 1 year in 80 children (37 conventional therapy and 43 rectal enemas in addition to conventional therapy) revealed that rectal compliance had not changed in either group and had not improved in successfully treated patients. CONCLUSIONS: Constipated children with severely increased rectal compliance have severe symptoms. However, increased rectal compliance is not related to treatment failure. Regular use of enemas to avoid rectal fecal impaction does not improve rectal compliance in pediatric FC.

A randomized controlled trial of enemas in combination with oral laxative therapy for children with chronic constipation.

BACKGROUND & AIMS: After 5 years of intensive oral laxative use, up to 30% of constipated children still have an unsuccessful outcome. Children refractory to oral laxatives might benefit from regular rectal evacuation by enemas. This randomized controlled trial compared the effects of additional treatment with rectal enemas (intervention) with conventional treatment alone (oral laxatives, control) in severely constipated children. METHODS: In a tertiary hospital in the Netherlands, 100 children, aged 8-18 years, with functional constipation for at least 2 years were randomly assigned to intervention or control groups. The control group received education, behavioral strategies, and oral laxatives. The intervention group was also given 3 rectal enemas/week, reduced by 1 enema/week every 3 months. Outcome measures were defecation and fecal incontinence frequency and overall success at 12, 26, 39, and 52 weeks. Overall success was defined as 3 or more defecations/week and less than 1 fecal incontinence episode/week, irrespective of laxative use. RESULTS: Defecation frequency normalized in both groups but was significantly higher in the intervention group compared with controls at 26 and 52 weeks (5.6 vs 3.9/week, P = .02, and 5.3 vs 3.9/week, P = .02, respectively). There were no significant differences between groups in reduction of fecal incontinence episodes (P = .49) and overall success rates (P = .67). After 1 year of treatment, the overall success rate was 47.1% in the intervention group versus 36.1% in the control group. CONCLUSIONS: There is no additional effect of enemas compared with oral laxatives alone as maintenance therapy for severely constipated children.

Longitudinal follow-up of children with functional nonretentive fecal incontinence.

BACKGROUND & AIMS: Functional nonretentive fecal incontinence (FNRFI), incontinence in the absence of signs of fecal retention, is a frustrating phenomenon in children. No data on long-term outcome are available. The aim was to investigate the long-term outcome of FNRFI patients after intensive medical treatment. METHODS: Between 1990 and 1999, 119 patients (96 boys) with FNRFI were enrolled in 2 prospective, randomized trials investigating the effect of biofeedback training and/or laxative treatment. Follow-up (FU) was performed at 6 months, 1 year, and thereafter annually until September 2004. A standardized questionnaire was used to evaluate symptoms. Success was defined as a fecal incontinence frequency <1 per 2 weeks. RESULTS: Median age (25th-75th percentiles) was 9.2 years (range, 7.9-11.6 years). A 90% FU was achieved at all stages of the study. After 2 years of intensive therapy, 33 of 112 (29.5%) patients were successfully treated. The cumulative success percentage after 7 years of FU was 80%. At the biologic ages of 12 and 18 years, 49.4% (40/81) and 15.5% (9/58), respectively, of the patients still had fecal incontinence. Duration of fecal incontinence, with 4 years of age as the starting age for fecal incontinence (when a child should be toilet trained), was not related to successful outcome or relapse. Relapse occurred in 37% of patients. CONCLUSIONS: Only 29% of the patients with FNRFI were successfully treated after 2 years of intensive treatment. Despite recovery in the majority of patients beyond puberty, at age 18 years, 15% continued to have fecal incontinence.

Diagnosis of Hirschsprung's disease: a prospective, comparative accuracy study of common tests.

OBJECTIVE: To compare the diagnostic accuracy of contrast enema (CE), anorectal manometry (ARM), and rectal suction biopsy (RSB) for the detection of Hirschsprung's disease (HD). STUDY DESIGN: Following a prospective protocol, infants suspected of HD underwent all 3 index tests. Children with positive results on 2 or more index tests or who continued to have severe bowel problems underwent a full thickness biopsy as reference standard. Clinical follow-up was the reference standard in all other children. RESULTS: Between 2000 and 2003, 111 consecutive patients (67 boys; median age, 5.3 months) in whom HD was suspected were enrolled. HD was found in 28 patients. RSB had the highest sensitivity (93%) and specificity (100%) rates, but values were not significantly different from CE (sensitivity, 76%; specificity, 97%) or from ARM (sensitivity, 83%; specificity, 93%). Inconclusive test results occurred in 8 infants with CE, in 15 infants with ARM because of agitation, and in 2 infants with RSB. CONCLUSION: RSB is the most accurate test for diagnosing HD, and it has the lowest rate of inconclusive test results.