Parenteral support and micronutrient deficiencies in children with short bowel syndrome: A comprehensive retrospective study.

BACKGROUND & AIMS: Short bowel syndrome (SBS) is the leading cause of chronic intestinal failure. The duration of parenteral support (PS) and the long-term micronutrient needs in children with SBS vary, based on their clinical and anatomical characteristics. Our study aimed to review the clinical course and identify high risk patient groups for prolonged PS and long-term micronutrient supplementation. METHODS: A retrospective review was conducted on electronic medical records of children with SBS and chronic intestinal failure who were enrolled in the multidisciplinary intestinal rehabilitation program at Manchester Children's Hospital, UK. Children were included in the review if they required PN for more than 60 days out of 74 consecutive days and had at least 3 years of follow-up. Statistical analysis was performed using IBM SPSS Statistics 24.0. RESULTS: 40 children with SBS achieved enteral autonomy (EA) and 14 remained dependent on PS after 36 months of follow up. Necrotizing enterocolitis was the most common cause for intestinal resection (38.9%) followed by gastroschisis (22.2%), malrotation with volvulus (20.4%), segmental volvulus (9.3%) and long segment Hirschsprung disease (1.9%). Those who achieved EA had significantly longer intestinal length 27.5% (15.0-39.3) than those who remained on PS 6.0% (1.5-12.5) (p < 0.001). Type I SBS was only found in the PS cohort. Median PN dependence was 10.82 months [IQR 5.73-20.78]. Congenital diagnosis was associated with longer PN dependence (21.0 ± 20.0) than acquired (8.7 ± 7.8 months), (p = 0.02). The need for micronutrient supplementation was assessed after the transition to EA; 87.5% children had at least one micronutrient depletion, most commonly Vitamin D (64.1%), followed by iron (48.7%), Vitamin B12 (34.2%), and vitamin E (28.6%). Iron deficiency and vitamin A depletion were correlated with longer PS after multivariate analysis (OR: 1.103, 1.006-1.210, p = 0.037 and OR: 1.048, 0.998-1.102, p = 0.062 respectively). CONCLUSION: In our cohort, small bowel length was the main predictor for EA. Children on longer PS, had more often a congenital cause of resection and were at risk for micronutrient deficiencies in EA.

CLAUDE SYNDROME: A CASE REPORT.

Introduction: Detailed description of infarction of the midbrain is sparse likely due to the complex arterial supply of this region of the brain. Among the ventral midbrain syndromes reported is Claude syndrome. This syndrome caused majorly by a vascular insult to the ventromedial midbrain, characteristically presents with ipsilateral third cranial nerve palsy and contralateral hemiataxia. It is a rare syndrome and only a few cases have been reported since 1912 when it was first described by Henri Claude. Case presentation: 45-year-old male, who developed sudden onset dysarthria, right third cranial nerve palsy and left sided ataxia. An infarct in the right ventromedial midbrain was revealed on magnetic resonance imaging of the brain. Conclusion: We describe a case report of a middle-aged man with minimal vascular risk factors (ASCVD = 1.3%) for stroke, who presented with features suggestive of Claude syndrome.

The effects of anti-TNF-α treatment with adalimumab on growth in children with Crohn's disease (CD).

INTRODUCTION: Adalimumab is used to treat children with Crohn's disease (CD), but the effects of adalimumab on growth in CD have not been studied. AIM: To study growth and disease activity over 12 months (6 months prior to (T-6), baseline (T0) and for 6 months following (T+6) adalimumab). SUBJECTS AND METHODS: Growth and treatment details of 36 children (M: 22) who started adalimumab at a median (10th, 90th) age of 14.7 years (11.3, 16.8) were reviewed. RESULTS: Of 36 cases, 28 (78%) went into remission. Overall 42% of children showed catch up growth, which was more likely in: (i) those who achieved remission (median change in height SDS (ΔHtSDS) increased from -0.2 (-0.9, 1.0) at T0 to 0.2 (-0.6, 1.6) at T+6, (p=0.007)), (ii) in those who were on immunosuppression ΔHtSDS increased from -0.2 (-0.9, 1.0) at T0 to 0.1 (-0.8, 1.3) at T+6, (p=0.03) and (iii) in those whose indication for using adalimumab therapy was an allergic reaction to infliximab, median ΔHtSDS increased significantly from -0.3 (-0.9, 1.0) at T0 to 0.3 (-0.5, 1.6) at T+6, (p=0.02). Median ΔHtSDS also increased from -0.4 (-0.8, 0.7) at T0 to 0.0 (-0.6, 1.6) at T+6, (p=0.04) in 15 children who were on prednisolone therapy when starting adalimumab. CONCLUSION: Clinical response to adalimumab therapy is associated with an improvement in linear growth in a proportion of children with CD. Improved growth is more likely in patients entering remission and on immunosuppression but is not solely due to a steroid sparing effect.

A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease.

BACKGROUND: Adalimumab is efficacious therapy for adults with Crohn's disease (CD). AIM: To summarise the United Kingdom and Republic of Ireland paediatric adalimumab experience. METHODS: British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) members with Inflammatory Bowel Disease (IBD) patients <18 years old commencing adalimumab with at least 4 weeks follow-up. Patient demographics and details of treatment were then collected. Response and remission was assessed using the Paediatric Crohn's Disease Activity Index (PCDAI)/Physicians Global Assessment (PGA). RESULTS: Seventy-two patients [70 CD, 1 ulcerative colitis (UC), 1 IBD unclassified (IBDU)] from 19 paediatric-centres received adalimumab at a median age of 14.8 (IQR 3.1, range 6.1-17.8) years; 66/70 CD (94%) had previously received infliximab. A dose of 80 mg then 40 mg was used for induction in 41(59%) and 40 mg fortnightly for maintenance in 61 (90%). Remission rates were 24%, 58% and 41% at 1, 6 and 12 months, respectively. Overall 43 (61%) went into remission at some point, with 24 (35%) requiring escalation of therapy. Remission rates were higher in those on concomitant immunosuppression cf. those not on immunosuppression [34/46 (74%) vs. 9/24 (37%), respectively, (χ(2) 8.8, P=0.003)]. There were 15 adverse events (21%) including four (6%) serious adverse events with two sepsis related deaths in patients who were also on immunosuppression and home parenteral nutrition (3% mortality rate). CONCLUSIONS: Adalimumab is useful in treatment of refractory paediatric patients with a remission rate of 61%. This treatment benefit should be balanced against side effects, including in this study a 3% mortality rate.

Missed treatment opportunities for schistosomiasis mansoni, in an active programme for the treatment of urinary schistosomiasis in Plateau and Nasarawa states, Nigeria.

Both Schistosoma haematobium and S. mansoni are endemic in Nigeria. Since 1999 the ministries of health of Plateau and Nasarawa states, assisted by The Carter Center, have provided mass drug administrations with praziquantel to villages where >20% of the school-aged children tested with urine dipsticks have been found to have haematuria (presumed to be caused by S. haematobium). The current extent of S. mansoni in Nigeria remains relatively unknown because the tests needed to detect human infection with this parasite are difficult to perform in many endemic areas. In a cross-sectional survey involving 924 children, the prevalence of S. mansoni was determined in 30 villages (in four local government areas) that had been excluded from mass praziquantel administrations because the prevalence of haematuria in their school-aged children had been found to be <20%. Seventeen (57%) of the surveyed villages had sufficient S. mansoni (i.e. prevalences of at least 10%) to warrant treatment. The results indicated that, if both S. haematobium and S. mansoni are taken into account, 81% of the villages in the four local government areas studied require treatment, compared with 50% if only S. haematobium is considered. At the moment, the costs of the village-by-village diagnosis of S. haematobium and S. mansoni would be greater than those of the presumptive treatment of the school-aged children in all villages. Until improved and cheaper rapid diagnostic methods for S. mansoni become available, the cheapest approach to the overall problem of schistosomiasis in this part of Nigeria would therefore be wide-spread mass drug distributions, without screening for at-risk populations.

[Training course to improve management and distribution of antiretroviral treatment in Benin from December 4-8, 2006]. / Une formation pour mieux gérer et mieux dispenser les antirétroviraux (ARV) au Bénin. 4-8 décembre 2006.

A training course on managing and dispensing antiretroviral treatment was developed to improve the practices and behavior of personnel at 35 centers providing care for HIV/AIDS patients in Benin. This course proposes several ways to adapt the "Handbook of supply management at first-level health care facilities" (OMS) and to make successful use of "A method for better counseling and dispensing of medicines" developed by the Réseau Médicaments et Développement et le Centre de Pharmacovigilance (Alger).

Refeeding syndrome with enteral nutrition in children: a case report, literature review and clinical guidelines.

Refeeding syndrome is a potentially fatal complication of the nutritional management of severely malnourished patients. The syndrome almost always develops during the early stages of refeeding. It can be associated with a severe derangement in electrolyte and fluid balance, and result in significant morbidity and mortality. It is most often reported in adults receiving total parenteral nutrition (TPN), although refeeding with enteral feeds can also precipitate this syndrome. We report what we believe to be the first case of refeeding syndrome in an adolescent with newly diagnosed Crohn's disease. This developed within a few days of starting exclusive polymeric enteral nutrition. A systematic literature review revealed 27 children who developed refeeding syndrome after oral/enteral feeding. Of these, nine died as a direct result of complications of this syndrome. We discuss the implications of this syndrome on clinical practice and propose evidence-based guidelines for its management.

Immunoreactive epidermal growth factor receptors are present in gastrointestinal epithelial cells of preterm infants with necrotising enterocolitis.

INTRODUCTION: Epidermal growth factor (EGF) affects epithelial cell proliferation, differentiation and migration in the gastrointestinal tract of experimental animals, and increases proliferation when given intravenously to children with congenital microvillous atrophy or necrotising enteritis. The aim of the present study is to determine whether EGF receptors (EGFR) are present in the gut epithelium of preterm infants, and to discover whether neonatal necrotising enterocolitis (NEC) is associated with the absence of EGFR from mucosal cells. METHODS: Tissues were taken from involved colon and small intestine of four preterm infants with NEC, and control tissues were taken from four other neonates who had laparatomies for congenital malformations. Sections of the tissues were examined histopathologically after treatment with a monoclonal antibody against the external domain of the EGFR (Zymed Laboratories, San Francisco, CA, USA). RESULTS: Histopathological examination confirmed diagnosis of NEC in the involved bowel and controls showed appearance within normal limit. Immunoreactive EGFR were present on the epithelial cells of both the colon and small intestine, localised on the basolateral membrane of the cells of both subject and the controls. There was no apparent reduction in expression compared with controls. CONCLUSION: NEC in preterm infants is not associated with absence of EGFR. The presence of EGFR in gut epithelial cells raises the possibility of using EGF for prophylaxis or treatment of NEC.

Potency and stability of C terminal truncated human epidermal growth factor.

INTRODUCTION: Epidermal growth factor (EGF) is normally present as EGF(1-53). A variety of C terminal truncated forms have been used in preliminary trials for treating gastrointestinal injury but their relative potency and stability when used in a clinical setting are unclear. Therefore, we compared the biological activity of recombinant EGF(1-53), EGF(1-52), EGF(1-51), and the C terminal peptides EGF(44-53) and EGF(49-53). METHODS: Purity of forms was confirmed by mass spectrometry. Bioactivity of the different EGF forms was determined using [methyl-(3)H] thymidine incorporation into primary rat hepatocytes and their ability to reduce indomethacin (20 mg/kg subcutaneously)/restraint induced gastric injury in rats. Stability of EGF peptides was determined by serial sampling from a syringe driver system containing EGF/4% albumin in saline. RESULTS: Biological activity assays of EGF(1-53), EGF(1-52), and EGF(1-51) gave almost identical thymidine uptake dose-response curves (maximal responses increasing baseline uptake from 4400 (600) cpm (mean (SEM)) to about 22 000 (2000) cpm when EGF was added at 1. 6 nM). EGF(44-53) and EGF(49-53) did not stimulate (3)H thymidine uptake. Control rats had 47 (4) mm(2) damage/stomach, EGF(1-51), EGF(1-52), and EGF(1-53) at 0.16 and 0.80 nmol/kg/h each reduced gastric injury by about 50% and 80%, respectively (both doses p<0.01 compared with control but no significant difference between the different forms). EGF was stable at room temperature for seven days but biological activity decreased by 35% and 40% at two and three weeks, respectively (both p<0.01). Exposure to light did not affect bioactivity. CONCLUSION: EGF(1-51) and EGF(1-52) are as biologically active as full length EGF(1-53) but the C terminal penta- and decapeptides are ineffective. Clinical trials of EGF can probably use infusion systems for at least 48 hours at room temperature and with exposure to light, without reducing biological efficacy.

Magnetic resonance imaging of intestinal necrosis in preterm infants.

BACKGROUND AND OBJECTIVE: Noninvasive diagnosis of intestinal necrosis is important in planning surgery in preterm infants with necrotizing enterocolitis (NEC). We aimed to assess the potential of magnetic resonance imaging (MRI) for the diagnosis of intestinal necrosis. STUDY PARTICIPANTS AND METHODS: Abdominal MRI scans were performed in a group of preterm infants with suspected NEC and compared with surgical findings and to MRI results in a group of control infants. In addition, MRI was performed in 2 preterm infants with suspected NEC who did not require surgery. RESULTS: Six infants with a median birth weight of 1220 g (range, 760-1770 g) and median gestational age at birth of 30 weeks (range, 28-34 weeks) were studied at a median postnatal age of 10 days (range, 4-19 days). Four infants had a bubble-like appearance in part of the intestinal wall, intramural gas, and an abnormal fluid level within bowel lumen. At surgery, NEC was found in 5 infants and sigmoid volvulus in 1. The site of the bubble-like appearance corresponded to the site of intestinal necrosis at surgery. Four control infants with a median birth weight of 1500 g (range, 730-2130 g) and a median gestational age of 31 weeks (range, 26-36 weeks) had abdominal MRI at a median postnatal age of 8 days (range, 4-70 days). None of the above findings were seen in any control infant. The bubble-like appearance was not seen in the 2 infants with suspected NEC who did not require surgery. CONCLUSION: Abdominal MRI allows the noninvasive diagnosis of bowel necrosis. This may aid the timing of surgical intervention in preterm infants with a clinical diagnosis of NEC.gangrene, ischemia, MRI, necrotizing enterocolitis.