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ABSTRACT: BACKGROUND: Intestinal failure (IF) is a rare but devastating complication of Crohn's disease. The clinical and surgical factors that predispose to intestinal failure are poorly understood. We aimed to define clinical factors that predispose to intestinal failure. METHODS: A retrospective case-control study was performed using consecutive Crohn's disease (CD) patients with IF who were identified from a prospective database. Local population-based controls were selected with which to compare demographic, phenotypic and clinical outcomes. RESULTS: Eighty-two CD patients requiring long-term intravenous fluids or nutrition were studied. Diagnosis at age 16 years or less (p=0.01) and a family history of inflammatory bowel disease (p=0.02) were associated with a significantly higher risk for developing IF. Amongst the IF group, 53% had perioperative complications from intestinal resections contributing to long term intestinal failure. Furthermore, these patients had more abdominal surgeries (p=0.05) and stricturing disease was less common than in patients with primary active CD (p=0.01). Intestinal failure due to primary active Crohn's disease was associated with penetrating behaviour (p=0.02) and early age at first surgery (p=0.004). The need for intravenous nutrition as opposed to intravenous fluids correlated inversely with small intestine length (p<0.001). CONCLUSIONS: Crohn's disease resulting in intestinal failure relates to earlier age at diagnosis, family history of inflammatory bowel disease, stricturing disease, younger age at first surgery, and operative complications. These factors deserve consideration when planning therapy for Crohn's disease patients.
Journal of Gastroenterology and Hepatology 01/2013; · 2.87 Impact Factor
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ABSTRACT: OBJECTIVE:: Several randomized control trials (RCTs) have compared somatostatin and its analogues versus a control group in patients with enterocutaneous fistulas (ECF). This study meta-analyzes the literature and establishes whether it shows a beneficial effect on ECF closure. METHODS:: We searched MEDLINE, EMBASE, CINAHL, Cochrane, and PubMed databases according to PRISMA guidelines. Seventy-nine articles were screened. Nine RCTs met the inclusion criteria. Statistical analyses were performed using Review Manager 5.1. RESULTS:: Somatostatin analogues versus controlNumber of fistula closed: A significant number of ECF closed in the somatostatin analogue group compared to control group, P = 0.002.Time to closure: ECF closed significantly faster with somatostatin analogues compared to controls, P < 0.0001.Mortality: No significant difference between somatostatin analogues and controls, P = 0.68.Somatostatin versus controlNumber of fistula closed: A significant number of ECF closed with somatostatin as compared to control, P = 0.04.Time to closure: ECF closed significantly faster with somatostatin than controls, P < 0.00001.Mortality: No significant difference between somatostatin and controls, P = 0.63 CONCLUSIONS:: Somatostatin and octreotide increase the likelihood of fistula closure. Both are beneficial in reducing the time to fistula closure. Neither has an effect on mortality. The risk ratio (RR) for somatostatin was higher than the RR for analogues. This may suggest that somatostatin could be better than analogues in relation to the number of fistulas closed and time to closure. Further studies are required to corroborate these apparent findings.
Annals of surgery 08/2012; · 7.90 Impact Factor
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ABSTRACT: Aim: Present quality of life (QoL) instruments for inflammatory bowel disease (IBD) do not evaluate many social aspects of patients' lives that are potentially important in clinical decision making. We have developed a new Social Impact of Chronic Conditions - IBD questionnaire (SICC-IBD) to assess these areas. Method: A 34-item questionnaire was piloted to determine quality of life relating to education, personal relationships, employment, independence and finance. It was compared with the SF-36v2 and Inflammatory Bowel Disease (IBDQ) questionnaires in 150 patients with chronic ulcerative colitis on an endoscopic surveillance register who had never had surgery. Results: Reliability and validity testing enabled the questionnaire to be shortened to only 8 items. There was a high level of reliability (Cronbach's alpha = 0.72). The questionnaire correlated well with the social functioning domain of the SF-36 (r(s) =0.56) and was able to distinguish clinical severity of disease. Conclusion: The SICC-IBD is a new tool for assessment of patients with ulcerative colitis, which has identified new aspects of social disability for further study and for potential use as an additional tool in therapy decisions.
Colorectal Disease 11/2011; · 2.93 Impact Factor
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ABSTRACT: We present a 36-year-old female diagnosed with Crohn's disease at the age of 11 years. In 2001, she underwent a total colectomy and further small bowel resection as a result of active Crohn's. Her residual anatomy consisted of 150 cm of small bowel to an end jejunostomy. Subsequently, she developed short bowel syndrome with recurrent episodes of hypomagnesaemia, hypocalcaemia, and hypokalaemia. Dietetic assessment revealed her to be severely underweight at 37 kg with a bodymass index (BMI) of 14.4 kg/m(2) . During her admission, our patient underwent psychiatric assessment and was established on home parenteral nutrition (HPN). At the time of discharge, 1 month later, her weight had increased to 44 kg (BMI = 17.7 kg/m(2) ). Over the following 12-month period, she lost weight (BMI, 15.4 mg/m(2) ; weight, 39.5 kg) and she described a high stoma output (up to 17 L) and dehydration. Assessment of her oral intake found she was consuming an estimated 14,000 kcal and 600 g protein per day. At this time, the possibility of a new form of eating disorder was discussed with the patient and she agreed that her behavior i.e., using her stoma as a purging device, fulfilled the criteria for a diagnosis of bulimia nervosa and she was referred to a specialist eating disorder unit.
International Journal of Eating Disorders 03/2011; 45(2):302-4. · 2.95 Impact Factor
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ABSTRACT: Refeeding hypophosphataemia (RH) can result in sudden death. This study aimed to compare the incidence of RH between patients fed enterally and those fed parenterally.
The risk of RH in adult patients fed parenterally (PN) or nasogastrically (NG) was assessed by comparison of patient records with the UK NICE guidelines for refeeding syndrome, between December 2007 and December 2008. A fall in serum phosphate to less than 0.6 mmol/L was indicative of RH.
Of 321 patients,92 were at risk of RH. Of these, 23 (25%) patients developed RH (p = 0.003). 18 (33%) of NG fed, 'at-risk' patients developed RH vs 5 (13%) fed parenterally (p = 0.03). Death within 7 days and RH were not associated. The sensitivity and specificity of the NICE criteria for defining patient's risk of RH was calculated: 0.76 and 0.50 respectively for NG feeding; 0.73 and 0.38 respectively for parenteral feeding.
Patients fed by NG tube and deemed at risk of RH are more likely to develop RH than patients fed by PN. The higher risk with NG feeding may be due to the incretin effect from absorption of glucose. The UK guidelines lack specificity.
Clinical nutrition (Edinburgh, Scotland) 01/2011; 30(3):365-8. · 3.27 Impact Factor
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ABSTRACT: Enterocutaneous fistulas (ECF) are debilitating and usually result following complex abdominal surgery. While there is an association with inflammatory bowel disease (IBD), a large number of fistulas occur after surgery not related to IBD. The consequences of ECF include short bowel syndrome and the need for long term parenteral nutrition.ECF can heal spontaneously and in the case of IBD can be cured by medical therapy in some instances. Those that do not resolve spontaneously have to be cured by surgery which is complex and associated with a high morbidity. It is not considered traditional treatment to use the same medical therapy as in IBD to cure ECF caused by other conditions.A small case series has reported three patients with persistent ECF not related to IBD to have healed following use of Infliximab which is the treatment commonly used for ECF caused by IBD. Infliximab acts by inhibiting the activity of the inflammatory cytokine TNF- alpha. It is not known if this cytokine is present in ECF tissue in the absence of IBD.The aim of this study is to demonstrate the presence of inflammatory markers in tissue surrounding non-IBD ECF and in particular to quantify the presence of the cytokine TNF- alpha. We hypothesise that TNF - alpha levels are raised in non-IBD ECF.
Tissue and serum from ECF of IBD and non-IBD patients will be prospectively collected at St. Mark's Hospital Intestinal Failure Unit. The control group will consist of patients undergoing colonoscopy for bowel cancer screening, with normal findings. Biopsies of the terminal ileum will be obtained from this group during colonoscopy. The fistula tract and serum cytokine profiles of interleukins (IL)-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, TNF- alpha, IFN-y, MCP-1, EGF and VEGF will be assessed.
This study aims to assess the presence or absence of TNF- alpha expression in the ECF tissue in non-IBD origin. If our hypothesis is correct we would then be able to study the use of the TNF- alpha inhibitor Infliximab as a therapeutic option in the treatment of non-IBD ECF. Secondary aims include assessing the spectrum of inflammatory cytokines and markers present in tissue and serum of non-IBD ECF when compared with IBD ECF and normal controls.
ISRCTN44000447.
BMC Surgery 01/2011; 11:12. · 1.33 Impact Factor
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ABSTRACT: INTRODUCTION: Current medical management of short bowel syndrome (SBS) involves the use of lifelong parenteral nutrition (PN). Glucagon-like peptide-2 (GLP-2), an important intestinotrophic growth factor has been shown to increase intestinal absorption in SBS through augmentation of post-resection intestinal adaptation. This may lead to the reduction of PN dependence in patients with SBS. AREAS COVERED IN REVIEW: Advancing research of GLP-2 physiology has spurred the growing understanding of the diverse effects of GLP-2. The development of the degradation resistant GLP-2 analog, teduglutide (Gattex(TM), NPS Pharmaceuticals, Bedminster, NJ), has allowed its exploration as a therapeutic agent in a variety of clinical settings. Recent multicenter, placebo-controlled studies of GLP-2 in SBS patients demonstrate meaningful reductions in PN requirements with good safety profiles. The reparative and immunomodulatory effects of teduglutide may also be beneficial in patients with inflammatory bowel disease (IBD). Safety concerns about possible carcinogenic properties during long-term use require ongoing evaluation. SUMMARY: GLP-2 appears to offer a novel adjuvant treatment modality for SBS. Promise for its use in other clinical settings like IBD has been shown in small pilot studies.
Clinical and Experimental Gastroenterology 01/2011; 4:189-96.
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01/2009: pages 11 - 19; , ISBN: 9781405195805
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ABSTRACT: Long term parenteral nutrition rarely supplies the long chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). The aim of this study was to assess long chain n-3 PUFA status in patients receiving home parenteral nutrition (HPN).
Plasma phospholipid fatty acids were measured in 64 adult HPN patients and compared with 54 age, sex and BMI matched controls. Logistic regression analysis was used to identify factors related to plasma fatty acid fractions in the HPN patients, and to identify factors associated with the risk of clinical complications.
Plasma phospholipid fractions of EPA, DPA and DHA were significantly lower in patients receiving HPN. Factors independently associated with low fractions included high parenteral energy provision, low parenteral lipid intake, low BMI and prolonged duration of HPN. Long chain n-3 PUFA fractions were not associated with incidence of either central venous catheter associated infection or central venous thrombosis. However, the fraction of EPA were inversely associated with plasma alkaline phosphatase concentrations.
This study demonstrates abnormal long chain n-3 PUFA profiles in patients receiving HPN. Reduced fatty acid intake may be partly responsible. Fatty acid metabolism may also be altered.
Clinical nutrition (Edinburgh, Scotland) 12/2008; 27(6):822-31. · 3.27 Impact Factor
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ABSTRACT: Parenteral nutrition is life saving in patients with intestinal failure but liver dysfunction is commonly encountered, especially in neonates. Although abnormal liver function tests associated with short-term parenteral nutrition are usually benign and transient, liver dysfunction in both children and adults receiving long-term parenteral nutrition can progress to end-stage liver disease and liver failure. The aetiology of parenteral nutrition-associated liver disease is complex and multifactorial, with a range of patient, disease and nutrition-related factors implicated. Sepsis is of particular importance, as is the lack of enteral nutrition and overfeeding with intravenous glucose and/or lipid. Deficiencies of a number of amino acids including choline and taurine have also been implicated. Management of hepatic dysfunction in parenteral nutrition should initially focus on preventing its occurrence. Sepsis should be managed appropriately, enteral nutrition should be encouraged and maximised where possible and parenteral overfeeding should be avoided. Provision of parenteral lipid should be optimised to prevent the adverse effects of both deficiency and excess, and cyclical rather than continuous parenteral feeding should be administered. There is some evidence of benefit in neonates from oral antibiotics to prevent intestinal bacterial overgrowth and from oral ursodeoxycholic acid, but less to support their use in adults. Similarly, data to support widespread use of parenteral choline or taurine supplementation are lacking at present. Ultimately, severe parenteral nutrition-associated liver disease may necessitate referral for small intestine and/or liver transplantation.
Proceedings of The Nutrition Society 12/2007; 66(4):530-8. · 2.77 Impact Factor
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ABSTRACT: In the UK, restraining medical patients in order to provide care is widely considered to be outmoded and difficult to justify. The prevailing clinical intuition that restraining patients is generally wrong (even when restraint is essential in order to provide artificial nutrition and hydration) has prompted us to develop a policy that is compatible with common law, the Mental Capacity Act 2005 and the Human Rights Act 1998. The nature and scope of the problem are illustrated with clinical cases. These, in turn, serve to demonstrate the tension that arises between article 2, article 3 and article 8 rights, when incompetent patients are restrained in order to feed.
European Journal of Health Law 05/2007; 14(1):3-20.
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British journal of hospital medicine (London, England: 2005) 02/2007; 68(1):11-4. · 0.19 Impact Factor
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New England Journal of Medicine 10/2006; 355(13):1387; author reply 1387-8. · 53.30 Impact Factor
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ABSTRACT: Patients receiving parenteral nutrition (PN) still feel hungry despite adequate provision of calories intravenously. It is not known whether PN or its constituent macronutrients acutely affect appetite and to what degree this may be mediated by ghrelin and peptide YY (PYY).
Six medically stable patients (four men) with intestinal failure receiving PN received an isocaloric 200 kcal infusion on three separate occasions following a 12 h fast. The infusions consisted of either carbohydrate (10% dextrose), fat (10% intralipid) or mixed protein/carbohydrate (PN). Changes in ghrelin and peptide YY levels and changes in subjective symptoms of hunger, satiety and nausea during each macronutrient infusion were assessed.
None of the three infusions acutely affected subjective symptoms of hunger, satiety and nausea (P>0.05 ANOVA). Ghrelin levels decreased significantly during dextrose [-19.1 (-35.9, -12.4), regression coefficient (95% CI), P<0.001] and parenteral nutrition infusions [-18.2 (-26.8, -9.6), P<0.001]. Lipid infusion had no effect on ghrelin levels but led to a significant decrease in PYY [-0.076 (-0.0123, -0.028), P=0.004]. Dextrose and PN infusion had no significant effect on PYY levels.
Dextrose and PN infusions decrease ghrelin levels. Lipid infusion does not affect ghrelin levels but in contrast to oral nutrients leads to a significant decrease in PYY. Despite these changes, in patients receiving PN, macronutrient infusions do no acutely affect appetite.
Clinical Nutrition 09/2006; 25(4):626-33. · 3.73 Impact Factor
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ABSTRACT: Crohn's disease is strongly associated with double mutations in NOD2/CARD15. Three common mutations (Arg702Trp, Gly908Arg, Leu1007fs) impair innate immune responses to bacterial muramyl dipeptide. Rare NOD2 variants occur, but it is difficult to both identify them and assess their functional effect. We assessed the true frequency of defective muramyl dipeptide sensing in Crohn's disease and developed a rapid diagnostic assay.
An ex vivo assay was established and validated based on muramyl dipeptide stimulation of peripheral blood mononuclear cell cytokine production. Muramyl dipeptide-induced enhancement of interleukin (IL)-8 secretion and synergistic increase in lipopolysaccharide-induced IL-1beta secretion were studied. Assay results were compared with NOD2 genotype status (3 common mutations and rare variants) in 91 individuals including a prospective cohort of 49 patients with Crohn's disease.
The assay was highly sensitive and specific for detection of profound defects in muramyl dipeptide sensing caused by double NOD2 mutations (IL-8 P = 0.0002; IL-1beta P = 0.0002). Disease state, active inflammation, or concurrent use of immunosuppressive medication did not influence results. Healthy NOD2 heterozygotes had modest impairment of muramyl dipeptide induced IL-8 secretion (P = 0.003). Only 1 of 7 patients with Crohn's disease with both a common mutation and a rare variant had a profound muramyl dipeptide-sensing defect.
Profound defects in muramyl dipeptide sensing were found in 10% of patients with Crohn's disease. Defects were caused exclusively by inherited mutations in NOD2. The ex vivo assay has multiple potential applications as a clinical diagnostic tool to distinguish patients with muramyl dipeptide-sensing defects and for research investigation.
Inflammatory Bowel Diseases 08/2006; 12(7):598-605. · 4.86 Impact Factor
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ABSTRACT: Sufficient neovascularization of neotissue is currently a limiting factor for the engineering of large tissue constructs. 45S5 Bioglass has been investigated extensively in bone tissue engineering but there has been relatively little previous research on its application to soft-tissue engineering. The objectives of this study were to investigate the use of 45S5 Bioglass in soft-tissue engineering scaffolds using in vitro and in vivo models. A fibroblast cell line (208F) was used for in vitro evaluation of surfaces coated with 45S5 Bioglass. Increased proliferation of fibroblasts was observed after growth on polystyrene surfaces coated with low concentrations (0.01-0.2%wt/vol) of 45S5 Bioglass for 24 h in vitro, determined as a change in total cell number by measuring lactate dehydrogenase. At higher concentrations of 45S5 Bioglass and longer periods of incubation (48 and 72 h) on coated surfaces, cell proliferation was reduced. Light microscopy revealed that the morphology of fibroblasts grown on 45S5 Bioglass-coated surfaces was not altered at low concentrations, but at higher concentrations fibroblasts became vacuolated. Enzyme-linked immunosorbent assay of conditioned culture medium collected from fibroblasts grown for 24 h on surfaces coated with low concentrations of 45S5 Bioglass (0.01%wt/vol) was found to contain significantly higher concentrations of vascular endothelial growth factor. Histological examination of polyglycolic acid (PGA)/45S5 Bioglass composite scaffolds that had been implanted subcutaneously into rats revealed that 45S5 Bioglass-coated meshes were well tolerated. Light microscopy revealed that neovascularization into 45S5 Bioglass-coated meshes was significantly increased at 28 and 42 days. Electron microscopy revealed fibroblasts adhering closely to the PGA mesh but not to 45S5 Bioglass particles. The apparent ability of 45S5 Bioglass incorporated into scaffolds to increase neovascularization would be extremely beneficial during the engineering of larger soft-tissue constructs.
Biomaterials 01/2005; 25(27):5857-66. · 7.40 Impact Factor
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ABSTRACT: Polylactide-co-glycolide (PLGA) foams of tubular shape were assessed for their use as soft-tissue engineering scaffolds in vitro and in vivo. Porous membranes were fabricated by a thermally induced phase separation process of PLGA solutions in dimethylcarbonate. The parameters investigated were the PLGA concentration and the casting volume of solution. Membranes produced from 5 wt/v % polymer solutions and a 6 ml casting volume of polymer solution were selected for fabricating tubes of 3 mm diameter, 20 mm length and a nominal wall thickness of 1.5 mm. Scanning electron microscopy revealed that the structure of the tubular foams consisted of radially oriented and highly interconnected pores with a large size distribution (50-300 microm). Selected tubes were implanted subcutaneously into adult male Lewis rats. Although the lumen of the tubes collapsed within one week of implantation, histological examination of the implanted scaffolds revealed that the foam tubes were well tolerated. Cellular infiltration into the foams, consisting mainly of fibrovascular tissue, was evident after two weeks and complete within eight weeks of implantation. The polymer was still evident in the scaffolds after eight weeks of implantation. The results from this study demonstrate that the PLGA tubular foams may be useful as soft-tissue engineering scaffolds with modification holding promise for the regeneration of tissues requiring a tubular shape scaffold such as intestine.
Journal of Materials Science Materials in Medicine 07/2004; 15(6):729-34. · 2.32 Impact Factor
