Adherence to exclusive enteral nutrition by adults with active Crohn's disease is associated with conscientiousness personality trait: a sub-study.

BACKGROUND: It is probable that psychosocial factors predict adherence to exclusive enteral nutrition (EEN). Conscientiousness is an intrapersonal factor associated with greater medication adherence and healthy eating behaviours. This sub-study aimed to determine whether adherence to EEN was associated with conscientiousness. METHODS: Two groups of adults aged 16-40 years, were recruited to use EEN. Adults with active Crohn's disease used either EEN for 8 weeks or 2 weeks of EEN followed by 6 weeks of partial enteral nutrition (PEN). A control group of healthy adults used EEN for 2 weeks. Participants who reported eating food during EEN, ate more than one meal per day during PEN, or could not initiate or tolerate the oral nutritional supplements were defined as non-adherent. Conscientiousness was measured using the conscientiousness subset of the Big Five Inventory. RESULTS: Thirty-eight patients with active Crohn's disease (mean age 24.8 years) and 21 healthy adults (mean age 27.3 years) completed the conscientiousness questionnaire. In the Crohn's disease group, 23 (59%) completed and adhered to the treatments compared to 17 (81%) healthy adults; their conscientiousness scores were similar. Adherence and completion by the Crohn's disease group were associated with a greater mean conscientiousness score 35.57 (95% confidence interval = 32.88-38.25) compared to 30.13 (95% confidence interval = 26.53-33.73) in the non-adherent Crohn's disease group (P = 0.014). CONCLUSIONS: Conscientiousness was associated with treatment adherence. EEN can be a cognitively and emotionally demanding treatment for active adults with Crohn's disease; thus, considering personality traits may help determine suitable candidates.

Appropriate clinical use of human leukocyte antigen typing for coeliac disease: an Australasian perspective.

The past decade has seen human leukocyte antigen (HLA) typing emerge as a remarkably popular test for the diagnostic work-up of coeliac disease with high patient acceptance. Although limited in its positive predictive value for coeliac disease, the strong disease association with specific HLA genes imparts exceptional negative predictive value to HLA typing, enabling a negative result to exclude coeliac disease confidently. In response to mounting evidence that the clinical use and interpretation of HLA typing often deviates from best practice, this article outlines an evidence-based approach to guide clinically appropriate use of HLA typing, and establishes a reporting template for pathology providers to improve communication of results.

Perspectives of paediatric and adult gastroenterologists on transfer and transition care of adolescents with inflammatory bowel disease.

BACKGROUND: Programmes specific to inflammatory bowel disease (IBD) that facilitate transition from paediatric to adult care are currently lacking. AIM: We aimed to explore the perceived needs of adolescents with IBD among paediatric and adult gastroenterologists and to identify barriers to effective transition. METHODS: A web-based survey of paediatric and adult gastroenterologists in Australia and New Zealand employed both ranked items (Likert scale; from 1 not important to 5 very important) and forced choice items regarding the importance of various factors in facilitating effective transition of adolescents from paediatric to adult care. RESULTS: Response rate among 178 clinicians was 41%. Only 23% of respondents felt that adolescents with IBD were adequately prepared for transition to adult care. Psychological maturity (Mean = 4.3, standard deviation (SD) = 0.70) and readiness as assessed by adult caregiver (Mean = 4, SD = 0.72) were prioritised as the most important factors in determining timing of transfer. Self-efficacy and readiness as assessed by adult caregiver were considered the two most important factors to determine timing of transition by both groups of gastroenterologists. Poor medical and surgical handover (Mean = 4.10, SD = 0.8) and patients' lack of responsibility for their own care (Mean= 4.10, SD = 0.82) were perceived as major barriers to successful transition by both paediatric and adult gastroenterologists. CONCLUSIONS: Deficiencies exist in current transition care of adolescents with IBD in Australia and New Zealand. Standardising transition care practices with strategies aimed at optimising communication, patient education, self-efficacy and adherence may improve outcomes.

Meta-analysis: Intestinal ultrasound to evaluate colonic contents and constipation.

BACKGROUND: Constipation can be diagnosed clinically using the Rome criteria. Ultrasound (US), which lacks the radiation exposure of conventional X-ray, holds promise as a non-invasive tool to evaluate colonic contents and constipation. AIM: To examine the role of US in the assessment of constipation. METHODS: We performed a systematic search of Embase (OVID, 1984), Medline (Ovid, 1946), Cochrane Central, ClinicalTrials.gov and Australia New Zealand Clinical Trials Registry from database inception to 26 January 2024 according to PRISMA guidelines and prospectively registered with PROSPERO. All studies using US to assess constipation or colonic contents in either adults or children were included. Rectal diameter measurements were pooled in meta-analysis. Risk of bias was assessed using the Newcastle Ottawa Scales and Joanna Briggs Institute checklists. RESULTS: Of 12,232 studies screened, 51 articles (6084 patients; 3422 children) describing US to assess symptoms in patients with constipation were included. Most studies used Rome criteria to diagnose constipation. Rectal diameter was associated with clinical constipation in 29 paediatric studies (3331 patients). Meta-analysis showed the mean rectal diameter of constipated patients was significantly higher than controls (mean difference 12 mm, 95% confidence intervals (CI): 6.48, 17.93, p < 0.0001, n = 16 studies). Other features of constipation on US included posterior acoustic shadowing and echogenicity of luminal contents. CONCLUSION: US is an appealing imaging modality to assess luminal contents and constipation. Further well-designed studies are required to validate US metrics that accurately identify constipation.

Comparison of Fecal Calprotectin and Myeloperoxidase in Predicting Outcomes in Inflammatory Bowel Disease.

BACKGROUND: Biomarkers have been proposed as surrogate treatment targets for the management of inflammatory bowel disease (IBD); however, their relationship with IBD-related complications remains unclear. This study investigated the utility of neutrophil biomarkers fecal calprotectin (fCal) and fecal myeloperoxidase (fMPO) in predicting a complicated IBD course. METHODS: Participants with IBD were followed for 24 months to assess for a complicated IBD course (incident corticosteroid use, medication escalation for clinical disease relapse, IBD-related hospitalizations/surgeries). Clinically active IBD was defined as Harvey-Bradshaw index >4 for Crohn's disease (CD) and simple clinical colitis activity index >5 for ulcerative colitis (UC). Area under the receiver-operating-characteristics curves (AUROC) and multivariable logistic regression assessed the performance of baseline symptom indices, fCal, and fMPO in predicting a complicated disease IBD course at 24 months. RESULTS: One hundred and seventy-one participants were included (CD, n = 99; female, n = 90; median disease duration 13 years [interquartile range, 5-22]). Baseline fCal (250 µg/g; AUROC = 0.77; 95% confidence interval [CI], 0.69-0.84) and fMPO (12 µg/g; AUROC = 0.77; 95% CI, 0.70-0.84) predicted a complicated IBD course. Fecal calprotectin (adjusted OR = 7.85; 95% CI, 3.38-18.26) and fMPO (adjusted OR = 4.43; 95% CI, 2.03-9.64) were associated with this end point after adjustment for other baseline variables including clinical disease activity. C-reactive protein (CRP) was inferior to fecal biomarkers and clinical symptoms (pdifference < .05) at predicting a complicated IBD course. A combination of baseline CRP, fCal/fMPO, and clinical symptoms provided the greatest precision at identifying a complicated IBD course. CONCLUSIONS: Fecal biomarkers are independent predictors of IBD-related outcomes and are useful adjuncts to routine clinical care.

Longer-term outcomes of nutritional management of Crohn's disease in children.

BACKGROUND: While the short-term benefits of exclusive enteral nutrition (EEN) for induction of remission in children with Crohn's disease (CD) are well documented, the longer-term outcomes are less clear. AIM: This retrospective study aimed to ascertain the outcomes for up to 24 months following EEN in a group of children with CD. METHODS: Children treated with EEN as initial therapy for newly diagnosed CD over a 5-year period were identified. Details of disease activity, growth, and drug requirements over the period of follow-up were noted. Outcomes in children managed with EEN were compared to a group of children initially treated with corticosteroids. RESULTS: Over this time period, 31 children were treated with EEN and 26 with corticosteroids. Twenty-six (84 %) of the 31 children treated with EEN entered remission. Children treated with EEN exhibited lower pediatric Crohn's disease activity index (PCDAI) scores at 6 months (p = 0.02) and received lower cumulative doses of steroids over the study period (p < 0.0001) than the group treated with corticosteroids. Height increments over 24 months were greater in the EEN group (p = 0.01). Although the median times to relapse were the same, the EEN group had a lower incidence of relapse in each time interval and survival curve analysis showed lower risk of relapse (p = 0.008). CONCLUSIONS: EEN lead to multiple benefits beyond the initial period of inducing remission for these children, with positive outcomes over 2 years from diagnosis. Of particular clinical relevance to growing children was the reduced exposure to corticosteroids.

Fecal M2-PK in children with Crohn's disease: a preliminary report.

BACKGROUND AND AIMS: Although active inflammatory changes in chronic Crohn's disease (CD) can be detected with serum inflammatory markers, these have low specificity and sensitivity. Stool markers of inflammation, such as M2-pyruvate kinase (M2-PK), permit more direct assessment of mucosal inflammation. The aim of this study was to assess levels of M2-PK in children with active CD and to compare to levels in healthy control children. METHODS: Fecal levels of M2-PK were measured by immunoassay using stored stool samples from children with untreated (active) CD and healthy control children. Correlations between M2-PK levels and disease activity scores and serum inflammatory markers were performed. Comparison was also made between M2PK and a second fecal inflammatory marker, S100A12. RESULTS: Mean fecal M2-PK levels were higher in the 17 patients with active CD than in the 21 healthy controls (p = 0.0007). M2-PK levels did not correlate with disease activity scores or serum inflammatory markers. There was a trend for children with ileocolonic disease to have higher levels of M2-PK in their stool compared to those with colonic disease or isolated ileal disease. Fecal M2PK did not correlate with fecal S100A12 in children with active CD. CONCLUSION: Fecal M2-PK is increased in children with active CD, indicating that this marker may be a useful non-invasive marker for gut inflammation. Further studies of M2PK are required in additional settings with larger cohorts of children with CD and with comparison to other stool markers.

Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe ulcerative colitis: a prospective multicentre comparison of predicting outcomes and monitoring response.

OBJECTIVE: To compare four faecal markers for their ability to predict steroid refractoriness in severe paediatric ulcerative colitis (UC). Construct validity and responsiveness to change were also assessed. METHODS: This was a prospective multicentre cohort study. Stool samples from 101 children (13.3 + or - 3.6 years; Pediatric UC Activity Index (PUCAI) at admission 72 + or - 12 points) were obtained at the third day of intravenous steroid therapy. Repeated samples at discharge were obtained from 24 children. Predictive validity was assessed using diagnostic utility statistics to predict steroid failure (ie, the need for salvage treatment). Concurrent validity was assessed using correlational analysis with the following constructs: PUCAI, Lindgren and Seo scores, physician's global assessment, albumin, erythrocyte sedimentation rate and C-reactive protein (CRP). Responsiveness was assessed using test utility and correlational strategies. RESULTS: Median values (IQR) were very high at baseline for all four markers (calprotectin 4215 microg/g (2297-8808); lactoferrin 212 microg/g (114-328); M2-pyruvate kinase (M2-PK) 363 U/g (119-3104); and S100A12 469 microg/g (193-1112)). M2-PK was numerically superior to the other three markers and CRP in predicting response to corticosteroid treatment (area under the receiver operating characteristic (ROC) curve 0.75 (95% CI 0.64 to 0.85; p<0.001) vs <0.65 for the others). However, it did not add to the predictive ability of the PUCAI (area under the ROC 0.81 (95% CI 0.73 to 0.89)). M2-PK also had the highest construct validity but with a modest mean correlation with all constructs (r=0.3; p<0.05). None of the markers was responsive to change (Spearman's rho correlation with change in the PUCAI <0.1; p>0.05, area under the ROC curve <0.65; p>0.05). CONCLUSIONS: The four markers were greatly elevated in severe paediatric UC. Only M2-PK had good construct and predictive validity, and none was responsive to change. The PUCAI, a simple clinical index, performed better than the faecal markers in predicting outcome following a course of intravenous corticosteroids in severe UC.

Nutritional status of children with coeliac disease.

AIMS: The main aim of this study was to assess the nutritional status of children with newly diagnosed Coeliac disease (CD)with comparison to matched controls. A further aim was to assess relationships between presentation patterns and nutrition in childhood CD. METHODS: The nutritional status of newly diagnosed CD was assessed by anthropometry, Bioelectrical Impedance and serum leptin levels, and contrasted to age and gender matched controls. RESULTS: Twenty-five children with CD (mean age of 8.2 +/- 4.5 years) and 25 control children (mean age 8.1 +/- 4.4.) were enrolled. Thirteen (52%) children with CD had gastrointestinal symptoms with 14 having a family history of CD. At presentation 8.7% were wasted, 4.2% were stunted and 20.8% overweight, although none were obese. Mean height and weight for age, other nutritional parameters and serum leptin did not differ between the groups. Serum leptin correlated with BMI in both groups. CONCLUSIONS: Children with CD more commonly present with atypical symptoms than with classical features. Variations in nutrition (under to overnutrition) may be seen at diagnosis, without relationship to the presence of symptoms. Leptin levels were not altered specifically in the setting of CD. Nutritional assessment remains important in the assessment and management of CD in children.

Sustained modulation of intestinal bacteria by exclusive enteral nutrition used to treat children with Crohn's disease.

BACKGROUND: The use of exclusive enteral nutrition to treat paediatric Crohn's disease (CD) is widely accepted, although the precise mechanism(s) of action remains speculative. AIM: To investigate the changes to key intestinal bacterial groups of Eubacteria, Bacteroides, Clostridium coccoides, Clostridium leptum and Bifidobacteria, during and after exclusive enteral nutrition treatment for CD in paediatric patients and correlate these changes to disease activity and intestinal inflammation. METHODS: Stool was collected from six children at diagnosis of CD, during exclusive enteral nutrition and 4 months post-therapy, and from seven healthy control children. The diversity of bacteria was assessed by polymerase chain reaction-denaturing gradient gel electrophoresis with changes to bacterial diversity measured by Bray-Curtis similarity, intestinal inflammation assessed by faecal S100A12 and the disease activity assessed by PCDAI. RESULTS: A significantly greater change in intestinal bacterial composition was seen with exclusive enteral nutrition treatment compared with controls. Further, the intestinal bacteria remained altered 4 months following exclusive enteral nutrition completion. Changes in the composition of Bacteroides were associated with reduced disease activity and inflammation. CONCLUSIONS: Exclusive enteral nutrition reduces bacterial diversity and initiates a sustained modulation of all predominant intestinal bacterial groups. Exclusive enteral nutrition may reduce inflammation through modulating intestinal Bacteroides species. The implications of these results for exclusive enteral nutrition therapy and CD pathogenesis should now be the subject of further investigation.

Thiopurine metabolite monitoring in paediatric inflammatory bowel disease.

BACKGROUND: Measurement of thiopurine metabolite levels may be useful as a clinical tool to optimize thiopurine treatment of paediatric inflammatory bowel disease (IBD). AIM: The authors evaluated correlations between 6-thioguanine nucleotide (6-TGN) and therapeutic response, metabolite levels and drug toxicity. METHODS: Fifty-six paediatric IBD patients treated with thiopurines had 326 metabolite level measurements and were retrospectively reviewed. Clinical status and laboratory parameters were compared with metabolite levels. RESULTS: There was significant correlation between 6-TGN levels and therapeutic response, with higher median 6-TGN levels among patients with therapeutic response than those with non-therapeutic response (194 vs. 146 pmol/8 x 10(8) RBC; P = 0.0004). Patients with 6-TGN levels >235 pmol/8 x 10(8) RBC were more likely to achieve therapeutic response than those below the cut-off (odds ratio, 2.5; 95% CI, 1.5-4.1). Patients who developed leukopenia tended to have higher median 6-TGN levels than those without leukopenia (261 vs. 160 pmol/8 x 10(8) RBC) but the difference was not statistically significant. There was no correlation between 6-methylmercaptopurine levels and hepatotoxicity. Two patients developed acute pancreatitis. Metabolite level measurements were helpful in identifying non-compliance in nine patients. CONCLUSIONS: Monitoring of thiopurine metabolite levels is useful to guide and optimize dosing, as an adjunct to clinical judgement, blood count and liver biochemistry measurements to minimize the risk of drug toxicity and to confirm non-compliance.

Childhood inflammatory bowel disease: parental concerns and expectations.

AIM: To document the concerns and expectations of parents of children with inflammatory bowel disease (IBD) within the context of a multidisciplinary IBD clinic, and to highlight the importance of a holistic approach to the care of these children. METHODS: The parents of 60 children with IBD were surveyed by mailed questionnaire. Parents were asked to provide details of their concerns regarding their child's condition and to express their expectations of medical care. In addition, enquiry was made in respect to the respondents' learning about IBD. RESULTS: Forty-six questionnaires (77%) returned. Fifty-two percent of the patients were male. Patients were aged a mean of 10.9 (+/-4.1) years and diagnosed at an average age of 2.1 (+/-1.8) years previously. The most common concerns expressed by the parents related to the side- effects of medications and the future prospects for their child. Overall, parents were satisfied with aspects of care within the IBD clinic but many suggested additional personnel such as counselors or educators should be available. Parents also reported the need for continuing education and easy access to up-to-date information. CONCLUSION: Parents of children and adolescents with IBD have many common concerns regarding their child's condition. On-going attention to holistic care, including psychosocial and educational elements for patients and families, is appropriate in the context of the chronic and unpredictable nature of IBD.

Somatic noxious mechanical stimulation induces Fos expression in the postsynaptic dorsal column neurons in laminae III and IV of the rat spinal dorsal horn.

This study was conducted to ascertain the possible expression of Fos-like immunoreactivity (Fos-LI) in the postsynaptic dorsal column (PSDC) neurons in response to noxious mechanical stimulation of the forepaw glabrous area of normal rats. For this purpose, Fos immunohistochemistry along with Fluoro-Gold (FG) retrograde tracing was utilized. After repeated noxious pinching of the forepaw glabrous area, there was a marked increase in number of Fos-LI neurons in the dorsal horn, including Rexed's laminae III and IV, at C5-T1 spinal cord segments ipsilateral to the stimulation. Between segments C5 and T1, about 40% of the Fos-LI neurons in laminae III and IV were distributed at segment C7. In the rats subjected to the noxious pinch coupled with FG injection into the right cuneate nucleus, PSDC neurons double labeled with Fos and FG were localized in the ipsilateral laminae III and IV extending from segment C5 to T1, with about 70% of them distributed at segments C6 and C7. At segment C6 or C7, double-labeled neurons made up about 10% of the PSDC neurons that projected their axons to the cuneate nucleus. Most of the double-labeled neurons appeared fusiform with their primary dendrites projected dorso-ventrally. The present results suggest that the morphologically distinct, subclasses of PSDC neurons in spinal laminae III and IV may contribute to the central transmission of mechanical nociceptive information through the dorsal column into the cuneate nucleus.

A beta-fiber intensity stimulation of chronically constricted median nerve induces c-fos expression in thalamic projection neurons of the cuneate nucleus in rats with behavioral signs of neuropathic pain.

This study was aimed to investigate the possible involvement of neurons in the cuneate nucleus (CN) in the processing of A beta afferent inputs evoked by electrical stimulation of constricted median nerve in rats with behavioral signs of neuropathic pain. Immunohistochemical localization of Fos protein was used to examine the neuronal activation, and the combination of Fos immunohistochemistry with the retrograde labeling of Fluoro-Gold (FG) injected into the ventrobasal complex of the thalamus was used to characterize the activated neurons. Two weeks after unilateral median nerve constriction injury, the rats exhibited behavioral signs of neuropathic pain in the affected forepaws. In rats after nerve injury but without electrical stimulation, some Fos-like immunoreactive (Fos-LI) neurons were detected in the dorsal horn of the seventh cervical segment (C7) but none was found in the CN. Similar features were also noted when the stimulation of the intact median nerve served as an additional control. After A beta-fiber intensity stimulation of the previously constricted median nerve, an increase in number of Fos-LI neurons occurred in the medial half of the ipsilateral C7 dorsal horn as well as in the ipsilateral CN. In the latter, the Fos-LI neurons were located in the median nerve projection territory throughout the nucleus. Most of the Fos-LI neurons were distributed in the middle region of the CN, with about 78% of them emitting FG fluorescence indicating that they were cuneothalamic projection neurons. The results of this study suggest that the dorsal column-medial lemniscal system may contribute to the transmission and modulation of A beta-fiber mediated neuropathic pain signals.

Understanding disease outcome following acquisition of Helicobacter pylori infection during childhood.

Helicobacter pylori causes chronic active (type B) gastritis in the overwhelming majority of infected individuals. The relative contribution of virulence factors in the bacterium and host responses to the microbial infection in determining which subjects will go on to develop complications - such as peptic ulceration, gastric cancers and gastric lymphomas - is the subject of current investigative activities.