Transition to adult health services is a vulnerable phase in young persons with chronic disease. We describe how young persons with inflammatory bowel disease in Germany and Austria experience care ...during the transitional age, focusing on differences by type of provider (pediatric vs. adult specialist, no specialist).
This was a follow up survey in patients previously registered with a pediatric IBD registry. Patients aged 15 to 25 received a postal questionnaire, including a measure of health care experience and satisfaction. Descriptive analyses were stratified by age. Sub-analyses in the 18-20 year age group compared health care experience by type of provider. Determinants of early or late transfer were examined using multinomial logistic regression.
619 patients responded to the survey; 605 questionnaires were available for analysis. Usual age of completing transition was 18. Earlier transfer was more common with low parental SES (OR 1.8, 95% CI 0.7 to 4.6), and less common with advanced schooling (OR 0.5, 95% CI 0.2 to 1.2). Structured transition was uncommon. 48% of the respondents had not received any preceding transition advice. Overall satisfaction with IBD care was high, especially with respect to interpersonal aspects, but less so in aspects of continuity of care.
Despite high overall patient satisfaction, relevant deficiencies in transitional care were documented. Some of these were associated with lower parental social status. Differences in health care satisfaction by type of provider (adult vs. pediatric) were small.
Gain-of-function mutations in guanylyl cyclase C (GCC) result in persistent diarrhea with perinatal onset. We investigated a specific GCC inhibitor, SSP2518, for its potential to treat this disorder.
...We investigated the effect of SSP2518 on GCC-mediated intracellular cyclic guanosine monophosphate (cGMP) levels and on GCC-mediated chloride secretion in intestinal organoids from 3 patients with distinct activating GCC mutations and from controls, with and without stimulation of GCC with heat-stable enterotoxin.
Patient-derived organoids had significantly higher basal cGMP levels than control organoids, which were lowered by SSP2518 to levels found in control organoids. In addition, SSP2518 significantly reduced cGMP levels and chloride secretion in patient-derived and control organoids (P < 0.05 for all comparisons) after heat-stable enterotoxin stimulation.
We reported in this study that the GCC inhibitor SSP2518 normalizes cGMP levels in intestinal organoids derived from patients with GCC gain-of-function mutations and markedly reduces cystic fibrosis transmembrane conductance regulator-dependent chloride secretion, the driver of persistent diarrhea.
AIM To investigate the relation of two different mutations to the outcome of partial external biliary diversion(PEBD)in severe bile salt export pump(BSEP) deficiency.METHODS Mutations in the gene ...encoding BSEP leading to severe BSEP deficiency in two unrelated patients were identified by genomic sequencing. Native liver biopsies and transiently transfected human embryonic kidney(HEK) 293 cells expressing either wild-type or mutated BSEP were subjected to immunofluorescence analysis to assess BSEP transporter localization. Bile acid profiles of patient and control bile samples were generated by ultra-performance liquid chromatographytandem mass spectrometry. Wild-type and mutant BSEP transport of ~3H-labeled taurocholate(TC) and taurochenodeoxycholate(TCDC) was assessed by vesicular transport assays.RESULTS A girl(at 2 mo) presented with pruritus, jaundice and elevated serum bile salts(BS). PEBD stabilized liver function and prevented liver transplantation. She was heterozygous for the BSEP deletion p.T919 del and the nonsense mutation p.R1235 X. At the age of 17 years relative amounts of conjugated BS in her bile were normal, while total BS were less than 3% as compared to controls. An unrelated boy(age 1.5 years) presenting with severe pruritus and elevated serum BS was heterozygous for the same nonsense and another missense mutation, p.G1032 R. PEBD failed to alleviate pruritus, eventually necessitating liver transplantation. BS concentration in bile was about 5% of controls. BS were mainly unconjugated with an unusual low amount of chenodeoxycholate derivatives(< 5%). The patients’ native liver biopsies showed canalicular BSEP expression. Both BSEP p.T919 del and p.G1032 R were localized in the plasma membrane in HEK293 cells. In vitro transport assays showed drastic reduction of transport by both mutations. Using purified recombinant BSEP as quantifiable reference, per-molecule transport rates for TC and TCDC were determined to be 3 and 2 BS molecules per wild-type BSEP transporter per minute, respectively.CONCLUSION In summary, our findings suggest that residual function of BSEP as well as substrate specificity influence the therapeutic effectiveness of PEBD in progressive familial intrahepatic cholestasis type 2(PFIC-2).
Background:
Inflammatory bowel disease (IBD) is a polygenetic disorder. Our group previously showed that a variant within the CXCL9 gene is associated with pediatric Crohn's disease. As CXCL9, ...CXCL10, and CXCL11 are the 3 ligands to the receptor CXCR3, the aim of this study was to investigate the colonic transcriptional activity of the CXCR3 axis and to perform SNP genotyping of a CXCL11 polymorphism in a large pediatric and adult IBD cohort.
Methods:
mRNA expression of CXCR3, CXCL9, CXCL10, CXCL11, and IL8 was analyzed in colonic biopsies using real‐time PCR. CXCL11 rs6817952 nucleotide substitution was determined in 501 German individuals with IBD (336 CD, 165 UC) including 258 children and 243 adults as well as in 231 controls by a TaqMan SNP genotyping assay.
Results:
CXCR3 axis genes were significantly overexpressed in inflamed colonic tissue of pediatric CD and UC patients. The prevalence of hetero‐ and homozygous variants of the rs6817952 genotype was higher in pediatric but not in adult CD patients compared with that in controls (P = 0.04). Moreover, carriers of the hetero‐ and homozygous genotype variants of rs6817952 were at increased risk for UC in all age groups (P = 0.009).
Conclusions:
Our study provides evidence of the significant overexpression of the CXCR3 axis in active IBD, suggesting it has a role in IBD pathogenesis. The rs6817952 A variant is a risk allele for pediatric CD and UC in all age groups. Therapeutic studies will have to show whether the blockade of chemokine receptors such as CXCR3 can modulate intestinal inflammation in a clinical application. Inflamm Bowel Dis 2010
Objective
Among patients with inflammatory bowel disease (IBD), the risk of thromboembolism (TE) is increased, representing a relevant cause of morbidity and mortality. In contrast to other ...extraintestinal IBD manifestations, TE receives much less attention because of its low incidence, estimated at merely 0.4–0.9% in hospitalised children with IBD.
Methods
Cases with TE, as documented in the German-Austrian Paediatric IBD registry gesellschaft für pädiatrische gastroenterologie und ernährung – large paediatric patient registry (CEDATA-GPGE), were analyzed retrospectively. For all patients with signs of TE, a questionnaire was filled in by the treating paediatric gastroenterologist.
Results
Over 10 years, 4,153 paediatric patients with IBD (0–18 years) were registered in the registry, and 12 of them identified with TE. Eight patients were diagnosed with ulcerative colitis (UC), three with Crohn’s disease (CD), and one with IBD-unclassified. The median age at IBD diagnosis was 10 years and at the manifestation of TE 13 years, respectively, with a median latency to TE of 2 years. Prevalence of TE was 0.3%, with a significantly higher risk for patients with UC than CD (OR 5.9, CI 1.56–22.33,
p
= 0.008). More girls than boys were affected (f:m = 7:5) without reaching significance. Approximately 90% of patients experienced TE during active disease, with relevant cerebral and limb involvement in 6/12 patients. Various risk factors, e.g., hospitalisation, coagulopathy, or anaemia were identified. TE management included intensive care and surgery. Among the 12 patients, 11 recovered fully, in which one patient has focal epilepsy as a sequela.
Conclusion
Paediatric patients with IBD have a substantially increased risk for TE. Risk factors, such as those identified should be considered when managing paediatric IBD and preventive measures for those hospitalised taken routinely. Initiating pharmacological thromboprophylaxis is challenging for the lack of published trials on efficacy and safety in paediatric IBD but should be considered carefully in each case.
Progressive familial intrahepatic cholestasis (PFIC) usually presents with pruritus, jaundice, hepatomegaly, and growth failure. A group of PFIC is recognized by marked elevation of total serum bile ...acids, decreased serum apolipoprotein A-1, and high-density lipoprotein, but normal gamma-glutamyltranspeptidase and cholesterol. Although medical therapy generally fails, partial external biliary diversion (DIV) has been used with promising results for cholestasis. However, little has been reported of its effect on linear growth, synthetic liver function, and lipid metabolism.
DIV was performed on six noncirrhotic children with PFIC, all suffering from severe pruritus and cholestasis, refractory to medical treatment. Stature was below -1 (median, -2.3) standard deviation score (SDS) for height in all cases. All patients had markedly enhanced bile acids (307 +/- 72 microl/L), markedly decreased high-density lipoprotein (20 +/- 7 mg/dl), and apolipoprotein A-1 (58 +/- 37 mg/dl), but normal gamma-glutamyltranspeptidase and cholesterol. In addition, cholinesterase activity, monoethylglycinexylidide test, and Fischer's ratio indicated a significantly reduced synthetic liver function in all children but the youngest.
After DIV, all patients were consistently relieved of pruritus, and experienced normalization of all liver function tests, including cholinesterase activity, monoethylglycinexylidide test, and Fischer's ratio, as well as the serum lipid profile within 1 yr. In addition, a marked catch-up growth (median, +/- 1.3 SDS) was evident after 1 yr in all cases.
This report shows an excellent result of DIV in noncirrhotic PFIC patients and compares favorably with other reports. All patients experienced complete remission, including normalization of synthetic liver function and lipid metabolism. For the first time we have shown that DIV can also be associated with an accelerated growth in these patients.
Congenital sodium diarrhoea (CSD) refers to a form of secretory diarrhoea with intrauterine onset and high faecal losses of sodium without congenital malformations. The molecular basis for CSD ...remains unknown. We clinically characterised a cohort of infants with CSD and set out to identify disease-causing mutations by genome-wide genetic testing.
We performed whole-exome sequencing and chromosomal microarray analyses in 4 unrelated patients, followed by confirmatory Sanger sequencing of the likely disease-causing mutations in patients and in their family members, followed by functional studies.
We identified novel de novo missense mutations in GUCY2C, the gene encoding receptor guanylate cyclase C (GC-C) in 4 patients with CSD. One patient developed severe, early-onset IBD and chronic arthritis at 4 years of age. GC-C is an intestinal brush border membrane-bound guanylate cyclase, which functions as receptor for guanylin, uroguanylin and Escherichia coli heat-stable enterotoxin. Mutations in GUCY2C were present in different intracellular domains of GC-C, and were activating mutations that enhanced intracellular cyclic guanosine monophosphate accumulation in a ligand-independent and ligand-stimulated manner, following heterologous expression in HEK293T cells.
Dominant gain-of-function GUCY2C mutations lead to elevated intracellular cyclic guanosine monophosphate levels and could explain the chronic diarrhoea as a result of decreased intestinal sodium and water absorption and increased chloride secretion. Thus, mutations in GUCY2C indicate a role for this receptor in the pathogenesis of sporadic CSD.
The cover image is based on the Review Extrahepatic manifestations of progressive familial intrahepatic cholestasis syndromes: Presentation of a case series and literature review by Eva‐Doreen Pfi ...ster et al., https://doi.org/10.1111/liv.15200.
The removal of bolus impaction within the esophagus is an indication for emergency endoscopy. The current guideline of the European Society of Gastrointestinal Endoscopy (ESGE) recommends gently ...pushing the bolus into the stomach. This view is discerned by many endoscopists because of the increased risk of complications. In addition, the use of an endoscopic cap for bolus removal is not mentioned.
In a retrospective analysis from 2017 to 2021 we investigated 66 adults and 11 children with acute bolus impaction within the esophagus.
Eosinophilic esophagitis, reflux esophagitic /peptic stenosis and Schatzki Ring caused 57.6%, esophageal and bronchial carcinoma 18%, esophageal motility disorders 4.5%, Zenkers diverticulum 1.5% and radiation esophagitis 1.5% of the bolus obstructions. The reason remained unclear in 16.7% of the cases. The spectrum was comparable in children with additional 2 cases with esophageal atresia and stenosis. The reason was unclear in 2 cases. Removal of bolus impaction was successful in 92.4% in adults and 100% in children. Bolus obstruction in adults was successfully removed solely by endoscopic cap in 57.6% and 75% in children. Pushing the bolus into the stomach without disintegration was possible in only 9% of cases.
Flexible endoscopy is an effective ermergency intervention for removal of bolus obstruction within the esophagus. Uncontrolled pushing the bolus into the stomach without view cannot be recommended. An endoscopic cap is a good extension for safe bolus removal.
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