Search

Infantile hypercalcemia (IH) is a rare genetic disorder characterized by hypercalcemia, hypercalciuria, low parathyroid hormone, and nephrocalcinosis during the first months of life. Biallelic variants in the genes CYP24A1 and SCL34A1 cause IH1 and 2, respectively. We present the case of a newborn with an antenatal diagnosis of IH2 due to the identification of echogenic, yet normal-sized kidneys at 23 weeks gestation. Trio whole-exome sequencing initially identified only a heterozygous pathogenic variant in SLC34A1. Re-analysis of the exome data because of the clinical suspicion of IH2 revealed a 21-basepair deletion in trans that had initially been filtered out because of its high allele frequency. The diagnosis of IH2 enabled postnatal screening for hypercalcemia, present already at week 1, resulting in early treatment with phosphate supplementation and vitamin D avoidance. In the subsequent course, biochemical parameters were normalized, and the patient showed no obvious clinical complications of IH2, apart from the nephrocalcinosis. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the value of magnetization transfer (MT) MRI and texture analysis (TA) of T2-weighted MR images (T2WI) in the assessment of intestinal fibrosis in a mouse model. Methods: Chronic colitis was induced in mice by cyclic administration of dextran sodium sulphate (DSS) resulting in chronic inflammation and progressive bowel fibrosis. Mice underwent 7-T MR imaging at various time points. Bowel wall MT ratio (MTR) and textural features (skewness, kurtosis, entropy), extracted by a filtration histogram technique, were correlated with histopathology. Performance of both techniques were validated using antifibrotic therapy. Finally, a retrospective study was conducted in five patients with Crohn's disease (CD) who underwent bowel surgery. Results: MTR and texture entropy correlated with histopathological fibrosis (r =.85 and.81, respectively). Entropy was superior to MTR for monitoring bowel fibrosis in the presence of coexisting inflammation (linear regression R2 =.93 versus R2 =.01). Furthermore, texture entropy was able to assess antifibrotic therapy response (placebo mice versus treated mice at endpoint scan; Δmean = 0.128, p <.0001). An increase in entropy was indicative of fibrosis accumulation in human CD strictures (inflammation: 1.29; mixed strictures: 1.4 and 1.48; fibrosis: 1.73 and 1.9). Conclusion: MT imaging and TA of T2WI can both noninvasively detect established intestinal fibrosis in a mouse model. However, TA is especially useful for the longitudinal quantification of fibrosis in mixed inflammatory-fibrotic tissue, as well as for antifibrotic treatment response evaluation. This accessible post-processing technique merits further validation as the benefits for clinical practice as well as antifibrotic trial design would be numerous. Key Points: • Magnetization transfer MRI and texture analysis of T2-weighted MR images can detect established bowel fibrosis in an animal model of gut fibrosis. • Texture entropy is able to identify and monitor bowel fibrosis progression in an inflammatory context and can assess the response to antifibrotic treatment. • A proof-of-concept study in five patients with Crohn's disease suggests that texture entropy can detect and grade fibrosis in human intestinal strictures. [ABSTRACT FROM AUTHOR]

Background: Endoscopic ultrasound-guided rendezvous (EUS-RV) is a recently added alternative salvage technique to percutaneous transhepatic cholangiography rendezvous (PTC-RV) for achieving biliary cannulation in failed ERCP. Comparative data on these two techniques are lacking. The aim of this study is to evaluate the efficacy and safety of EUS-RV versus PTC-RV in a tertiary referral center. Methods: A case–control study was conducted in the tertiary referral center, Ghent University Hospital. All consecutive patients that underwent a rendezvous procedure between February 2014 and March 2022 for failed biliary cannulation were included. Patients that underwent PTC-RV (between February 2014 and February 2018) were compared to those who underwent EUS-RV (between March 2018 and March 2022). A sub-analysis was performed for malignant biliary strictures (MBO), benign biliary strictures (BBO) and common bile duct stones (CBDS). The primary endpoints of interest were technical success rate and complication rate. These outcome variables were compared among techniques using Fisher's exact test. Statistical analyses were performed using STATA version 15. Results: A total of 59 consecutive procedures in 57 patients were included for analysis; 20/59 (33.9%) were PTC-RV; the remaining 39/59 (66.1%) procedures were EUS-RV. Two patients in the PTC-RV group underwent two procedures. Of the PTC-RV procedures, 18/20 (90.0%) were technically successful, as compared to 28/39 EUS-RV procedures (71.8%) (P = 0.184; Fig. 1). Adverse events were reported in 7/20 PTC-RV procedures (35.0%) and in 13/39 EUS-RV procedures (33.3%) (P = 1.000). In 5/20 PTC-RV procedures (25.0%) and 4/39 EUS-RV procedures (10.3%), the adverse event was considered major (defined as AGREE classification of 3 or more; P = 0.249). Conclusions: EUS-RV has an acceptable success rate and is not associated with an increased risk of adverse events as compared to PTC-RV. [ABSTRACT FROM AUTHOR]

Background: Patients with malignant hilar biliary strictures can suffer from obstructive jaundice. Controversy remains on the optimal approach to obtain preoperative or palliative biliary drainage in these patients. A systematic review and meta-analysis was conducted to compare the two modalities most commonly used in this scenario: endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC).Methods: MEDLINE via PubMed was searched for relevant articles published from 2005 to April 2019. Following outcome measures were used to compare ERCP and PTC: therapeutic success rate, cholangitis, pancreatitis, bleeding, tube dislocation, reintervention rate, mortality such as 30d mortality and in-hospital death, median survival time, drainage patency, duration until decompression and hospital stay. Risk of bias assessment for the retrospective studies was conducted by NOS. RoB 2 was used for RCT. A meta-analysis was performed by using Review Manager 5.3. The certainty of evidence was appraised using GRADE.Results: Eleven articles of which one RCT and ten retrospective cohort studies fulfilled the inclusion criteria for data-analysis (1417 patients; 784 ERCP, 633 PTC). The combined odds ratio (OR) for therapeutic succes was 3.5 times higher in the PTC group (95% CI 2.05-5.97; high certainty). In terms of cholangitis, ERCP carried a 1.7-fold risk as compared to PTC (95% CI 0.92-3.08; moderate certainty). Patients who underwent ERCP were 11.50 times more likely to undergo a reintervention (95% CI 3.51-37.70; moderate certainty). ERCP was comparable to PTC in terms of pancreatitis (low certainty), bleeding (high certainty) and tube dislocation rate (moderate certainty). Mortality tended to be numerically higher in the PTC group but low patient numbers, selection bias and study heterogeneity did not allow uniform comparative analysis.Conclusions: In patients with malignant hilar biliary strictures, PTC is associated with a better therapeutic success rate, less cholangitis and lower reintervention rate as compared to ERCP. [ABSTRACT FROM AUTHOR]

Background and study aims: Lumen-apposing stents (LAMS) are approved to treat peripancreatic collections and for gallbladder and bile duct drainage. Over the last years, LAMS have also been used for off-label indications including gastrojejunostomy, gastro-gastrostomy and drainage of postsurgical collections. We aimed to analyze indications, technical/clinical success rates and complications of all LAMS placed over the last 2 years. Patients and methods: Data from 61 consecutive LAMS (Hot Axios, Boston Scientific) in 57 patients were analyzed. Technical success was defined as successful deployment of the LAMS in the desired position. Clinical success was defined as follows: for pancreatic collections: resolution without the need for non-endoscopic interventions; for choledochoduodenostomy: ≥ 50% drop in baseline serum bilirubin within 2 weeks AND patient can receive chemotherapy if indicated; for gastrojejunostomy: resolution of gastric outlet obstruction and successful re-initiation of oral intake; for gastro-gastrostomy: successful endoscopic access to the excluded stomach; for gallbladder or postsurgical collection drainage: resolution of sepsis. Results: Indications were drainage of peripancreatic collections in 24 cases (39.3%), choledochoduodenostomy in 13 (21.3%), gastrojejunostomy in 6 (9.8%), gastro-gastrostomy in 13 (21.3%), gallbladder drainage in 1 (1.6%) and postsurgical collection drainage in 4 (6.6%). Overall technical and clinical success rates were high (57/61; 93.4% and 54/61; 88.5%, respectively). Clinical success rate for non-approved indications was 95.6% (22/23 cases). Complications occurred in 13 patients (21.3%, 4 serious). Conclusions: LAMS are increasingly used in interventional endoscopy. In our cohort, more than one third of LAMS are placed for off-label indications, with a high success rate and acceptable complication rate. [ABSTRACT FROM AUTHOR]

Fatigue is a highly prevalent but relatively ignored problem in IBD patients. It is one of the most burdensome symptoms to the patient with an important impact on the quality of life. Therefore, fatigue is a highly relevant patient-reported outcome that should be included not only in disease activity measurement but also in the endpoints of clinical trials in IBD. However, most of the currently available scoring systems to quantify fatigue are not specifically designed for patients with IBD and none of them has undergone a complete validation process for IBD-related fatigue. Fatigue is more prevalent in patients with active disease and may improve or disappear when remission is reached. Far more complex is the persistence or onset of fatigue in quiescent IBD which presents in up to 40% of the patients. In this subgroup of patients, fatigue can be related to smoldering systemic inflammation, a poor sleep quality, anemia, nutritional deficiencies, or comorbidities. In most cases, however, no direct cause can be identified. The lack of knowledge on the mechanisms that drive fatigue in IBD hamper the development of specific drugs to treat the condition and only psychological support can be offered to the patient. Rodent models are indispensable to increase our understanding of the molecular pathways that lead to fatigue in chronic intestinal inflammation, and to develop novel therapies. [ABSTRACT FROM AUTHOR]

Colonic adenocarcinoma-derived Caco-2 and T84 epithelial cell lines are frequently used as in vitro model systems of functional epithelial barriers. Both are utilised interchangeably despite evidence that differentiated Caco-2 cells are more reminiscent of small intestinal enterocytes than of colonocytes, whereas differentiated T84 cells are less well characterised. The aim of this study was, therefore, to further characterise and compare differentiated Caco-2 and T84 cells. The objectives were to (1) compare the brush border morphology, (2) measure the expression of enterocyte- and colonocyte-specific genes and (3) compare their response to butyrate, which is dependent on the monocarboxylate transporter 1 (MCT1), an apical protein expressed primarily in colonocytes. T84 microvilli were significantly shorter than those of Caco-2 cells, which is a characteristic difference between small intestinal enterocytes and colonocytes. Also, enterocyte-associated brush border enzymes expressed in differentiated Caco-2 cells were not increased during T84 maturation, whereas colonic markers such as MCT1 were more abundant in differentiated T84 cells compared to differentiated Caco-2 cells. Consequently, T84 cells displayed a dose-responsive improvement of barrier function towards butyrate, which was absent in Caco-2 cells. On the other hand, differences in epithelial toll-like receptor expression between Caco-2 and T84 monolayers did not result in a corresponding differential functional response. We conclude that differentiated Caco-2 and T84 cells have distinct morphological, biochemical and functional characteristics, suggesting that T84 cells do not acquire the biochemical signature of mature small intestinal enterocytes like Caco-2 cells, but retain much of their original colonic characteristics throughout differentiation. These findings can help investigators select the appropriate intestinal epithelial cell line for specific in vitro research purposes. [ABSTRACT FROM AUTHOR]

The introduction of biologic therapy has revolutionized the treatment of inflammatory bowel disease (IBD). However, like all therapeutic proteins, monoclonal antibodies have immunogenic potential which is influenced by multiple drug- and patient-related factors. The reported incidence of anti-drug antibodies (ADAs) towards biologic drugs in IBD varies greatly in the literature and depends not only on differences in sensitization but also on the assay methodology and the timepoint of measurement. Sensitization with formation of ADAs is associated with an increased risk of infusion reactions, accelerated drug clearance, and a loss of response (LOR) to drug. Recently, a greater understanding of the pharmacokinetics of therapeutic antibodies has led to the development of new strategies to reduce immunogenicity and more efficient use of these drugs. These preventive strategies include regular scheduled dosing with maintenance of stable therapeutic trough drug concentrations, and co-administration of an immunosuppressive. Sub-therapeutic drug concentrations with low levels of ADAs can generally be overcome with dose escalation, whereas the presence of high concentrations of ADAs requires a switch to another therapeutic agent. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) is frequently complicated by intestinal strictures, which are commonly treated by endoscopic balloon dilation (EBD). However, available data on this area of treatment is limited. The aim of this study was to depict the heterogeneity of endoscopic management of CD-associated strictures among international CD specialists to identify common treatment standards.Methods: IBD experts of the International Organization for the Study of Inflammatory Bowel Disease (IOIBD), the European Crohn's and Colitis Organization (ECCO), and from the Prospective Value In IBD trials (PROVIT) completed a web-based questionnaire to evaluate their endoscopic experience, practice setting, and number of EBDs performed annually. Additionally, two case scenarios and technical practice parameters were investigated.Results: A total of 126 subjects from 15 countries completed the survey. The maximal length of dilated stricture was 4.5 ± 1.7 cm. The most commonly used maximal balloon size was graded as 15-18 mm. While 87.2 % of the participants favored EBD for anastomotic strictures, only 58.6 % did so in the case of naïve strictures. Only 35.7 % of physicians dilated actively inflamed strictures. Interventional endoscopists were more likely to dilate only clinically symptomatic strictures (p = 0.046). Surgeons favored surgical treatment of de novo ileocecal strictures compared to gastroenterologists (p = 0.026), reported a shorter stricture length being amendable by EBD (p = 0.045), and more frequently used concomitant therapies (p = 0.001). Operator experience increased the likelihood of EBD use in actively inflamed strictures (p = 0.002), maximum length of stricture, and maximum balloon size (p = 0.001).Conclusions: EBD is a widely used treatment approach for stricturing CD. Individual approaches differ significantly based on background of the operator, experience level, and practice setting. [ABSTRACT FROM AUTHOR]

Background: We studied the correlation between prenatal diagnosis and postmortem investigations in pregnancies terminated for renal malformations. Methods: Over a 5-year period, 77 cases of termination of pregnancy (TOP) for renal malformations were reviewed. Chromosomal anomalies ( n = 9) and cases without conventional or virtual autopsy were excluded ( n = 15). In 53 cases, prenatal ultrasound diagnosis and conventional autopsy findings were compared. In addition, we compared the accuracy of conventional and virtual autopsy findings in 17 cases. Results: Full agreement was observed in 60.4 % (32/53) of cases. In 26.4 % (14/53) of the cases, the presence of additional malformations did not alter the final diagnosis. However, in 11.3 % (6/53) the final diagnosis was adjusted because of major additional findings. One case showed a total disagreement. Conventional and virtual autopsy were in full agreement in 52.9 % (9/17). Postmortem magnetic resonance imaging (MRI) description and detection of malformations was less complete and failed to correctly diagnose 5/17 cases (29.4 %). In 17.6 % (3/17) of the cases, postmortem MRI revealed malformations not confirmed by conventional autopsy. Conclusions: A high correlation between prenatal ultrasound and postmortem investigations was observed. Conventional autopsy remains the gold standard to reveal additional major and minor malformations, leading to a correct final diagnosis. The added value of virtual necropsy for renal pathology was limited. [ABSTRACT FROM AUTHOR]

Background: During inflammation in the gastrointestinal tract, the production of nitric oxide (NO) is mediated by the mucosal conversion of l-arginine. Recently, it was shown that the gut microbiota can also produce NO. Aims: The effect of gut luminal NO on inflammatory processes of an experimental colitis mice model was investigated by administrating NO directly to the colon, mimicking microbial NO production. Methods: Twenty-four mice received daily intrarectal treatment with a NO donor in 2 doses and 8 mice were treated with placebo. Starting 1 day later, 18 of these mice were fed ad libitum with 4% of dextran sodium sulfate (DSS) in their drinking water to induce colitis. At day 6, histopathology (both the inflammation and damage score), myeloperoxidase (MPO)-activity, colon length and colonic permeability were evaluated. Results: Co-administration of NO during DSS exposure inhibited the induction of an increasing colonic MPO-activity. This protective effect of NO was confirmed by the histological inflammation score showing a similar trend. The colonic permeability was restored when very low levels of NO were administered to the DSS-mice. On the other hand, the colon length of the NO-treated DSS-mice was negatively correlated with the NO dose and the histological damage score was not improved. Conclusions: Our results indicate that intrarectal administration of NO has clear anti-inflammatory effects in experimental colitis, but does not prevent colonic damage. Therefore, NO-producing microorganisms in the gut lumen should be accounted as a modulating process during colitis. [ABSTRACT FROM AUTHOR]

Purpose of Review: Gastrointestinal bleeding originating from the small bowel (SB) poses a challenge to the treating gastroenterologist. Once diagnosed, management is not a walk in the park either. This review intends to summarize the current state-of-the-art evidence in a complete way with special attention for vascular and ulcerative lesions, to provide the reader with a clinical guide and flow chart towards SB bleeding.Recent Findings: Absence of SB bleeding lesions on CE does not directly yield better prognosis; although having a lower rebleeding rate the first 2 years, rebleeding in the long term is high. Push enteroscopy can play an early role in patients with SB bleeding if suspicion of angioectasia is high, since these lesions tend to be located in the proximal SB. Endoscopic management of angioectasia is, however, difficult and shows poor results.Summary: Capsule endoscopy (CE) or device-assisted enteroscopy (DAE) remain the diagnostic mainstay in SB bleeding, choosing one over the other based upon patient characteristics and expected lesions. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Incidence, Prevention and Management of Anti-Drug Antibodies Against Therapeutic Antibodies in Inflammatory Bowel Disease" which appeared in the 2017 issue.