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1.
Systematic Review and Meta-Analysis: Accuracy of Both Gamma Delta+ Intraepithelial Lymphocytes and Coeliac Lymphogram Evaluated by Flow Cytometry for Coeliac Disease Diagnosis.
Fernández-Bañares, F, Carrasco, A, Martín, A, Esteve, M
Nutrients. 2019;(9)
Abstract
UNLABELLED It has been suggested that in doubtful cases of coeliac disease, a high CD3+ T-cell receptor gamma delta+ (TCRγδ+) intraepithelial lymphocyte count increases the likelihood of coeliac disease. AIM: To evaluate the diagnostic accuracy of both an isolated increase of TCRγδ+ cells and a coeliac lymphogram (increase of TCRγδ+ plus decrease of CD3- intraepithelial lymphocytes) evaluated by flow cytometry in the diagnosis of coeliac disease. METHODS The literature search was conducted in MEDLINE and EMBASE. The inclusion criteria were: an article that allows for the construction of a 2 × 2 table of true and false positive and true and false negative values. A diagnostic accuracy test meta-analysis was performed. RESULTS The search provided 49 relevant citations, of which 6 were selected for the analysis, which represented 519 patients and 440 controls. Coeliac lymphogram: The pooled S and Sp were 93% and 98%, without heterogeneity. The area under the SROC curve (AUC) was 0.98 (95% CI, 0.97-0.99). TCRγδ+: Pooled S and Sp were both 95%, with significant heterogeneity. The AUC was 0.97 (95% CI, 0.95-0.98). Conclusions: Both TCRγδ+ count and coeliac lymphogram assessed by flow cytometry in duodenal mucosal samples are associated with a high level of diagnostic accuracy for and against coeliac disease.
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2.
Transcriptional and Post-Transcriptional Regulation of Duodenal P-Glycoprotein and MRP2 in Healthy Human Subjects after Chronic Treatment with Rifampin and Carbamazepine.
Brueck, S, Bruckmueller, H, Wegner, D, Busch, D, Martin, P, Oswald, S, Cascorbi, I, Siegmund, W
Molecular pharmaceutics. 2019;(9):3823-3830
Abstract
To predict the outcome of intestinal drug transporter induction on pharmacokinetics, signaling of the DNA message along with messenger RNA (mRNA) transcription and protein translation leading to transporter function must be understood. We quantified the gene expression of PXR and CAR, gene expression and protein abundance of P-glycoprotein (P-gp), multidrug-resistance-associated protein 2 (MRP2) and breast-cancer-resistance protein, the content of 754 microRNAs in human duodenal biopsy specimens, and pharmacokinetics of talinolol and ezetimibe before and after the treatment with rifampin and carbamazepine. Rifampin significantly induced the transcription of ABCB1 and ABCC2 and protein abundance of P-gp but not of MRP2. The abundance of P-gp was significantly correlated to the plasma exposure of ezetimibe and its glucuronide. Carbamazepine induced the mRNA expressions of CAR, ABCB1, and ABCC2 but did not elevate protein abundance. Using in silico prediction tools and luciferase reporter assays, microRNAs were identified that can contribute to ligand-specific regulation of intestinal drug transporters and different changes in drug disposition after induction with rifampin and carbamazepine.
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3.
Intracellular Localization of Microbial Transglutaminase and Its Influence on the Transport of Gliadin in Enterocytes.
Stricker, S, de Laffolie, J, Rudloff, S, Komorowski, L, Zimmer, KP
Journal of pediatric gastroenterology and nutrition. 2019;(3):e43-e50
Abstract
OBJECTIVE Celiac disease (CD) is a systemic inflammatory disorder, characterized by the destruction of duodenal epithelium. The CD8 T cells involved are associated with cross-presentation. In addition to other factors, the rising prevalence of CD might be induced by microbial transglutaminase (mTG) an enzyme frequently used in food production that shares enzymatic and antigenic properties of tissue transglutaminase (TG2), the autoantigen in CD. We hypothesized that mTG and gliadin are transported into the endoplasmic reticulum (ER), indicating cross-presentation of both antigens. METHODS Apical incubation of duodenal biopsies from CD and control patients was performed with mTG alone or with mTG and simultaneously with Frazer's fraction. Evaluation was carried out by immunofluorescence and electron microscopy. RESULTS Approximately 6% to 9% of the intracellular mTG and gliadin were transported to the ER of enterocytes. RACE cells (Rapid uptake of Antigen into the Cytosol of Enterocytes) displayed an enhanced antigen uptake into a dilated ER. mTG strongly localized at the basolateral membrane and the lamina propria. CONCLUSIONS mTG and gliadin are transported to the ER of enterocytes and to a greater extent to the ER of RACE cells, suggesting cross-presentation of exogenous antigens. The strong localization of mTG at the basolateral membrane and the lamina propria may also indicate a potential antigenic interaction with cells of the immune system. Since mTG may not only been taken up with food stuffs but could also be released by bacteria within the intestinal microbiota, further investigations are needed regarding the role of mTG in CD pathogenesis.
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4.
Ileal interposition coupled with duodenal diverted sleeve gastrectomy versus standard medical treatment in type 2 diabetes mellitus obese patients: long-term results of a case-control study.
Foschi, D, Sorrentino, L, Tubazio, I, Vecchio, C, Vago, T, Bevilacqua, M, Rizzi, A, Corsi, F
Surgical endoscopy. 2019;(5):1553-1563
Abstract
BACKGROUND Randomized controlled trials have demonstrated that bariatric surgery is effective in obtaining remission of type 2 diabetes mellitus (T2DM) in obese patients, yet no data exist in the literature from prospective studies with ileal interposition with duodenal diversion sleeve gastrectomy (II-DD-SG). The aim of this case-control study is to investigate if II-DD-SG is superior to medical treatment in T2DM obese patients. METHODS Thirty obese patients (BMI > 30) affected by T2DM were recruited for surgery (II-DD-SG) between 2008 and 2011 and were matched with an equal control group which received standard medical treatment. Anthropometric measures, glucose metabolism, cardiovascular risk factors were determined baseline and during follow-up. The primary end point was T2DM remission; reduction of body weight, BMI, and cardiovascular risk factors were secondary end-points. RESULTS Shortly after II-DD-SG, normalization of glucose plasma levels and glycated hemoglobin was observed followed by a significant decrease in body weight and BMI. At one-year follow-up, insulin resistance strongly declined as did insulin plasma levels. Complete remission was observed in 26 patients (86%); 2 (6.6%) had partial remission, and two (6.6%) were still diabetic. After 5 years, 17 of 25 patients on follow-up (68%) showed complete remission of T2DM and 56% had remission of cardiovascular risk factors. Only two patients receiving medical treatment showed complete remission of T2DM (p < 0.0001 versus II-DD-SG). No significant changes of anthropometric parameters and lipid metabolism were recorded. CONCLUSIONS II-DD-SG is an effective surgical procedure, able to induce complete and prolonged remission of T2DM in obese patients as opposed to medical treatment.
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5.
Is Early Reimplantation of the Duodenal-Jejunal Bypass Liner Viable?
Leventi, E, Günthert, SJ, Stier, C, Staikov, P, Stein, J, Farrag, K
Obesity surgery. 2019;(5):1690-1693
Abstract
The endoscopically implanted duodenal-jejunal bypass liner (DJBL) is an impermeable fluoropolymer device which prevents food making contact with the proximal intestine, thus inducing weight loss and improvement of type 2 diabetes mellitus (T2DM). However, weight and HbA1c levels generally increase post explantation. This study investigated the safety and feasibility of early DJBL reimplantation in five patients with obesity whose glucose levels had relapsed post explantation, examining the effect of reimplantation on weight loss, BMI and T2DM management. All DJBL implantation and explantation procedures were performed without complications. Despite reduction of T2DM medications, reduction in body weight and HbA1c levels resumed after reimplantation. In conclusion, early reimplantation of DJBL appears feasible, safe and effective.
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6.
Celiac Disease: Updates on Pathology and Differential Diagnosis.
Dai, Y, Zhang, Q, Olofson, AM, Jhala, N, Liu, X
Advances in anatomic pathology. 2019;(5):292-312
Abstract
Celiac disease is a gluten-triggered immune-mediated disorder, characterized by inflammation of the enteric mucosa following lymphocytic infiltration and eventually resulting in villous blunting. There have been many developments in refining diagnostic laboratory tests for celiac disease in the last decade. Biopsy-sparing diagnostic guidelines have been proposed and validated in a few recent prospective studies. However, despite these developments, histologic evaluation of duodenal mucosa remains one of the most essential diagnostic tools as it helps in the diagnosis of celiac disease in individuals who do not fulfill the biopsy-sparing diagnostic criteria and in those not responding to a gluten-free diet. Histologic evaluation also allows for the assessment of mucosal recovery after treatment and in the identification of concurrent intestinal diseases. Therefore, pathologists should be familiar with the histologic spectrum of celiac disease and need to be aware of other disorders with similar symptoms and histopathology that may mimic celiac disease. This review aims to provide pathologists with updates on celiac laboratory testing, biopsy-sparing diagnostic criteria, histopathology, complications, and differential diagnoses of celiac disease.
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7.
Recent understanding of the pathophysiology of functional dyspepsia: role of the duodenum as the pathogenic center.
Miwa, H, Oshima, T, Tomita, T, Fukui, H, Kondo, T, Yamasaki, T, Watari, J
Journal of gastroenterology. 2019;(4):305-311
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Abstract
Over almost 30 years since functional dyspepsia (FD) was defined, researchers have endeavored to elucidate the pathophysiology of functional gastrointestinal disorders. Now a consensus is emerging that the gastric symptoms of FD are caused mainly by gastric motility abnormalities and gastric hypersensitivity. The involvement of other causative factors including acid, Helicobacter pylori, psychological factors, and diet has been debated, but how they are involved in the manifestation of dyspeptic symptoms remains unclear. We believe that most of those factors cause FD symptoms by inducing gastric motility abnormalities and gastric hypersensitivity via the duodenum. Here, we discuss 2 possible reasons why patients with FD experience chronic upper abdominal symptoms: (1) the possibility that the contents of the duodenum of patients with FD differ from those of healthy persons and the different contents stimulate the duodenum, and (2) the possibility that the duodenum of patients with FD is more sensitive to noxious stimuli because of low-grade inflammation and increased mucosal permeability.
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Theobromine does not affect postprandial lipid metabolism and duodenal gene expression, but has unfavorable effects on postprandial glucose and insulin responses in humans.
Smolders, L, Mensink, RP, Boekschoten, MV, de Ridder, RJJ, Plat, J
Clinical nutrition (Edinburgh, Scotland). 2018;(2):719-727
Abstract
BACKGROUND & AIMS Chocolate consumption is associated with a decreased risk for CVD. Theobromine, a compound in cocoa, may explain these effects as it favorably affected fasting serum lipids. However, long-term effects of theobromine on postprandial metabolism as well as underlying mechanisms have never been studied. The objective was to evaluate the effects of 4-week theobromine consumption (500 mg/day) on fasting and postprandial lipid, lipoprotein and glucose metabolism, and duodenal gene expression. METHODS In a randomized, double-blind crossover study, 44 healthy men and women, with low baseline HDL-C concentrations consumed 500 mg theobromine or placebo daily. After 4-weeks, fasting blood was sampled and subjects participated in a 4-h postprandial test. Blood was sampled frequently for analysis of lipid and glucose metabolism. In a subgroup of 10 men, 5 h after meal consumption duodenal biopsies were taken for microarray analysis. RESULTS 4-weeks theobromine consumption lowered fasting LDL-C (-0.21 mmol/L; P = 0.006), and apoB100 (-0.04 g/L; P = 0.022), tended to increase HDL-C (0.03 mmol/L; P = 0.088) and increased hsCRP (1.2 mg/L; P = 0.017) concentrations. Fasting apoA-I, TAG, FFA, glucose and insulin concentrations were unchanged. In the postprandial phase, theobromine consumption increased glucose (P = 0.026), insulin (P = 0.011) and FFA (P = 0.003) concentrations, while lipids and (apo)lipoproteins were unchanged. In duodenal biopsies, microarray analysis showed no consistent changes in expression of genes, pathways or gene sets related to lipid, cholesterol or glucose metabolism. CONCLUSIONS It is not likely that the potential beneficial effects of cocoa on CVD can be ascribed to theobromine. Although theobromine lowers serum LDL-C concentrations, it did not change fasting HDL-C, apoA-I, or postprandial lipid concentrations and duodenal gene expression, and unfavorably affected postprandial glucose and insulin responses. This trial was registered on clinicaltrials.gov under study number NCT02209025.
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Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) as a revisional surgery.
Wu, A, Tian, J, Cao, L, Gong, F, Wu, A, Dong, G
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2018;(11):1686-1690
Abstract
BACKGROUND Few studies of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) as the revision surgery for laparoscopic adjustable gastric banding (LAGB) have been published. OBJECTIVES To explore the efficacy and safety of SADI-S as the revision surgery for LAGB. SETTING The research was completed by the University Hospital. METHODS From November 2013 to November 2015, a total of 22 weight-regain patients who previously underwent LAGB received SADI-S as the revision surgery at the People's Liberation Army General Hospital. Preoperative clinical characteristics as well as the data at 1, 3, 6, 12, 18, and 24 months after operation were collected and analyzed. RESULTS The operation time of SADI-S was 105 ± 12.2 minutes, and intraoperative blood loss was 27.3 ± 5.8 mL. The percentage of excess weight loss was 20.55 ± 9.10%, 40.1 ± 6.02%, 63.52 ± 10.43%, 70.72 ± 8.54%, 78.34 ± 9.25%, and 81.57 ± 11.12% at 1, 3, 6, 12, 18 and 24 months after surgery, respectively. The 2-year complete remission rate of type 2 diabetes was 17 of 18, and the partial remission rate was 1 of 18 after operation. The glycated hemoglobin was 8.7% ± 1.1%, 7.7% ± .9%, 6.2% ± .6%, 5.7% ± .5%, 5.5% ± .6%, 6.0% ± .9%, and 5.7% ± .8% preoperatively and at 1, 3, 6, 12, 18, and 24 months after the operation, respectively. One case presented incisional hernia and was repaired. There was no conversion to laparotomy. Vitamins and trace elements were administrated long term to these patients after the operation, and no patients experienced vitamin or trace element deficiencies. CONCLUSION SADI-S is safe and effective as a revision surgery for patients who experienced weight regain after LAGB. However, multicenter randomized controlled studies with larger sample sizes are needed to explore the long-term efficacy and safety of SADI-S.
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Case report on pathogenetic link between gluten and IgA nephropathy.
Costa, S, Currò, G, Pellegrino, S, Lucanto, MC, Tuccari, G, Ieni, A, Visalli, G, Magazzù, G, Santoro, D
BMC gastroenterology. 2018;(1):64
Abstract
BACKGROUND A relationship between IgA nephropathy (IgAN) and celiac disease (CD) has been reported. We show the pathogenetic link for the first time. CASE PRESENTATION A 39-year-old man with cystic fibrosis (CF) and CF-related diabetes started to present gross hematuria, back pain and headache. At admission, laboratory analysis showed increase in serum creatinine of 1.5 mg/dl, together with hematuria and mild proteinuria (1 g/24 h). He underwent a renal biopsy to investigate the cause of hematuria and renal failure. Biopsy was consistent with IgAN. In view of patient reported dyspepsia, an upper gastrointestinal endoscopy with duodenal biopsies was undertaken and was normal. We looked for mucosal deposits of tTG-2 in the duodenum and the renal mesangium. tTG-2 deposits were found both in the duodenum and in renal biopsies, where they topographically replicated mesangial IgA deposits. After one year on a continued gluten containing diet, the patient developed a Marsh 2 type duodenal pathology. CONCLUSIONS Our findings suggest a connection between CD and IgAN in terms of an immune-mediated gluten-induced pathogenesis even in the absence of villous atrophy and serum celiac autoantibodies.