Analysis of Circulating Food Antigen-Specific T-Cells in Celiac Disease and Inflammatory Bowel Disease.

To demonstrate and analyze the specific T-cell response following barrier disruption and antigen translocation, circulating food antigen-specific effector T-cells isolated from peripheral blood were analyzed in patients suffering from celiac disease (CeD) as well as inflammatory bowel disease (IBD). We applied the antigen-reactive T-cell enrichment (ARTE) technique allowing for phenotypical and functional flow cytometric analyses of rare nutritional antigen-specific T-cells, including the celiac disease-causing gliadin (gluten). For CeD, patient groups, including treatment-refractory cases, differ significantly from healthy controls. Even symptom-free patients on a gluten-free diet were distinguishable from healthy controls, without being previously challenged with gluten. Moreover, frequency and phenotype of nutritional antigen-specific T-cells of IBD patients directly correlated to the presence of small intestinal inflammation. Specifically, the frequency of antigen specific T-cells as well as pro-inflammatory cytokines was increased in patients with active CeD or Crohn's disease, respectively. These results suggest active small intestinal inflammation as key for the development of a peripheral food antigen-specific T-cell response in Crohn's disease and celiac disease.

The combination of clinical parameters and immunophenotyping of intraepithelial lymphocytes allows to assess disease severity in refractory celiac disease.

BACKGROUND: Flow cytometry of intestinal lymphocytes is discussed to be a stronger predictor of enteropathy-associated T-cell lymphoma development in refractory celiac disease than T-cell clonality analysis. AIMS: To investigate possible associations between clinical characteristics of refractory celiac disease patients and aberrant intraepithelial lymphocytes and to evaluate the accuracy of immunophenotyping for the identification of high-risk refractory celiac disease. METHODS: Flow cytometry of isolated lymphocytes from duodenal biopsies of controls and celiac disease patients was performed and results were compared to clinical data. RESULTS: Flow cytometry analysis was performed on 42 controls, 37 non-complicated celiac disease and 30 refractory celiac disease cases with or without T-cell receptor clonality. Elevated aberrant intraepithelial lymphocyte counts were significantly associated with severe malabsorption. A 15% cut-off (aberrant lymphocytes among all lymphocytes) had the best discriminatory ability to identify high-risk patients. However, this technique failed to identify some high-risk cases (sensitivity 63%, specificity 100%). The severity of malabsorption was added to the criteria for high-risk refractory celiac disease, improving the correct patients' allocation (sensitivity 100%, specificity 96%). CONCLUSION: Immunophenotyping of aberrant intraepithelial lymphocytes is a good predictor for high-risk refractory celiac disease. Furthermore, adding the evaluation of malabsorption to the diagnostic assessment of refractory celiac disease optimizes accuracy.

Effectiveness of Capsule Endoscopy and Double-Balloon Enteroscopy in Suspected Complicated Celiac Disease.

BACKGROUND & AIMS: Complicated celiac disease (CCD) is a rare but severe condition with a poor prognosis. Guidelines recommend use of capsule endoscopy (CE) to explore the small bowel (SB), followed by a double-balloon enteroscopy (DBE) in selected cases with suspected CCD. Our study aimed to evaluate the diagnostic yield (DY) of CE and DBE in identifying and monitoring CCD. METHODS: Consecutive suspected CCD patients were enrolled prospectively to undergo CE and/or DBE in the presence of: persistent symptoms despite a correct gluten-free diet (GFD), increased anti-transglutaminase antibodies titer, lack of adherence to the GFD, and CCD monitoring. The DY of CE and DBE were calculated. The incidence of neoplastic complications and mortality were assessed. RESULTS: In total, 130 patients (97 women; age, 49 ± 16 y) underwent 151 CEs and 23 DBEs. The DY of CE was 46%. Patients older than age 50 years (at CE examination or at CD diagnosis) with a CD duration shorter than 5 years were at higher risk of positive CE (relative risk, 1.6 and 1.7 in case of enrollement or CD diagnosis after 50 years of age, and 1.5 in case of short CD duration; P < .05) than their counterparts. Up to 40% of SB lesions were unreachable by upper endoscopy. At the end of the diagnostic work-up, 25 patients with premalignant/malignant lesions were identified: 12 type 1 refractory CD (RCD-1), 7 type 2 RCD (RCD-2), and 6 enteropathy-associated T-cell lymphoma (EATL). Six patients died: 2 patients with RCD-2 and 4 patients with EATL. CONCLUSIONS: In case of suspected CCD, CE should be the first-line approach to detect complications and to identify patients deserving DBE. Older and symptomatic patients with suspected CCD deserve a careful evaluation of the SB, especially during the first years after diagnosis.

PuraStat in gastrointestinal bleeding: results of a prospective multicentre observational pilot study.

BACKGROUND: A recently developed haemostatic peptide gel for endoscopic application has been introduced to improve the management of gastrointestinal bleeding. The aim of this pilot study was to evaluate the feasibility, safety, efficacy and indication profiles of PuraStat in a clinical setting. METHODS: In this prospective observational multicentre pilot study, patients with acute non-variceal gastrointestinal bleeding (upper and lower) were included. Primary and secondary application of PuraStat was evaluated. Haemoglobin, prothrombin time, platelets and transfusion behaviour were documented before and after haemostasis. The efficacy of PuraStat was assessed during the procedure, at 3 days and 1 week after application. RESULTS: 111 patients with acute gastrointestinal bleeding were recruited into the study. 70 percent (78/111) of the patients had upper gastrointestinal bleeding and 30% (33/111) had lower gastrointestinal bleeding. After primary application of PuraStat, initial haemostatic success was achieved in 94% of patients (74/79, 95% CI 88-99%), and in 75% of the patients when used as a secondary haemostatic product, following failure of established techniques (24/32, 95% CI 59-91%). The therapeutic success rates (absence of rebleeding) after 3 and 7 days were 91% and 87% after primary use, and 87% and 81% in all study patients. Overall rebleeding rate at 30 day follow-up was 16% (18/111). In the 5 patients who finally required surgery (4.5%), PuraStat allowed temporary haemostasis and stabilisation. CONCLUSIONS: PuraStat expanded the therapeutic toolbox available for an effective treatment of gastrointestinal bleeding sources. It could be safely applied and administered without complications as a primary or secondary therapy. PuraStat may additionally serve as a bridge to surgery in order to achieve temporary haemostasis in case of refractory severe bleeding, possibly playing a role in preventing immediate emergency surgery.

Results from the German registry for refractory celiac disease.

Refractory celiac disease (RCD) refers to a rare subgroup of patients with celiac disease who show clinical signs of malabsorption despite a gluten-free diet. RCD is divided into an autoimmune phenotype (RCD type I) and pre-lymphoma (RCD type II). To reflect the clinical reality in managing this disease in Germany, a national register was established based on a questionnaire developed specifically for this purpose. Between 2014 and 2020, a total of 53 patients were registered. The diagnosis of RCD was confirmed in 46 cases (87%). This included 27 patients (59%) with RCD type I and 19 patients (41%) with RCD type II. A wide range of diagnostic and therapeutic measures was used. Therapeutically, budesonide was used in 59% of the RCD patients regardless of the subtype. Nutritional therapy was used in only 5 patients (11%). Overall mortality was 26% (12 patients) with a clear dominance in patients with RCD type II (9 patients, 47%). In summary, RCD needs to become a focus of national guidelines to increase awareness, establish standards, and thus enable the treating physician to make the correct diagnosis in a timely manner. Moreover, we concluded that when treating such patients, contacting a specialized center is recommended to ensure sufficient management.

Expression of tricellular tight junction proteins and the paracellular macromolecule barrier are recovered in remission of ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) has a relapsing and remitting pattern, wherein the underlying mechanisms of the relapse might involve an enhanced uptake of luminal antigens which stimulate the immune response. The tricellular tight junction protein, tricellulin, takes charge of preventing paracellular passage of macromolecules. It is characterized by downregulated expression in active UC and its correct localization is regulated by angulins. We thus analyzed the tricellulin and angulin expression as well as intestinal barrier function and aimed to determine the role of tricellulin in the mechanisms of relapse. METHODS: Colon biopsies were collected from controls and UC patients who underwent colonoscopy at the central endoscopy department of Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin. Remission of UC was defined basing on the clinical appearance and a normal Mayo endoscopic subscore. Intestinal barrier function was evaluated by electrophysiological and paracellular flux measurements on biopsies mounted in Ussing chambers. RESULTS: The downregulated tricellulin expression in active UC was recovered in remission UC to control values. Likewise, angulins were in remission UC at the same levels as in controls. Also, the epithelial resistance which was decreased in active UC was restored in remission to the same range as in controls, along with the unaltered paracellular permeabilities for fluorescein and FITC-dextran 4 kDa. CONCLUSIONS: In remission of UC, tricellulin expression level as well as intestinal barrier functions were restored to normal, after they were impaired in active UC. This points toward a re-sealing of the impaired tricellular paracellular pathway and abated uptake of antigens to normal rates in remission of UC.

Double-Balloon Enteroscopy in Detecting Small-Bowel Neuroendocrine Neoplasms: A Single-Center Prospective Study.

BACKGROUND AND AIM: Small-bowel neuroendocrine neoplasm (sbNEN) diagnosis has improved with double-balloon enteroscopy (DBE). DBE efficacy in the detection of sbNENs is unknown. We aimed to report the experience at a single referral center for NENs. METHODS: All consecutive patients with a suspected sbNEN selected for diagnostic DBE were enrolled. RESULTS: Between 2011 and 2016, 25 patients were referred for a suspected sbNEN. In 15/25 patients, a primary NEN was detected outside the small bowel; in 4, NEN was excluded. After extensive workup, 6 patients (4 males, median age 50 years) underwent DBE (3 anterograde, 2 retrograde, and 1 both; median time: 60 min; median insertion 200 cm). DBE was positive in 3 patients: one had an ileal 2-cm NEN G1, one had an ileal 1.3-cm NEN G1, and one had an ileal 1-cm NEN G2, all surgically removed. Of the 3 other patients, one had a metastatic NEN of unknown primary, the other two had small intestinal NENs, both surgically removed (1.6-cm G1 and G2 NEN). DBE showed a sensitivity of 60% and, in absence of false-positive results, a specificity of 100%. Accuracy resulted 67%. No complications were observed. CONCLUSIONS: In line with data from the literature, the present series showed that DBE is a safe and effective procedure in the diagnosis of sbNENs. Further studies are needed to better clarify the diagnostic role of DBE in the neuroendocrine tumor setting and its relationship with other techniques.

Leptin Downregulates Angulin-1 in Active Crohn's Disease via STAT3.

Crohn's disease (CD) has an altered intestinal barrier function, yet the underlying mechanisms remain to be disclosed. The tricellular tight junction protein tricellulin is involved in the maintenance of the paracellular macromolecule barrier and features an unchanged expression level in CD but a shifted localization. As angulins are known to regulate the localization of tricellulin, we hypothesized the involvement of angulins in CD. Using human biopsies, we found angulin-1 was downregulated in active CD compared with both controls and CD in remission. In T84 and Caco-2 monolayers, leptin, a cytokine secreted by fat tissue and affected in CD, decreased angulin-1 expression. This effect was completely blocked by STAT3 inhibitors, Stattic and WP1066, but only partially by JAK2 inhibitor AG490. The effect of leptin was also seen at a functional level as we observed in Caco-2 cells an increased permeability for FITC-dextran 4 kDa indicating an impaired barrier against macromolecule uptake. In conclusion, we were able to show that in active CD angulin-1 expression is downregulated, which leads to increased macromolecule permeability and is inducible by leptin via STAT3. This suggests that angulin-1 and leptin secretion are potential targets for intervention in CD to restore the impaired intestinal barrier.

Efficacy of a High-Iron Dietary Intervention in Women with Celiac Disease and Iron Deficiency without Anemia: A Clinical Trial.

BACKGROUND AND AIM: Iron deficiency without anemia (IDWA) is a common finding in celiac disease (CD) and can also persist in case of good compliance and clinical response to a strict gluten-free diet (GFD). This scenario usually presents in CD women of child-bearing age in whom the imbalance between menstrual iron loss and inadequate iron intake from their diet plays the major role. A recommended approach to this condition is yet to be established. This study aimed to compare, in this subset of patients, the efficacy of a dietary approach consisting of an iron-rich diet against the traditional pharmacological oral-replacement therapy. MATERIAL AND METHODS: Between February and December 2016, consecutive CD female patients of child-bearing age as referred to our outpatient center with evidence of IDWA (ferritin <15 ng/mL or 15-20 ng/L with transferrin saturation <15%) were enrolled. After the completion of a 7-day weighed food intake recording to assess the usual iron dietary intake, the patients were randomized in two arms to receive a 12-week iron-rich diet (iron intake >20 mg/die) versus oral iron supplementation with ferrous sulfate (FS) (105 mg/day). Blood tests and dietary assessments were repeated at the end of treatment. The degree of compliance and tolerability to the treatments were assessed every month by means of specific questionnaires and symptoms evaluation. RESULTS: A total of 22 women were enrolled and divided in the diet group (n = 10, age 37 ± 8 years) and in the FS group (n = 12, age 38 ± 10 years). The food intake records demonstrated an inadequate daily intake of iron in all the enrolled subjects. At the end of the treatments, ferritin levels were higher in the FS group (8.5 (5) versus 34 (30.8), p = 0.002). Compliance and tolerability were similar in both treatment groups (89% versus 87%, p = ns). CONCLUSIONS: These findings did not support any equivalent efficacy of an iron-rich diet compared to a FS supplementation in non-anemic iron-deficient women affected by CD. However, the diet appeared a well-tolerated approach, and adequate dietary instructions could effectively increase the daily iron consumption, suggesting a role in the long-term management of IDWA, especially in patients who do not tolerate pharmacological supplementation.

Efficacy and safety of device-assisted enteroscopy ERCP in liver transplantation: A systematic review and meta-analysis.

BACKGROUND: Enterobiliary anastomoses are the main source of complications after liver transplantation. An endoscopic approach combining device-assisted enteroscopy and ERCP (DAE-ERCP) is technically feasible in postsurgical anatomy. AIMS: This study aimed at assessing the efficacy, feasibility, and safety of DAE-ERCP in liver-transplanted patients (LT) and other subsets (non-LT). METHODS: A systematic review and meta-analysis of studies involving DAE procedures in LT patients (between January 2000 and May 2017) was conducted. The main endpoints were as follows: endoscopic, diagnostic, therapeutic, and overall success rates, complications, and the need for surgery. RESULTS: A total of 155 studies were retrieved, and 6 relevant trials were analyzed. Overall, 132 subjects (72 LT and 60 non-LT) undergoing 257 DAE-ERCP (135 and 122) were included. Complications were rare (4/257), and no deaths occurred. These are the pooled success rates among LT and non-LT patients: 80%-100% and 82%-95% (enteroscopic), 75%-100% and 89%-100% (diagnostic), 67%-100% and 92%-100% (therapeutic), and 60%-100% and 79%-83% (overall results). The requirement for surgery was similar in the two subgroups. CONCLUSION: In managing biliary complications, the high diagnostic and therapeutic success rates of DAE-ERCP combined with its safety and feasibility encourage its application as a first-line approach to transplanted patients.

Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells.

Intestinal epithelial barrier function in celiac disease (CeD) patients is altered. However, the mechanism underlying this effect is not fully understood. The aim of the current study was to evaluate the role of monocytes in eliciting the epithelial barrier defect in CeD. For this purpose, human monocytes were isolated from peripheral blood mononuclear cells (PBMCs) from active and inactive CeD patients and healthy controls. PBMCs were sorted for expression of CD14 and co-cultured with intestinal epithelial cells (IECs, Caco2BBe). Barrier function, as well as tight junctional alterations, were determined. Monocytes were characterized by profiling of cytokines and surface marker expression. Transepithelial resistance was found to be decreased only in IECs that had been exposed to celiac monocytes. In line with this, tight junctional alterations were found by confocal laser scanning microscopy and Western blotting of ZO-1, occludin, and claudin-5. Analysis of cytokine concentrations in monocyte supernatants revealed higher expression of interleukin-6 and MCP-1 in celiac monocytes. However, surface marker expression, as analyzed by FACS analysis after immunostaining, did not reveal significant alterations in celiac monocytes. In conclusion, CeD peripheral monocytes reveal an intrinsically elevated pro-inflammatory cytokine pattern that is associated with the potential of peripheral monocytes to affect barrier function by altering TJ composition.

Low Sensitivity of Simtomax Point of Care Test in Detection of Celiac Disease in a Prospective Multicenter Study.

BACKGROUND & AIMS: Point of care tests (POCTs) might be used to identify patients with undiagnosed celiac disease who require further evaluation. We performed a large multicenter study to determine the performance of a POCT for celiac disease and assessed celiac disease prevalence in endoscopy centers. METHODS: We performed a prospective study of 1055 patients (888 adults; median age, 48 yrs and 167 children; median age, 10 yrs) referred to 8 endoscopy centers in Germany, for various indications, from January 2016 through June 2017. Patients were tested for celiac disease using Simtomax, which detects immunoglobulin (Ig)A and IgG antibodies against deamidated gliadin peptides (DGP). Results were compared with findings from histologic analyses of duodenal biopsies (reference standard). The primary aim was to determine the accuracy of this POCT for the detection of celiac disease, to identify candidates for duodenal biopsy. A secondary aim was to determine the prevalence of celiac disease in adult and pediatric populations referred for outpatient endoscopic evaluation. RESULTS: The overall prevalence of celiac disease was 4.1%. The POCT identified individuals with celiac disease with 79% sensitivity (95% CI, 64%-89%) and 94% specificity (95% CI, 93%-96%). Positive and negative predictive values were 37% and 99%. When we analyzed the adult and pediatric populations separately, we found the test to identify adults with celiac disease (prevalence 1.2%) with 100% sensitivity and 95% specificity. In the pediatric population (celiac disease prevalence 19.6%), the test produced false-negative results for 9 cases; the test therefore identified children with celiac disease with 72% sensitivity (95% CI 53%-86%). Analyses of serologic data revealed significantly lower DGP titers in the false-negative vs the true-positive group. CONCLUSIONS: In a study of more than 1000 adults and children, we found the Simtomax POCT to detect celiac disease with lower overall levels of sensitivity than expected. Although the test identifies adults with celiac disease with high levels of sensitivity and specificity, the prevalence of celiac disease was as low as 1.2% among adults. The test's lack of sensitivity might be due to the low intensity of the POCT bands and was associated with low serum DGP titers. Study ID no: DRKS00012499.

Oxidative stress as a biomarker for monitoring treated celiac disease.

INTRODUCTION: High levels of reactive oxygen species (ROS) and impaired antioxidant defense systems lead to oxidative stress (OxS) and tissue injury in different intestinal and extra intestinal conditions, including celiac disease (CD). The aim of the present study was to investigate the role and potential use of ROS and other biomarkers of OxS in the clinical management of CD. METHODS: We collected duodenal specimens and blood samples from naïve patients (N-CD), patients on a gluten free diet (GFD) including responders (CD-GFD) and non-responders (NRCD). We measured plasmatic ROS production (electron paramagnetic resonance, EPR), lipid peroxidation (thiobarbituric acid-reactive substances, TBARS), protein oxidation (protein carbonyl, PC), total antioxidant capacity (TAC), nitric oxides and glutathione (GSH) in erythrocytes. RESULTS: Fifty-four patients affected by CD were enrolled (17 N-CD, 18 CD-GFD and 19 NRCD; 44 F; age 44 ± 13 years). A significant increase of plasmatic OxS biomarkers (ROS, peroxidated lipids, oxidized proteins, and nitrate concentrations) and decrease of antioxidant species (TAC and GSH levels) were found in NRCD and N-CD compared to CD-GFD. Comparably, a significant direct relationship between the severity of duodenal atrophy, ROS production rates and TBARS was found; conversely, TAC and GSH presented an inverse correlation. DISCUSSION: OxS is involved in CD tissue damage and correlates with the degree of duodenal atrophy. These findings suggest the possible role of OxS biomarkers as indicators of CD activity during the clinical follow-up.

Transglutaminase 2 Mediates the Cytotoxicity of Resveratrol in a Human Cholangiocarcinoma and Gallbladder Cancer Cell Lines.

Resveratrol is a polyphenolic compound extracted from plants and is also a constituent of red wine. Our aim was to evaluate if the cytotoxic effect of resveratrol (RES) on cholangiocarcinoma (CC) and gallbladder cancer (GBC) cell lines could be abolished by TG2 inhibition. Human CC and GBC cell lines (SK-ChA-1 and MZ-ChA-1), grown in a three-dimensional cell culture system (MCTS, multicellular tumor spheroids), were treated for 72 h with RES (32, 64 µM) alone or combined with different TG2 inhibitors (Cystamine, B003, T101). We investigated: cells viability; cell morphology with light microscopy (LM) and transmission electron microscopy (TEM); immunoreactivity with immunohistochemistry; Q-Banding karyotype analysis; TG2 activity; Western blotting. RES treatment induced a significant inhibition of cell growth, ranging from 24% to 76% in both cell lines. The inhibitors successfully reduced TG2 activity without any variation of protein quantity as demonstrated by immunohistochemistry and Western blot. TG2 inhibition resulted in cell growth normalization. In addition, morphologic analysis by light and transmission electron microscopy confirmed the cytotoxic effect of RES and its reduction consequent to TG2 inhibition. Our data demonstrated a connection between the cytotoxic effect of RES in SK-ChA-1 and MZ-ChA-1 and TG2 activity.

Sucrosomial Iron Supplementation in Anemic Patients with Celiac Disease Not Tolerating Oral Ferrous Sulfate: A Prospective Study.

Patients with celiac disease (CD) frequently suffer from iron deficiency anemia (IDA) and may benefit from iron supplementation. However, intolerance to iron sulfate and duodenal atrophy could reduce the efficacy of this supplementation. This study evaluated the efficacy of a new sucrosomial iron formulation in patients with CD. Consecutive patients with CD and IDA were divided into two groups: patients with a known intolerance to iron sulfate were treated with sucrosomial iron (30 mg of iron/day), while those receiving iron supplementation for the first time were assigned to iron sulfate (105 mg of iron/day). Forty-three patients were enrolled (38 females, mean age 49 ± 9 years). After a follow-up of 90 days both groups showed an increase in Hb levels compared to baseline (+10.1% and +16.2% for sucrosomial and sulfate groups, respectively), and a significant improvement in all iron parameters, with no statistical difference between the two groups. Patients treated with sucrosomial iron reported a lower severity of abdominal symptoms, such as abdominal and epigastric pain, abdominal bloating, and constipation, and a higher increase in general well-being (+33% vs. +21%) compared to the iron sulfate group. Sucrosomial iron can be effective in providing iron supplementation in difficult-to-treat populations, such as patients with CD, IDA, and known intolerance to iron sulfate.

Ultrasound Elasticity Imaging Predicts Therapeutic Outcomes of Patients With Crohn's Disease Treated With Anti-Tumour Necrosis Factor Antibodies.

BACKGROUND AND AIMS: Ultrasound elasticity imaging is a non-invasive technique developed to evaluate fibrosis. Measuring tissue strain by ultrasound elasticity imaging can reliably detect severe ileal fibrosis in patients with Crohn's disease [CD]. We have hypothesised that a more severe range of fibrosis might influence the therapeutic response to anti-tumour necrosis factor [TNF] treatment. The aim of this study was to assess the ability of ultrasound elasticity imaging to predict the therapeutic outcome for CD patients. METHODS: Consecutive patients with ileal/ileocolonic CD, starting anti-TNF treatment, were enrolled for the study. These patients underwent bowel ultrasound and ultrasound elasticity imaging at baseline and at 14 and 52 weeks after anti-TNF treatment. Bowel wall stiffness was quantified by calculating the strain ratio between the mesenteric tissue and the bowel wall. Strain ratio ≥ 2 was used to identify severe ileal fibrosis. Transmural healing at 14 and 52 weeks was defined as bowel wall thickness ≤ 3 mm. RESULTS: Thirty patients with CD were enrolled. Five patients underwent surgery for bowel obstruction. The frequency of surgeries was significantly greater in patients with a strain ratio ≥ 2 at baseline [p = 0.003]. A significant reduction of the bowel thickness was observed after 14 and 52 weeks of anti-TNF treatment [p < 0.005]. A significant inverse correlation was observed between the strain ratio values at baseline and the thickness variations following anti-TNF therapy [p = 0.007]; 27% of patients achieved transmural healing at 14 weeks. The baseline strain ratio was significantly lower in patients with transmural healing [p < 0.05]. CONCLUSIONS: This study shows that ultrasound elasticity imaging predicts therapeutic outcomes for CD patients treated with anti-TNF.

Harmful and Beneficial Effects of Anticoagulants in Patients With Cirrhosis and Portal Vein Thrombosis.

BACKGROUND & AIMS: Vitamin K antagonists (VKAs) promote recanalization of portal vein thrombosis (PVT) in patients with cirrhosis. However, the benefit of PVT recanalization might be offset by major and minor bleeding associated with use of anticoagulants. We evaluated harmful and beneficial effects of VKA in patients with PVT and cirrhosis. METHODS: We performed a retrospective study of 63 consecutive patients with cirrhosis given anticoagulants for the first detection of non-neoplastic PVT from 2003 to 2015 in Italy. We collected data on bleeding events in these patients and compared them with those from patients without cirrhosis with venous thromboembolism (VTE) (n = 160) for up to 4 years. Time in the therapeutic range, based on the international normalized ratio, was used to determine the quality of anticoagulation. We also collected data from 139 patients with cirrhosis who did not receive VKAs (controls), to analyze portal hypertension-related events. We performed survival analyses to determine the effects of VKA in patients with PVT vs controls. RESULTS: The group with VTE and the group with PVT were comparable in age, sex, and time in the therapeutic range, but patients with VTE received VKAs for a longer time period (31.1 ± 16.9 mo vs 23.3 ± 16.2 mo; P = .002). The incidence of major or minor bleeding was higher in patients with PVT than patients with VTE (major, 24% vs 7%; P = .012; minor, 29% vs 19%; P = .024). Patients with PVT had a higher rate of major bleeding from the upper-gastrointestinal tract than patients with VTE (P = .019), but there were no significant differences in other types of major bleeding (P = .376). Patients with PVT and controls had the same rate of upper-gastrointestinal bleeding. Complete recanalization in patients with PVT receiving VKA (n = 31) was independently associated with increased portal hypertension-related event-free and transplantation-free survival times. CONCLUSIONS: In a retrospective analysis of 63 patients with cirrhosis given anticoagulants for PVT, we found VKA use to increase risk of minor bleeding, compared with patients without cirrhosis given VKA. However, this risk is offset by the ability of VKA to increase portal hypertension-related, event-free, and transplantation-free survival of patients with PVT recanalization. Portal hypertension, rather than anticoagulants, could account for the difference in risk of major bleeding between patients with PVT vs patients with VTE.

Role of capsule endoscopy in alarm features and non-responsive celiac disease: A European multicenter study.

BACKGROUND AND AIM: The role of capsule endoscopy (CE) in established celiac disease (CD) remains unclear. Our objective was to analyze the usefulness of CE in the suspicion of complicated CD. METHODS: This was a retrospective multicenter study. One hundred and eighty-nine celiac patients (mean age: 46.6 ± 16.6, 30.2% males) who underwent CE for alarm symptoms (n = 86, 45.5%) or non-responsive CD (n = 103, 54.5%) were included. Diagnostic yield (DY), therapeutic impact and safety were analyzed. RESULTS: Capsule endoscopy was completed in 95.2% of patients (small bowel transit time: 270.5 ± 100.2 min). Global DY was 67.2%, detecting atrophic mucosa (n = 92, 48.7%), ulcerative jejunoileitis (n = 21, 11.1%), intestinal lymphoma (n = 7, 3.7%) and other enteropathies (n = 7, 3.7%, six Crohn's disease cases and one neuroendocrine tumor). The DY of CE was significantly higher in patients presenting with non-responsive disease compared to patients with alarm symptoms (73.8% vs 59.3%, P = 0.035). The new findings of the CE modified management in 59.3% of the cases. There were no major complications. CONCLUSION: Capsule endoscopy may be a moderately helpful and safe diagnostic tool in the suspicion of complicated CD, modifying the clinical course of these patients.

Capsule endoscopy in young patients with iron deficiency anaemia and negative bidirectional gastrointestinal endoscopy.

BACKGROUND: Recent data imply young patients (age ≤50 years) undergoing small-bowel (SB) capsule endoscopy (CE) for iron deficiency anaemia (IDA) show higher diagnostic yield (DY) for sinister pathology. We aimed to investigate DY of CE in a large cohort of young IDA patients, and evaluate factors predicting significant SB pathology. MATERIALS AND METHODS: This was a retrospective, multicentre study (2010-2015) in consecutive, young patients (≤50 years) from 18 centres/12 countries, with negative bidirectional gastrointestinal (GI) endoscopy undergoing SBCE for IDA. Exclusion criteria: previous/ongoing obscure-overt GI bleeding; age <19 or >50 years; comorbidities associated with IDA. Data retrieved: SBCE indications; prior investigations; medications; SBCE findings; final diagnosis. Clinical and laboratory data were analysed by multivariate logistic regression. RESULTS: Data on 389 young IDA patients were retrieved. In total, 169 (43.4%) were excluded due to incomplete clinical data; data from 220 (122F/98M; mean age 40.5 ± 8.6 years) patients were analysed. Some 71 patients had at least one clinically significant SBCE finding (DY: 32.3%). They were divided into two groups: neoplastic pathology (10/220; 4.5%), and non-neoplastic but clinically significant pathology (61/220; 27.7%). The most common significant but non-neoplastic pathologies were angioectasias (22/61) and Crohn's disease (15/61). On multivariate analysis, weight loss and lower mean corpuscular volume(MCV) were associated with significant SB pathology (OR: 3.87; 95%CI: 1.3-11.3; p = 0.01; and OR: 0.96; 95%CI: 0.92-0.99; p = 0.03; respectively). Our model also demonstrates association between use of antiplatelets and significant SB pathology, although due to the small number of patients, definitive conclusions cannot be drawn. CONCLUSION: In IDA patients ≤50 years with negative bidirectional GI endoscopy, overall DY of SBCE for clinically significant findings was 32.3%. Some 5% of our cohort was diagnosed with SB neoplasia; lower MCV or weight loss were associated with higher DY for SB pathology.

Non-invasive evaluation of intestinal disorders: The role of elastographic techniques.

Over the recent years the non-invasive techniques for the evaluation of the small bowel have been playing a major role in the management of chronic intestinal diseases, such as inflammatory bowel diseases (IBD). The diagnostic performances of magnetic resonance imaging, computed tomography and ultrasound in the field of small bowel disorders, have been assessed and established for more than two decades. Newer sonographic techniques, such as strain elastography and shear wave elastography, have been put forward for the assessment of disease activity and characterization of IBD-related damage in the setting of Crohn's disease and other gastrointestinal disorders. The data from the preliminary research and clinical studies have shown promising results as regards the ability of elastographic techniques to differentiate inflammatory from fibrotic tissue. The distinction between IBD activity (inflammation) and IBD-related damage (fibrosis) is currently considered crucial for the assessment and management of patients. Moreover, all the elastographic techniques are currently being considered in the setting of other intestinal disorders (e.g., rectal tumors, appendicitis). The aim of this paper is to offer both a comprehensive narrative review of the non-invasive techniques available for the assessment of small-bowel disorders, with particular emphasis on inflammatory bowel diseases, and a summary of the current evidence on the use of elastographic techniques in this setting.