IBD on PubMed

Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs.

New papers on PubMed -

Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs.

Nature. 2016 Nov 09;:

Authors: Cummings RJ, Barbet G, Bongers G, Hartmann BM, Gettler K, Muniz L, Furtado GC, Cho J, Lira SA, Blander JM

Abstract
Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies. The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear. Here we show that mouse apoptotic intestinal epithelial cells (IECs), which undergo continuous renewal to maintain optimal barrier and absorptive functions, are not merely extruded to maintain homeostatic cell numbers, but are also sampled by a single subset of dendritic cells and two macrophage subsets within a well-characterized network of phagocytes in the small intestinal lamina propria. Characterization of the transcriptome within each subset before and after in situ sampling of apoptotic IECs revealed gene expression signatures unique to each phagocyte, including macrophage-specific lipid metabolism and amino acid catabolism, and a dendritic-cell-specific program of regulatory CD4(+) T-cell activation. A common 'suppression of inflammation' signature was noted, although the specific genes and pathways involved varied amongst dendritic cells and macrophages, reflecting specialized functions. Apoptotic IECs were trafficked to mesenteric lymph nodes exclusively by the dendritic cell subset and served as critical determinants for the induction of tolerogenic regulatory CD4(+) T-cell differentiation. Several of the genes that were differentially expressed by phagocytes bearing apoptotic IECs overlapped with susceptibility genes for inflammatory bowel disease. Collectively, these findings provide new insights into the consequences of apoptotic cell sampling, advance our understanding of how homeostasis is maintained within the mucosa and set the stage for development of novel therapeutics to alleviate chronic inflammatory diseases such as inflammatory bowel disease.

PMID: 27828940 [PubMed - as supplied by publisher]

The utility of faecal calprotectin to predict post-operative recurrence in Crohńs disease.

New papers on PubMed -

Related Articles

The utility of faecal calprotectin to predict post-operative recurrence in Crohńs disease.

Scand J Gastroenterol. 2016;51(6):720-6

Authors: Herranz Bachiller MT, Barrio Andres J, Fernandez Salazar L, Ruiz-Zorrilla R, Sancho Del Val L, Atienza Sanchez R

Abstract
OBJECTIVE: Endoscopic recurrence in Crohńs disease occurs in up to 80% of patients during the first year after surgery. Due to this, these patients need close monitoring. Faecal calprotectin has been proposed to be used as a non-invasive marker to monitor inflammatory activity. Up to now the use of faecal markers in endoscopic recurrence has been scarcely studied and with contradictory results.
MATERIAL AND METHODS: This was a cross-sectional observational study of diagnostic validity. It included all patients with Crohńs disease (CD) and ileocolic resection retrospectively who had had an ileocolonoscopy and a determination of faecal calprotectin before this colonoscopy, from 2007 to 2015.
RESULTS: Ninety-seven patients were included. We observed that the mean value of faecal calprotectin increased as the Rutgeerts score increased. The variable of that most statistical significance obtained in bivariate analysis was faecal calprotectin (p < 0.0001). Area under curve (AUC) of faecal calprotectin in endoscopic recurrence was 0.74 (95% CI: 0.644-0.842), and an optimal cut-off of 60 mcrgr/gr, obtained a score of 0.45 using Youden test. This indicated that calprotectin would have 88% Sensitivity and 58% Specificity in detecting any recurrence, the NPV was approximately 83,9%. None of the other variables studied had a significant correlation.
CONCLUSION: Faecal calprotectin predicts endoscopic recurrence in CD patients who have gone through surgery, however the cut-off point is still a problem so we cannot recommend calprotectin as a substitute of colonoscopy for CD monitoring and treatment adjustment.

PMID: 26758472 [PubMed - indexed for MEDLINE]

Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease.

New papers on PubMed -

Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease.

Sci Rep. 2016 Nov 09;6:36797

Authors: Giacomin P, Zakrzewski M, Jenkins TP, Su X, Al-Hallaf R, Croese J, de Vries S, Grant A, Mitreva M, Loukas A, Krause L, Cantacessi C

Abstract
A reduced diversity of the gastrointestinal commensal microbiota is associated with the development of several inflammatory diseases. Recent reports in humans and animal models have demonstrated the beneficial therapeutic effects of infections by parasitic worms (helminths) in some inflammatory disorders, such as inflammatory bowel disease (IBD) and coeliac disease (CeD). Interestingly, these studies have described how helminths may alter the intestinal microbiota, potentially representing a mechanism by which they regulate inflammation. However, for practical reasons, these reports have primarily analysed the faecal microbiota. In the present investigation, we have assessed, for the first time, the changes in the microbiota at the site of infection by a parasitic helminth (hookworm) and gluten-dependent inflammation in humans with CeD using biopsy tissue from the duodenum. Hookworm infection and gluten exposure were associated with an increased abundance of species within the Bacteroides phylum, as well as increases in the richness and diversity of the tissue-resident microbiota within the intestine, results that are consistent with previous reports using other helminth species in humans and animal models. Hence, this may represent a mechanism by which parasitic helminths may restore intestinal immune homeostasis and exert a therapeutic benefit in CeD, and potentially other inflammatory disorders.

PMID: 27827438 [PubMed - in process]

An HDAC6 inhibitor confers protection and selectively inhibits B-cell infiltration in DSS-induced colitis in mice.

New papers on PubMed -

An HDAC6 inhibitor confers protection and selectively inhibits B-cell infiltration in DSS-induced colitis in mice.

J Pharmacol Exp Ther. 2016 Nov 8;:

Authors: Do A, Reid RC, Lohman RJ, Sweet MJ, Fairlie DP, Iyer A

Abstract
Small molecule histone deacetylase (HDAC) inhibitors with anti-inflammatory activity may be candidates for targeting intestinal inflammatory pathways in inflammatory bowel disease (IBD). This study investigated whether treatment with a potent HDAC6 inhibitor, BML-281, could protect against colonic inflammation and prevent inflammatory cell infiltration into the colon to drive disease pathology in a mouse model of acute DSS-colitis. Control and acute DSS-colitis mice were treated with BML-281 (1mg/kg/day s.c. & 10mg/kg/day s.c.) for 8 days. Changes in disease pathology, colonic structure, function, alterations in inflammatory milieu together with colonic inflammatory cell flux, were assessed by weight loss and disease activity index in vivo and by flow cytometry, gene expression and histology ex vivo. Anti-inflammatory responses of BML-281 on human polymorphonucleocytes were assessed in vitro. Administration of BML-281 to DSS-treated mice attenuated colitis, weight loss and disease pathology, including changes in colon structure and function, by eliciting broad-spectrum anti-inflammatory effects and preventing infiltration and activation of key immune cells in the lamina propria of the intestinal epithelium. Among different immune cells, BML-281 particularly suppressed the infiltration of CD19+ B-cells into the inflamed colonic lamina propria. This study supports the targeting of HDAC6 as an anti-inflammatory strategy for treating colon inflammation progressing to IBD. Some HDAC inhibitors are used in the clinic to treat cancer, and the results here for BML-281 highlights the potential for HDAC6 inhibitors to be evaluated in a clinical setting for preventing and treating colonic inflammation and IBD in humans.

PMID: 27827303 [PubMed - as supplied by publisher]

Diagnostic Efficacy of Single-Pass Abdominal Multidetector-Row CT: Prospective Evaluation of a Low Dose Protocol.

New papers on PubMed -

Diagnostic Efficacy of Single-Pass Abdominal Multidetector-Row CT: Prospective Evaluation of a Low Dose Protocol.

Br J Radiol. 2016 Nov 9;:20160612

Authors: Camera L, Liccardo I, Romano F, Liuzzi R, Rispo A, Imbriaco M, Testa A, Luglio G, De Fronzo S, Castiglione F, Bucci L, Brunetti A

Abstract
OBJECTIVES: To evaluate the diagnostic efficacy of single-pass contrast-enhanced multi-detector CT (CE-MDCT) performed with a low radiation-high contrast (LR-HC) dose protocol in selected patients with non traumatic acute bowel disease.
METHODS: Sixty-five (32 M; 33 F; aged 20-67 years) consecutive patients with non traumatic acute bowel disease underwent single-pass CE-MDCT performed 70-100 sec after i.v. bolus injection of a non ionic iodinated contrast media (370 mgI/ml). In forty-six patients (70%) with a clinical and/or ultrasonographic (US) suspicion of Inflammatory Bowel Disease up to 1.2-1.4 L of a 7% PEG solution was orally administered 45-60' prior to the CT examination. Patients were then divided in two groups according to the age: A (20-44 years; n= 34); B (45-70 years; n=31). Noise Index (NI) and contrast medium dose were selected as follows: A (NI=15; 2,5 ml/kg); B (NI =12,5; 2ml/kg). All patients of group A underwent thyroid functional tests at 4-6 wks. Final diagnoses were obtained by open (n=12) or laparoscopic surgery (n=4), endoscopy w/out biopsy (n=24), clinical (n=19) and/or instrumental (US) (n=6) follow-up at 11 + 4 months (range 6-18 mo.). Statistical analysis was performed by Chi-Square and Student's t-Test for categorical and continuous variables, respectively.
RESULTS: Sensitivity and specificity were 91.3 vs 95.4% (p = 0.905) and 90.9 vs 88.8% (p = 0.998) with an overall diagnostic accuracy of 91.1 vs 93.5% (p = 0.756) whereas the radiation (mSv) and contrast media dose (ml) were 7.5 ± 2.8 and 155 ± 30 for Group A and 14.1 ± 5.3 and 130 ±24 for Group B (p < 0.001), respectively. No patients of group A showed laboratory signs of thyreotoxicosis at follow-up.
CONCLUSIONS: The LR-HC has proved to be a safe and a dose-effective protocol in the evaluation of selected young patients with non traumatic acute bowel disease. Advances in Knowledge: As reaching the highest benefit to risk ratio (AHARA) appears to be the current principle of MDCT imaging an increased amount of iodinated contrast media (0.7-0.9 grI/ml) can be safely administered to young patients (< 40 yrs) with normal thyroid and renal function to compensate for the lower image quality resulting from low dose CT protocols performed with standard FBP algorithm. Such an approach will result in a significant reduction of the radiation dose which could be otherwise achieved only using iterative reconstruction algorithms combined to either low tube voltage and/or low tube current protocols. An optimal scan delay (Tdelay) for a venous phase caudo-cranial acquisition can be calculated by the following formula: Tdelay = CI + 25 - TSD where CI is the duration of the contrast injection, 25 is the average of the sum of abdominal aortic and peak hepatic arrival times and TSD is the scan duration. With such an approach, the radiation exposure resulting from bolus tracking, albeit performed with low dose scans, can be spared in patients with normal transit times.

PMID: 27826994 [PubMed - as supplied by publisher]

Risk factors detection in chronic thromboembolic pulmonary hypertension, a tool for risk quantification?

New papers on PubMed -

Risk factors detection in chronic thromboembolic pulmonary hypertension, a tool for risk quantification?

Bratisl Lek Listy. 2016;117(10):577-582

Authors: Bohacekova M, Kaldararova M, Valkovicova T, Remkova A, Vesely J, Simkova I

Abstract
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by chronic thromboembolic obstruction in the pulmonary bed. The definitive pathogenesis remains incompletely explained, although multiple risk factors of CTEPH have been identified. The purpose of the study was to evaluate the risk profile of patients with CTEPH and the representativeness of risk factors, identify possible new CTEPH risk factors and specify the epidemiology of CTEPH in our country.
METHODS: In 81 patients with CTEPH, well known risk factors were analyzed, and a detailed analysis of selected hematological parameters was investigated at a specialized hematology laboratory.
RESULTS: CTEPH risk factors were identified as follows: pulmonary embolism (PE), deep vein thrombosis (DVT), thyreopathy, blood type other than "0", inflammatory bowel disease, malignancy, splenectomy, pacemaker. When compared to healthy controls, the following was observed: a significant decrease in platelet count, higher mean platelet volume, higher spontaneous platelet aggregation, increase in von Willebrand factor and fibrinogen. The median of risk factors representativeness was 3 (PE, DVT, blood type other than "0"). The prevalence of CTEPH in adult population in our country is estimated to be 1.8 per 100,000 inhabitants.
CONCLUSION: In the study we confirmed multiple established risk factors of CTEPH, set their representativeness, identified some platelet abnormalities which could be a potential new risk marker and specified the prevalence of CTEPH (Tab. 5, Ref. 35).

PMID: 27826972 [PubMed - in process]

Infliximab quantitation in human plasma by liquid chromatography-tandem mass spectrometry: towards a standardization of the methods?

New papers on PubMed -

Related Articles

Infliximab quantitation in human plasma by liquid chromatography-tandem mass spectrometry: towards a standardization of the methods?

Anal Bioanal Chem. 2016 Nov 8;

Authors: Jourdil JF, Lebert D, Gautier-Veyret E, Lemaitre F, Bonaz B, Picard G, Tonini J, Stanke-Labesque F

Abstract
Infliximab (IFX) is a chimeric monoclonal antibody targeting tumor necrosis factor-alpha. It is currently approved for the treatment of certain rheumatic diseases or inflammatory bowel diseases. Clinical studies have suggested that monitoring IFX concentrations could improve treatment response. However, in most studies, IFX was quantified using ELISA assays, the resulting discrepancies of which raised concerns about their reliability. Here, we describe the development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for IFX quantification in human plasma. Full-length stable-isotope-labeled antibody (SIL-IFX) was added to plasma samples as internal standard. Samples were then prepared using Mass Spectrometry Immuno Assay (MSIA™) followed by trypsin digestion and submitted to multiple reaction monitoring (MRM) for quantification of IFX. The chromatographic run lasted 13 min. The range of quantification was 1 to 26 mg/L. For two internal quality controls spiked with 6 and 12 mg/L of IFX, the method was reproducible (coefficients of variation (CV%): 12.7 and 2.1), repeatable (intra-day CV%: 5.5 and 5.0), and accurate (inter-day and intra-day deviations from nominal values: +6.4 to +3.7 % and 5.5 to 9.2 %, respectively). There was no cross - contamination effect. Samples from 45 patients treated with IFX were retrospectively analyzed by LC-MS/MS and results were compared to those obtained with an in-house ELISA assay and the commercial Lisa Tracker® method. Good agreement was found between LC-MS/MS and in-house ELISA (mean underestimation of 13 % for in-house ELISA), but a significant bias was found with commercial ELISA (mean underestimation of 136 % for commercial ELISA). This method will make it possible to standardize IFX quantification between laboratories. Graphical Abstract Interassay comparison of the three methods: LC-MS/MS vs inhouse ELISA assay or vs Lisa Tracker® ELISA assays, Passing & Bablok (a) and Bland & Altman (b) for the comparison of LC-MS/MS vs in-house ELISA assay; Passing & Bablok

PMID: 27826630 [PubMed - as supplied by publisher]

Chitinase 3-like-1 is produced by human Th17 cells and correlates with the level of inflammation in juvenile idiopathic arthritis patients.

New papers on PubMed -

Related Articles

Chitinase 3-like-1 is produced by human Th17 cells and correlates with the level of inflammation in juvenile idiopathic arthritis patients.

Clin Mol Allergy. 2016;14:16

Authors: Capone M, Maggi L, Santarlasci V, Rossi MC, Mazzoni A, Montaini G, Cimaz R, Ramazzotti M, Piccinni MP, Barra G, De Palma R, Liotta F, Maggi E, Romagnani S, Annunziato F, Cosmi L

Abstract
BACKGROUND: CHI3L1 is a chitinase-like protein without enzymatic activity, produced by activated macrophages, chondrocytes, neutrophils. Recent studies on arthritis, asthma, and inflammatory bowel diseases suggest that chitinases are important in inflammatory processes and tissue remodeling, but their production by human T cells, has never been reported.
METHODS: A microarray analysis of gene expression profile was performed on Th17 and classic Th1 cell clones and CHI3L1 was found among the up-regulated genes on Th17 cells. Different types of helper T cell clones (TCCs) were then evaluated by Real Time PCR (RT-PCR) for CHI3L1 mRNA expression; protein expression was investigated in cell lysates by western blotting and in cultures supernatants by ELISA. ELISA was also used to measure CHI3L1 in the serum and in the synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients.
RESULTS: At mRNA level CHI3L1 was highly expressed by Th17, Th17/Th1, non classic Th1 and even in Th17/Th2 cell clones, whereas it was virtually absent in CD161- classic Th1 and Th2 TCCs. CHI3L1 was also detected in cell culture supernatants of Th17 and Th17-derived cells but not of classic Th1. Moreover CHI3L1 was higher in the SF than in serum of JIA patients, and it positively correlated with the frequency of Th17 and non-classic Th1 cells in SF. CHI3L1 in SF also positively correlated with the C reactive protein (CRP) serum levels, and with the levels of some proinflammatory cytokines, such as IL-6 and p40, which is the common subunit of IL12 and IL23.
CONCLUSIONS: Here we describe for the first time CHI3L1 production by T cells owing the Th17 family. Moreover the positive correlation found between the frequency of Th17 and Th17-derived cell subsets and CHI3L1 levels in SF of JIA patients, in agreement with the suggested role of these cells in inflammatory process, candidates CHI3L1 as a possible biological target in JIA treatment.

PMID: 27826220 [PubMed - in process]

Repression of microRNA Function Mediates Inflammation-associated Colon Tumorigenesis.

New papers on PubMed -

Related Articles

Repression of microRNA Function Mediates Inflammation-associated Colon Tumorigenesis.

Gastroenterology. 2016 Nov 5;:

Authors: Yoshikawa T, Wu J, Otsuka M, Kishikawa T, Suzuki N, Takata A, Ohno M, Ishibashi R, Yamagami M, Nakagawa R, Kato N, Miyazawa M, Han J, Koike K

Abstract
BACKGROUND & AIMS: Little is known about the mechanisms by which chronic inflammation contributes to carcinogenesis, such as the development of colon tumors in patients with inflammatory bowel diseases. Specific microRNA (miRNAs) can function as suppressors or oncogenes, and widespread alterations in miRNA expression have been associated with tumorigenesis. We studied whether alterations in miRNA function contribute to inflammation-associated colon carcinogenesis.
METHODS: We studied the effects of inflammatory cytokines such as tumor necrosis factor (TNF), interleukin-1 alpha (IL1A), and IL1 beta (IL1B) on miRNA function, measured by activity of reporter constructs containing miRNA-binding sites in their 3' untranslated regions, in human 293T embryonic kidney, Caco-2, HT29, and HCT116 colon carcinoma cells, as well as dicer +/+ and dicer -/- and Apobec3 +/+ and Apobec3 -/- mouse embryonic fibroblasts. Cells were analyzed by immunoblots, immunohistochemistry, and flow cytometry. We generated transgenic mice expressing reporter constructs regulated by LET7B, MIR122, and MIR29b response elements; some mice were given injections of miRNA inhibitors (anti-MIR122 or anti-LET7B), a negative control, or TNF. Liver tissues were collected and analyzed by immunoblotting. Reporter mice were given azoxymethane followed by dextran sulfate sodium to induce colitis and colon tumors; some mice were given the ROCK inhibitor fasudil along with these agents (ROCK inhibitors increase miRNA function). Colon tissues were collected and analyzed by immunohistochemistry, immunoblots, and fluorescence microscopy.
RESULTS: Incubation of cell lines with inflammatory cytokines reduced the ability of miRNAs to downregulate expression from reporter constructs; dicer was required for this effect, so these cytokines relieve miRNA-dependent reductions in expression. The cytokines promoted degradation of APOBEC3G, which normally promotes miRNA loading into argonaute 2-related complexes. Mice with colitis had reduced miRNA function, based on increased expression of reporter genes. Administration of fasudil to mice did not reduce the severity of colitis that developed but greatly reduced the numbers of colon tumors formed (average 2 tumors/colon in mice given fasudil vs 9 tumors/colon in mice given control agent). We made similar observations in IL10-deficient mice.
CONCLUSIONS: We found inflammatory cytokines to reduce the activities of miRNAs. In mice with colitis, activities of miRNAs are reduced; administration of an agent that increases miRNA function prevents colon tumor formation in these mice. This pathway might be targeted to prevent colon carcinogenesis in patients with inflammatory bowel diseases.

PMID: 27825961 [PubMed - as supplied by publisher]

The Effects of Ivabradine on Cardiac Function after Myocardial Infarction are Weaker in Diabetic Rats.

New papers on PubMed -

Related Articles

The Effects of Ivabradine on Cardiac Function after Myocardial Infarction are Weaker in Diabetic Rats.

Cell Physiol Biochem. 2016;39(5):2055-2064

Authors: Cao X, Sun Z, Zhang B, Li X, Xia H

Abstract
BACKGROUND/AIMS: Plasma norepinephrine (NE) and brain natriuretic peptide (BNP, termed BNP-45 in rats) are considered as essential neurohormones indicating heart failure progression. The purposes of this study were to examine the effects of ivabradine (IBD) on cardiac function and plasma NE and BNP-45 after chronic ischemic heart failure (CHF) in non-diabetic rats and diabetic rats. We further determined if sympathetic NE uptake-1 (a major pathway to metabolize NE) mechanism is responsible for the role played by IBD.
METHODS: We ligated rat's coronary artery to induce CHF; and injected streptozotocin (STZ) to induce diabetic hyperglycemia. Echocardiography was employed to determine cardiac function. We used ELISA to examine plasma NE and BNP-45; and Western Blot analysis to examine the protein levels of NE uptake-1 in sympathetic nerves.
RESULTS: CHF increased the levels of NE and BNP-45 in non-STZ rats and STZ rats. Systemic injection of IBD significantly attenuated the augmented NE and BNP-45 and impaired left ventricular function induced by CHF in those rats. This effect appeared to be less in STZ rats. A liner relation was observed between the NE/BNP-45 levels and left ventricular function after administration of IBD. Also, IBD was observed to have a recovery effect on the downregulated NE uptake-1 evoked by CHF, but to a smaller degree in STZ rats.
CONCLUSION: Our data revealed specific signaling mechanisms by which IBD improves the cardiac function as IBD alleviates impaired NE uptake-1and thereby decreases heightened NE and BNP-45 induced by CHF. Our data also demonstrated that the effects of IBD are weakened after diabetic hyperglycemia likely due to worsen NE uptake-1 pathway. Thus, targeting sympathetic NE uptake-1 signaling molecules has clinical implications for treatment and management of CHF in diabetes. Our data were also to shed light on strategies for application of this drug because NE and BNP play an important role in regulation of progression and prognosis of CHF, and in particular, because IBD affects NE uptake-1 pathway in hyperglycemic animals to a less degree.

PMID: 27825166 [PubMed - in process]

Inflammatory Bowel Disease: How Effective Is TNF-α Suppression?

New papers on PubMed -

Related Articles

Inflammatory Bowel Disease: How Effective Is TNF-α Suppression?

PLoS One. 2016;11(11):e0165782

Authors: Lo WC, Arsenescu V, Arsenescu RI, Friedman A

Abstract
Crohn's Disease (CD) results from inappropriate response toward commensal flora. Earlier studies described CD as a Th1 mediated disease. Current models view both phenotypes as a continuum of various permutations between Th1, Th2 and Th17 pathways compounded by a range of Treg disfunctions. In the present paper, we develop a mathematical model, by a system of differential equations, which describe the dynamic relations among these T cells and their cytokines. The model identities four groups of CD patients according to up/down regulation of Th1 and Th2. The model simulations show that immunosuppression by TNF-α blockage benefits the group with Th1High/Th2Low while, by contrast, the group with Th1Low/Th2High will benefit from immune activation.

PMID: 27824890 [PubMed - in process]

Long-term Outcomes of Sphincter-Saving Procedures for Diffuse Crohn's Disease of the Large Bowel.

New papers on PubMed -

Related Articles

Long-term Outcomes of Sphincter-Saving Procedures for Diffuse Crohn's Disease of the Large Bowel.

Dis Colon Rectum. 2016 Dec;59(12):1183-1190

Authors: Li Y, Stocchi L, Mu X, Cherla D, Remzi FH

Abstract
BACKGROUND: Total abdominal colectomy with ileorectal anastomosis for Crohn's colitis is acceptable in the presence of a suitable rectum. Intentional IPAA has been proposed for diffuse Crohn's proctocolitis without enteric or anoperineal disease.
OBJECTIVE: The aim of this study was to evaluate the long-term outcomes of sphincter-saving procedures for large-bowel Crohn's disease.
DESIGN: Patients with preoperative Crohn's disease diagnosis undergoing intentional IPAA and ileorectal anastomosis were included.
SETTINGS: The study was conducted at a tertiary care research center.
PATIENTS: Ileorectal anastomosis was performed in 75 patients with Crohn's disease, whereas 32 patients underwent intentional IPAA.
MAIN OUTCOME MEASURES: Long-term functional results and permanent stoma requirement of sphincter-saving operations were assessed. Quality of life and postoperative medication use were also compared with a control group of patients undergoing total proctocolectomy and end ileostomy.
RESULTS: Patients undergoing ileorectal anastomosis were older and had longer disease duration, higher prevalence of perianal and penetrating disease, and history of small-bowel resection than those receiving IPAA. Indications for surgery, preoperative use of immunomodulators, and postoperative use of biologics were also significantly different. Although functional defecatory outcomes were comparable, reported quality of life 3 years after surgery was significantly better in patients who underwent IPAA than in patients with ileorectal anastomosis. Patients with IPAA were associated with significantly lower cumulative rates of surgical recurrence (HR = 0.28 (95% CI, 0.09-0.84); p = 0.017), indefinite stoma diversion (HR = 0.35 (95% CI, 0.13-0.99); p = 0.039), and proctectomy with end ileostomy (HR = 0.27 (95% CI, 0.07-0.96); p = 0.030) than those with ileorectal anastomosis.
LIMITATIONS: The study was limited by its retrospective nature and small sample size.
CONCLUSIONS: Contemporary patients selected to have intentional IPAA for Crohn's colitis have disease characteristics very different from those selected to have ileorectal anastomosis. Long-term follow-up confirms intentional IPAA as an acceptable option in selected patients with Crohn's colitis.

PMID: 27824704 [PubMed - in process]

Fistula-Associated Anorectal Cancer in the Setting of Crohn's Disease.

New papers on PubMed -

Related Articles

Fistula-Associated Anorectal Cancer in the Setting of Crohn's Disease.

Dis Colon Rectum. 2016 Dec;59(12):1168-1173

Authors: Shwaartz C, Munger JA, Deliz JR, Bornstein JE, Gorfine SR, Chessin DB, Popowich DA, Bauer JJ

Abstract
BACKGROUND: Cancer arising from perianal fistulas in patients with Crohn's disease is rare. There are only a small series of articles that describe sporadic cases of perianal cancer in Crohn's disease fistulas. Therefore, there are no clear guidelines on how to appropriately screen patients at risk and choose proper management.
OBJECTIVE: The purpose of this study was to describe patients diagnosed with cancer in perianal fistulas in the setting of Crohn's disease.
DESIGN: The study involved an institutional review board-approved retrospective review of medical charts of patients with perianal Crohn's disease. The data extracted from patient charts included demographic and clinical characteristics.
SETTINGS: Patients seen at the Mount Sinai Medical Center were included.
PATIENTS: We identified patients who were diagnosed with perianal cancer in biopsies of fistula tracts.
MAIN OUTCOME MEASURES: We observed the number of patients with Crohn's disease who had fistulas, cancer in fistula tract, and time to diagnosis.
RESULTS: The charts of 2382 patients with fistulizing perianal Crohn's disease were reviewed. Cancer in a fistula tract was diagnosed in 19 (0.79%) of these patients, 9 with squamous-cell carcinoma and 10 with adenocarcinoma. The majority of the 19 patients (68%) had symptoms typical of perianal fistula. The mean time from diagnosis of Crohn's disease to fistula diagnosis and from fistula diagnosis to cancer diagnosis was 19.4 and 6.0 years. In 5 patients (26%), cancer was not diagnosed in the first biopsy obtained from the fistula tract.
LIMITATIONS: This is a retrospective chart review of a rare outcome; the results may not be generalizable.
CONCLUSIONS: Routine biopsies of long-standing fistula tracts in patients with Crohn's disease should be strongly considered and may yield an earlier diagnosis of cancer in the fistula tracts.

PMID: 27824702 [PubMed - in process]

Physical Activity Habits, Limitations, and Predictors in People with Inflammatory Bowel Disease: A Large Cross-sectional Online Survey.

New papers on PubMed -

Related Articles

Physical Activity Habits, Limitations, and Predictors in People with Inflammatory Bowel Disease: A Large Cross-sectional Online Survey.

Inflamm Bowel Dis. 2016 Nov 01;

Authors: Tew GA, Jones K, Mikocka-Walus A

Abstract
BACKGROUND: Limited evidence suggests that physical activity has beneficial effects in people with inflammatory bowel disease (IBD). This study aimed to determine the physical activity habits of adults with IBD, the limitations to physical activity they experience because of their disease, and the extent to which their physical activity is affected by various demographic, clinical, and psychological factors.
METHODS: Data were collected on 859 adult participants (52% with Crohn's disease, 75% women) through an online survey conducted between May and June 2016. Measures included physical activity (International Physical Activity Questionnaire), psychological symptoms (Hospital Anxiety and Depression Scale), fatigue (subitems of IBD fatigue scale), exercise perceptions (Exercise Benefits/Barriers Scale), and disease activity. Regression analyses were used to identify predictors of physical activity.
RESULTS: Only 17% of respondents were categorized as "high active." Self-reported physical activity levels decreased, and fatigue and psychological scores increased, with increasing disease activity. Walking was the most common activity performed (57% of respondents) and running/jogging the most commonly avoided (34%). Many participants (n = 677) reported that IBD limited their physical activity, for reasons including abdominal/joint pain (70%), fatigue/tiredness (69%), disease flare-up (63%), and increased toilet urgency (61%). Physical activity was independently associated with depression, disease activity, and perceived barriers to exercise in people with Crohn's disease, and depression and age in people with ulcerative or indeterminate colitis (all P ≤ 0.038).
CONCLUSIONS: This survey highlights several important factors that should be considered by designers of future physical activity interventions for people with IBD.

PMID: 27824653 [PubMed - as supplied by publisher]

Macrophages Versus Escherichia coli: A Decisive Fight in Crohn's Disease.

New papers on PubMed -

Related Articles

Macrophages Versus Escherichia coli: A Decisive Fight in Crohn's Disease.

Inflamm Bowel Dis. 2016 Nov 01;

Authors: Buisson A, Bringer MA, Barnich N, Vazeille E

Abstract
The pathophysiology of Crohn's disease (CD), a chronic inflammatory bowel disease, remains imperfectly elucidated. Consequently, the therapeutic armamentarium remains limited and has not changed the natural history of CD hitherto. Accordingly, physicians need to identify new therapeutic targets to be able to alter the intestinal damage. The most recent hypothesis considered CD as resulting from an abnormal interaction between microbiota and host immune system influenced by genetics and environmental factors. Several experimental and genetic evidence point out intestinal macrophages in CD etiology. An increase of macrophages number and the presence of granulomas are especially observed in the intestinal mucosa of patients with CD. These macrophages could be defective and particularly in responses to infectious agents like CD-associated Escherichia coli. This review focuses on, what is currently known regarding the role of macrophages, macrophages/E. coli interaction, and the impact of CD therapies on macrophages in CD. We also speculate that macrophages modulation could lead to important translational implications in CD with the end goal of promoting gut health.

PMID: 27824652 [PubMed - as supplied by publisher]

Infliximab Selectively Modulates the Circulating Blood Monocyte Repertoire in Crohn's Disease.

New papers on PubMed -

Related Articles

Infliximab Selectively Modulates the Circulating Blood Monocyte Repertoire in Crohn's Disease.

Inflamm Bowel Dis. 2016 Nov 01;

Authors: Slevin SM, Dennedy MC, Connaughton EP, Ribeiro A, Ceredig R, Griffin MD, Egan LJ

Abstract
BACKGROUND: Infliximab (IFX), an anti-tumour necrosis factor alpha (TNFα) monoclonal antibody, provides clinical benefits in treating Crohn's disease (CD) but its mechanisms of action are not fully elucidated. This study investigated blood monocyte repertoires and the acute effects of IFX infusion on monocyte subset phenotype and function in IFX-treated patients with CD.
METHODS: Monocytes and monocyte subsets were enumerated and phenotypically characterized by multicolor flow cytometry in freshly isolated blood from healthy controls (n = 21) and patients with CD treated with (IFX, n = 24) and without (non-IFX, n = 20) IFX. For the IFX-CD group, blood was sampled immediately before (tough-IFX) and after (peak-IFX) infusion. Monocyte responses to lipopolysaccharide were analyzed by whole-blood intracellular cytokine staining.
RESULTS: Non-IFX and IFX-CD patients had increased numbers of intermediate (CD14CD16) monocytes compared with healthy controls, whereas classical (CD14CD16) and nonclassical (CD14CD16) monocytes were numerically reduced in the IFX-CD group alone. In all groups, monocyte subsets expressed high surface levels of transmembrane (tm)TNFα. After IFX infusion, a significant reduction in monocyte numbers occurred. Post-IFX monocytopenia was proportionately greatest for classical and intermediate subsets, correlated with postinfusion IFX levels and was not associated with monocyte apoptosis. In contrast, lipopolysaccharide-induced production of TNFα and IL-12 by monocytes was significantly reduced in peak-IFX compared with trough-IFX blood samples.
CONCLUSIONS: Actively managed CD is associated with monocyte repertoire skewing suggestive of chronic inflammatory stimulation. Infused IFX acutely targets monocytes, likely by binding to tmTNFα, resulting in a non-apoptosis-related decline in circulating monocyte numbers and blunting of the inflammatory response of monocytes remaining in the blood.

PMID: 27824651 [PubMed - as supplied by publisher]

VSL#3 Probiotic Stimulates T-cell Protein Tyrosine Phosphatase-mediated Recovery of IFN-γ-induced Intestinal Epithelial Barrier Defects.

New papers on PubMed -

Related Articles

VSL#3 Probiotic Stimulates T-cell Protein Tyrosine Phosphatase-mediated Recovery of IFN-γ-induced Intestinal Epithelial Barrier Defects.

Inflamm Bowel Dis. 2016 Nov 01;

Authors: Krishnan M, Penrose HM, Shah NN, Marchelletta RR, McCole DF

Abstract
BACKGROUND: VSL#3 is a probiotic compound that has been used in the treatment of inflammatory bowel disease. T-cell protein tyrosine phosphatase (TCPTP) is the protein product of the inflammatory bowel disease candidate gene, PTPN2, and we have previously shown that it protects epithelial barrier function. The aim of this study was to investigate whether VSL#3 improves intestinal epithelial barrier function against the effects of the inflammatory bowel disease-associated proinflammatory cytokine, interferon-gamma (IFN-γ) through activation of TCPTP.
METHODS: Polarized monolayers of T84 intestinal epithelial cells were treated with increasing concentrations of VSL#3 to determine effects on TCPTP expression and enzymatic activity. Therapeutic effects of VSL#3 against barrier disruption by IFN-γ were measured by transepithelial electrical resistance and fluorescein isothiocyanate-dextran permeability. A novel TCPTP-deficient HT-29 intestinal epithelial cell line was generated to study the role of TCPTP in mediating the effects of VSL#3. Tight junction protein distribution was assessed with confocal microscopy.
RESULTS: VSL#3 increased TCPTP protein levels and enzymatic activity, correlating with a VSL#3-induced decrease in IFN-γ signaling. VSL#3 corrected the decrease in transepithelial electrical resistance and the increase in epithelial permeability induced by IFN-γ. Moreover, the restorative effect of VSL#3 against IFN-γ signaling, epithelial permeability defects, altered expression and localization of the tight junction proteins claudin-2, occludin, and zonula occludens-1, were not realized in stable TCPTP/(PTPN2)-deficient HT-29 intestinal epithelial cells.
CONCLUSIONS: VSL#3 reduces IFN-γ signaling and IFN-γ-induced epithelial barrier defects in a TCPTP-dependent manner. These data point to a key role for TCPTP as a therapeutic target for restoration of barrier function using probiotics.

PMID: 27824650 [PubMed - as supplied by publisher]

Pages

Subscribe to IBD Scotland aggregator - Recent IBD publications