New papers on PubMed

A national patient and public colorectal research agenda: Integration of consumer perspectives in bowel disease through early consultation.

A national patient and public colorectal research agenda: Integration of consumer perspectives in bowel disease through early consultation.

Colorectal Dis. 2016 Nov 21;:

Authors: McNair AG, Heywood N, Tiernan J, Verjee A, Bach SP, Fearnhead NS, ORACLE Collaboration

Abstract
AIM: There is a recognised need to include the views of patients and the public in prioritising health research. This study aimed 1) to explore patients' views on colorectal research and 2) to prioritise research topics with patients and the public.
METHOD: In phase 1, twelve charitable organisations and patient groups with an interest in bowel disease were invited to attend a consultation exercise. Participants were briefed on 25 colorectal research topics prioritised by members of the Association of Coloproctology of Great Britain and Ireland. Focus groups were conducted and discussions recorded with field notes. Analysis was conducted using principles of thematic analysis. In phase 2, a free public consultation was undertaken. Participants were recruited from newspaper advertisements, were briefed on the same research topics, and asked to rate the importance of each on a 5-point Likert scale. Descriptive statistics were used to rank the topics. Univariable linear regression compared recorded demographic details with mean topic scores.
RESULTS: Focus groups were attended by 12 patients who highlighted the importance of patient-centred information for trial recruitment and when selecting outcome measures. Some 360 people attended the public consultation, of whom 299(83%) were recruited. Participants rated "What is the best way to treat early cancer in the back passage?" highest, with 227(85%) scoring it 4 or 5. There was no correlation between participant demographics and mean topic scores.
CONCLUSION: The present study prioritised a colorectal research agenda with the input of patients and the public. Further research is required to translate this agenda into real improvements in patient care. This article is protected by copyright. All rights reserved.

PMID: 27870254 [PubMed - as supplied by publisher]

Classic IL-6R signalling is dispensable for intestinal epithelial proliferation and repair.

Classic IL-6R signalling is dispensable for intestinal epithelial proliferation and repair.

Oncogenesis. 2016 Nov 21;5(11):e270

Authors: Aden K, Breuer A, Rehman A, Geese H, Tran F, Sommer J, Waetzig GH, Reinheimer TM, Schreiber S, Rose-John S, Scheller J, Rosenstiel P

Abstract
Inflammatory bowel disease is characterized by disturbed cytokine signalling in the mucosa. Inhibition of the proinflammatory interleukin (IL)-6 pathway is a promising new therapeutic strategy, but safety concerns arise as IL-6 signalling also contributes to epithelial repair of the intestinal mucosa. To which extent IL-6 classic or trans-signalling contributes to intestinal repair remains elusive. We tested the influence of IL-6 classic signalling on intestinal repair and proliferation. Whereas IL-6 induced STAT3 phosphorylation in the colonic cancer cell lines, primary non-malignant intestinal organoids did not respond to IL-6 classic signalling. Mice deficient in intestinal IL-6R (IL-6R(ΔIEC) mice) did not display increased susceptibility to acute dextran sulfate sodium (DSS)-induced colitis. In the azoxymethane DSS model IL-6R(ΔIEC) mice were not protected from inflammation-induced carcinogenesis but showed comparable tumor load to wild-type mice. These data indicate that classic signalling is not the major pathway to transduce IL-6 stimuli into the intestinal epithelium.

PMID: 27869785 [PubMed - in process]

Gastrointestinal comorbidities which complicate the treatment of anorexia nervosa.

Gastrointestinal comorbidities which complicate the treatment of anorexia nervosa.

Eat Disord. 2016 Nov 21;:1-12

Authors: Mascolo M, Geer B, Feuerstein J, Mehler PS

Abstract
Patients with anorexia nervosa often voice a multitude of symptoms in regards to their gastrointestinal tract. These complaints can complicate the treatment of their eating disorder as they distract attention from the important goal of weight restoration. Moreover, the restricting of certain food groups also makes the task of weight restoration substantially more difficult, or may result in binging. Therefore a working knowledge of common gastrointestinal comorbidities, such as celiac disease, irritable bowel syndrome, inflammatory bowel disease, and gastroparesis, is useful when treating a patient who has anorexia nervosa.

PMID: 27869566 [PubMed - as supplied by publisher]

Immunology Update: Biologics.

Immunology Update: Biologics.

FP Essent. 2016 Nov;450:11-21

Authors: Starr SP

Abstract
Biologics are substances made from a living organism or its products. These include genes, proteins (eg, antibodies, receptors, enzymes, inhibitors), recombinant proteins, and fusion proteins. Biologics often are produced using recombinant DNA technology. For example, monoclonal antibodies are produced by inserting human genes into immortalized cell cultures, which then produce the gene product (ie, an antibody) in large quantity. Another approach is to fuse genetic material from nonhuman sources (eg, mice) with human genetic material. The fused gene is inserted into a tissue culture that produces the gene product (ie, a chimeric monoclonal antibody). Biologics are used to manage many conditions, including malignant and nonmalignant conditions. They are widely used in the treatment of human epidermal growth factor receptor 2 (ERBB2 [formerly HER2 or HER2/neu])-positive breast cancer. They also are used in the treatment of leukemias, lymphomas, and colorectal and lung cancer. Biologics improve outcomes in autoimmune disorders, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, inflammatory bowel disease, and multiple sclerosis. Other uses include erythropoietin for renal failure-associated anemia and the new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for treatment of patients with persistently elevated low-density lipoprotein levels despite statin treatment who are at high risk of cardiovascular events.

PMID: 27869438 [PubMed - in process]

PRDX2 up-regulation in inflammatory bowel disease: friend or foe?

PRDX2 up-regulation in inflammatory bowel disease: friend or foe?

J Gastroenterol Hepatol. 2016 Nov 21;:

Authors: Senhaji N, Zaid Y, El Khalfi B, Fahimi M, Martin J, Badre W, Nadifi S, Soukri A

Abstract
BACKGROUND: Inflammatory bowel diseases (IBD) are chronic multi-factorial inflammatory disorders. Accumulating investigations have provided compelling evidence that describe the interplay of a complex genetic landscape and inappropriate inflammatory response to intestinal microbes in disease etiopathogenesis, but still pose challenges in diagnostic practices.
METHOD: In this study, comparative proteomic analysis was conducted to identify disease specific proteins underlying IBD pathogenetic mechanisms. Total blood proteins of the IBD patients and healthy subjects were analyzed with one-dimensional electrophoresis; differentially expressed bands were excised and subjected to MALDI-TOF/TOF-MS/MS along with nLC-ESI-MS/MS analysis. Presence of glycosylation, hydroxylation and phosphorylation post-translational modifications was further investigated by immunoprecipitation.
RESULTS: PRDX2 and Hemoglobin-subunits proteins, which are closely involved in the response to oxidative stress, were identified. PRDX2 was selected for further validation using Western blot and RT-PCR. PRDX2 over-expression was restricted to the protein level within the membrane fraction. Immunoprecipitation identified PRDX2 to be post-translationally glycosylated and phosphorylated.
CONCLUSION: Our findings demonstrate the implication of PRDX2 in IBD. Future studies are required to establish its functional role and to determine the clinical utility.

PMID: 27869326 [PubMed - as supplied by publisher]

A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation.

A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and Inflammation.

Sci Rep. 2016 Nov 21;6:37531

Authors: Takahashi S, Yoshimura T, Ohkura T, Fujisawa M, Fushimi S, Ito T, Itakura J, Hiraoka S, Okada H, Yamamoto K, Matsukawa A

Abstract
Rapid and adequate mucosal healing is important for a remission of ulcerative colitis (UC) patients. Here, we examined whether Spred2, a member of the Sprouty-related EVH1-domain-containing proteins that inhibit the Ras/Raf/ERK pathway, plays a role in colonic mucosal homeostasis and inflammation by using Spred2 knockout (KO) mice. We first detected increased epithelial cell proliferation and cadherin 1 expression in the colon of naïve Spred2 KO mice compared to wild-type mice. Interestingly, Spred2 KO mice were resistant to dextran sulfate sodium (DSS)-induced acute colitis as indicated by lower levels of body weight loss and disease activity index. Histologically, epithelial cell injury and inflammation were milder in the colonic mucosa of Spred2 KO mice on day 3 and almost undetectable by day 8. Experiments with bone chimeric mice indicated that Spred2-deficiency in non-hematopoietic cells was responsible for the reduced sensitivity to DSS. Finally, Spred2 KO mice developed significantly fewer tumors in response to azoxymethane plus DSS. Taken together, our results demonstrate, for the first time, that Spred2 plays an important role in the regulation of colonic epithelial cell proliferation and inflammation by potentially down-regulating the activation of ERK. Thus, Spred2 may be a new therapeutic target for the treatment of UC.

PMID: 27869219 [PubMed - in process]

Structural and immunomodulatory differences among lactobacilli exopolysaccharides isolated from intestines of mice with experimentally induced inflammatory bowel disease.

Structural and immunomodulatory differences among lactobacilli exopolysaccharides isolated from intestines of mice with experimentally induced inflammatory bowel disease.

Sci Rep. 2016 Nov 21;6:37613

Authors: Górska S, Sandstrőm C, Wojas-Turek J, Rossowska J, Pajtasz-Piasecka E, Brzozowska E, Gamian A

Abstract
Characteristic changes in the microbiota biostructure and a decreased tolerance to intestinal bacteria have been associated with inflammatory bowel disease (IBD). However, few studies have examined the constituents of the intestinal microbiota, including the surface molecules of the bacteria, in healthy and IBD subsets. Here, we compare the chemical structures and immunomodulatory properties of the exopolysaccharides (EPS) of lactobacilli isolated from mice with induced IBD (IBD "+") versus those of healthy mice (IBD "-"). Classical structural analyses were performed using nuclear magnetic resonance spectroscopy and mass spectrometry. Immunomodulatory properties were assessed by stimulation of dendritic cells derived from mouse bone marrow or human peripheral mononuclear blood cells. Our results revealed that EPS produced by IBD "+" species are structurally different from those isolated from IBD "-". Moreover, the structurally different EPS generate different immune responses by dendritic cells. We speculate that resident strains could, upon gut inflammation, switch to producing EPS with specific motifs that are absent from lactobacilli IBD "-", and/or that bacteria with a particular EPS structure might inhabit the inflamed intestinal mucosa. This study may shed light on the role of EPS in IBD and help the development of a specific probiotic therapy for this disease.

PMID: 27869188 [PubMed - in process]

The contribution of clinical and psychosocial factors to fatigue in 182 patients with inflammatory bowel disease: a cross-sectional study.

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The contribution of clinical and psychosocial factors to fatigue in 182 patients with inflammatory bowel disease: a cross-sectional study.

Aliment Pharmacol Ther. 2016 Nov 20;:

Authors: Artom M, Czuber-Dochan W, Sturt J, Murrells T, Norton C

Abstract
BACKGROUND: Fatigue is a frequently reported and predominant symptom experienced by patients with inflammatory bowel disease (IBD) and its impact has been associated with poorer quality of life (QoL). The complex interplay between disease-related variables and potentially modifiable psychosocial factors in IBD-fatigue has yet to be unravelled.
AIM: To evaluate the contribution of clinical, sociodemographic and psychosocial factors to the severity and impact of IBD-fatigue and QoL.
METHOD: In a cross-sectional study, 182 patients with IBD were recruited from three tertiary referral hospitals' out-patient clinics in London. Fatigue was assessed utilising the Inflammatory Bowel Disease-Fatigue Scale (IBD-F), the Multidimensional Fatigue Inventory (MFI); and QoL by the Inflammatory Bowel Disease Questionnaire (IBDQ). Patients completed self-report questionnaires evaluating emotional, cognitive and behavioural factors potentially correlated with fatigue. Sociodemographic data were collected. Disease-related and laboratory data were retrieved from patients' hospital electronic medical records.
RESULT: In hierarchical regression models, disease activity was the only clinical factor consistently associated with severity and impact of fatigue and QoL (P = 0.01). More negative fatigue perceptions were significantly associated with greater IBD-F1 scores (P = 0.01). When controlling for clinical factors (disease activity and anti-TNF therapy), negative perceptions of fatigue, and all-or-nothing and avoidance behaviours explained an additional 41% of the variance in fatigue impact (IBD-F2).
CONCLUSIONS: Apart from disease activity, emotional and behavioural factors and patients' negative fatigue perceptions may be key factors to be addressed. Further exploration of these factors in longitudinal and intervention studies may help to develop effective models of fatigue management.

PMID: 27868215 [PubMed - as supplied by publisher]

Review: capsule colonoscopy-a concise clinical overview of current status.

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Review: capsule colonoscopy-a concise clinical overview of current status.

Ann Transl Med. 2016 Oct;4(20):398

Authors: Yung DE, Rondonotti E, Koulaouzidis A

Abstract
The colon capsule endoscopy (CCE) was first introduced in 2007. Currently, the main clinical indications for CCE are completion of incomplete colonoscopy, polyp detection and investigation of inflammatory bowel disease (IBD). Although conventional colonoscopy is the gold standard in bowel cancer screening, incomplete colonoscopy remains a problem as lesions are missed. CCE compares favourably to computer tomography colonography (CTC) in adenoma detection and has therefore been proposed as a method for completing colonoscopy. However the data on CCE remains sparse and current evidence does not show its superiority over CTC or conventional colonoscopy in bowel cancer screening. CCE also seems to show good correlation with conventional colonoscopy when used to evaluate IBD, but there are not many published studies at present. Other significant limitations include the need for aggressive bowel preparation and the labour-intensiveness of CCE reading. Therefore, much further software and hardware development is required to enable CCE to fulfill its potential as a minimally-invasive and reliable method of colonoscopy.

PMID: 27867950 [PubMed - in process]

Nutritional Aspects of Gastrointestinal Wound Healing.

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Nutritional Aspects of Gastrointestinal Wound Healing.

Adv Wound Care (New Rochelle). 2016 Nov 1;5(11):507-515

Authors: Mukherjee K, Kavalukas SL, Barbul A

Abstract
Significance: Although the wound healing cascade is similar in many tissues, in the gastrointestinal tract mucosal healing is critical for processes such as inflammatory bowel disease and ulcers and healing of the mucosa, submucosa, and serosal layers is needed for surgical anastomoses and for enterocutaneous fistula. Failure of wound healing can result in complications including infection, prolonged hospitalization, critical illness, organ failure, readmission, new or worsening enterocutaneous fistula, and even death. Recent Advances: Recent advances are relevant for the role of specific micronutrients, such as vitamin D, trace elements, and the interplay between molecules with pro- and antioxidant properties. Our understanding of the role of other small molecules, genes, proteins, and macronutrients is also rapidly changing. Recent work has elucidated relationships between oxidative stress, nutritional supplementation, and glucose metabolism. Thresholds have also been established to define adequate preoperative nutritional status. Critical Issues: Further work is needed to establish standards and definitions for measuring the extent of wound healing, particularly for inflammatory bowel disease and ulcers. In addition, a mounting body of evidence has determined the need for adequate preoperative nutritional supplementation for elective surgical procedures. Future Directions: A large portion of current work is restricted to model systems in rodents. Therefore, additional clinical and translational research is needed in this area to promote gastrointestinal wound healing in humans, particularly those suffering from critical illness, patients with enterocutaneous fistula, inflammatory bowel disease, and ulcers, and those undergoing surgical procedures.

PMID: 27867755 [PubMed - in process]

Osteonecrosis of both knees in a woman with Crohn's disease.

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Osteonecrosis of both knees in a woman with Crohn's disease.

World J Gastrointest Pharmacol Ther. 2016 Nov 6;7(4):579-583

Authors: Barbosa M, Cotter J

Abstract
Osteonecrosis is a very rare complication of Crohn's disease (CD). It is not clear if it is related to corticosteroid therapy or if it occurs as an extraintestinal manifestation of inflammatory bowel disease. We present the case of a patient with CD who presented with osteonecrosis of both knees. A 22 years old woman was diagnosed with CD in April 2012 (Montreal Classification A2L1 + L4B3p). She was started on prednisolone (40 mg/d), azathioprine (100 mg/d) and messalazine (3 g/d). In July 2012, due to active perianal disease, infliximab therapy was initiated. In September 2012, she had a pelvic abscess complicated by peritonitis and an ileal segmental resection and right hemicolectomy were performed. In December 2012 she was diagnosed with bilateral septic arthritis of both knees with walking impairment. She was treated with amoxicillin-clavulanic acid, started a physical rehabilitation program and progressively improved. However, then, bilateral knee pain exacerbated by movement developed. Magnetic resonance imaging showed multiple osseous medullary infarcts in the distal extremity of the femurs, proximal extremity of the tibiae and patellas and no signs of subchondral collapse, which is consistent with osteonecrosis. The patient recovered completely and maintains therapy with azathioprine and messalazine. A review of the literature is also done.

PMID: 27867692 [PubMed - in process]

Family history and disease outcomes in patients with Crohn's disease: A comparison between China and the United States.

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Family history and disease outcomes in patients with Crohn's disease: A comparison between China and the United States.

World J Gastrointest Pharmacol Ther. 2016 Nov 6;7(4):556-563

Authors: Wang PQ, Hu J, Al Kazzi ES, Akhuemonkhan E, Zhi M, Gao X, de Paula Pessoa RH, Ghazaleh S, Cornelius T, Sabunwala SA, Ghadermarzi S, Tripathi K, Lazarev M, Hu PJ, Hutfless S

Abstract
AIM: To investigate the differences in family history of inflammatory bowel disease (IBD) and clinical outcomes among individuals with Crohn's disease (CD) residing in China and the United States.
METHODS: We performed a survey-based cross-sectional study of participants with CD recruited from China and the United States. We compared the prevalence of IBD family history and history of ileal involvement, CD-related surgeries and IBD medications in China and the United States, adjusting for potential confounders.
RESULTS: We recruited 49 participants from China and 145 from the United States. The prevalence of family history of IBD was significantly lower in China compared with the United States (China: 4.1%, United States: 39.3%). The three most commonly affected types of relatives were cousin, sibling, and parent in the United States compared with child and sibling in China. Ileal involvement (China: 63.3%, United States: 63.5%) and surgery for CD (China: 51.0%, United States: 49.7%) were nearly equivalent in the two countries.
CONCLUSION: The lower prevalence of familial clustering of IBD in China may suggest that the etiology of CD is less attributed to genetic background or a family-shared environment compared with the United States. Despite the potential difference in etiology, surgery and ileal involvement were similar in the two countries. Examining the changes in family history during the continuing rise in IBD may provide further insight into the etiology of CD.

PMID: 27867689 [PubMed - in process]

A20 inhibits lipopolysaccharide-induced inflammation in enterocytes.

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A20 inhibits lipopolysaccharide-induced inflammation in enterocytes.

World J Gastrointest Pharmacol Ther. 2016 Nov 6;7(4):540-549

Authors: Zheng CF, Shi JR, Huang Y, Wang SN

Abstract
AIM: To examine the role of A20 in the regulation of intestinal epithelial cells (IECs) inflammation.
METHODS: Using gene transfection, both stable overexpression and knockdown A20-expressed HT-29 cell lines were established. Accordingly, the cells were divided into the following groups: The control group, the A20 overexpression group, the A20 knockdown group and the respective controls. A20 was stimulated with lipopolysaccharide (LPS) in a dose- and time-dependent manner and was detected using western blotting and real-time polymerase chain reaction (PCR) analyses. Immunofluorescence and western blotting analyses were performed to investigate the role of A20 in the regulation of nuclear factor (NF)-κB activation and translocation into the nucleus. ELISA and real-time PCR were performed to examine A20 in regulating the release of the following inflammatory cytokines: Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-8.
RESULTS: The expression of A20 in IECs was inducible. When intestinal epithelial cells were subjected to the stimulation of LPS, the expression of A20 was increased, and the expression of A20 was induced in a dose- and time-dependent manner. The expression of A20 was very low in HT-29 cells without LPS stimulation but rapidly increased and was maintained at a high level 2-4 h after stimulation with LPS. These levels gradually declined with a change in time-course, and the expression of A20 increased with increasing LPS stimulation. Western blotting and immunofluorescence revealed that overexpression of A20 can inhibit NF-κB activation and its translocation to the nucleus. The overexpression of A20 can reduce the levels of proinflammatory cytokines involved in the pathophysiology of inflammatory bowel disease. There was no significant difference in the expression of IL-8 mRNA in the control group, A20 overexpression group or A20 knockdown group without LPS stimulation (P > 0.05); however, while after 2 h, 4 h and 8 h stimulation with LPS, the expression of IL-8 in the A20 overexpression group was lower than the control group and the A20 knockdown group (P < 0.05 or P < 0.01). The expression of TNF-α was different at different time points after 8 h of LPS stimulation (F = 31.33, DF = 5, P < 0.001), and the expression of TNF-α increased as the LPS stimulation time increased. Upon LPS stimulation, lower levels of TNF-α were detected in the A20 overexpression cell lines (P < 0.05). There were no significant differences in the induction of IL-6 and IL-1β among the control group, A20 overexpression group and A20 knockdown group (P > 0.05).
CONCLUSION: A20 plays an important role in limiting inflammation by inhibiting LPS-induced NF-κB responses in the gut luminal. A20 may be a potential therapeutic tool for inflammatory diseases.

PMID: 27867687 [PubMed - in process]

How I treat my inflammatory bowel disease-patients with thiopurines?

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How I treat my inflammatory bowel disease-patients with thiopurines?

World J Gastrointest Pharmacol Ther. 2016 Nov 6;7(4):524-530

Authors: Meijer B, Mulder CJ, van Bodegraven AA, de Boer NK

Abstract
Thiopurines are essential drugs to maintain remission in patients with inflammatory bowel disease (IBD). Thiopurines used in IBD are azathioprine (2.0-2.5 mg/kg), mercaptopurine (1.0-1.5 mg/kg) and thioguanine (0.2-0.3 mg/kg). However, mainly due to numerous adverse events associated with thiopurine use, almost 50% of the patients have to discontinue conventional thiopurine treatment. Extensive monitoring and the application of several treatment strategies, such as split-dose administration, co-administration with allopurinol or dose reduction/increase, may increase the chance of successful therapy. With this review, we provide practical information on how thiopurines are initiated and maintained in two thiopurine research centers in The Netherlands. We provide clinical information concerning safety issues, indications and management of therapy that may serve as a guide for the administration of thiopurines in IBD patients in daily practice.

PMID: 27867685 [PubMed - in process]

Eosinophilic gastroenteritis: Approach to diagnosis and management.

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Eosinophilic gastroenteritis: Approach to diagnosis and management.

World J Gastrointest Pharmacol Ther. 2016 Nov 6;7(4):513-523

Authors: Abou Rached A, El Hajj W

Abstract
Eosinophilic gastroenteritis (EGE) is a rare and benign inflammatory disorder that predominantly affects the stomach and the small intestine. The disease is divided into three subtypes (mucosal, muscular and serosal) according to klein's classification, and its manifestations are protean, depending on the involved intestinal segments and layers. Hence, accurate diagnosis of EGE poses a significant challenge to clinicians, with evidence of the following three criteria required: Suspicious clinical symptoms, histologic evidence of eosinophilic infiltration in the bowel and exclusion of other pathologies with similar findings. In this review, we designed and applied an algorithm to clarify the steps to follow for diagnosis of EGE in clinical practice. The management of EGE represents another area of debate. Prednisone remains the mainstay of treatment; however the disease is recognized as a chronic disorder and one that most frequently follows a relapsing course that requires maintenance therapy. Since prolonged steroid treatment carries of risk of serious adverse effects, other options with better safety profiles have been proposed; these include budesonide, dietary restrictions and steroid-sparing agents, such as leukotriene inhibitors, azathioprine, anti-histamines and mast-cell stabilizers. Single cases or small case series have been reported in the literature for all of these options, and we provide in this review a summary of these various therapeutic modalities, placing them within the context of our novel algorithm for EGE management according to disease severity upon presentation.

PMID: 27867684 [PubMed - in process]

Treatment of pregnant women with a diagnosis of inflammatory bowel disease.

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Treatment of pregnant women with a diagnosis of inflammatory bowel disease.

World J Gastrointest Pharmacol Ther. 2016 Nov 6;7(4):490-502

Authors: Poturoglu S, Ormeci AC, Duman AE

Abstract
The frequency of diagnosis of inflammatory bowel disease (IBD) has increased in younger populations. For this reason, pregnancy in patients with IBD is a topic of interest, warranting additional focus on disease management during this period. The main objective of this article is to summarize the latest findings and guidelines on the management of potential problems from pregnancy to the breastfeeding stage. Fertility is decreased in patients with active IBD. Disease remission prior to conception will likely decrease the rate of pregnancy-related complications. Most of the drugs used for IBD treatment are safe during both pregnancy and breastfeeding. Two exceptions are methotrexate and thalidomide, which are contraindicated in pregnancy. Anti-tumor necrosis factor agents are not advised during the third trimester as they exhibit increased transplacental transmission and potentially cause immunosuppression in the fetus. Radiological and endoscopic examinations and surgical interventions should be performed only when absolutely necessary. Surgery increases the fetal mortality rate. The delivery method should be determined with consideration of the disease site and presence of progression or flare up. Treatment planning should be a collaborative effort among the gastroenterologist, obstetrician, colorectal surgeon and patient.

PMID: 27867682 [PubMed - in process]

Pyoderma Gangrenosum in the Urologist Clinic.

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Pyoderma Gangrenosum in the Urologist Clinic.

Curr Urol. 2016 Oct;9(3):159-162

Authors: Ludwig DJ, Roshani H, Steffens MG, Moll FC, Teepe RG

Abstract
Pyoderma gangrenosum is a rare non-infectious skin disorder. It is often associated with systemic diseases, like the inflammatory bowel disease, rheumatological disease and (hematological) malignancy. The diagnosis is affirmed through a process of elimination and is principally based on clinical presentation and course. We present a 59-year-old male with T-cell large granular lymphocyte leukemia and pyoderma gangrenosum of penis and scrotum. Finally the patient was successfully treated with systemic prednisolone.

PMID: 27867335 [PubMed - in process]

Sphingolipids in neutrophil function and inflammatory responses: Mechanisms and implications for intestinal immunity and inflammation in ulcerative colitis.

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Sphingolipids in neutrophil function and inflammatory responses: Mechanisms and implications for intestinal immunity and inflammation in ulcerative colitis.

Adv Biol Regul. 2016 Nov 14;:

Authors: Espaillat MP, Kew RR, Obeid LM

Abstract
Bioactive sphingolipids are regulators of immune cell function and play critical roles in inflammatory conditions including ulcerative colitis. As one of the major forms of inflammatory bowel disease, ulcerative colitis pathophysiology is characterized by an aberrant intestinal inflammatory response that persists causing chronic inflammation and tissue injury. Innate immune cells play an integral role in normal intestinal homeostasis but their dysregulation is thought to contribute to the pathogenesis of ulcerative colitis. In particular, neutrophils are key effector cells and are first line defenders against invading pathogens. While the activity of neutrophils in the intestinal mucosa is required for homeostasis, regulatory mechanisms are equally important to prevent unnecessary activation. In ulcerative colitis, unregulated neutrophil inflammatory mechanisms promote tissue injury and loss of homeostasis. Aberrant neutrophil function represents an early checkpoint in the detrimental cycle of chronic intestinal inflammation; thus, dissecting the mechanisms by which these cells are regulated both before and during disease is essential for understanding the pathogenesis of ulcerative colitis. We present an analysis of the role of sphingolipids in the regulation of neutrophil function and the implication of this relationship in ulcerative colitis.

PMID: 27866974 [PubMed - as supplied by publisher]

Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity.

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Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity.

Cell Metab. 2016 Nov 16;:

Authors: Arts RJ, Novakovic B, Ter Horst R, Carvalho A, Bekkering S, Lachmandas E, Rodrigues F, Silvestre R, Cheng SC, Wang SY, Habibi E, Gonçalves LG, Mesquita I, Cunha C, van Laarhoven A, van de Veerdonk FL, Williams DL, van der Meer JW, Logie C, O'Neill LA, Dinarello CA, Riksen NP, van Crevel R, Clish C, Notebaart RA, Joosten LA, Stunnenberg HG, Xavier RJ, Netea MG

Abstract
Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by β-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to β-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by β-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues.

PMID: 27866838 [PubMed - as supplied by publisher]

Predictors of tissue healing in ulcerative colitis patients treated with anti-TNF.

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Predictors of tissue healing in ulcerative colitis patients treated with anti-TNF.

Dig Liver Dis. 2016 Oct 20;:

Authors: Viazis N, Giakoumis M, Bamias G, Goukos D, Koukouratos T, Katopodi K, Karatzas P, Triantos C, Tsolias C, Theocharis G, Daikos GL, Ladas SD, Karamanolis DG, Mantzaris GJ

Abstract
AIM: To identify factors predicting mucosal healing in ulcerative colitis patients treated with anti-TNFα agents with or without azathioprine.
METHODS: In a prospective, multicenter, one-year study biologic naïve patients aged 25-65 years, with corticosteroid-dependent or refractory colitis received combination treatment with anti-TNFα and azathioprine for 6 months followed by anti-TNFα monotherapy. Patients who denied combination therapy or were outside this age range received anti-TNFα monotherapy (controls). Before and at weeks 12 and 54 of treatment the total Mayo score was calculated. Mucosal healing was defined as endoscopic subscore of 0. Mucosal expression of T helper (Th) cell-lineage specific transcription factors (Tbet, Gata3, Rorc, FoxP3) before treatment was also associated with mucosal healing.
RESULTS: Of 67 patients, 58 (86.6%) received combination and 9 (13.4%) anti-TNFα monotherapy. Overall 29 (43.3%) patients achieved mucosal healing; rates were higher in patients receiving combination therapy vs. monotherapy (p=0.03) and in azathioprine naïve vs. exposed patients in the combination group (p=0.01). Mucosal healing was associated with lower pre-treatment mucosal expression of transcription factor Th1-Tbet (p<0.05) and higher expression of Th17-Rorc (p<0.05).
CONCLUSIONS: Mucosal healing was associated with combination therapy, especially in biologic and azathioprine-naïve patients and pre-treatment mucosal expression of specific Th specific transcripting factors (Tbet and Rorc).

PMID: 27866814 [PubMed - as supplied by publisher]

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