关键词： Monoclonal Antibody   Integrin   Pharmacokinetics   Therapeutic Drug Monitoring  

摘要： BACKGROUND & AIMS: Trough concentrations of vedolizumab were found to correlate with clinical response in phase 3 studies of patients with ulcerative colitis (UC) or Crohn's disease (CD). Nevertheless, there are no solid data to support monitoring of vedolizumab trough concentrations in treated patients. We investigated the correlation between vedolizumab exposure and response in a real-world population and aimed to identify patient factors that affect exposure and response. METHODS: We performed a retrospective cohort study of 179 consecutive patients (66 with UC and 113 with CD) who began vedolizumab therapy from September 1, 2015, through October 1, 2016, at University Hospitals Leuven, Belgium. Serum concentrations of vedolizumab were measured before all infusions up to week 30. Effectiveness endpoints included endoscopic healing (UC, Mayo endoscopic sub-score <= 1;CD, absence of ulcers), clinical response (physicians' global assessment), and biologic response or remission (based on level of C-reactive protein) and were assessed at week 14 (for patients with UC) and week 22 (for patients with CD). A stepwise forward addition-backward elimination modeling approach was performed to identify factors independently associated with vedolizumab exposure and response. RESULTS: Vedolizumab trough concentrations >30.0 mu g/mL at week 2, >24.0 mu g/mL at week 6, and >14.0 mu g/mL during maintenance therapy associated with a higher probability of attaining the effectiveness endpoints for patients with UC or CD (P < .05). Higher body mass and more severe disease (based on high level of C-reactive protein and low level of albumin and/or hemoglobin) at the start of vedolizumab therapy associated with lower trough concentrations of vedolizumab over the 30-week period and a lower probability of achieving mucosal healing (P < .05). Mucosal healing was achieved in significantly more patients with UC than patients with CD, even though a diagnosis of UC was not an independent predic

关键词： HYPERTROPHY   FIBROSIS   INFLAMMATION   DRUG therapy   ULCERATIVE colitis   ANTI-inflammatory agents  

摘要： Linked Content This article is linked to Morar et al and Rieder et al papers. To view these articles visit and .

关键词： Crohn disease   Ulcerative colitis   Quality improvement   ImproveCareNow   Inflammatory bowel disease  

摘要： Pediatric patients with inflammatory bowel disease (IBD) stand to benefit from quality improvement (QI) due to the chronic nature of the disease, frequent interaction with the health care system, and exposure to high risk treatments. The use of QI in health care has led to significant improvements in quality and reliability of care. Despite these advances, significant deficits in providing high-quality pediatric IBD care persist. This article describes a brief history of health care QI, identifies gaps and challenges in delivery of quality pediatric IBD care, highlights several IBD QI initiatives, and concludes with future directions for improving pediatric IBD outcomes.

关键词： Inflammatory bowel diseases   Laparoscopy   Morbidity   Mortality   Percorso Diagnostico Terapeutico   Assistenziale   Restorative proctocolectomy   Surgery   Ulcerative colitis  

摘要： Background: Laparoscopic ileo-pouch-anal anastomosis (IPAA) has been reported as having low morbidity and several advantages. Aims: To evaluate safety, efficacy and long-term results of laparoscopic IPAA, performed in elective or emergency settings, in consecutive unselected IBD patients. Methods: All the patients received totally laparoscopic 2-stage (proctocolectomy and IPAA - stoma closure) or 3-stage (colectomy - proctectomy and IPAA - stoma closure) procedure according to their presentation. Results: From July 2007 to July 2016, 160 patients entered the study. 50.6% underwent a 3-stage procedure and 49.4% a 2-stage procedure. Mortality and morbidity were 0.6% and 24.6%. Conversion rate was 3.75%. 8.7% septic complications were associated with steroids and Infliximab treatment (p=0.0001). 3-stage patients were younger (p=0.0001), with shorter disease duration (p=0.0001), minor ASA scores of 2 and 3 (p=0.0007), lower inflammatory index and better nutritional status (p=0.003 and 0.0001), fewer Clavien-Dindo's grade II complications (p=.0001), reduced rates of readmission and reoperation at 90 days (p=0.03), and shorter hospitalization (p=D001), but with similar pouch and IPAA leakage, compared to 2-stage patients. 8 years pouch failure and definitive ileostomy were 5.1% and 3.7%. Conclusion: A totally laparoscopic approach is safe and feasible, with very low mortality and morbidity rates and very low conversion rate, even in multi-stage procedures and high-risk patients. (C) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

关键词： INFLAMMATORY bowel diseases   ELECTRONIC records   SEXUAL dysfunction   MINORITIES   REPRODUCTIVE health  

摘要： Background High levels of voluntary childlessness and pregnancy-related fears have been reported amongst inflammatory bowel disease (IBD) patients. Aims To investigate what factors determine IBD patients' childbearing decisions;and to examine psychosocial consequences of IBD on various aspects of patients' reproductive health. Methods Six electronic databases were searched in a pre-specified and structured manner. Results A total of 41 articles with data on 7122 patients were included. Between one-fifth to one-third of IBD patients had chosen voluntary childlessness. Around 50% of all IBD patients have poor knowledge of pregnancy-related issues in IBD. Poor knowledge of pregnancy-related issues in IBD was associated with voluntary childlessness. Observational studies have found preconception counselling is associated with patients choosing parenthood. Pregnancy-related fears and concerns are multifaceted, stemming partly from lack of knowledge of pregnancy-related issues in IBD. Many female patients are considered at increased risk for pregnancy because between one-fifth to one-third of patients do not use contraception. Research evidence for sexual dysfunction after disease diagnosis and treatment is inconsistent. There are limited data on patients' pregnancy, postpartum and parenting experiences. A few shortcomings of the literature are evident;sample sizes were small, participation rates were low, use of non-validated questionnaires was common, and few studies included men and/or ethnic minority groups. The design of intervention studies is also weak. Conclusion This review recommends pre-conception counselling for all IBD patients of childbearing age to tackle poor knowledge and allow patients to make an informed decision on their reproductive health.

关键词： Yoga   Mind-body intervention   Inflammatory bowel disease   Adolescent   Complementary and alternative medicine   Integrative medicine  

摘要： Objectives: To determine whether utilizing yoga as an adjunctive therapy to the medical standard of care for adolescents with inflammatory bowel disease (IBD) is: (1) feasible and acceptable, (2) effective in reducing disease severity, intestinal inflammation and improving wellness. Design: Prospective, non-randomized, 8-week pilot study for adolescents with a diagnosis of IBD. Feasibility and acceptability of the intervention were assessed weekly and post-intervention via surveys and a focus group (week 8). Disease severity, intestinal inflammation, and wellness measures were assessed at baseline and post-intervention (week 8). Intervention: Over the 8-week study period, patients were assigned three 60-minute, in-person yoga classes at weeks 1, 3 and 8, and three 30-minute, online yoga videos per week. Main outcome measures: Primary outcome measures were feasibility and acceptability. Secondary outcome measures assessed preliminary clinical efficacy by examining pre- and post-intervention change in disease severity (PUCAI), intestinal inflammation (fecal calprotectin), and six wellness measures (PROMIS-37). Results: Nine adolescents with IBD participated. Eight participated in one or more yoga videos per week and all nine attended at least two in-person yoga classes. Focus group themes revealed that the intervention was well liked, with all participants reporting reduced stress, improved emotional self-awareness, and increased ability to identify and manage the physical symptoms of IBD. Participants had difficulty, however, completing the yoga videos due to time limitations and competing priorities. We lacked power to detect any statistically significant changes in PUCAI, calprotectin, or any of the six PROMIS-37 domains. Conclusions: A combination of in-person instructor led yoga with video-based yoga is a feasible and acceptable adjunct therapy for adolescents with IBD. Participants reported reduced stress and improved ability to identify and manage physical symp

摘要： Introduction : Malignancies are the second most common cause of death after cardiovascular diseases in patients with inflammatory bowel disease (IBD). Indeed, patients with IBD have an increased risk for developing a variety of extraintestinal malignancies, in particular, lymphomas and mostly non-Hodgkin lymphomas. In the spectrum of lymphoproliferative disorders, Hodgkin lymphoma-type is rare, only a few cases with Hodgkin's lymphoma (HL) in IBD patients have so far been reported. We report two new cases. Case 1 : A 44 year old male presented in 2010 with a history of abdominal pain, intermittent diarrhea, and rectal bleeding. The clinical, endoscopic, and pathologic findings were consistent with ulcerative colitis. Initial medical treatment was Azathioprine (50 mg, three times a day), Prednisolone (50 mg, one time a day), and 5-aminosalicylic acid (800 mg, three times a day). He was also diagnosed as having type 2 diabetes, treated with insulin. The patient was continually treated with Azathioprine through 5 years, with reduced dose (100 mg/d) because of hematological toxicity. In 2016, the patient was readmitted with severe pneumonia. He reported having abdominal pain, weight loss, night sweat, and intermittent fever for three to four months before admission. A computed tomography was performed, showed retroperitoneal, peri-aortic and iliac bilateral lymphadenopathy. Needle biopsy was performed out and histology revealed large cells of Hodgkin's type, and intense staining for CD30 and CD15 all in favor of the diagnosis of HL. Case 2 : The second patient is a 30-year-old man with ileocecal Crohn disease diagnosed at age 23 years. Remission was induced with corticosteroids and maintained by Azathioprine (150 mg/d). Three month before his admission to our unit, he complains from intermittent fever, decline in general condition. Cervical and axillary lymphadenopathy were noted. The lymph node biopsy revealed mixed-cellularity Hodgkin lymphoma. Computed tomography sca

摘要： Background: Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders of the gastrointestinal tract that affect approximately 70,000 children in the U.S. Anemia is the most common extra-intestinal symptom in children with IBD and is present in up to three-quarters of patients, most commonly due to iron deficiency. Despite its prevalence and impact, iron deficiency remains undertreated in children with IBD. Oral iron supplementation is often considered inefficient for such patients due to intolerance, sub-optimal absorption, and the potential to worsen local disease inflammation within the gastrointestinal tract. In adults with IBD, intravenous (IV) iron is commonly used and capable of improving iron status even in the setting of persistent inflammation. Newer IV iron formulations with decreased dosing requirements and improved safety profiles have reduced barriers to its use in pediatric patients. However, minimal published data exist on the use of IV iron in pediatric IBD. Objective: To evaluate trends in diagnosis of iron deficiency and its management utilizing a large national children's hospital database in pediatric patients with IBD over a 5 year period. We hypothesized that the use of IV iron to treat iron deficiency anemia (IDA) would increase and receipt of blood transfusion would subsequently decrease over time. Methods: In this retrospective multicenter cohort study, we used the Pediatric Health Information System (PHIS) de-identified administrative database containing data from 48 not-for-profit tertiary care pediatric hospitals in the U.S. ICD-9 and ICD-10 codes for Crohn's disease and ulcerative colitis identified all inpatient admissions for IBD from January 2012 through December 2017. Diagnostic codes were also used to identify those patients with anemia or iron deficiency during their admission. Procedure codes were assessed for receipt of transfusions, and pharmaceutical billing codes were assessed for iron (intravenous and oral

摘要： Background: Patients with inflammatory bowel diseases (IBD) exhibit chronic inflammation of the digestive tract associated with a prothrombotic shift in the plasmatic coagulation system as well as heightened platelet reactivity and preactivation. Recently, microbial and platelet-derived inorganic polyphosphate has been shown to inhibit tissue factor pathway inhibitor (TFPI), thus, influencing the hemostatic balance during inflammation. We hypothesized that polyphosphate plays a role in the pathophysiology of inflammatory bowel disease resulting in refractoriness to TFPI activity. Aims: We aimed to determine the hemostatic sensitivity to exogenous TFPI in IBD patients and healthy controls. Methods: Plasma from pediatric patients with active Crohn's disease (CD) (N=10) or ulcerative colitis (UC) (N=10) and age-matched healthy controls (N=20) was spiked with recombinant TFPI (150 ng/ml). Thrombin generation with/without exogenous TFPI was performed using Calibrated Automated Thrombography. Differences in lag time of thrombin generation with/without TFPI were calculated (∆lag time). Results: Without addition of exogenous TFPI, IBD patients exhibited a shorter lag time than controls (IBD: 2.65±0.41 min; Controls: 3.72±0.48 min, P<0.001) Addition of exogenous TFPI prolonged the lag time significantly in healthy controls (∆lag time= 4.69±0.61 min; P<0.001), while the lag time was just slightly prolonged in IBD patients (CD: ∆lag time=0.92±0.37 min; P<0.001; UC: ∆lag time=0.34±27 min; P<0.05). Conclusion: Plasma samples from pediatric IBD patients exhibit refractoriness towards the anticoagulant activity of exogenous TFPI. This hyposensitivity potentially extends to the action of endogenous TFPI which adds to the prothrombotic phenotype associated with IBD. Further studies are needed to determine potential associations with disease activity and the susceptibility to develop thrombosis.

关键词： Polymer-drug complexes   Solubility & stability   Site specific delivery   Inflammatory bowel disease   Toll-like Receptor-4   Curcumin  

摘要： Inflammatory Bowel Diseases (IBD) is a debilitating condition that affects similar to 70,000 new people every year and has been described as "an expensive disease with no known cure". In addition, IBD increases the risk of developing colon cancer. The current therapeutics for IBD focus on the established disease where the immune dysfunction and bowel damage have already occurred but do not prevent or delay the progression. The current work describes a polymer-based anti-inflammatory technology (Ora-Curcumin-S) specifically targeted to the luminal side of the colon for preventing and/or treating IBD. Ora-Curcumin-S was prepared by molecular complexation of curcumin with a hydrophilic polymer Eudragit (R) 5100 using co-precipitation method. Curcumin interacted with the polymer non-covalently and existed in an amorphous state as demonstrated by various physicochemical techniques. Ora-Curcumin-S is a polymer-drug complex, which is different than solid dispersions in that the interactions are retained even after dissolving in aqueous buffers. Ora-Curcumin-S was > 1000 times water soluble than curcumin and importantly, the enhanced solubility was pH-dependent, which was observed only at pHs above 6.8. In addition, around 90% of Ora-Curcumin-S was stable in phosphate buffer, pH 7.4 and simulated intestinal fluid after 24 h, in contrast to 10-20% unformulated curcumin. Ora-Curcumin-S inhibited Monophosphoryl Lipid-A and E. colt induced inflammatory responses in dendritic cells and cells over expressing Toll-Like Receptor-4 (TLR-4) suggesting that Ora-Curcumin-S is a novel polymer-based TLR-4 antagonist. Preliminary pharmacokinetics in mice showed targeted delivery of soluble curcumin to the colon lumen without exposing to the systemic circulation. Furthermore, Ora-Curcumin-S significantly prevented colitis and associated injury in a mouse model of ulcerative colitis estimated using multiple preclinical parameters: colonoscopy pictures, body weight, colon length, colon edema