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1.
Medicine (Baltimore). 2018 Sep;97(39):e12486. doi: 10.1097/MD.0000000000012486.

Validation of a self-reported work disability questionnaire for ulcerative colitis.

Author information

1
Digestive Disease Department, Burgos Healtcare complex, Burgos.
2
Departament de Medicina, University Autònoma de Barcelona.

Abstract

Ulcerative colitis (UC) may severely limit patients' capacity to work. Recently, we validated a work disability questionnaire (WDQ) for Crohn disease. As UC shares clinical characteristics with Crohn disease, we hypothesized that the questionnaire might also be useful for UC. The study was aimed to validate the WDQ for use in UC.Consecutive patients with UC (n = 142, 67 women; age 48 ± 1) completed the UC-WDQ and the inflammatory bowel disease questionnaire-9 (IBDQ-9), and EuroQoL-5D quality-of-life questionnaires. Validation of the UC-WDQ included an assessment of its construct validity, including: discriminant validity, convergent validity, and reproducibility (test-retest). We also calculated the intraclass correlation and the Cronbach alpha.The UC-WDQ is a valid and reliable tool for measuring work disability in patients with UC.

PMID:
30278537
PMCID:
PMC6181479
DOI:
10.1097/MD.0000000000012486
[Indexed for MEDLINE]
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2.
Medicine (Baltimore). 2018 Sep;97(39):e12294. doi: 10.1097/MD.0000000000012294.

Association of miRNA-146a rs2910164 and miRNA-196 rs11614913 polymorphisms in patients with ulcerative colitis: A meta-analysis and review.

Author information

1
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University.
2
Department of Epidemiology, Medical School of Jinan University, Guangzhou, Guangdong Province.
3
Department of Gastroenterological Surgery, First Hospital of Jiaxing, Jiaxing, Zhejiang, China.

Abstract

BACKGROUND:

It has been reported that the single nucleotide polymorphisms (SNPs) miRNA-196 (miR-196) rs11614913 and miRNA-146a (miR-146a) rs2910164 are related to susceptibility to ulcerative colitis (UC). Because the previously reported results have been mixed and uncertain, the aim of this study was to perform a meta-analysis and review to assess the relationship between these 2 SNPs and UC risk.

METHODS:

In this analysis, 5 studies involving 1023 cases and 1769 controls for miR-196 rs11614913 and 4 studies involving 827 cases and 1451 controls for miR-146 rs2910164 were included. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size.

RESULTS:

A decreased risk of UC was identified in homozygote comparison (GG vs CC: OR = 0.69, 95% CI: 0.52-0.93, P = .02), recessive comparison (GG vs CG + CC: OR = 0.74, 95% CI: 0.59-0.92, P = .007), and dominant comparison (GG + CG vs CC: OR = 0.79, 95% CI: 0.65-0.97, P = .02) of miR-146 rs2910164 in Asian but not Caucasian population. No evidence of an association was shown between the rs11614913 polymorphism and UC risk in allelic, heterozygote, homozygote, recessive, and dominant models in both Caucasian and Asian populations (P > .05).

CONCLUSIONS:

MiR-146 rs2910164, but not miR-196 rs11614913, was associated with a decreased risk of UC in Asian population. However, the results should be treated with caution because of the limited sample size and heterogeneity. Well-designed studies with large sample sizes and more ethnic groups are needed to validate the risks identified in the current meta-analysis and review.

PMID:
30278502
PMCID:
PMC6181578
DOI:
10.1097/MD.0000000000012294
[Indexed for MEDLINE]
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3.
Medicine (Baltimore). 2018 Sep;97(38):e12337. doi: 10.1097/MD.0000000000012337.

Shen-Ling-Bai-Zhu-San for ulcerative colitis: Protocol for a systematic review and meta-analysis.

Author information

1
Xi'an Hospital of Traditional Chinese Medicine, Xi'an.
2
Shaanxi land Enigineering Construction Group, Shanxi Province, China.

Abstract

BACKGROUND:

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) at the colonic mucosa and submucosa. Shen-Ling-Bai-Zhu-San (SLBZS) is one of the most common formulations of traditional Chinese medicine (TCM) for the treatment of UC. However, its effects and safety remain uncertain. This protocol is described for a systematic review to investigate the beneficial effects and safety of SLBZS for UC.

METHODS:

We will systematically search for eligible studies in PubMed, the Cochrane library, Embase, the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), and Wanfang Data (WAN FANG) until August 2018. The primary outcomes are the induction of remission and the maintenance of remission. The summary results will be pooled using the random-effects model or fixed-effects model according to the heterogeneity of the included studies.

RESULTS:

The results will be submitted to a peer-reviewed journal for publication.

CONCLUSION:

The conclusion of our systematic review will provide evidence to judge whether SLBZS is an effective intervention for patient with UC.

PROSPERO REGISTRATION NUMBER:

PROSPERO CRD 42018100477.

PMID:
30235688
PMCID:
PMC6160248
DOI:
10.1097/MD.0000000000012337
[Indexed for MEDLINE]
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4.
BMC Gastroenterol. 2018 Sep 15;18(1):140. doi: 10.1186/s12876-018-0868-x.

Vedolizumab use after failure of TNF-α antagonists in children and adolescents with inflammatory bowel disease.

Author information

1
Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
2
Departments of Pediatrics, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria. Benjamin.Hetzer@i-med.ac.at.
3
Departments of Pediatrics, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria.
4
Department of Mathematics, Paris Lodron University, Salzburg, Austria.
5
Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, Salzburg, Austria.
6
Department of Pediatric Nephrology and Gastroenterology, Medical University Vienna, Vienna, Austria.

Abstract

BACKGROUND:

Vedolizumab is safe and effective in adult patients with Crohn's disease (CD) and ulcerative colitis (UC); however, data in children with inflammatory bowel disease (IBD) are scarce. Therefore, we evaluated vedolizumab use in a cohort of Austrian paediatric patients with IBD.

METHODS:

Twelve patients (7 female; 7 CD; 5 UC), aged 8-17 years (median, 15 years), with severe IBD who received vedolizumab after tumour necrosis factor α antagonist treatment were retrospectively analysed. Clinical activity scores, relevant laboratory parameters, and auxological measures were obtained at infusion visits.

RESULTS:

In the CD group, 1/7 patient discontinued therapy due to a severe systemic allergic reaction; 1/7 and 2/7 patients achieved complete and partial response, respectively, at week 14; and 3/7 patients discontinued therapy due to a primary non-response or loss of response. In the UC group, complete clinical remission was achieved at weeks 2, 6, and 14 in 2/5, 1/5 and 1/5 patients respectively; partial response was observed in one patient at week 2. CD activity scores did not significantly change from baseline to week 38 (median 47.5 vs. 40 points, p = 1,0), while median UC activity scores changed from 70 to 5 points (p < 0,001). Substantial weight gain and increased albumin and haemoglobin levels were observed in both groups.

CONCLUSION:

These results demonstrate that vedolizumab can be an effective treatment for individual paediatric patients with IBD who are unresponsive, intolerant, or experience a loss of efficacy in other therapies. However, vedolizumab appears to be more effective in paediatric UC than in paediatric CD.

KEYWORDS:

Crohn’s disease; Integrin antagonist; Paediatrics; Ulcerative colitis

PMID:
30219028
PMCID:
PMC6139155
DOI:
10.1186/s12876-018-0868-x
[Indexed for MEDLINE]
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5.
6.
Cell Mol Gastroenterol Hepatol. 2018 Jun 30;6(3):350-351. doi: 10.1016/j.jcmgh.2018.06.004. eCollection 2018.

Ulcerative Colitis-Associated Carcinoma: Epithelial SMAD4-Mediated Signaling Is a Key Guardian.

Author information

1
Département d'Anatomie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Pavillon de Recherche Appliquée sur le Cancer, Université de Sherbrooke, Sherbrooke, Québec, Canada.
PMID:
30182046
PMCID:
PMC6121135
DOI:
10.1016/j.jcmgh.2018.06.004
[Indexed for MEDLINE]
Free PMC Article
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7.
Medicine (Baltimore). 2018 Aug;97(35):e12036. doi: 10.1097/MD.0000000000012036.

Ulcerative colitis in an adult patient mimicking Henoch-Schönlein purpura: A case report.

Abstract

RATIONALE:

Ulcerative colitis (UC) is one of the chronic inflammatory diseases of the intestinal tract. UC being misdiagnosed as Henoch-Schönlein purpura (HSP) in the elderly has seldom been reported about.

PATIENT CONCERNS:

A 64-year-old man was admitted to the hospital with petechiae and palpable purpura in lower limbs and abdominal pain for about 1 month.

DIAGNOSES:

Colonoscopy demonstrated severe inflammation in the colon, mucosal congestion, and edema, and multiple hemorrhages and ulcerations, with purulent adhesions. A histopathologic examination of the colon biopsies revealed extensive infiltration of immune cells and mucosal ulcerations in the intestine. UC was diagnosed.

INTERVENTIONS:

The patient was treated with prednisone (1.0 mg/kg/d) with progressive dose reduction.

OUTCOMES:

The skin lesions were healed within 4 weeks, and his abdominal pain was alleviated remarkably. He is currently under follow-up.

LESSONS:

As the treatment used for patients with HSP was not effective, it was advised that UC should be taken into consideration.

PMID:
30170414
DOI:
10.1097/MD.0000000000012036
[Indexed for MEDLINE]
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8.
Medicine (Baltimore). 2018 Aug;97(34):e12087. doi: 10.1097/MD.0000000000012087.

Trichuris suis ova therapy in inflammatory bowel disease: A meta-analysis.

Author information

1
Digestive Endoscopy Center.
2
Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan.
3
Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei.
4
Department of Gastroenterology.
5
Department of Intensive Care Unit, Haimen People's Hospital, Haimen, Nantong, Jiangsu, P.R. China.

Abstract

BACKGROUND:

In recent years, Trichuris suis ova (TSO) therapy in inflammatory bowel disease (IBD) has attracted much attention. However, efficacy and safety of TSO therapy are still not well described. The aim of the study was to perform a meta-analysis to assess the effectiveness of TSO therapy in IBD.

METHODS:

PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library were searched from inception to August 2017. Only randomized, double-blind, placebo-controlled trials (RCTs) were included. The pooled estimate rates were performed by meta-analysis and reported according to the standard Cochrane guidelines and the PRISMA statement.

RESULTS:

In ulcerative colitis study (3 RCTs, n = 74), the induced rates of clinical remission and clinical response were 10.8% (4/37) and 53.8% (21/39) in TSO group, while 6.7% (2/30) and 29.0% (9/31) in placebo group (all P > .26). Twenty-two (9/41) percent of patients in TSO group experienced at least 1 adverse event compared with 27.3% (9/33) of placebo [relative ratio (RR) 0.75, 95% confidence interval (95% CI) 0.17-3.27]. In Crohn disease study (3 RCTs, n = 538), 40.7% (74/182) of patients in TSO group achieved clinical remission compared with 42.9% (90/210) of placebo (RR 0.95, 95% CI 0.75-1.20); 45.9% (141/307) of patients in TSO group entered clinical response compared with 45.1% (151/335) of placebo (RR 1.02, 95% CI 0.86-1.21). There were sparse data of adverse events reporting both TSO and placebo group (RR 1.00, 95% CI 0.88-1.13).

CONCLUSION:

TSO therapy showed no statistical benefit for IBD patients, so it suggested clinicians consider its value carefully before putting into clinical practice. Perhaps continued investigations of larger sample size are necessary due to the previous results with lack of power.

PMID:
30142867
PMCID:
PMC6113037
DOI:
10.1097/MD.0000000000012087
[Indexed for MEDLINE]
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9.
Medicine (Baltimore). 2018 Aug;97(34):e11897. doi: 10.1097/MD.0000000000011897.

Effectiveness and safety of adalimumab to treat outpatient ulcerative colitis: A real-life multicenter, observational study in primary inflammatory bowel disease centers.

Author information

1
Territorial Gastroenterology Service, ASL BAT, Andria.
2
Division of Gastroenterology, ASL Roma 6, Albano Laziale (Roma).
3
Division of Gastroenterology, "Belcolle" Hospital, Viterbo.
4
Division of Gastroenterology, "Santa Caterina Novella" Hospital, Galatina (LE).
5
Division of Gastroenterology, A.O. "Ospedali Riuniti," Foggia.
6
Division of Digestive Endoscopy, "S. Maria Goretti" Hospital, Latina.
7
Digestive Endoscopy Unit, ULSS4 Alto Vicentino, Santorso (VI).
8
Department of Health Science, University of Catanzaro, Catanzaro.
9
Division of Gastroenterology, PTP "Nuovo Regina Margherita," Roma.
10
Division of Gastroenterology, "Brotzu" Hospital, Cagliari.
11
Division of Gastroenterology, "S. Paolo" Hospital, Bari.
12
Division of Gastroenterology, "Ciaccio-Pugliese" Hospital, Catanzaro.
13
Territorial Gastroenterology Service, PST Catanzaro Lido, Catanzaro.
14
Ambulatory for IBD Treatment, "Valle D'Itria" Hospital, Martina Franca (TA).
15
Division of Gastroenterology, "Veris Delli Ponti" Hospital, Scorrano (LE).
16
Division of General Surgery, "P. Colombo" Hospital, ASL Roma 6, Velletri (Roma), Italy.

Abstract

Adalimumab (ADA) was approved in Italy for the treatment of ulcerative colitis (UC) unresponsive to standard treatments in 2014, but no data from real life are currently available. The aim of the present study was to assess the real-life efficacy and safety of ADA in managing UC outpatients in some Italian primary inflammatory bowel disease (IBD) centers after approval of ADA reimbursement.Consecutive UC outpatients with at least 3-month follow-up were retrospectively evaluated. The primary end point was the induction and maintenance of remission in UC, defined as Mayo score ≤2.One hundred seven patients were included. At 3-month follow-up, obtained in 102 (95.3%) patients, 56 (54.9%) patients achieved a clinical remission. At univariate analysis, both Mayo partial score >7 and Mayo subscore for endoscopy = 3 at entry showed to be significantly associated with the lack of remission induction.During a median (95% confidence interval [CI]) follow-up of 18 (12-24) months, 56.6% of patients were under clinical remission; clinical response was achieved in 89.2% of cases. Mucosal healing was achieved in 66 (76.7%) patients, and colectomy occurred in 3 (2.8%) patients. Both C-reactive protein and fecal calprotectin values significantly decreased during follow-up. Steroids discontinuation occurred in 67 (66.7%) patients, and ADA dose escalation was adopted in 9 (16.1%) patients under remission. No factor was significantly related to the maintenance of clinical remission.This first Italian experience found ADA safe and effective to induce and maintain remission in real-life UC outpatients.

PMID:
30142791
PMCID:
PMC6112877
DOI:
10.1097/MD.0000000000011897
[Indexed for MEDLINE]
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10.
Expert Opin Drug Saf. 2018 Sep;17(9):963-969. doi: 10.1080/14740338.2018.1510914. Epub 2018 Aug 21.

The safety of beclomethasone dipropionate in the treatment of ulcerative colitis.

Author information

1
a Department of Medicine and Surgery (DIMEC), IBD unit, S. Orsola-Malpighi Hospital , University of Bologna , Bologna , Italy.

Abstract

Beclomethasone dipropionate (BDP) is a second-generation corticosteroid that uses novel drug technologies to ensure colonic targeting and potentially reducing systemic corticosteroid concentrations. It is approved for treatment of patients with mild-to-moderate ulcerative colitis (UC) who do not respond to mesalazine. The gut-selective mechanism of action has the potential to improve the safety profile of BDP compared with other conventional corticosteroids. Areas covered: We reviewed the mechanism of action, efficacy, and safety of BDP in the treatment of UC. The positioning of BDP in management algorithms is also discussed. Expert opinion: The highly selective mechanism of action of BDP restricts the steroid-related side effects. BDP is efficacious in the treatment of active UC. Topical formulation is the first choice in distal UC, while oral formulation is used in patients with an extensive involvement of the colon. The rates of adverse events (AE), serious AEs, and steroid-related side-effects are similar to placebo and mesalamine and slightly inferior to traditional corticosteroids.

KEYWORDS:

Inflammatory bowel disease; adverse events; beclomethasone dipropionate; safety; steroids; ulcerative colitis

PMID:
30101623
DOI:
10.1080/14740338.2018.1510914
[Indexed for MEDLINE]
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11.
Medicine (Baltimore). 2018 Aug;97(32):e11772. doi: 10.1097/MD.0000000000011772.

Diagnostic utility of serological biomarkers in patients with Crohn's disease: A case-control study.

Author information

1
Department of Gastroenterology.
2
Statistics Department, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.

Abstract

The aim of this study was to examine the expression of serological markers in patients with inflammatory bowel disease in China, and determine the diagnostic utility of serological markers, individually and in combination, for the diagnosis and differential diagnosis of Crohn's disease (CD).Serum samples were obtained from 160 participants in Eastern China. Among the participants, 98 were diagnosed with CD, 33 had ulcerative colitis (UC), and 29 were healthy controls (HC). The serum samples were tested for the presence of antibodies against outer membrane porin C (anti-OmpC), Pseudomonas fluorescens bacterial sequence I2 (anti-I2), anti-laminarin (anti-L), anti-chitin (anti-C), anti-chitobioside carbohydrate antibody (ACCA), anti-laminaribioside carbohydrate antibody (ALCA), anti-mannobioside carbohydrate antibody (AMCA), and anti-Saccharomyces cerevisiae antibody (ASCA) by indirect enzyme-linked immunosorbent assay (ELISA).Individually, anti-C, anti-L, ASCA-IgG, and ALCA lacked diagnostic value in the differentiation of CD. ASCA-IgA remained the most accurate marker for the diagnosis of CD, with an area under the curve (AUC) of 0.77; however, its sensitivity and specificity were both lower than 75%. Among the combinations of the 5 markers with significant diagnosing ability for CD, combinations with any 2 of the 3 markers, ASCA IgA, AMCA, and ACCA positive, provided the best accuracy in the diagnosis and differential diagnosis of CD (sensitivity and specificity both above 75%) and had the highest Youden index.Serological antibodies, when considered in combination, have remarkable value in the diagnosis and differential diagnosis of CD. Especially, the combination of any 2 of the 3 markers, ASCA-IgA, AMCA, ACCA positive, appears to be optimal.

PMID:
30095633
PMCID:
PMC6133474
DOI:
10.1097/MD.0000000000011772
[Indexed for MEDLINE]
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12.
Medicine (Baltimore). 2018 Aug;97(32):e11440. doi: 10.1097/MD.0000000000011440.

Pooled analysis of the comparative efficacy between tacrolimus and infliximab for ulcerative colitis.

Abstract

BACKGROUND:

Acute moderate-to-severe steroid-refractory ulcerative colitis (UC) has a poor prognosis and requires optimal rescue therapy. A pooled analysis was conducted to assess tacrolimus and infliximab (IFX) as rescue agents in patients with moderate-to-severe and steroid-refractory UC.

METHODS:

A literature search identified studies that investigated tacrolimus and IFX in moderate-to-severe steroid-refractory patients with UC. The primary outcome was short-term clinical response to treatment, including the remission and response rates. Secondary outcomes included the rates of colectomy at 3 months and adverse events rate.

RESULTS:

A total of 6 studies comprising 438 cases were eligible for inclusion. The pooled analysis showed that the short-term clinical response rate, clinical remission rate, and 3-month colectomy rate were 72.1%, 52.4%, and 10.1%, respectively, for those receiving tacrolimus, and 76.9%, 48.8%, and 12.4%, respectively, for those receiving IFX. No significant difference was, however, seen for tacrolimus compared with IFX with regard to clinical remission rate (odds ratio [OR] =1.08, 95% confidence interval [CI] = 0.77-1.49, P = .67), clinical response rate (OR = 0.92, 95% CI = 0.63-1.34, P = .66), and 3-month colectomy rate (OR = 0.86, 95% CI = 0.39-1.93, P = .72). More adverse events were, however, observed in the Tac group (OR = 2.16, 95% CI = 1.25-3.76, P = .006).

CONCLUSIONS:

Our meta-analysis suggested that both tacrolimus and IFX appeared to be effective and safe for the rescue therapy of moderate-to-severe active UC and steroid-refractory UC. Therefore, tacrolimus is another choice for these patients.

PMID:
30095612
PMCID:
PMC6133612
DOI:
10.1097/MD.0000000000011440
[Indexed for MEDLINE]
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13.
Dis Colon Rectum. 2018 Sep;61(9):1013-1015. doi: 10.1097/DCR.0000000000001174.

Expert Commentary on the Management of Ulcerative Colitis.

Author information

1
Mayo Clinic, Rochester, Minnesota.

Comment on

PMID:
30086049
DOI:
10.1097/DCR.0000000000001174
[Indexed for MEDLINE]
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15.
BMC Gastroenterol. 2018 Aug 1;18(1):120. doi: 10.1186/s12876-018-0853-4.

Faecal calprotectin level for assessing endoscopic activity and predicting future clinical course in patients with moderately active ulcerative colitis undergoing granulomonocytapheresis: a prospective cohort study.

Author information

1
Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, 10-8 Hazuyamacho, Yokkaichi, 510-0016, Japan.
2
Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, 10-8 Hazuyamacho, Yokkaichi, 510-0016, Japan. nao-taka@sannet.ne.jp.

Abstract

BACKGROUND:

Calprotectin is a stable neutrophil protein, which can be measured in faecal samples. The faecal level of calprotectin increases during disease activity in ulcerative colitis (UC). Nonetheless, the relevance of faecal calprotectin (FC) measurement during granulomonocytapheresis (GMA) for UC has not yet been fully evaluated. This prospective study was to investigate the value of FC for assessing disease activity and predicting clinical course in UC patients undergoing GMA therapy.

METHODS:

One hundred and eighty-four patients with moderately active UC with endoscopic activity (Mayo endoscopic subscore [MES] = 2 or 3) received Adacolumn GMA therapy (10 apheresis sessions over consecutive 5 weeks). Patients who achieved clinical remission were subsequently given maintenance medications for 12 months. FC levels were measured at entry and after treatment.

RESULTS:

After GMA, 80 of the 184 patients (43%) achieved clinical remission, and 51 (28%) achieved mucosal healing (MH; MES = 0 or 1). The median FC level significantly decreased in patients who achieved MH (P = 0.02), but not in those without MH. Thirty-four patients (43%) relapsed during the 12-month follow-up. The median FC level at the end of GMA therapy was significantly higher in patients who subsequently relapsed than in those who maintained remission (149.5 vs 45.5 μg/g, P < 0.001). A cut off value of 114 μg/g had a sensitivity of 76% and a specificity of 85% to predict future relapse.

CONCLUSIONS:

Our findings indicate that FC is a relevant biomarker, which is convenient to measure for assessing endoscopic activity and predicting relapse in patients who achieve remission following a course of GMA therapy.

KEYWORDS:

Endoscopic activity; Faecal calprotectin; Granulomonocytapheresis; Predicting relapse; Ulcerative colitis

PMID:
30068300
PMCID:
PMC6090982
DOI:
10.1186/s12876-018-0853-4
[Indexed for MEDLINE]
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16.
Best Pract Res Clin Gastroenterol. 2018 Feb - Apr;32-33:95-102. doi: 10.1016/j.bpg.2018.05.016. Epub 2018 May 23.

Can IL-23 be a good target for ulcerative colitis?

Author information

1
IBD Centre, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy. Electronic address: mariangela.allocca@humanitas.it.
2
IBD Centre, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy.
3
IBD Centre, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy.
4
Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy.

Abstract

A considerable percentage of patients with ulcerative colitis (UC) do not respond to therapies, including anti-tumor necrosis factor (TNF) drugs and vedolizumab, or lose response over time. Hence the continuing need to find new therapeutic strategies and novel drugs to control this chronic debilitating disease. Increased levels of interleukin (IL)-23 and T helper (Th) 17 cell cytokines have been found in intestinal mucosa, plasma, and serum of patients with inflammatory bowel disease (IBD). IL23-blocking has been shown to reduce the severity of inflammation in experimental colitis. Lastly, ustekinumab, a monoclonal antibody (mAb) to the p40 subunit of IL-12 and IL-23, has showed good efficacy and safety profile in patients with Crohn's disease (CD). This review aims to discuss the available data on IL-23 and Th17 cell pathways in UC, in order to define the role of IL-23 as possible target for the treatment of UC.

KEYWORDS:

Crohn's disease; IL-23; Inflammatory bowel disease; Monoclonal antibody anti-IL23; Th17 cell pathway cytokines; Ulcerative colitis

PMID:
30060945
DOI:
10.1016/j.bpg.2018.05.016
[Indexed for MEDLINE]
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17.
Best Pract Res Clin Gastroenterol. 2018 Feb - Apr;32-33:9-15. doi: 10.1016/j.bpg.2018.05.004. Epub 2018 Jun 20.

Can we move directly from 5-ASA to a biologic agent in ulcerative colitis?

Author information

1
Department of Gastroenterology, University of Ghent, Ghent, Belgium. Electronic address: pieter.hindryckx@uzgent.be.
2
Department of Gastroenterology, Ljubljana University Medical Centre, Ljubljana, Slovenia.

Abstract

European consensus guidelines and reimbursement policies position biologic drugs for ulcerative colitis (UC) as a third-line treatment, after failure of 5-aminosalicylic acid (5-ASA) and corticosteroids/thiopurines. While 5-ASA have a very favorable safety profile, (prolonged) use of corticosteroids and thiopurines is associated with potentially serious adverse events. The therapeutic landscape of UC is rapidly evolving and selective biologic drugs with improved safety are being introduced. The first biosimilars have entered the market, leading to improved cost-effectiveness of older biologic drugs. In addition, new insights have been gained in the importance of stringent therapeutic targets such as mucosal and histological healing to improve the long-term outcome of UC patients, and in the role of therapeutic drug monitoring and treatment optimization in this regard. In this manuscript we tackle the question of whether we should move directly from 5-ASA treatment to biologic drugs to offer better and/or safer care to UC patients.

KEYWORDS:

Biologic drugs; Histological healing; Mucosal healing; Safety; Thiopurines; Treat-to-target; Ulcerative colitis

PMID:
30060944
DOI:
10.1016/j.bpg.2018.05.004
[Indexed for MEDLINE]
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18.
Best Pract Res Clin Gastroenterol. 2018 Feb - Apr;32-33:89-93. doi: 10.1016/j.bpg.2018.05.015. Epub 2018 May 23.

JAK inhibitors: Novel developments in management of ulcerative colitis.

Author information

1
Humanitas University, Department of Biomedical Sciences, Rozzano, Milan, Italy; Humanitas Clinical and Research Institute, IBD Center, Rozzano, Milan, Italy. Electronic address: gionataf@gmail.com.
2
Humanitas University, Department of Biomedical Sciences, Rozzano, Milan, Italy.
3
Humanitas Clinical and Research Institute, IBD Center, Rozzano, Milan, Italy.
4
Humanitas University, Department of Biomedical Sciences, Rozzano, Milan, Italy; Humanitas Clinical and Research Institute, IBD Center, Rozzano, Milan, Italy. Electronic address: sdanese@hotmail.com.

Abstract

Janus kinase inhibitors are small molecules, orally administered, under development for the treatment of ulcerative colitis. These molecules reduce the immune response, blocking the signal transduction of multiple cytokines implicated in the activation of inflammation. Currently multiple JAK inhibitors are being evaluated in clinical trials. The aim of this review is to examine the efficacy and the safety of the JAK inhibitors being tested and to discuss the available data on the use of these drugs in moderate-to-severe ulcerative colitis, in order to understand how these new molecules can fit into the therapeutic algorithm of patients with ulcerative colitis.

KEYWORDS:

JAK inhibitors; Small molecules; Ulcerative colitis

PMID:
30060943
DOI:
10.1016/j.bpg.2018.05.015
[Indexed for MEDLINE]
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19.
Best Pract Res Clin Gastroenterol. 2018 Feb - Apr;32-33:79-87. doi: 10.1016/j.bpg.2018.05.014. Epub 2018 Jun 8.

The impact of biologics in surgical outcomes in ulcerative colitis.

Author information

1
Department of Gastroenterology, Universidade Federal de São Paulo, São Paulo, Brazil; IBD Advanced Visiting Fellowship, Humanitas Research Hospital, Rozzano, Milan, Italy. Electronic address: marjorieargollo@hotmail.com.
2
IBD Outpatient, Catholic University of Paraná, Curitiba, Brazil; IBD Advanced Visiting Fellowship, University of Calgary, Calgary, Canada.
3
Division of Colon and Rectal Surgery, Humanitas Clinical and Research Center, Rozzano, Italy.
4
Department of Gastroenterology, Universidade Federal de São Paulo, São Paulo, Brazil.
5
IBD Center, Department of Gastroenterology, Humanitas Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy. Electronic address: sdanese@hotmail.com.

Abstract

Ulcerative Colitis (UC) is an immune mediated condition characterized by inflammation of colonic mucosa, associated with progressive damage of the colon and possible complications, such as hemorrhage, perforation and cancer. It is strongly advocated a treat to target approach in patients with UC consisting in an early and aggressive inflammatory control. Some patients can require colectomy for medically refractory disease or to treat colonic neoplasia. Even though the first line biologic therapy targeting the tumor necrosis factor-alfa (TNF-α) is associated with improvement of the inflammation in some patients, others do not respond at first or lose response over time. Novel drugs targeting different inflammatory pathways have been studied in UC, however, it remains unclear whether surgical rates have been reduced in the biological era. Controversy also exists if biological agents impair surgical postoperative complication rates in UC. The aim of this review is to describe all relevant data available and briefly summarize the real impact of biologics in surgical outcomes in ulcerative colitis.

KEYWORDS:

Colectomy; Colitis; Colorectal surgery; Tumor necrosis factor-alpha; Ulcerative

PMID:
30060942
DOI:
10.1016/j.bpg.2018.05.014
[Indexed for MEDLINE]
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20.
Best Pract Res Clin Gastroenterol. 2018 Feb - Apr;32-33:71-78. doi: 10.1016/j.bpg.2018.05.017. Epub 2018 Jun 14.

Surgery in ulcerative colitis: When? How?

Author information

1
Department of Medical and Surgical Sciences, O.U. of General Surgery, University of Catanzaro, Catanzaro, Italy; Department of Colorectal Surgery, S. Rita Clinic, Vercelli, Italy.
2
Colorectal Surgery Unit, IBD Outpatient Clinics, Catholic University of Paranà, Curitiba, Brazil.
3
Humanitas University, Department of Biomedical Sciences, Via Manzoni 113, 20089, Rozzano, Milano, Italy; Humanitas Clinical and Research Center, Colon and Rectal Surgery Unit, Via Manzoni 113, 20089, Rozzano, Milano, Italy. Electronic address: antonino.spinelli@hunimed.eu.

Abstract

Ulcerative Colitis (UC) is an idiopathic chronically-remitting inflammatory bowel disorder characterized by a contiguous inflammation of the colonic mucosa affecting the rectum that generally extends proximally in a continuous manner through the entire colon. Patients typically experience intermittent exacerbations, with symptoms characterized by bloody diarrhea associated with urgency and tenesmus. The anatomical extent of mucosal involvement is the most important factor determining disease course and is an important predictor of colectomy. The precise etiology of UC is unknown. However, a combination of genetic predisposition and environmental factors seems to have a key role in the development of the disease. UC usually is mildly active but it can be a life-threatening condition because of colonic and systemic complications, and later in the disease course due to the development of colorectal cancer. Interestingly, even if pathogenetic features detected in patients with sporadic CRC can be also found in UC-related colorectal cancer (UC-CRC), this latter is, usually, driven by an inflammation-driven pathway rising from a non-neoplastic inflammatory epithelium to dysplasia to cancer. Thus, a long-term follow-up with colonoscopy surveillance has been recommended. Approximately 15% of UC patients develop an acute attack of severe colitis, and 30% of these patients require colectomy. The initial treatment strategy in UC typically follows the traditional step-up approach. One third of the patients will not respond to steroid therapy and cyclosporine and infliximab are the most common salvage agents employed in these cases in order to avoid emergent surgery. Unfortunately, although a significant short-term benefit have been observed after infliximab treatment, the colectomy rate have remained stable. Surgery in UC depends on the stage of the disease as well as patient's status and is divided into the following settings: urgent, emergent and elective. Despite many efforts the surgical management of UC remains a significant challenge. A multidisciplinary management of UC is key in order to define the best timing and the best procedure for each patient in an individualized basis.

KEYWORDS:

Inflammatory bowel disease; Medications; Multidisciplinary management; Surgery; Timing; Ulcerative colitis

PMID:
30060941
DOI:
10.1016/j.bpg.2018.05.017
[Indexed for MEDLINE]
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