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Expression of TOB/BTG family members in patients with inflammatory bowel disease.
Fonseca-Camarillo, G, Furuzawa-Carballeda, J, Priego-Ranero, ÁA, Martínez-Benítez, B, Barreto-Zúñiga, R, Yamamoto-Furusho, JK
Scandinavian journal of immunology. 2021;(4):e13004
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In recent years, the role of anti-proliferative TOB proteins in the regulation of immune response by inhibiting T cell activation has been demonstrated. Nevertheless, no previous studies have explored their expression in patients with IBD. The aim of the study was to characterize the gene and protein expression of the TOB/BTG family in intestinal tissue of patients with IBD. This is an observational and cross-sectional study that included 63 IBD patients. Gene expression of TOB/BTG family was measured by RT-PCR. Protein expression of TOB/CD16 and BTG/Ki-67 was evaluated by immunohistochemistry. TOB/BTG family mRNAs were detected and quantitated by RT-qPCR in rectal and ileum biopsies from UC patients and CD patients, respectively, and non-inflammatory control tissues. Results showed that TOB1 and BTG1 gene expression was decreased in the colonic mucosa from patients with UC compared with the control group. The TOB2 and BTG2 genes were over-expressed in the colonic mucosa of patients with UC in remission compared with the active UC and control group. The high TOB2 gene expression was associated with histological remission (P = .01). TOB1/CD16, TOB2/CD16, BTG1/Ki-67, BTG2/Ki-67 and BTG4/Ki-67 single and double positive cells were mostly NK, macrophages, epithelial cells, connective tissue cells and perivascular inflammatory infiltrates in tissues from patients with UC and CD. This is the first depiction of the TOB/BTG family gene and protein expression in rectal and ileum tissues by a CD16+ subpopulation in IBD.
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Risk of COVID 19 in patients with inflammatory bowel diseases compared to a control population.
Maconi, G, Bosetti, C, De Monti, A, Boyapati, RK, Shelton, E, Piazza, N, Carvalhas Gabrielli, AM, Lenti, MV, Bezzio, C, Ricci, C, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2021;(3):263-270
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BACKGROUND It is unclear whether patients with inflammatory bowel disease (IBD) are at increased risk of COVID-19. OBJECTIVES This observational study compared the prevalence of COVID-19 symptoms, diagnosis and hospitalization in IBD patients with a control population with non-inflammatory bowel disorders. METHODS This multicentre study, included 2733 outpatients (1397 IBD patients and 1336 controls), from eight major gastrointestinal centres in Lombardy, Italy. Patients were invited to complete a web-based questionnaire regarding demographic, historical and clinical features over the previous 6 weeks. The prevalence of COVID-19 symptoms, diagnosis and hospitalization for COVID-19 was assessed. RESULTS 1810 patients (64%) responded to the questionnaire (941 IBD patients and 869 controls). IBD patients were significantly younger and of male sex than controls. NSAID use and smoking were more frequent in controls. IBD patients were more likely treated with vitamin-D and vaccinated for influenza. Highly probable COVID-19 on the basis of symptoms and signs was less frequent in the IBD group (3.8% vs 6.3%; OR:0.45, 95%CI:0.28-0.75). IBD patients had a lower rate of nasopharyngeal swab-PCR confirmed diagnosis (0.2% vs 1.2%; OR:0.14, 95%CI:0.03-0.67). There was no difference in hospitalization between the groups (0.1% vs 0.6%; OR:0.14, 95%CI:0.02-1.17). CONCLUSION IBD patients do not have an increased risk of COVID-19 specific symptoms or more severe disease compared with a control group of gastroenterology patients.
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Transition of inflammatory bowel disease patients from pediatric to adult care: an observational study on a joint-visits approach.
Corsello, A, Pugliese, D, Bracci, F, Knafelz, D, Papadatou, B, Aloi, M, Cucchiara, S, Guidi, L, Gasbarrini, A, Armuzzi, A
Italian journal of pediatrics. 2021;(1):18
Abstract
BACKGROUND Transition from pediatric to adult care of patients affected by Inflammatory Bowel Disease (IBD) is a critical step that needs specific care and multidisciplinary involvement. The aim of our study was to evaluate the outcome of the transition process of a cohort of IBD patients, exploring their readiness and the possible impact on quality of life. METHODS This observational study followed transitioned IBD patients from pediatric to adult care. Transition was carried-out through combined visits, jointly performed by the pediatrician and the adult gastroenterologist. Clinical data were collected before and after transition. A subgroup of patients was submitted to an anonymous online questionnaire of 38 items based on the validated questionnaires TRAQ and SIBDQ within the first 6 months from the beginning of the transition process. RESULTS Eighty-two patients with IBD were enrolled, with a mean age at transition of 20.2±2.7 years. Before transition, 40.2% of patients already had major surgery and 64.6% started biologics. At transition, 24% of patients were in moderate to severe active phase of their disease and 40% of them had already been treated with ≥ 2 biologics. The mean score of the TRAQ questionnaires collected is 3.4±1.5 and the mean score of SIBDQ is 53.9±9.8. A significant association was found between a TRAQ mean score > 3 and a SIBDQ > 50 (p=0.0129). Overall, 75% of patients had a positive opinion of the transition model adopted. CONCLUSIONS A strong association has been found between TRAQ and SIBDQ questionnaires, showing how transition readiness has a direct impact on the quality of life of the young adult with IBD.
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Fecal Microbiota Transplantation Is Highly Effective in Real-World Practice: Initial Results From the FMT National Registry.
Kelly, CR, Yen, EF, Grinspan, AM, Kahn, SA, Atreja, A, Lewis, JD, Moore, TA, Rubin, DT, Kim, AM, Serra, S, et al
Gastroenterology. 2021;(1):183-192.e3
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BACKGROUND & AIMS Fecal microbiota transplantation (FMT) is used commonly for treatment of Clostridioides difficile infections (CDIs), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers. METHODS Patients undergoing FMT in clinical practices across North America were eligible. Participating investigators enter de-identified data into an online platform, including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes. RESULTS Of the first 259 participants enrolled at 20 sites, 222 had completed short-term follow-up at 1 month and 123 had follow-up to 6 months; 171 (66%) were female. All FMTs were done for CDI and 249 (96%) used an unknown donor (eg, stool bank). One-month cure occurred in 200 patients (90%); of these, 197 (98%) received only 1 FMT. Among 112 patients with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (n = 5 [2%]) and abdominal pain (n = 4 [2%]); 3 patients (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%). CONCLUSIONS This prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT.
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Vedolizumab Therapy is Ineffective for Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A GETAID Multicentre Cohort Study.
Caron, B, Peyrin-Biroulet, L, Pariente, B, Bouhnik, Y, Seksik, P, Bouguen, G, Caillo, L, Laharie, D, Carbonnel, F, Altwegg, R, et al
Journal of Crohn's & colitis. 2019;(10):1239-1247
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BACKGROUND Whether vedolizumab may be effective as a treatment for primary sclerosing cholangitis [PSC] in patients with inflammatory bowel disease [IBD] remains controversial. METHODS We performed a retrospective observational study of consecutive patients with IBD and PSC, treated with vedolizumab for at least 30 weeks in 22 centres of GETAID from January 2015 to June 2016. The outcomes included a decrease in the serum alkaline phosphatase [ALP] concentration of at least 50% from baseline to Week 30 or 54, a change in any serum liver enzymes concentrations, and an assessment of the efficacy and safety of vedolizumab in IBD. RESULTS Among 75 patients with active IBD and PSC treated with vedolizumab, 21 patients discontinued vedolizumab before Week 30 [due to lack of efficacy in 19 and malignancy in two patients]. In the remaining 54 patients, a decrease in the serum ALP concentration of at least 50% from baseline to Weeks 30 and 54 was observed in four [7%] and four [11%] patients, respectively. No significant change was observed in serum liver enzyme concentrations at week 30 or 54. After a median follow-up period of 19.4 [14.0-29.9] months, nine cases of digestive neoplasia [colorectal neoplasia in seven and cholangiocarcinoma in two] were reported. CONCLUSIONS In patients with IBD and PSC, vedolizumab did not improve serum liver enzyme concentrations at week 30 or 54. Nine cases of digestive cancer occurred during the follow-up period, confirming the need for a tight surveillance programme in this population.
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Clear liquid diet before bowel preparation predicts successful chromoendoscopy in patients with inflammatory bowel disease.
Megna, B, Weiss, J, Ley, D, Saha, S, Pfau, P, Grimes, I, Li, Z, Caldera, F
Gastrointestinal endoscopy. 2019;(2):373-379.e2
Abstract
BACKGROUND AND AIMS Chromoendoscopy (CE) has been shown to generate both a superior diagnostic yield and dysplasia detection rate than conventional white-light endoscopy and requires a high-quality bowel preparation. The aim of this study was to identify predictors of the ability to perform CE in patients with inflammatory bowel disease (IBD). METHODS We performed an observational study of patients with IBD undergoing colorectal cancer surveillance examinations with CE. Same-day colonoscopy surveys were used to collect patient and procedural variables. Multivariate logistic regression was used to establish odds ratios of successful completion of CE. RESULTS Eighty-eight patients with IBD were enrolled. We found that patients who did not follow a clear liquid diet before colonoscopy had much lower odds of being able to undergo CE (odds ratio, 0.106; 95% confidence interval, 0.013-0.845; P < .034). Further, we found that previously identified risk factors (older age, history of diabetes mellitus, the timing and split dosing of preparation solution, and procedure time (AM or PM), chronic narcotic use, and history of constipation) for inadequate bowel preparation were not associated with the ability to perform CE. CONCLUSIONS Following a clear liquid diet the entire day before the procedure was highly predictive of the ability to perform CE. However, established risk factors for inadequate bowel preparation did not inhibit the ability to perform CE in our population. Endoscopists performing CE should consider recommending that patients follow a clear liquid diet the entire day before their examination.
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Sunlight exposure in inflammatory bowel disease outpatients: Predictive factors and correlation with serum vitaminD.
Olmedo-Martín, RV, González-Molero, I, Olveira, G, Amo-Trillo, V, Jiménez-Pérez, M
Gastroenterologia y hepatologia. 2019;(10):604-613
Abstract
INTRODUCTION Sunlight exposure is the main source of vitaminD. Our aim was to describe both sun exposure and sun protection behaviour in a series of patients with inflammatory bowel disease (IBD), and to study their potential association with vitaminD concentration. PATIENTS AND METHODS A cross sectional, observational study. The clinical-demographic variables were obtained via clinical interviews and medical history review. The sunlight exposure assessment was carried out using the Sun Exposure Questionnaire and the concentration of 25-hydroxy vitaminD (25OHD) was measured by an electro-chemiluminescence immunoassay. Questionnaires were conducted on quality of life, physical activity, weekly vitaminD intake and sun protection behaviour. RESULTS 149 patients were included. In 69% of patients, deficient or insufficient 25OHD values were recorded. 67% showed low sun exposure. A modest significant correlation was observed between the total score of the solar exposure questionnaire and the 25OHD concentration in the complete series (r=0.226, P=.006) and in the summer (r=0.274, P=.01). The sun protection behaviour questionnaire score did not influence the 25OHD concentration. In the multivariate analysis, only the presence of clinical activity was associated with low sun exposure (OR=3.23). DISCUSSION Sun exposure according to the questionnaire used was low, was associated with the presence of clinical activity and was weakly correlated with serum 25OHD concentration. More studies are needed to explore the use of individual questionnaires for sun exposure and its relationship with vitaminD in patients with IBD.
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Time-to-reach Target Calprotectin Level in Newly Diagnosed Patients With Inflammatory Bowel Disease.
Haisma, SM, Verkade, HJ, Scheenstra, R, van der Doef, HPJ, Bodewes, FAJA, van Rheenen, PF
Journal of pediatric gastroenterology and nutrition. 2019;(4):466-473
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OBJECTIVES Treatment targets in inflammatory bowel disease (IBD) move away from controlling symptoms towards complete recovery of the intestinal mucosa. Currently, the most frequently used noninvasive surrogate marker of mucosal healing is a faecal calprotectin concentration in the target range. This study tested if there was a relation between time-to-reach target calprotectin and first flare. METHODS We prospectively included new-onset IBD patients ages 17 and younger in a cloud-based registry (FastForwardCare) and followed them for at least 52 weeks. They were treated according to Dutch national guidelines that advocate a step-up approach. Time-to-reach target was defined as the first calprotectin measurement below 250 μg/g after the start of induction therapy. Time-to-first flare was the time from the first calprotectin measurement below 250 μg/g until reappearance of symptoms with calprotectin values above 250 μg/g. RESULTS We included 76 patients (luminal Crohn disease [CD] 43); ulcerative colitis [UC] 33). Median age at diagnosis was, respectively 14.5 and 14.1 years. Median time-to-reach target calprotectin was 37 weeks in CD and 11 weeks in UC patients (Log-rank test, P = 0.001). Once the calprotectin target was reached, time-to-first flare was significantly longer in CD than in UC patients (Log-rank test, P = 0.001). CD patients with time-to-reach target calprotectin ≤12 weeks after conventional induction therapy (ie, exclusive enteral nutrition or steroids) had a more favorable disease course in the first year than those with time-to-reach target calprotectin >12 weeks (Log-rank test, P = 0.057). In UC patients, time-to-reach target calprotectin ≤12 weeks is not associated with a favorable disease course in the first year. CONCLUSIONS The findings of this prospective registry suggest that a quick response to conventional therapy predicts a favorable disease course in new-onset paediatric CD, but not in UC. The concept "time-to-reach target calprotectin level" rationalizes the indefinite term "response to treatment" and is well suited for studying treatment effectiveness in real-world practices.
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Thiopurine Therapy for Inflammatory Bowel Disease During Pregnancy Is Not Associated with Anemia in the Infant.
Koslowsky, B, Sadeh, C, Grisaru-Granovsky, S, Miskin, H, Goldin, E, Bar-Gil Shitrit, A
Digestive diseases and sciences. 2019;(8):2286-2290
Abstract
INTRODUCTION Thiopurine exposure throughout pregnancy in patients with inflammatory bowel diseases (IBD) is common and teratogenically safe. Late consequences of in utero exposure to thiopurines and its metabolite, 6-thioguanine nucleotides (6-TGN), such as neonatal and infant anemia are still disputed. AIM: To evaluate whether 6-TGN exposure during pregnancy influences anemia in infants at 1 year of life. METHODS A comparative observational study was performed between 2009 and 2015 at a multidisciplinary IBD clinic dedicated to pregnant women. The hemoglobin level and signs of anemia between 9 and 15 months after birth of infants born to women exposed to thiopurines throughout the entire pregnancy was compared to infants of women with no thiopurine exposure during pregnancy. RESULTS Altogether, 34 patients, 21 in the study group and 13 in the control group, were included. The median duration of maternal thiopurine exposure prior to pregnancy was 24 months (range 12-72 months), and median dosage was 100 mg (range 50-175 mg). Maternal IBD activity, infants' iron supplementation, and iron deficiency diagnoses were similar between both groups. The infants' mean hemoglobin level (gr/dL) in the thiopurine-exposed women versus the control group was 11.48 ± 0.8 versus 11.54 ± 0.6, respectively, p = 0.81. The composite risk of any sign of infant anemia was numerically higher in the thiopurine-exposed women, 10 (47%), compared to non-exposed women, 3 (23%), p = 0.17. The mean corpuscular volume, red cell distribution width, white blood cell, and platelet counts were similar among groups. CONCLUSIONS Thiopurine therapy during pregnancy in women with IBD is safe for long-term neonatal outcomes; still large-scale confirmatory studies are required.
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Safety and efficacy of intravenous iron isomaltoside for correction of anaemia in patients with inflammatory bowel disease in everyday clinical practice.
Stein, J, Walper, A, Klemm, W, Farrag, K, Aksan, A, Dignass, A
Scandinavian journal of gastroenterology. 2018;(9):1059-1065
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AIMS: Iron deficiency anaemia (IDA) is common in patients with inflammatory bowel disease (IBD), who are often treated with intravenous iron. This observational study aimed to investigate the effectiveness and safety of iron isomaltoside in routine practical care of IDA in IBD patients. METHODS The study included 197 IBD patients designated for treatment with iron isomaltoside. Treatment was administered according to routine practice. Data were recorded at baseline and after approximately 4, 8, and 16 weeks. Efficacy data included haemoglobin (Hb) levels and haematinics, while safety data included adverse drug reactions and safety laboratory variables. RESULTS Patients received a mean (range) cumulative dose of 1304 (100-3500) mg iron isomaltoside. Hb increased from 10.7(±1.6) g/dL at baseline to 13.1(±1.5) g/dL at the final visit. In addition, serum iron, ferritin and transferrin saturation increased and soluble transferrin receptor decreased. Calprotectin decreased, as did IBD symptom scores, Harvey-Bradshaw Index (Crohn's disease) and partial Mayo score (Ulcerative colitis). About 8% of patients reported transient adverse reactions, most commonly skin reactions, nausea and vomiting, and 2% SAEs, most frequently tachycardia. CONCLUSION Iron isomaltoside was demonstrated to be effective and had a good safety profile in IBD patients in everyday clinical practice in Germany.