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BACKGROUND: Therapeutic strategies for patients with ulcerative colitis (UC) are based on patient- and disease-related factors in combination with drug characteristics but fail to predict success in individual patients. A considerable proportion of UC patients do not respond to the biological vedolizumab. Therefore, pretreatment biomarkers for therapeutic efficacy are urgently needed. Mucosal markers related to the integrin-dependent T lymphocyte homing could be potent predictors. METHODS: We prospectively included 21 biological- and steroid-naive UC patients with moderate-to-severe disease activity planned to escalate therapy to vedolizumab. At week 0, before initiating treatment, colonic biopsy specimens were obtained for immunophenotyping and immunohistochemistry. Clinical and endoscopic disease activity were determined at week 16 after 4 infusions of vedolizumab. In addition, we retrospectively included 5 UC patients who were first treated with anti-tumor necrosis factor α before receiving vedolizumab to compare with biological-naive patients. RESULTS: Abundance of α4ß7 on more than 8% of all CD3+ T lymphocytes in colonic biopsies at baseline was predictive for responsiveness to vedolizumab (sensitivity 100%, specificity 100%). The threshold for the proportion of MAdCAM-1+ and PNAd+ of all venules in the biopsies predictive for responsiveness to vedolizumab was ≥2.59% (sensitivity 89%, specificity 100%) and ≥2.41% (sensitivity 61%, specificity 50%), respectively. At week 16, a significant decrease of α4ß7+CD3+T lymphocytes was demonstrated in responders (18% [12%-24%] to 8% [3%-9%]; Pâ =â .002), while no difference was seen in nonresponders (4% [3%-6%] to 3%; Pâ = .59). CONCLUSIONS: UC responders to vedolizumab have a higher percentage of α4ß7+CD3+ T lymphocytes and a higher proportion of MAdCAM-1+ venules in colonic biopsies than nonresponders before initiating therapy. Both analyses could be promising predictive biomarkers for therapeutic response and may lead to more patient tailored treatment in the future.
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Time to evaluate diet quality and give dietary advice is limited in clinical IBD practice. The Eetscore is a web-based tool that assesses diet quality according to the Dutch dietary guidelines and provides personalised dietary advice. We aimed to assess diet quality of IBD patients using the Eetscore and to study changes in diet quality, health-related quality of life (HRQoL) and clinical disease activity over time. A prospective cohort study was performed in 195 adult IBD patients. Participants were invited to fill out questionnaires (Eetscore-FFQ, short IBDQ and p-HBI/p-SCCAI) at baseline and after 1 and 4 months. The Eetscore calculates diet quality based on 16 food components (10 points per component, total score 0-160; the higher the better) and provides dietary advice per component based on the assessment. At baseline, mean diet quality was 98±19. Diet quality was positively associated with age, female gender and level of education. Component scores were highest for red meat, wholegrain products, and sweetened beverages, and lowest for legumes, nuts, and processed meat. Over time, diet quality increased to 107±21 at 4 months (p<0.001). Each 10-point improvement in diet quality was associated with an increase in HRQoL (ß=0.4 (95%CI 0.02; 0.7), p=0.04). Clinical disease activity did not change. In conclusion, diet quality of IBD patients significantly improved following personalised dietary advice of the Eetscore. Improvement of diet quality was associated with a slight improvement in HRQoL. The Eetscore is a practical and useful tool to monitor and support a healthy diet in IBD patients.
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BACKGROUND AND AIMS: Newly diagnosed inflammatory bowel disease [IBD] patients need to deal with the physical and emotional impact of the disease. We aimed to evaluate care for recently diagnosed IBD patients from the patient perspective and assess themes for improvement. METHODS: A mixed-method study with adult IBD patients 4-15 months after diagnosis was performed. First, relevant themes were identified through semi-structured interviews until data saturation. Next, a questionnaire assessing satisfaction with care [SATI-Q] was developed and validated with 15 items divided into two domains: medical care and information and psychosocial care. Higher scores indicate higher patient satisfaction [0-100]. RESULTS: We interviewed 20 patients. Next, 84/107 patients completed the SATI-Q: 51% female, aged 37 years (interquartile range [IQR 25-58]), 36% Crohn's disease, disease duration 9 months [IQR 6-12] and 74% in clinical remission. The median SATI-Q score was 82 [IQR 72-92]. Patients were more satisfied with medical care than with information and psychosocial care (score 92 [IQR 81-98] vs 74 [IQR 60-90], p < 0.001). Patients were least satisfied with the attention given to IBD-related emotions and information on IBD medication, diet and future perspectives [77, 76, 57 and 54% of patients satisfied]. Patients [81%] preferred spoken information. Only 26-27% preferred brochures and websites. CONCLUSIONS: In this study, the SATI-Q questionnaire was developed and validated to assess patient satisfaction with care in early IBD. Our findings suggest that psychosocial care and information on IBD medication, diet influence and future perspectives for recently diagnosed IBD patients require improvement.
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Rectocolite hémorragique , Maladie de Crohn , Maladies inflammatoires intestinales , Adulte , Maladie de Crohn/diagnostic , Maladie de Crohn/thérapie , Femelle , Humains , Maladies inflammatoires intestinales/diagnostic , Maladies inflammatoires intestinales/thérapie , Mâle , Amélioration de la qualité , Enquêtes et questionnairesRÉSUMÉ
BACKGROUND: Monitoring of IBD patients on intravenous biologic treatment is recommended but time-consuming for patients and nurses. We developed a mobile application (app) to promote self-management and studied its feasibility in clinical practice. METHODS: Adult IBD patients treated with intravenous infliximab or vedolizumab used the app over four biologic treatments. The app includes information modules and an interactive timeline with notifications of blood tests and health checks before treatment. RESULTS: In total, 55 patients participated of whom 71% had Crohn's disease and 85% used infliximab. Compliance with health checks and blood tests was 67% before the first biologic treatment and 70, 87, and 80% before the second, third, and fourth treatment, respectively. The median number of times the app was used per treatment varied from 6 to 8 times (≥4 considered sufficient). Patients were satisfied with the app [median VAS score 8 (IQR 7-9)] and remained equally satisfied with IBD care [score 8 (IQR 8-9) before and after app use]. Nurses contacted all patients by telephone before the first biologic treatment, as previous standard care. Before the second, third, and fourth treatment only 47, 35, and 49% of patients were contacted. The majority (92%) wanted to continue using the app after the study. CONCLUSIONS: Monitoring of IBD patients treated with intravenous biologics using an app is feasible. We saw high compliance, sufficient app use, and high patient satisfaction. Moreover, health-care utilization was reduced and almost all patients preferred using the app over previous standard care (ClinicalTrials.gov NCT04254614).
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Produits biologiques , Rectocolite hémorragique , Maladies inflammatoires intestinales , Applications mobiles , Adulte , Produits biologiques/usage thérapeutique , Rectocolite hémorragique/traitement médicamenteux , Études de faisabilité , Humains , Maladies inflammatoires intestinales/traitement médicamenteux , Infliximab/usage thérapeutiqueRÉSUMÉ
BACKGROUND AND AIMS: Segmentation of patients based on psychological determinants of subjective health may provide new ways to personalized care. The cross-disease segmentation model developed by Bloem & Stalpers discriminates patients based on disease acceptance and perceived control. We aimed to validate the segmentation model, compare segments and evaluate whether segments independently correlate with quality of life in inflammatory bowel disease [IBD]. METHODS: A cross-sectional study of adult IBD patients was performed with questionnaires on quality of life [32-item inflammatory bowel disease questionnaire], acceptance and perceived control [six items with 7-point Likert scale]. Four segments were formed [cut-off > 5]: [I] high acceptance, high control; [II] high acceptance, low control [III]; low acceptance, high control and; [IV] low acceptance, low control. RESULTS: We included 686 patients. The acceptance and perceived control scales were unidimensionally structured and internally consistent. Segments differed significantly in age, smoking behaviour, diagnosis, disease duration, extra-intestinal manifestations, IBD medication, clinical disease activity and quality of life. High acceptance (standardized beta coefficient [ß] 0.25, p < 0.001), high perceived control [ß 0.12, p < 0.001] or both [ß 0.53, p < 0.001], were associated with a significantly better health-related quality of life compared with low acceptance and low perceived control. Sociodemographic and clinical factors explained 25% of the variance in quality of life. The explained variance significantly increased to 45% when the patients' segment was added to the model [ΔR2 20%, p < 0.001]. CONCLUSIONS: The segmentation model based on disease acceptance and perceived control is valid in IBD patients and discriminates different segments that correlate independently with quality of life. This may open new strategies for patient care.
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Maladies inflammatoires intestinales/complications , Perception , Qualité de vie/psychologie , Adaptation psychologique , Adulte , Sujet âgé , Comportement , Études cas-témoins , Études transversales , Femelle , Humains , Maladies inflammatoires intestinales/psychologie , Mâle , Adulte d'âge moyen , Enregistrements/statistiques et données numériques , Enquêtes et questionnairesRÉSUMÉ
BACKGROUND: Immunotherapy, targeting programmed death-1 (PD-1) enhances antitumor T-cell activity in patients with malignancies. Blocking PD-1 or its ligand may lead to fulminant colitis as serious adverse event in these patients. Since little is known of the presence and role of PD-1+T cells in colitis of different etiologies, we determined PD-1+T cells in mucosal specimens of patients with inflammatory bowel disease, infectious colitis (InfC), immunotherapy-related colitis (ImC) and healthy controls (HC). METHODS: Newly diagnosed patients with ulcerative colitis (UC, n = 73), Crohn's disease (CD, n = 50), InfC (n = 5), ImC (n = 8) and HC (n = 8) were included. Baseline inflamed colonic biopsies were studied with immunohistochemistry and flowcytometry. RESULTS: Using immunohistochemistry, PD-1 was not present on lymphocytes in the epithelium of all patients, nor in HC. The percentage PD-1+ of all lymphocytes in the lamina propria was 40% in UC, 5% in InfC, 3% in ImC and 0% in HC. Flowcytometry showed significant higher percentages of PD-1+T cells in inflamed biopsy specimens of UC patients (22%) compared to all other groups: CD patients (13%), InfC (12%), ImC (5%) and HC (6%). CONCLUSION: There are relevant differences in distribution and frequencies of mucosal PD-1+ T-cell subsets in patients with UC, CD, InfC and ImC, supporting the hypothesis that these types of colitis are driven by different immunological pathways. The increased numbers of PD-1+ and PD-L1+ lymphocytes in the colonic mucosa of UC patients suggest that the PD-1/PD-L1 pathway might be more activated in UC than in CD.
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Rectocolite hémorragique , Colite , Maladie de Crohn , Humains , Muqueuse intestinale , Récepteur-1 de mort cellulaire programméeRÉSUMÉ
BACKGROUND AND AIMS: Fatigue significantly impacts the quality of life of patients with inflammatory bowel disease (IBD). This study aimed to assess the effect of a personalized, intensive exercise program on fatigue, health-related quality of life (HRQoL), and cardiorespiratory fitness in patients with quiescent IBD and severe fatigue. METHODS: A pilot study was performed including IBD patients in remission with severe fatigue. The 12-week exercise program consisted of three times per week 1-h sessions, including aerobic- and progressive-resistance training at personalized intensity based on a cardiopulmonary exercise test (CPET) and one-repetition maximum. CPET was repeated after 12 weeks. Fatigue and HRQoL were assessed using the checklist individual strength and 32-item IBD questionnaire. RESULTS: Twenty-five IBD patients with mean age of 45 (± 2.6) years were included of which 22 (88%) completed the exercise program. Fatigue significantly improved from 105 (± 17) points on the checklist individual strength before, to 66 (± 20) after completion of exercise program (p < 0.001). Patients' HRQoL significantly improved from 156 (± 21) to 176 (± 19) (p < 0.001). When looking at the subdomains of HRQoL, significant improvement was seen in emotional (58 ± 12 vs. 69 ± 9.1, p = 0.003), systemic (19 ± 3.9 vs. 24 ± 4.7, p < 0.001), and social function (25 ± 5.4 vs. 30 ± 3.9, p < 0.001). Bowel symptoms did not change (53 ± 7.7 vs. 55 ± 7.3, p = 0.208). Repeat CPET showed a significant improvement in maximum power patients were able to deliver (2.4 ± 0.5 vs. 2.7 ± 0.5 W/kg, p = 0.002). CONCLUSIONS: A personalized, intensive exercise program can lead to significant improvement of fatigue, HRQoL, and cardiorespiratory fitness in patients with quiescent IBD and severe fatigue.
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Traitement par les exercices physiques/psychologie , Fatigue/psychologie , Maladies inflammatoires intestinales/psychologie , Aptitude physique/psychologie , Qualité de vie/psychologie , Adulte , Études de cohortes , Traitement par les exercices physiques/méthodes , Fatigue/diagnostic , Fatigue/thérapie , Femelle , Humains , Maladies inflammatoires intestinales/diagnostic , Maladies inflammatoires intestinales/thérapie , Mâle , Adulte d'âge moyen , Aptitude physique/physiologie , Projets pilotes , Résultat thérapeutiqueRÉSUMÉ
PURPOSE: Laparoscopy-assisted transgastric endoscopic retrograde cholangiopancreatography (LAERCP) is an alternative for the anatomically challenging conventional ERCP in patients with a Roux-en-Y gastric bypass (RYGB) as it allows access to the biliary tree via the gastric remnant. We investigated the efficacy and safety of LAERCP. MATERIAL AND METHODS: We retrospectively reviewed all charts from RYGB patients who underwent a LAERCP between January 2009 and August 2019 in a non-academic referral center for bariatric surgery. Patients who underwent pancreatic therapy were excluded. We collected demographic, clinical, and outcome data. An adverse event was defined as any complaint related to the LAERCP up to 30 days after the procedure and graded according to the ASGE lexicon. RESULTS: We identified 100 LAERCP in 86 patients with RYGB (70% female, median age 54 years). Same-session cholecystectomy was performed in 35 LAERCP (35%). The papilla of Vater was visualized in 100% of LAERCP with a therapeutic success rate of 94%. Stone extraction succeeded in 88.8% and sphincterotomy was performed in 96.7%. We identified 30 adverse events in 28 procedures, of which eight endoscopy-related, 14 laparoscopy-related, and eight non-specified (f.i. fever, allergic reaction). In total, six severe adverse events were reported concerning post-ERCP pancreatitis (n = 2), laparoscopy-related hemorrhage (n = 1), abscess (n = 1), shock (n = 1), and pneumonia (n = 1). No patient died due to LAERCP. CONCLUSION: LAERCP is an effective and relatively safe procedure for biliary diseases in patients with RYGB.
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Dérivation gastrique , Laparoscopie , Obésité morbide , Cholangiopancréatographie rétrograde endoscopique/effets indésirables , Femelle , Dérivation gastrique/effets indésirables , Humains , Mâle , Adulte d'âge moyen , Obésité morbide/chirurgie , Études rétrospectivesRÉSUMÉ
PNAd and MAdCAM-1 addressins on venules are of importance in T-cell homing and potential therapeutic targets in ulcerative colitis (UC). Normally, PNAd+ high endothelial venules (HEVs) are only present in lymphoid organs, whereas small numbers of MAdCAM-1+ venules can be seen in non-lymphoid tissue. We aimed to study their presence in the intestinal mucosa of UC patients at diagnosis and during follow-up, and their correlation with disease activity. Colonic biopsy specimens of 378 UC patients were analyzed by immunohistochemistry for CD3, CD20, ERG, MECA-79 (PNAd) and MECA-376 (MAdCAM-1) and compared to healthy controls (HC). The proportion of PNAd+HEVs in UC at diagnosis was 4.9% (IQR 2.0%-8.3%), while none were detected in HC. During follow-up, PNAd+HEVs completely disappeared in remission (n = 93), whereas the proportion in active disease was similar to baseline (n = 285, p = 0.39). The proportion of MAdCAM-1+venules in UC at baseline was 5.8% (IQR 2.6-10.0). During follow-up, the proportion in remission was comparable to diagnosis, but upregulated (7.5% (IQR 4.4-10.9), p = 0.001) in active disease. In conclusion, PNAd+HEVs appear in UC during active inflammation which could thus serve as a marker for disease activity, whereas MAdCAM-1+venules remain present after inflammation is resolved and increase after subsequent flares, reflecting chronicity and potentially serving as a therapeutic target.
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Rectocolite hémorragique/immunologie , Immunoglobulines/physiologie , Muqueuse intestinale/physiopathologie , Veinules/physiopathologie , Adulte , Rectocolite hémorragique/anatomopathologie , Évolution de la maladie , Femelle , Humains , Mâle , Adulte d'âge moyenRÉSUMÉ
Background: The Dutch guidelines for esophageal and gastro-esophageal junction (GEJ) cancer recommend discussion of patients by a multidisciplinary tumor board (MDT). Despite this recommendation, one previous study in the Netherlands suggested that therapeutic guidance was missing for palliative care of patients with esophageal cancer. The aim of the current study was therefore to assess the impact of an MDT discussion on initial palliative treatment and outcome of patients with esophageal or GEJ cancer.Material and methods: The population-based Netherlands Cancer Registry was used to identify patients treated for esophageal or GEJ cancer with palliative intent between 2010 and 2017 in 7 hospitals. We compared patients discussed by the MDT with patients not discussed by the MDT in a multivariate analysis. Primary outcome was type of initial palliative treatment. Secondary outcome was overall survival.Results: A total of 389/948 (41%) patients with esophageal or GEJ cancer were discussed by the MDT before initial palliative treatment. MDT discussion compared to non-MDT discussion was associated with more patients treated with palliative intent external beam radiotherapy (38% vs. 21%, OR 2.7 [95% CI 1.8-3.9]) and systemic therapy (30% vs. 23%, OR 1.6 [95% CI 1.0-2.5]), and fewer patients treated with stent placement (4% vs. 12%, OR 0.3 [95% CI 0.1-0.6]) and best supportive care alone (12% vs. 33%, OR 0.2 [95% CI 0.1-0.3]). MDT discussion was also associated with improved survival (169 days vs. 107 days, HR 1.3 [95% CI 1.1-1.6]).Conclusion: Our study shows that MDT discussion of patients with esophageal or GEJ cancer resulted in more patients treated with initial palliative radiotherapy and chemotherapy compared with patients not discussed by the MDT. Moreover, MDT discussion may have a positive effect on survival, highlighting the importance of MDT meetings at all stages of treatment.
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Tumeurs de l'oesophage/thérapie , Jonction oesogastrique/anatomopathologie , Communication interdisciplinaire , Soins palliatifs/normes , Équipe soignante/normes , Tumeurs de l'estomac/thérapie , Sujet âgé , Association thérapeutique , Tumeurs de l'oesophage/épidémiologie , Tumeurs de l'oesophage/anatomopathologie , Femelle , Humains , Mâle , Pays-Bas/épidémiologie , Pronostic , Tumeurs de l'estomac/épidémiologie , Tumeurs de l'estomac/anatomopathologie , Taux de survieRÉSUMÉ
BACKGROUND AND AIMS: Endoscopic dilation (ED) is still the mainstay of therapeutic management of benign esophageal strictures (BESs). This study aimed to establish risk factors for refractory BESs and assess long-term clinical outcomes of ED. METHODS: We performed a retrospective study in 891 patients who underwent ED from 2003 to 2018 for BESs. We searched electronic medical records in 6 tertiary care centers in the Netherlands for data on clinical outcome of ED. Median follow-up was 39 months. The primary endpoint was risk factors for refractory BESs, defined as factors associated with an increased number of ED sessions during follow-up. Secondary endpoints were time from first to last ED session and adverse events. RESULTS: Dilation up to 13 to 15 mm was associated with a higher number of ED sessions than dilation up to 16 to 18 mm (5.0 vs 4.1; hazard ratio [HR], 1.4; P = .001). Compared with peptic strictures, anastomotic (4.9 vs 3.6; HR, 2.1; P < .001), radiation (5.0 vs 3.6; HR, 3.0; P < .001), caustic (7.2 vs 3.6; HR, 2.7; P < .001), and postendotherapy (3.9 vs 3.6; HR, 1.8; P = .005) strictures were associated with a higher number of ED sessions. After 1 year of follow-up, the proportions of patients who remained free of ED was 75% in anastomotic, 71% in radiation, 70% in peptic, 83% in postendotherapy, and 62% in caustic strictures. Esophageal perforation occurred in 23 ED sessions (.4%) in 22 patients (2.4%). CONCLUSIONS: More than 60% of patients with BESs remain free of ED after 1 year of follow-up. Because dilation up to 16 to 18 mm diameter was associated with fewer ED sessions during follow-up, we suggest that clinicians should consider dilation up to at least 16 mm to reduce the number of ED sessions in these patients.
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Sténose de l'oesophage , Dilatation , Sténose de l'oesophage/étiologie , Sténose de l'oesophage/thérapie , Études de suivi , Humains , Pays-Bas , Études rétrospectives , Facteurs de risque , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: The integrin CD103 is proposed to be a potential therapeutical target in inflammatory bowel disease (IBD), as it can form a heterodimeric integrin with ß7 (Etrolizumab, anti-ß7 integrin) on epithelial T cells. Therefore, we aimed to study the frequencies of different intestinal CD103+T-cell subsets, both CD4+ and CD8+, in newly diagnosed, untreated IBD patients at baseline and during follow-up, compared with healthy controls. METHODS: Intestinal biopsies from inflamed segments during colonoscopy and peripheral blood samples were prospectively taken from IBD patients at diagnosis and during follow-up. Blood and single cell suspensions from biopsies were analyzed for CD103+ T-cell subpopulations by flow cytometry and expressed as median percentages of the total T-cell population. RESULTS: In total, 75 Crohn's disease (CD) patients, 49 ulcerative colitis (UC) patients, and 16 healthy controls were included. At presentation, IBD patients displayed lower percentages of CD103+T-cell subsets in inflamed biopsies: 3% (1 to 5) CD103+CD4+ in IBD vs 5% (5 to 7) in healthy controls (P = 0.007) and 9% (4 to 15) CD103+CD8+ compared with 42% (23 to 57) in healthy controls (P = 0.001). The majority of intestinal T cells was composed of CD103-CD4+ T cells (65% [52 to 74]) in IBD compared with 30% (21 to 50) in healthy controls (P = 0.001). In patients with endoscopic remission during follow-up (n = 27), frequencies of CD103+ and CD103-T-cell subsets were comparable with healthy controls. CONCLUSION: At diagnosis, active inflammation in IBD was associated with decreased percentages of both CD103+CD4+ and CD103+CD8+T-cell subsets in colon and ileum biopsies. In active disease during follow-up, these T-cell populations remained low but increased in remission to values comparable with healthy controls. A shift toward more CD103-T cells was observed during active inflammation.
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Lymphocytes T CD4+/immunologie , Lymphocytes T CD8+/immunologie , Rectocolite hémorragique/immunologie , Maladie de Crohn/immunologie , Tube digestif/immunologie , Intestins/immunologie , Sous-populations de lymphocytes T/immunologie , Adulte , Antigènes CD/métabolisme , Études cas-témoins , Rectocolite hémorragique/diagnostic , Rectocolite hémorragique/chirurgie , Maladie de Crohn/diagnostic , Maladie de Crohn/chirurgie , Femelle , Études de suivi , Humains , Intégrines alpha/métabolisme , Mâle , Adulte d'âge moyen , Études prospectives , Jeune adulteRÉSUMÉ
BACKGROUND: Staple line leakage after bariatric surgery can be treated by endoscopic placement of a self-expandable stent. The success rate of stent placement is generally high, but migration is a frequent adverse event that hampers successful treatment. The Niti-S Beta stent is a fully covered double-bump stent that was specifically designed to prevent migration. This study aimed to evaluate the effectiveness and adverse event rate of the Niti-S Beta stent. METHODS: A retrospective study was performed in three high-volume bariatric centers. All consecutive patients between 2009 and 2016 who underwent placement of a Beta stent for staple line leakage were included. Primary outcome was resolution of the leakage; secondary outcome was the adverse event rate including migration. RESULTS: Thirty-eight patients were included. Twenty-five (66%) had resolution of the leakage. Success rate was higher in patients who were treated with implantation of a Beta stent as initial treatment (100%) than in patients who were treated with a stent after revisional surgery had failed (55%, p = 0.013). Migration occurred in 12 patients (32%). There were two severe adverse events requiring surgical intervention, including a bleeding from an aorto-esophageal fistula. CONCLUSIONS: The success rate and the migration rate of the Beta stent seem comparable to other stents in this retrospective study. Despite the novel double-bump structure of the stent, the migration rate does not seem to be decreased.
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Désunion anastomotique/chirurgie , Chirurgie bariatrique/effets indésirables , Matériaux revêtus, biocompatibles , Endoscopie , Endoprothèses métalliques auto-expansibles , Agrafage chirurgical/effets indésirables , Désunion anastomotique/étiologie , Femelle , Migration d'un corps étranger/complications , Humains , Mâle , Adulte d'âge moyen , Études rétrospectivesRÉSUMÉ
INTRODUCTION: A dysregulated intestinal T cell response is presumed in patients with inflammatory bowel disease [IBD]. In this longitudinal study, we investigated the changes in intestinal T lymphocyte subsets in IBD at first presentation and over time during endoscopic active or inactive disease, and relate them to disease activity and outcome. METHODS: We included 129 newly diagnosed patients (87 Crohn's disease [CD], 42 ulcerative colitis [UC]) and 19 healthy controls [HC]. Follow-up biopsy specimens were analysed from 70 IBD patients. Immunophenotyping of specimens was performed by flow cytometry identifying lymphocyte subpopulations. RESULTS: IBD patients at diagnosis displayed higher percentages of CD4 T+ cells, Tregs, and central memory T cells [TCM] and with lower percentages of CD8 and CD103 T lymphocytes than HC. Follow-up specimens of patients with endoscopic inactive disease showed T cell subset recovery comparable to HC. Endoscopic active disease at follow-up coincided with T cell subsets similar to those at diagnosis. In UC, lower baseline percentages of CD3 cells was associated with milder disease course without the need of an immunomodulator, whereas in CD, higher baseline percentages of CD4 and Tregs were associated with complicated disease course. CONCLUSIONS: The intestinal T cell infiltrate in IBD patients with active endoscopic disease is composed of increased percentages of CD4+ T cells, Tregs, and TCM, with lower percentages of CD8+ T cells and CD103+ T cells, compared with HC and endoscopic inactive IBD. Baseline percentages of CD3, CD4, and Tregs were associated with disease outcome. Further research is needed to demonstrate the predictive value of these lymphocyte subsets.
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Rectocolite hémorragique/immunologie , Maladie de Crohn/immunologie , Muqueuse intestinale/immunologie , Sous-populations de lymphocytes T , Adulte , Antigènes CD/métabolisme , Biopsie , Antigènes CD3/métabolisme , Numération des lymphocytes CD4 , Lymphocytes T CD8+ , Études cas-témoins , Rectocolite hémorragique/traitement médicamenteux , Rectocolite hémorragique/anatomopathologie , Maladie de Crohn/traitement médicamenteux , Maladie de Crohn/anatomopathologie , Évolution de la maladie , Endoscopie gastrointestinale , Femelle , Humains , Immunité muqueuse , Immunophénotypage , Intégrines alpha/métabolisme , Muqueuse intestinale/anatomopathologie , Études longitudinales , Mâle , Adulte d'âge moyen , Indice de gravité de la maladie , Sous-populations de lymphocytes T/métabolisme , Lymphocytes T régulateurs , Jeune adulteRÉSUMÉ
BACKGROUND: Data on serum antibodies in untreated adult inflammatory bowel disease (IBD) patients at diagnosis are scarcely available, and results on the stability of antibody presence over time are inconsistent. Our aim was to investigate antibodies in newly diagnosed, untreated IBD patients in relation to disease phenotype and course. Furthermore, we analyzed antibody presence over time. METHODS: Baseline anti-Saccharomyces cerevisiae antibodies (ASCA), anti-chitobioside carbohydrate antibodies (ACCA), anti-laminaribioside carbohydrate antibodies (ALCA) and anti-mannobioside carbohydrate antibodies (AMCA) were measured with enzyme-linked immunosorbent assays and perinuclear anti-neutrophilic cytoplasmic antibodies (pANCA) was measured by indirect immunofluorescence in serum of 120 untreated IBD patients at diagnosis and 19 healthy controls. Antibodies were related to disease outcomes. Serial measurements were available in 71 patients. RESULTS: The combination of pANCA and ASCA enabled good discrimination between UC and CD (p = .004). Antibody presence was relatively stable over time, even though there were significant changes in concentrations. There was a trend towards larger fluctuations in concentration with immunosuppressive medication. Baseline pANCA in UC patients correlated with calprotectin values (rho = .545, p = .019) and change in pANCA status over time was associated with disease activity at that moment. No associations were found with antibodies at diagnosis and disease outcomes. CONCLUSION: Antibody profiles at diagnosis support the distinction between CD and UC. Anti-glycan antibodies are reasonably stable over time, but may fluctuate under the influence of immunosuppressive treatment which may explain the inconsistency in findings hitherto. The appearance or disappearance of pANCA antibodies during follow-up correlated with disease activity in UC and may be used in disease monitoring.
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Anticorps anti-cytoplasme des polynucléaires neutrophiles/sang , Anticorps antibactériens/sang , Rectocolite hémorragique/sang , Maladie de Crohn/sang , Immunoglobuline A/sang , Immunoglobuline G/sang , Adulte , Études cas-témoins , Rectocolite hémorragique/diagnostic , Rectocolite hémorragique/traitement médicamenteux , Maladie de Crohn/diagnostic , Maladie de Crohn/traitement médicamenteux , Fèces/composition chimique , Femelle , Études de suivi , Humains , Immunosuppresseurs/usage thérapeutique , Complexe antigénique L1 leucocytaire/analyse , Mâle , Phénotype , Polyosides/immunologie , Pronostic , Saccharomyces cerevisiae/immunologie , Indice de gravité de la maladie , Jeune adulteRÉSUMÉ
BACKGROUND AND AIMS: More than half of patients with Crohn's disease [CD] develop disease complications requiring aggressive medical therapy or surgery over time. However, predicting disease course and treatment response remains difficult. We therefore identified distinctive serum analytes associated with disease activity and course in newly diagnosed, untreated patients at presentation and during their follow-up. METHODS: In a pilot study, a multiplex immunoassay analysis on 36 markers was performed on serum from 20 CD patients at the time of primary diagnosis following endoscopic evaluation. The 12 most potent markers associated with disease activity, phenotype and course were analysed in a consecutive cohort of 66 CD patients at diagnosis and follow-up [n = 39]. A healthy control group [n = 20] was included as a reference. RESULTS: CD patients had higher baseline levels of sTNF-R2 [p = 0.001], sIL-2R [p = 0.0001], and MMP-1 [p = 0.001] compared with healthy controls. Serial measurements revealed that these three analytes dropped statistically significantly from baseline level during remission and were high during exacerbation. Great decline of sTNF-R1 levels was found during remission, with 6.7-fold lower levels than in healthy controls [p = 0.015]. Patients who did not respond to initial prednisone treatment had higher baseline levels of sTNF-R2 [p = 0.001]. Patients experiencing relapses during follow-up had lower baseline sTNF-R2 and VCAM levels compared with patients with long-lasting remission. CONCLUSIONS: In a large cohort of newly diagnosed untreated CD patients, we identified candidate serum markers [sTNF-R1, sTNF-R2, sIL-2R, and MMP-1] associated with disease activity. Furthermore, sTNF-R2 was associated with prednisone response and, together with VCAM, with long-lasting remission.
Sujet(s)
Marqueurs biologiques/sang , Maladie de Crohn/diagnostic , Évolution de la maladie , Phénotype , Indice de gravité de la maladie , Adulte , Anti-inflammatoires/usage thérapeutique , Études cas-témoins , Maladie de Crohn/sang , Maladie de Crohn/traitement médicamenteux , Femelle , Études de suivi , Humains , Dosage immunologique , Chimiothérapie d'induction , Chimiothérapie de maintenance , Mâle , Adulte d'âge moyen , Projets pilotes , Prednisone/usage thérapeutique , Récidive , Résultat thérapeutiqueRÉSUMÉ
OBJECTIVE: For palliation of extrahepatic bile duct obstruction, self-expandable metal stents (SEMS) are superior to plastic stents in terms of stent patency and occurrence of stent dysfunction. We assessed health-related quality of life (HRQoL) after stent placement to investigate whether this also results in a difference in HRQoL between patients treated with a plastic stent or SEMS. PATIENTS AND METHODS: This randomized multicenter trial included 219 patients who were randomized to receive plastic stent (n=73) or SEMS [uncovered (n=75) and covered (n=71); n=146] placement. HRQoL was assessed with two general questionnaires (EQ-5D-3L and QLQ-C30) and one disease-specific questionnaire (PAN-26). Scores were analyzed using linear mixed model regression and included all patients with baseline and at least one follow-up measurement. RESULTS: HRQoL data were available in 140 of 219 patients (64%); 71 patients (32%) declined participation and in eight patients (4%) only baseline questionnaires were available. On the QLQ-C30, the interaction between follow-up time and type of stent was significantly different on two of five functional scales [physical functioning (P=0.004) and emotional functioning (P=0.01)] in favor of patients with a SEMS. In addition, patients with SEMS reported significantly less frequent symptoms of fatigue (P=0.01), loss of appetite (P=0.02), and nausea and vomiting (0.04) over time. The EQ-VAS score decreased with time in both treatment groups, indicating a statistically significant decrease in HRQoL over time. CONCLUSION: In patients with inoperable malignant extrahepatic bile duct obstruction, SEMS placement results in better scores for general and disease-specific HRQoL over time compared with plastic stent placement.
Sujet(s)
Cholangiopancréatographie rétrograde endoscopique/méthodes , Cholestase extrahépatique/chirurgie , Matières plastiques , Qualité de vie , Endoprothèses métalliques auto-expansibles , Sujet âgé , Sujet âgé de 80 ans ou plus , Cholestase extrahépatique/étiologie , Femelle , Humains , Mâle , Adulte d'âge moyen , Soins palliatifs , Tumeurs du pancréas/complications , Tumeurs du pancréas/anatomopathologie , Endoprothèses , Enquêtes et questionnairesRÉSUMÉ
BACKGROUND AND AIMS: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device that induces weight loss and improves glycemic control in patients with type 2 diabetes mellitus (T2DM). The aim of the current study was to assess the effects of DJBL explantation on glycemic control and body weight. METHODS: This prospective, observational study included only patients with T2DM who had the DJBL implanted for at least 6 months and had a follow-up of at least 12 months after explantation. The primary endpoints were changes in glycosylated hemoglobin A1c (HbA1c) and body weight during the 12 months after explantation. Secondary endpoints were changes in fasting plasma glucose, blood pressure, and plasma lipid levels. RESULTS: In total, 59 patients completed the 12-month follow-up after explantation. During this period body weight increased by 5.6 (standard deviation, 6.4) kg (P < .001) and HbA1c rose from 65 (SD 17) to 70 (SD 20) mmol/mol (P < .001). However, body weight remained 8.0 (SD 8.6) kg (P < .001) lower than before implantation, that is, corresponding to a net total body weight loss of 7.4% (SD 7.6) (P < .001). Although HbA1c was significantly higher 12 months after explantation compared with baseline and the mean daily dose of insulin used was comparable, the number of patients on insulin remained significantly lower than before implantation. CONCLUSIONS: Explantation of the DJBL is associated with weight gain and worsening of glycemic control, although some beneficial effects remained detectable 12 months after explantation. A change in strategy is needed to preserve the beneficial effects of DJBL treatment. (Clinical trial registration number: 746∖100111.).
Sujet(s)
Chirurgie bariatrique , Glycémie/métabolisme , Ablation de dispositif , Diabète de type 2/métabolisme , Duodénum/chirurgie , Jéjunum/chirurgie , Obésité/chirurgie , Prise de poids , Adulte , Pression sanguine , Poids , Diabète de type 2/traitement médicamenteux , Femelle , Hémoglobine glyquée/métabolisme , Humains , Hypoglycémiants/usage thérapeutique , Insuline/usage thérapeutique , Mâle , Adulte d'âge moyen , Obésité/métabolisme , Études prospectivesRÉSUMÉ
BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopic treatment for patients with type 2 diabetes mellitus (T2DM) and (morbid) obesity. The aim of the current study was to determine its efficacy and safety profile. METHODS: Inclusion criteria for treatment with a DJBL were: age 18-70 years, BMI 28-45 kg/m2, and T2DM with a HbA1c > 48 mmol/mol. Primary outcomes were changes in HbA1c and body weight. Secondary outcomes included changes in blood pressure, lipids, and anti-diabetic medication. Predictive factors for success of treatment with the DJBL were determined. RESULTS: Between 2011 and 2014, 185 out of 198 patients successfully underwent a DJBL implantation procedure, with an intended implantation time of 12 months. In these 185 patients, body weight decreased by 12.8 ± 8.0 kg (total body weight loss of 11.9 ± 6.9 %, p < 0.001), HbA1c decreased from 67 to 61 mmol/mol (p < 0.001) despite a reduction in anti-diabetic medication, and blood pressure and serum lipid levels all decreased. In total, 57 (31 %) DJBLs were explanted early after a median duration of 33 weeks. Adverse events occurred in 17 % of patients. C-peptide ≥1.0 nmol/L and body weight ≥107 kg at screening were independent predictive factors for success. CONCLUSIONS: Treatment with the DJBL in T2DM patients with (morbid) obesity results in improvement in glucose control, a reduction in anti-diabetic medication, and significant weight loss. The largest changes are observed within the first 3-6 months. Initial C-peptide levels and body weight may help to select patients with the greatest chance of success.