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4. Randomized clinical trial: Long-term Staphylococcus aureus decolonization in patients on home parenteral nutrition.

Author

Gompelman, M., Wezendonk, G.T.J., Wouters, Y., Beurskens-Meijerink, J., Fragkos, K.C., Rahman, F.Z., Coolen, J.P.M., Weerdenburg, I.J.M. van, Wertheim, H.F.L., Kievit, W., Akkermans, R.P., Serlie, M.J., Bleeker-Rovers, C.P., Wanten, G.J.A., Gompelman, M., Wezendonk, G.T.J., Wouters, Y., Beurskens-Meijerink, J., Fragkos, K.C., Rahman, F.Z., Coolen, J.P.M., Weerdenburg, I.J.M. van, Wertheim, H.F.L., Kievit, W., Akkermans, R.P., Serlie, M.J., Bleeker-Rovers, C.P., and Wanten, G.J.A.

Abstract

Item does not contain fulltext, BACKGROUND & AIMS: Staphylococcus aureus decolonization has proven successful in prevention of S. aureus infections and is a key strategy to maintain venous access and avoid hospitalization in patients receiving home parenteral nutrition (HPN). We aimed to determine the most effective and safe long-term S. aureus decolonization regimen. METHODS: A randomized, open-label, multicenter clinical trial was conducted. Adult intestinal failure patients with HPN support and carrying S. aureus were randomly assigned to a 'continuous suppression' (CS) strategy, a repeated chronic topical antibiotic treatment or a 'search and destroy' (SD) strategy, a short and systemic antibiotic treatment. Primary outcome was the proportion of patients in whom S. aureus was totally eradicated during a 1-year period. Secondary outcomes included risk factors for decolonization failure and S. aureus infections, antimicrobial resistance, adverse events, patient compliance and cost-effectivity. RESULTS: 63 participants were included (CS 31; SD 32). The mean 1-year S. aureus decolonization rate was 61% (95% CI 44, 75) for the CS group and 39% (95% CI 25, 56) for the SD group with an OR of 2.38 (95% CI 0.92, 6.11, P = 0.07). More adverse effects occurred in the SD group (P = 0.01). Predictors for eradication failure were a S. aureus positive caregiver and presence of a (gastro)enterostomy. CONCLUSION: We did not demonstrate an increased efficacy of a short and systemic S. aureus decolonization strategy over a continuous topical suppression treatment. The latter may be the best option for HPN patients as it achieved a higher long-term decolonization rate and was well-tolerated (NCT03173053).

Published
2023

7. Genomic profiling of Acute lymphoblastic leukemia in ataxia telangiectasia patients reveals tight link between ATM mutations and chromothripsis

Author

Ratnaparkhe, M, Hlevnjak, M, Kolb, T, Jauch, A, Maass, K K, Devens, F, Rode, A, Hovestadt, V, Korshunov, A, Pastorczak, A, Mlynarski, W, Sungalee, S, Korbel, J, Hoell, J, Fischer, U, Milde, T, Kramm, C, Nathrath, M, Chrzanowska, K, Tausch, E, Takagi, M, Taga, T, Constantini, S, Loeffen, J, Meijerink, J, Zielen, S, Gohring, G, Schlegelberger, B, Maass, E, Siebert, R, Kunz, J, Kulozik, A E, Worst, B, Jones, D T, Pfister, S M, Zapatka, M, Lichter, P, and Ernst, A

Published
2017
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9. CLINICAL SPECTRUM OF PRECURSOR B-CELL LYMPHOBLASTIC MALIGNANCIES: A LARGE COHORT STUDY OF 364 PEDIATRIC PATIENTS

Author

Kroeze, E., primary, Bakker, M., additional, Boer, J., additional, Hagleitner, M., additional, Burkhardt, B., additional, Padilla, L., additional, Mori, T., additional, Attarbaschi, A., additional, Verdú-Amorós, J., additional, Pillon, M., additional, Anderzhanova, L., additional, Kabíčková, E., additional, Chiang, A., additional, Kebudi, R., additional, Mellgren, K., additional, Lasic, J., additional, Jazbec, J., additional, Meijerink, J., additional, Beishuizen, A., additional, and Loeffen, J., additional

Published
2022
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12. Surgical and Survival Outcomes Following Pelvic Exenteration for Locally Advanced Primary Rectal Cancer Results From an International Collaboration

Author

Kelly ME, Glynn R, Aalbers AGJ, Alberda W, Antoniou A, Austin KK, Beets GL, Beynon J, Bosman SJ, Brunner M, Buchler MW, Burger JWA, Campain N, Christensen HK, Codd M, Coscia M, Colquhoun A, Daniels I, Davies RJ, de Wilt JHW, Deutsch C, Dietz D, Eglinton T, Fearnhead N, Frizelle FA, Garcia-Sabrido JL, George M, Gentilini L, Harris DA, Harji D, Herriot AG, Hohenberger W, Jenkins JT, Kanemitsu Y, Karen Kar Loen C, Kim H, Koh CE, Kok N, Kontovounisios C, Kulu Y, Law WL, Laurberg S, Le GN, Lydrup ML, Lynch AC, Martling A, Meijerink J, Merkel S, McDermott FD, McGrath J, Nielsen MB, Nieuwenhuijzen GAP, Nordling MA, Northover JMA, O’Connell PR, Patsouras D, Poggioli G, Radwan RW, Rasheed S, Rasmussen PC, Rutten HJT, Sagar PM, Schizas A, Shida D, Smart N, Solomon MJ, Stocchi L, Tekkis PP, Tsukamoto S, Turner W, Tuynman J, Ulrich A, van Leeuwenhoek A, van Ramshorst GH, Vasquez-Jimenez W, Verhoef C, Versteegen M, Wakeman C, Warrier S, Yip J, Winter DC., Kelly ME, Glynn R, Aalbers AGJ, Alberda W, Antoniou A, Austin KK, Beets GL, Beynon J, Bosman SJ, Brunner M, Buchler MW, Burger JWA, Campain N, Christensen HK, Codd M, Coscia M, Colquhoun A, Daniels I, Davies RJ, de Wilt JHW, Deutsch C, Dietz D, Eglinton T, Fearnhead N, Frizelle FA, Garcia-Sabrido JL, George M, Gentilini L, Harris DA, Harji D, Herriot AG, Hohenberger W, Jenkins JT, Kanemitsu Y, Karen Kar Loen C, Kim H, Koh CE, Kok N, Kontovounisios C, Kulu Y, Law WL, Laurberg S, Le GN, Lydrup ML, Lynch AC, Martling A, Meijerink J, Merkel S, McDermott FD, McGrath J, Nielsen MB, Nieuwenhuijzen GAP, Nordling MA, Northover JMA, O’Connell PR, Patsouras D, Poggioli G, Radwan RW, Rasheed S, Rasmussen PC, Rutten HJT, Sagar PM, Schizas A, Shida D, Smart N, Solomon MJ, Stocchi L, Tekkis PP, Tsukamoto S, Turner W, Tuynman J, Ulrich A, van Leeuwenhoek A, van Ramshorst GH, Vasquez-Jimenez W, Verhoef C, Versteegen M, Wakeman C, Warrier S, Yip J, Winter DC., and Surgery

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Colorectal cancer, medicine.medical_treatment, International Cooperation, Cohort Studies, 03 medical and health sciences, Young Adult, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, international collaboration, locally advanced, rectal cancer, surgical outcomes, survival outcomes, SDG 3 - Good Health and Well-being, Clinical endpoint, Medicine, Humans, Survival rate, Neoadjuvant therapy, Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, Pelvic exenteration, business.industry, Rectal Neoplasms, Retrospective cohort study, Middle Aged, medicine.disease, Prognosis, Total mesorectal excision, Surgery, Pelvic Exenteration, Survival Rate, Treatment Outcome, 030220 oncology & carcinogenesis, Resection margin, 030211 gastroenterology & hepatology, Female, business
Abstract

Objective: The aim of the study was to analyze data from an international collaboration, and ascertain prognostic indicators that inform clinical decision-making and practices regarding the role of pelvic exenteration for locally advanced primary rectal cancer (LARC). Background: With improved national screening programs fewer patients present with LARC. Despite this, select cohorts of patients require pelvic exenteration. To date, the majority of outcome data are from single-center series. Methods: Anonymized data from 14 countries on patients who had pelvic exenteration for LARC between 2004 and 2014 were accumulated. The primary endpoint was overall survival. The impact of resection margin, nodal status, bone resection, and use of neoadjuvant therapy (before exenteration) on survival was evaluated using multivariable analysis. Results: Of 1291 patients, 778 (60.3%) were male with a median (range) age of 63 (18–90) years; 78.1% received neoadjuvant therapy. Bone resection en bloc was performed in 8.2% of patients (n¼ 106), and 22.6% (n¼ 292) had resection combined with flap reconstruction. Negative resection margin (R0 resection) was achieved in 79.9%. The 30-day postoperative mortality was 1.5%. The median overall survival following R0, R1, and R2 resection was 43, 21, and 10 months (P < 0.001) with a 3-year survival of 56.4%, 29.6%, and 8.1%, respectively (P < 0.001); 37.8% of patients experienced one or more major complication. Neoadjuvant therapy increased the risk of 30-day morbidity (P < 0.012). Multivariable analysis identified resection margin and nodal status as significant determinants of overall survival (other than advanced age). Conclusions: Attainment of negative resection margins (R0) is the key to survival. Neoadjuvant therapy may improve survival; however, it does so at the increased risk of postoperative morbidity.

Published
2019

14. Factors affecting outcomes following pelvic exenteration for locally recurrent rectal cancer

Author

Kelly M. E., Glynn R., Aalbers A. G. J., Abraham-Nordling M., Alberda W., Antoniou A., Austin K. K., Beets G. L., Beynon J., Bosman S. J., Brunner M., Buchler M. W., Burger J. W. A., Campain N., Christensen H. K., Codd M., Coscia M., Colquhoun A. J., Daniels I. R., Davies R. J., de Wilt J. H. W., Deutsch C., Dietz D., Eglinton T., Fearnhead N., Frizelle F. A., Garcia-Sabrido J. L., George M. L., Gentilini L., Harris D. A., Harji D., Heriot A. G., Hohenberger Brunner W., Jenkins J. T., Kanemitsu Y., Chan K. K. L., Kim H., Koh C. E., Kok N. F., Kontovounisios C., Kulu Y., Law W. L., Le G. N., Lee P., Lydrup M. L., Lynch A. C., Martling A., Meijerink J., Merkel S., McDermott F. D., McGrath J. S., Nielsen Christensen M. B., Nieuwenhuijzen G. A. P., Nordling M. A., Northover J. M. A., O'Connell P. R., Patsouras D., Poggioli G., Radwan R. W., Rasheed S., Rasmussen P. C., Rothbarth J., Rutten H. J. T., Sagar P. M., Schizas A. M. P., Shida D., Smart N. J., Solomon M. J., Stocchi L., Tekkis P. P., Tsukamoto S., Turner W. H., Tuynman J., Ulrich A., van Leeuwenhoek A., van Ramshorst G. H., Vasquez-Jimenez W., Verhoef C., Versteegen M., Wakeman C., Warrier S., Yip J., Winter D. C., Surgery, Kelly M.E., Glynn R., Aalbers A.G.J., Abraham-Nordling M., Alberda W., Antoniou A., Austin K.K., Beets G.L., Beynon J., Bosman S.J., Brunner M., Buchler M.W., Burger J.W.A., Campain N., Christensen H.K., Codd M., Coscia M., Colquhoun A.J., Daniels I.R., Davies R.J., de Wilt J.H.W., Deutsch C., Dietz D., Eglinton T., Fearnhead N., Frizelle F.A., Garcia-Sabrido J.L., George M.L., Gentilini L., Harris D.A., Harji D., Heriot A.G., Hohenberger Brunner W., Jenkins J.T., Kanemitsu Y., Chan K.K.L., Kim H., Koh C.E., Kok N.F., Kontovounisios C., Kulu Y., Law W.L., Le G.N., Lee P., Lydrup M.L., Lynch A.C., Martling A., Meijerink J., Merkel S., McDermott F.D., McGrath J.S., Nielsen Christensen M.B., Nieuwenhuijzen G.A.P., Nordling M.A., Northover J.M.A., O'Connell P.R., Patsouras D., Poggioli G., Radwan R.W., Rasheed S., Rasmussen P.C., Rothbarth J., Rutten H.J.T., Sagar P.M., Schizas A.M.P., Shida D., Smart N.J., Solomon M.J., Stocchi L., Tekkis P.P., Tsukamoto S., Turner W.H., Tuynman J., Ulrich A., van Leeuwenhoek A., van Ramshorst G.H., Vasquez-Jimenez W., Verhoef C., Versteegen M., Wakeman C., Warrier S., Yip J., Winter D.C., AGEM - Re-generation and cancer of the digestive system, and CCA - Cancer Treatment and quality of life

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, 030230 surgery, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, medicine, Clinical endpoint, Humans, Survival rate, Survival analysis, Neoadjuvant therapy, Aged, Rectal Neoplasm, Pelvic exenteration, Rectal Neoplasms, business.industry, Odds ratio, Middle Aged, Survival Analysis, Neoadjuvant Therapy, Pelvic Exenteration, Surgery, Radiation therapy, Treatment Outcome, 030220 oncology & carcinogenesis, Resection margin, Female, Survival Analysi, Neoplasm Recurrence, Local, business, Human
Abstract

Background Pelvic exenteration for locally recurrent rectal cancer (LRRC) is associated with variable outcomes, with the majority of data from single-centre series. This study analysed data from an international collaboration to determine robust parameters that could inform clinical decision-making. Methods Anonymized data on patients who had pelvic exenteration for LRRC between 2004 and 2014 were accrued from 27 specialist centres. The primary endpoint was survival. The impact of resection margin, bone resection, node status and use of neoadjuvant therapy (before exenteration) was assessed. Results Of 1184 patients, 614 (51·9 per cent) had neoadjuvant therapy. A clear resection margin (R0 resection) was achieved in 55·4 per cent of operations. Twenty-one patients (1·8 per cent) died within 30 days and 380 (32·1 per cent) experienced a major complication. Median overall survival was 36 months following R0 resection, 27 months after R1 resection and 16 months following R2 resection (P < 0·001). Patients who received neoadjuvant therapy had more postoperative complications (unadjusted odds ratio (OR) 1·53), readmissions (unadjusted OR 2·33) and radiological reinterventions (unadjusted OR 2·12). Three-year survival rates were 48·1 per cent, 33·9 per cent and 15 per cent respectively. Bone resection (when required) was associated with a longer median survival (36 versus 29 months; P < 0·001). Node-positive patients had a shorter median overall survival than those with node-negative disease (22 versus 29 months respectively). Multivariable analysis identified margin status and bone resection as significant determinants of long-term survival. Conclusion Negative margins and bone resection (where needed) were identified as the most important factors influencing overall survival. Neoadjuvant therapy before pelvic exenteration did not affect survival, but was associated with higher rates of readmission, complications and radiological reintervention.

Published
2018
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16. Infant T-cell acute lymphoblastic leukaemia with t(6;7) (TCRB-MYB) translocation

Author

Ramdeny, P, Mullanfroze, K, de Lorenzo, P, Valsecchi, M, Meijerink, J, Pieters, R, Baruchel, A, Vora, A, Ramdeny, PS, Valsecchi, MG, Ramdeny, P, Mullanfroze, K, de Lorenzo, P, Valsecchi, M, Meijerink, J, Pieters, R, Baruchel, A, Vora, A, Ramdeny, PS, and Valsecchi, MG

Abstract

T-ALL is rare in infancy with only 10 (1.5%) of 651 patients of that subtype in the Interfant-06 infant ALL trial. We report 3 cases of t(6;7) (TCR/MYB) infant T-cell Acute Lymphoblastic Leukaemia who appear to have a distinct clinical presentation with CNS disease and refractory disease or late relapse.

Published
2021

25. Evaluation of quality of life and caregiver burden in home parenteral nutrition patients: A cross sectional study

Author

Beurskens-Meijerink, J., Huisman-de Waal, G.J., Wanten, G.J.A., Beurskens-Meijerink, J., Huisman-de Waal, G.J., and Wanten, G.J.A.

Abstract

Item does not contain fulltext, BACKGROUND & AIMS: Home total parenteral nutrition (HPN) is indicated in long-term intestinal failure (IF) to maintain or improve the nutritional status, guarantee patient survival and improve quality of life (QoL). The patients "caregiver" is often an essential partner to help perform daily activities. The aim of this study was to compare QoL, experienced distress and (if present) caregiver burden for relatives in two distinct categories of IF patients, i.e. those with short bowel syndrome as compared to those suffering from intestinal dysmotility. METHODS: All HPN patients and their caregivers of our HPN population were invited for this study. Qol and distress were assessed using the validated HPN-Qol and the "Lastmeter" (distress thermometer) questionnaire (for HPN patients) or the Caregiver Strain Index (CSI) (for caregivers) for the short bowel and dysmotility groups as well as for the combination. RESULTS: During the year 2016 a total of 193 patients and their caregivers were invited. Fifty-six patients (37%) reported not to have a caregiver. Overall, 147 patients (76%) and 91 caregivers (63%) completed the questionnaires. The most common underlying conditions leading to IF were short bowel syndrome (SBS, 48%) and intestinal dysmotility disorders (42%). Both the SBS and the dysmotility group had a reasonable Qol (SBS 6 vs. dysmotility 5.8) but the experienced distress was significantly higher in the latter group (SBS 5 vs. dysmotility 7). The distress of the dysmotility group was mainly determined by fatigue, abdominal pain, immobility, inability to work/go to school, limited contact with friends, nausea and vomiting, bloating, abdominal pain, troubles with sleeping, dizziness, inability to eat, being cold, fatigue and decreased taste. The Qol of patients with SBS was not significantly affected by aspects associated with HPN. The caregiver of dysmotility patients experienced a higher burden when compared with the caregiver in the SBS group (strain 0-13, ≥7 ref

Published
2020

30. IL-7R: Mutations in T-ALL and polymorphisms in autoimmunity: 74

Author

Durum, Scott K., Li, W. Q., Zenatti, P., Ribeiro, D., Zuurbier, L., Silva, M. C., Paganin, M., Tritapoe, J., Hixon, J. A., Silveira, A. B., Cardoso, B. A., Sarmento, L. M., Correia, N., Toribio, M. L., Kobarg, J., Horstmann, M., Pieters, R., Brandalise, S. R., Ferrando, A. A., Meijerink, J. P., Yunes, J. A., and Barata, J. T.

Published
2013
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36. Minimally invasive surgery techniques in pelvic exenteration: a systematic and meta-analysis review

Author

Srinivasaiah N., Shekleton F., Kelly M. E., Harji D., Malietzis G., Askari A., Aalbers A. G. J., Alberda W., Antoniou A., Austin K. K., Beets G. L., Berg P. L., Beynon J., Bosman S. J., Brunner M., Burger J. W. A., Campain N., Christensen H. K., Coscia M., Colquhoun A. J., Coyne P., Daniels I. R., Davies R. J., de Wilt J. H. W., Denost Q., Deutsch C., Dietz D., Duff M., Eglinton T., Fearnhead N., Frizelle F. A., Garcia-Sabrido J. L., George M. L., Gentilini L., Griffiths B., Harris D. A., Evans M., Heriot A. G., Hohenberger W., Hoe C. M., Holm T., Kanemitsu Y., Chan K. K. L., Kim H., Koh C. E., Kok N. F., Kontovounisios C., Law W. L., Laurberg S., Lee P., Lydrup M. L., Lynch A. C., Martling A., Meijerink J., Mentha A., Merkel S., McDermott F. D., McGrath J. S., Nielsen M. B., Nieuwenhuijzen G. A. P., Nilsson P. J., Abraham-Nordling M., O'Connell P. R., Patsouras D., Poggioli G., Radwan R. W., Rasheed S., Rasmussen P. C., Rothbarth J., Rutten H. J. T., Sagar P. M., Schizas A. M. P., Shida D., Smart N. J., Solomon M. J., Sorensen M. M., Stocchi L., Tekkis P. P., Tsukamoto S., Turner W. H., Tuynman J. B., van Ramshorst G. H., van Zoggel D., Vasquez-Jimenez W., Verhoef C., Verstegen M., Wakeman C., Warrier S., Yip J., Winter D. C., Jenkins J. T., Srinivasaiah N., Shekleton F., Kelly M.E., Harji D., Malietzis G., Askari A., Aalbers A.G.J., Alberda W., Antoniou A., Austin K.K., Beets G.L., Berg P.L., Beynon J., Bosman S.J., Brunner M., Burger J.W.A., Campain N., Christensen H.K., Coscia M., Colquhoun A.J., Coyne P., Daniels I.R., Davies R.J., de Wilt J.H.W., Denost Q., Deutsch C., Dietz D., Duff M., Eglinton T., Fearnhead N., Frizelle F.A., Garcia-Sabrido J.L., George M.L., Gentilini L., Griffiths B., Harris D.A., Evans M., Heriot A.G., Hohenberger W., Hoe C.M., Holm T., Kanemitsu Y., Chan K.K.L., Kim H., Koh C.E., Kok N.F., Kontovounisios C., Law W.L., Laurberg S., Lee P., Lydrup M.L., Lynch A.C., Martling A., Meijerink J., Mentha A., Merkel S., McDermott F.D., McGrath J.S., Nielsen M.B., Nieuwenhuijzen G.A.P., Nilsson P.J., Abraham-Nordling M., O'Connell P.R., Patsouras D., Poggioli G., Radwan R.W., Rasheed S., Rasmussen P.C., Rothbarth J., Rutten H.J.T., Sagar P.M., Schizas A.M.P., Shida D., Smart N.J., Solomon M.J., Sorensen M.M., Stocchi L., Tekkis P.P., Tsukamoto S., Turner W.H., Tuynman J.B., van Ramshorst G.H., van Zoggel D., Vasquez-Jimenez W., Verhoef C., Verstegen M., Wakeman C., Warrier S., Yip J., Winter D.C., and Jenkins J.T.

Subjects
Laparoscopic surgery, medicine.medical_specialty, medicine.medical_treatment, 03 medical and health sciences, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 0302 clinical medicine, Minimally invasive surgery, Surgical complication, medicine, Humans, Minimally Invasive Surgical Procedures, Pelvic Neoplasms, Robotic surgery, Neoplasm Staging, Surgical outcome, Pelvic exenteration, business.industry, Patient Selection, Mortality rate, Minimally Invasive Surgical Procedure, Surgery, Outcome and Process Assessment, Health Care, 030220 oncology & carcinogenesis, Relative risk, Meta-analysis, Cohort, 030211 gastroenterology & hepatology, business, Human
Abstract

BACKGROUND: Pelvic exenteration is potentially curative for locally advanced and recurrent pelvic cancers. Evolving technology has facilitated the use of minimally invasive surgical (MIS) techniques in selected cases. We aimed to compare outcomes between open and MIS pelvic exenteration.METHODS: A review of comparative studies was performed. Firstly, we evaluated the differences in surgical techniques with respect to operative time, blood loss, and margin status. Secondly, we assessed differences in 30-day morbidity and mortality rates, and length of hospital stay.RESULTS: Four studies that directly compared open and MIS exenteration were included. Analysis was performed on 170 patients; 78.1% (n = 133) had open pelvic exenteration, while 21.8% (n = 37) had a MIS exenteration. The median age for open exenteration was 57.7 years versus 63 years for MIS exenteration. Even though the operative time for MIS exenteration was 83 min longer (p CONCLUSION: MIS exenteration can be performed in highly selective cases, where there is favourable patient anatomy and tumour characteristics. When feasible, it is associated with reduced intra-operative blood loss, shorter length of hospital stay, and reduced morbidity.

Published
2018
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41. Intestinal Permeability Measured by Urinary Sucrose Excretion Correlates with Serum Zonulin and Faecal Calprotectin Concentrations in UC Patients in Remission

Author

Wegh, C.A.M., Roos, N.M., De, Hovenier, R., Meijerink, J., Besseling-Van Der Vaart, I., Hemert, S., Van, Witteman, B.J.M., Wegh, C.A.M., Roos, N.M., De, Hovenier, R., Meijerink, J., Besseling-Van Der Vaart, I., Hemert, S., Van, and Witteman, B.J.M.

Abstract

Background and Aims. Ulcerative colitis (UC) is associated with an increased intestinal permeability, possibly through a dysbiosis of intestinal bacteria. We investigated which markers are most relevant to assess intestinal permeability in UC patients and whether probiotics had an effect on these markers. Methods. In this twelve-week placebo-controlled randomized double-blind study, twenty-five subjects with UC in remission received either placebo or a multispecies probiotics. Samples of blood, urine, and faeces were taken at baseline, week 6, and week 12 to assess intestinal permeability and inflammation. Diaries and Bristol stool scale were kept to record stool frequency and consistency. Quality of life was scored from 32-224 with the inflammatory bowel disease questionnaire (IBD-Q). Results. This group of UC patients, in clinical remission, did not show increased intestinal permeability at baseline of this study. During the study, no significant group or time effects were found for intestinal permeability measured by the 5-sugar absorption test, serum zonulin, and faecal zonulin. Likewise, the inflammatory markers C-reactive protein (CRP), calprotectin, and the cytokines IFNγ, TNFα, IL-6, and IL-10 were not significantly affected. Stool frequency and consistency were not significantly affected either. The IBD-Q score, 194 for the probiotics group and 195 for the placebo group, remained unaffected. Correlations were tested between all outcomes; urinary sucrose excretion was significantly correlated with serum zonulin (r = 0.62) and faecal calprotectin (r = 0.55). Faecal zonulin was not significantly correlated with any of the other markers. Conclusion. Serum zonulin may be a more relevant biomarker of intestinal permeability than faecal zonulin, due to its correlation with other biomarkers of intestinal permeability. UC patients in remission did not show an effect of the probiotic treatment or a change in gut permeability. This should not discourage further stu

Published
2019

48. Nutrient-induced glucagon like peptide-1 release is modulated by serotonin

Author

Ripken, D., Wielen, N. van der, Wortelboer, H.M., Meijerink, J., Witkamp, R.F., and Hendriks, H.F.J.

Subjects
endocrine system, Serotonin, digestive, oral, and skin physiology, Biomedical Innovation, Nutrients, Small intestine, Rebaudioside A, MSB - Microbiology and Systems Biology, Life, ELSS - Earth, Life and Social Sciences, GLP-1, Biology, Healthy Living, hormones, hormone substitutes, and hormone antagonists
Abstract

Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists.Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50 mM) and rebaudioside A (12.5 mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release.Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155 μM) further enhanced casein and safflower oil induced-serotonin release.Exposure of ileal tissue segments to serotonin (30 μM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100 μM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10 μM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process. © 2016 The Authors.

Published
2016

50. The T-cell leukemia-associated ribosomal RPL10 R98S mutation enhances JAK-STAT signaling

Author

Girardi, T, primary, Vereecke, S, additional, Sulima, S O, additional, Khan, Y, additional, Fancello, L, additional, Briggs, J W, additional, Schwab, C, additional, de Beeck, J Op, additional, Verbeeck, J, additional, Royaert, J, additional, Geerdens, E, additional, Vicente, C, additional, Bornschein, S, additional, Harrison, C J, additional, Meijerink, J P, additional, Cools, J, additional, Dinman, J D, additional, Kampen, K R, additional, and De Keersmaecker, K, additional

Published
2017
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