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https://www.readbyqxmd.com/read/28534520/extracolonic-cancer-in-inflammatory-bowel-disease-data-from-the-geteccu-eneida-registry
#1
María Chaparro, M Ramas, J M Benítez, A López-García, A Juan, J Guardiola, M Mínguez, X Calvet, L Márquez, L I Fernández Salazar, L Bujanda, C García, Y Zabana, R Lorente, J Barrio, E Hinojosa, M Iborra, M Domínguez Cajal, M Van Domselaar, M F García-Sepulcre, F Gomollón, M Piqueras, G Alcaín, V García-Sánchez, J Panés, E Domènech, E García-Esquinas, F Rodríguez-Artalejo, J P Gisbert
OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. INCLUSION CRITERIA: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU...
May 23, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28533920/inflammatory-bowel-disease-efficient-remission-maintenance-is-crucial-for-cost-containment
#2
REVIEW
Giovanni C Actis, Rinaldo Pellicano
The inflammatory bowel diseases (IBD) are chronic incurable inflammatory disorders of the gut. Some 10% run a downhill course, requiring emergency medical support and often surgery; another small subset are monogenic, and, threatening pediatric patients, are the challenge of these days. The majority of the IBDs, however, are polygenic low-penetrance diseases, running a lifetime waxing-and-waning course. The prevalent trend is towards a slow worsening and steady cost increase. Each and all drugs of the available arsenal exhibit strengths and weaknesses: Mesalamines are chiefly effectively for mild-moderate colitis, and do not work in Crohn's; steroids do not control some 40% of the ulcerative colitis cases, and are not indicated for Crohn's; thiopurines are effective in the maintenance of the IBDs but do not prevent relapses on withdrawal; biologics are still being used empirically (not monitored) causing further increase of their cost over that of hospitalization...
May 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28525791/determination-of-thiopurine-s-methyltransferase-activity-by-hydrophilic-interaction-liquid-chromatography-hyphenated-with-mass-spectrometry
#3
Daniel Pecher, Svetlana Dokupilová, Zuzana Zelinková, Maikel Peppelenbosch, Veronika Mikušová, Peter Mikuš
Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurines used in the therapy of inflammatory bowel diseases (IBD). In this work a new progressive method for the determination of TPMT activity in red blood cells lysates was developed. Analysis was carried out by means of hydrophilic interaction liquid chromatography (HILIC) hyphenated with mass spectrometry (MS). In comparison with reversed-phase high-performance liquid chromatography (RP-HPLC), that has been typically applied in determination of TPMT activity, the HILIC significantly improved the analytical signal provided by MS, shortened analysis time, and improved chromatographic resolution...
May 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28523321/autoimmune-hepatitis-with-sclerosing-cholangitis-in-a-patient-with-thiopurine-methyltransferase-deficiency-case-presentation
#4
Sorin Claudiu Man, Cristina Nicoleta Schnell, Valentina Sas, Anca Dana Buzoianu, Dan Gheban
The association between two autoimmune diseases is known in the literature as overlap syndrome. We present the case of an 18-year-old boy, diagnosed at the age of 13 with an overlap syndrome between type I autoimmune hepatitis and sclerosing cholangitis. The response to immunosuppressant therapy was hampered by azathioprine-induced toxicity causing severe pancytopenia, as a result of thiopurine methyltransferase enzyme genetic deficiency. Treatment was replaced by mycophenolate mofetil. Although the relapse rate was reduced, the disease progressed to cirrhosis...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28516725/the-need-for-better-preventative-strategies-for-inflammatory-bowel-disease-patients-at-risk-of-herpes-zoster-virus
#5
William Bye, Miles Sparrow, Susie Connor, Jane Andrews, Katie Ellard, Watson Ng, Georgia Hume, Sally Antoniades, Alissa Walsh
BACKGROUND: Immunosuppressed IBD patients have an increased risk of HZV infection. The existing live-attenuated HZV vaccine is contraindicated in some of these patients and can only be used with caution in others. AIMS: To describe characteristics of IBD patients suffering HZV to enable implementation of risk mitigation strategies for those at highest risk. METHODS: Gastroenterologists completed a proforma for IBD patients who experienced HZV infection: IBD phenotype, details of HZV infection, immunosuppression and any change to treatment upon diagnosis of HZV...
May 17, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28507448/thiopurine-s-methyltransferase-polymorphisms-in-acute-lymphoblastic-leukemia-inflammatory-bowel-disease-and-autoimmune-disorders-influence-on-treatment-response
#6
REVIEW
Rachid Abaji, Maja Krajinovic
The thiopurine S-methyltransferase (TPMT) gene encodes for the TPMT enzyme that plays a crucial role in the metabolism of thiopurine drugs. Genetic polymorphisms in this gene can affect the activity of the TPMT enzyme and have been correlated with variability in response to treatment with thiopurines. Advances in the pharmacogenetics of TPMT allowed the development of dosing recommendations and treatment strategies to optimize and individualize prescribing thiopurine in an attempt to enhance treatment efficacy while minimizing toxicity...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28500740/children-with-low-risk-acute-lymphoblastic-leukemia-are-at-highest-risk-of-second-cancers
#7
Stine N Nielsen, Frank Eriksson, Susanne Rosthoej, Mette K Andersen, Erik Forestier, Henrik Hasle, Lisa L Hjalgrim, Ann Aasberg, Jonas Abrahamsson, Mats Heyman, Ólafur G Jónsson, Kaie Pruunsild, Goda E Vaitkeviciené, Kim Vettenranta, Kjeld Schmiegelow
BACKGROUND: The improved survival rates for childhood acute lymphoblastic leukemia (ALL) may be jeopardized by the development of a second cancer, which has been associated with thiopurine therapy. PROCEDURE: We retrospectively analyzed three sequential Nordic Society of Paediatric Haematology and Oncology's protocols characterized by increasing intensity of thiopurine-based maintenance therapy. We explored the risk of second cancer in relation to protocols, risk group, thiopurine methyltransferase (TPMT) activity, ALL high hyperdiploidy (HeH), and t(12;21)[ETV6/RUNX1]...
May 13, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28499322/azathioprine-allows-glucocorticoid-withdrawal-post-hoc-results-of-a-prospective-study-in-patients-with-inflammatory-bowel-diseases
#8
Niels Teich, Wolfgang Mohl, Bernd Bokemeyer, Burkhard Bündgens, Jürgen Büning, Stephan Miehlke, Dietrich Hüppe, Christian Maaser, Britta Siegmund, Carsten Schmidt, Andreas Stallmach
Background Azathioprine is recommended as first-line immunosuppressant in patients with steroid-dependent inflammatory bowel diseases (IBDs). However, data on steroid withdrawal after induction therapy in IBD patients are sparse. Methods In this post-hoc analysis of a prospective multicenter study, we analyzed the proportion and clinical characteristics of 324 azathioprine-tolerant patients as to whether they could terminate the glucocorticoid therapy after initiation of treatment with azathioprine. Results Systemic steroid therapy was required in 190 patients (58...
May 2017: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/28498350/comparison-of-direct-sequencing-real-time-pcr-high-resolution-melt-pcr-hrm-and-pcr-restriction-fragment-length-polymorphism-pcr-rflp-analysis-for-genotyping-of-common-thiopurine-intolerant-variant-alleles-nudt15-c-415c-t-and-tpmt-c-719a-g-tpmt-3c
#9
Wai-Ying Fong, Chi-Chun Ho, Wing-Tat Poon
Thiopurine intolerance and treatment-related toxicity, such as fatal myelosuppression, is related to non-function genetic variants encoding thiopurine S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15). Genetic testing of the common variants NUDT15:NM_018283.2:c.415C>T (Arg139Cys, dbSNP rs116855232 T allele) and TPMT: NM_000367.4:c.719A>G (TPMT*3C, dbSNP rs1142345 G allele) in East Asians including Chinese can potentially prevent treatment-related complications. Two complementary genotyping approaches, real-time PCR-high resolution melt (PCR-HRM) and PCR-restriction fragment length morphism (PCR-RFLP) analysis were evaluated using conventional PCR and Sanger sequencing genotyping as the gold standard...
May 12, 2017: Diagnostics
https://www.readbyqxmd.com/read/28489727/pharmacology-of-thiopurine-therapy-in-inflammatory-bowel-disease-and-complete-blood-cell-count-outcomes-a-five-year-database-study
#10
Berrie Meijer, Abraham J Wilhelm, Chris Jj Mulder, Gerd Bouma, Adriaan A van Bodegraven, Nanne Kh de Boer
BACKGROUND: Thiopurines Are The Prerequisite For Immunomodulation In Inflammatory Bowel disease (IBD) therapy. When administered in high (oncological) dose, thiopurine metabolites act as purine antagonists, causing DNA-strand breakage and myelotoxicity. In lower IBD dosages, the mode of action is primarily restricted to anti-inflammatory effects. Then, myelosuppression and hepatotoxicity are the most common adverse events of thiopurines. The aim of this study was to assess the effect of thiopurine metabolites on hematologic and hepatic parameters and to determine which patient characteristics are related to generation of thiopurine metabolites...
May 6, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28488312/immune-modulator-therapy-for-microscopic-colitis-in-a-case-series-of-73-patients
#11
T G Cotter, A K Kamboj, S B Hicks, W J Tremaine, E V Loftus, D S Pardi
BACKGROUND: Microscopic colitis (MC) is a common cause of chronic diarrhoea. Various treatment options have been described, but there are limited data describing outcomes of corticosteroid-sparing treatments. AIM: To evaluate the outcomes of patients with active MC treated with immune modulators. METHODS: All patients seen at Mayo Clinic, Rochester between January 1, 1997 and November 30, 2016 with a histological diagnosis of MC were identified...
May 10, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28481014/infliximab-and-adalimumab-drug-levels-in-crohn-s-disease-contrasting-associations-with-disease-activity-and-influencing-factors
#12
M G Ward, B Warner, N Unsworth, S-W Chuah, C Brownclarke, S Shieh, M Parkes, J D Sanderson, Z Arkir, J Reynolds, P R Gibson, P M Irving
BACKGROUND: Discriminative drug level thresholds for disease activity endpoints in patients with Crohn's disease. have been consistently demonstrated with infliximab, but not adalimumab. AIMS: To identify threshold concentrations for infliximab and adalimumab in Crohn's disease according to different disease endpoints, and factors that influence drug levels. METHODS: We performed a cross-sectional service evaluation of patients receiving maintenance infliximab or adalimumab for Crohn's disease...
May 8, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28476189/analysis-of-thiopurine-s-methyltransferase-deficient-alleles-in-acute-lymphoblastic-leukemia-patients-in-mexican-patients
#13
Silvia Jiménez-Morales, Mireya Ramírez-Florencio, Juan Manuel Mejía-Aranguré, Juan Carlos Núñez-Enríquez, Carolina Bekker-Mendez, José Luis Torres-Escalante, Janet Flores-Lujano, Elva Jiménez-Hernández, María Del Carmen Rodríguez-Zepeda, Yelda A Leal, Pablo Miguel González-Montalvo, Francisco Pantoja-Guillen, José Gabriel Peñaloza-Gonzalez, Erick Israel Gutiérrez-Juárez, Nora Nancy Núñez-Villegas, Maria Luisa Pérez-Saldivar, Francisco Xavier Guerra-Castillo, Luz Victoria Flores-Villegas, María Teresa Ramos-Cervantes, José Manuel Fragoso, María Guadalupe García-Escalante, Doris Del Carmen Pinto-Escalante, Julián Ramírez-Bello, Alfredo Hidalgo-Miranda
BACKGROUND AND AIMS: It has been demonstrated that heterozygote and homozygote thiopurine S-methyltransferase (TPMT) mutant allele carriers are at high risk to develop severe and potentially fatal hematopoietic toxicity after treatment with standard doses of 6-mercaptopurine (6-MP) and methotrexate (MX). Those drugs are the backbone of acute lymphoblastic leukemia (ALL) and several autoimmune disease treatments. We undertook this study to determine the frequency of the TPMT deficient alleles in children with ALL and non-ALL subjects from Mexico City and Yucatan, Mexico...
November 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/28475384/optimizing-pharmacologic-management-of-inflammatory-bowel-disease
#14
Shannon Chang, Stephen Hanauer
As our medical armamentarium for IBD continues to expand, it is essential that clinicians understand both optimizing and sequencing of individual and combination therapeutic approaches with available medications. Areas covered: This review summarizes dosing strategies and therapeutic drug monitoring for pharmacologic optimization in IBD. Aminosalicylates remain first-line therapies for mild-to-moderate UC but have limited evidence of efficacy in CD. Budesonide provides an alternative to aminosalicylates when targeted to appropriate sites in the distal small bowel and colon, as do conventional corticosteroids when applied rectally...
June 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28470355/association-of-nudt15-c-415c-t-allele-and-thiopurine-induced-leukocytopenia-in-asians-a-systematic-review-and-meta-analysis
#15
A L Zhang, J Yang, H Wang, J L Lu, S Tang, X J Zhang
BACKGROUND: Thiopurines, commonly used to treat autoimmune conditions and cancer, can be limited by life-threatening leucopenia. However, whether NUDT15 (nucleoside diphosphate-linked moiety X-type motif 15) is associated with thiopurine-induced leucopenia in Asians is controversial. METHODS: Relevant studies in English that were published until July 10, 2016 were identified through PubMed, EMbase, and other web knowledge databases. Study quality was assessed according to the Newcastle-Ottawa Scale (NOS) criteria...
May 3, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28468529/pharmacogenomics-in-pediatric-acute-lymphoblastic-leukemia-promises-and-limitations
#16
Zeina N Al-Mahayri, George P Patrinos, Bassam R Ali
Despite the significant advances achieved in pediatric acute lymphocytic leukemia (ALL) treatment, adverse side effects of drugs remain a challenging issue. Numerous ALL pharmacogenomic studies have been conducted to elucidate the predisposing genetic factors for their development. Plausible pharmacogenomic data are available for the osteonecrosis associated with glucocorticoids, the neurotoxicity associated with vincristine and the cardiotoxicity related to anthracyclines. However, these data have not been fully translated into the clinic due to several limitations, most importantly the lack of reliable evidence...
May 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28462921/one-amino-acid-makes-a-difference-characterization-of-a-new-tpmt-allele-and-the-influence-of-sam-on-tpmt-stability
#17
Yan Ping Heidi Iu, Sara Helander, Anna Zimdahl Kahlin, Chun Wah Cheng, Chi Chung Shek, Moon Ho Leung, Björn Wallner, Lars-Göran Mårtensson, Malin Lindqvist Appell
Thiopurine induced toxicity is associated with defects in the thiopurine methyltransferase (TPMT) gene. TPMT is a polymorphic enzyme, with most of the single nucleotide polymorphisms (SNPs) causing an amino acid change, altering the enzymatic activity of the TPMT protein. In this study, we characterize a novel patient allele c.719A > C, named TPMT*41, together with the more common variant *3C c.719A > G, resulting in an amino acid shift at tyrosine 240 to serine, p.Y240S and cysteine, p.Y240C respectively...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28457904/collagenous-colitis-requirement-for-high-dose-budesonide-as-maintenance-treatment
#18
Fernando Fernandez-Bañares, Marta Piqueras, Danila Guagnozzi, Virginia Robles, Alexandra Ruiz-Cerulla, María José Casanova, Javier P Gisbert, David Busquets, Yolanda Arguedas, Angeles Pérez-Aisa, Luis Fernández-Salazar, Alfredo J Lucendo
BACKGROUND: Controlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal. AIM: To evaluate the need for high-dose budesonide (≥6mg/d) to maintain clinical remission in CC. METHODS: Analysis of a multicentre retrospective cohort of 75 patients with CC (62.3±1.5years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015...
April 10, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28452864/azathioprine-with-allopurinol-lower-deoxythioguanosine-in-dna-and-transcriptome-changes-indicate-mechanistic-differences-to-azathioprine-alone
#19
Sally A Coulthard, Phil Berry, Sarah McGarrity, Simon McLaughlin, Azhar Ansari, Christopher P F Redfern
BACKGROUND: Use of azathioprine (AZA) for inflammatory bowel disease is limited by side effects or poor efficacy. Combining low-dose azathioprine with allopurinol (LDAA) bypasses side effects, improves efficacy, and may be appropriate as first-line therapy. We test the hypothesis that standard-dose azathioprine (AZA) and LDAA treatments work by similar mechanisms, using incorporation of the metabolite deoxythioguanosine into patient DNA, white-blood cell counts, and transcriptome analysis as biological markers of drug effect...
June 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28445188/tpmt-comt-and-acyp2-genetic-variants-in-paediatric-cancer-patients-with-cisplatin-induced-ototoxicity
#20
Signe Thiesen, Peng Yin, Andrea L Jorgensen, Jieying E Zhang, Valentina Manzo, Laurence McEvoy, Christopher Barton, Susan Picton, Simon Bailey, Penelope Brock, Harish Vyas, David Walker, Guy Makin, Srinivas Bandi, Barry Pizer, Daniel B Hawcutt, Munir Pirmohamed
OBJECTIVES: Cisplatin ototoxicity affects 42-88% of treated children. Catechol-O-methyltransferase (COMT), thiopurine methyltransferase (TPMT) and AYCP2 genetic variants have been associated with ototoxicity, but the findings have been contradictory. The aims of the study were as follows: (a) to investigate these associations in a carefully phenotyped cohort of UK children and (b) to perform a systematic review and meta-analysis. METHODS: We recruited 149 children from seven UK centres using a retrospective cohort study design...
June 2017: Pharmacogenetics and Genomics
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