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Featured researches published by Batia Weiss.


Journal of Crohns & Colitis | 2014

Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease

Frank M. Ruemmele; Gábor Veres; Kaija-Leena Kolho; Anne M. Griffiths; Arie Levine; Johanna C. Escher; J. Amil Dias; Arrigo Barabino; Christian Braegger; Jiri Bronsky; Stephan Buderus; J. Martín-de-Carpi; L. de Ridder; Ulrika L. Fagerberg; Jean-Pierre Hugot; Jaroslaw Kierkus; Sanja Kolaček; Sibylle Koletzko; Paolo Lionetti; Erasmo Miele; V.M. Navas López; Anders Paerregaard; Richard K. Russell; Daniela Elena Serban; Ron Shaoul; P. van Rheenen; Gigi Veereman; Batia Weiss; David C. Wilson; Axel Dignass

Children and adolescents with Crohns disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohns and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.


Clinical Gastroenterology and Hepatology | 2013

Addition of an Immunomodulator to Infliximab Therapy Eliminates Antidrug Antibodies in Serum and Restores Clinical Response of Patients With Inflammatory Bowel Disease

Shomron Ben Horin; Matti Waterman; Uri Kopylov; Miri Yavzori; Orit Picard; Ella Fudim; Halim Awadie; Batia Weiss; Yehuda Chowers

There are few therapeutic options for patients with inflammatory bowel disease who lose response to infliximab because they produced antibodies against the drug. We performed a retrospective analysis to investigate whether administration of immune modulators to 5 patients who developed antibodies to infliximab (ATI) restored response to this drug; 3 patients were given azathioprine/6-mercaptopurine and 2 patients were given methotrexate. Concentrations of infliximab and ATIs, and antitumor necrosis factor (TNF) activity, were analyzed using enzyme-linked immunosorbent assay-based competition assays of serum samples collected before and after patients were given the immunomodulator. In all patients, levels of ATIs gradually decreased and trough levels of infliximab increased; clinical responses were restored to all patients. In competition assays, immunomodulator-induced elimination of ATIs was associated with increased anti-TNF activity in serum. The addition of immunomodulators to therapy might be helpful to patients who have lost response to anti-TNF agents owing to formation of antidrug antibodies.


Immunity | 2014

Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function

Dror S. Shouval; Amlan Biswas; Jeremy A. Goettel; Katelyn McCann; Evan Conaway; Naresh Singh Redhu; Ivan D. Mascanfroni; Ziad Al Adham; Sydney Lavoie; Mouna Ibourk; Deanna D. Nguyen; Janneke N. Samsom; Johanna C. Escher; Raz Somech; Batia Weiss; Rita Beier; Laurie S. Conklin; Christen L. Ebens; Fernanda Stephanie Santos; Alexandre Rodrigues Ferreira; Mary Sherlock; Atul K. Bhan; Werner Müller; J. Rodrigo Mora; Francisco J. Quintana; Christoph Klein; Aleixo M. Muise; Bruce H. Horwitz; Scott B. Snapper

Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on T cells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4(+) T cell transfer, Rag2(-/-)Il10rb(-/-) mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb(-/-) anti-inflammatory macrophages ameliorated colitis induction by WT CD4(+) T cells in Rag2(-/-)Il10rb(-/-) mice. Similar alterations in the generation and function of anti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflammatory bowel disease. Collectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immune homeostasis in mice and humans.


Pediatric Pulmonology | 2010

Probiotic supplementation affects pulmonary exacerbations in patients with cystic fibrosis: a pilot study.

Batia Weiss; Yoram Bujanover; Yaakov Yahav; Daphna Vilozni; Elizabeth Fireman

Probiotics reduce intestinal inflammation in, and Lactobacillus GG (LGG) reduces pulmonary exacerbation rate cystic fibrosis (CF) patients. We intended to determine the effect of a mixed probiotic preparation on pulmonary exacerbations and inflammatory characteristics of the sputum in CF patients.


Journal of Crohns & Colitis | 2013

Long-term outcome of tumor necrosis factor alpha antagonist's treatment in pediatric Crohn's disease

Amit Assa; Corina Hartman; Batia Weiss; Efrat Broide; Yoram Rosenbach; Noam Zevit; Yoram Bujanover; Raanan Shamir

BACKGROUND Anti tumor necrosis factor alpha (TNFα) agents have become widely used in pediatric inflammatory bowel disease (IBD). So far, only few studies examined the long-term results of anti-TNFα treatment in children with IBD. METHODS The long-term outcome of pediatric patients with IBD was assessed retrospectively in a multicenter cohort of children treated with anti-TNFα beyond induction treatment. Short- and long-term response rates, predictors for loss of response, data on growth and laboratory parameters were assessed. RESULTS 120 patients [101 crohns disease (CD), 19 ulcerative colitis (UC) or indeterminate colitis (IC)] received either infliximab or adalimumab. The mean age at initiation of anti-TNFα was 13.4 ± 3.9 years and the median duration of anti-TNFα treatment was 15 months (range: 2-90). Overall, 89% of the cohort experienced short-term response following induction. Response was associated with improvement in weight and BMI Z-scores (p<0.001) but not with linear growth. Responders experienced a significant decrease in erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) during treatment (p<0.001). Albumin and hemoglobin both improved but only albumin increased significantly (p<0.001). The cumulative probability of losing response to anti-TNFα treatment was 17%, 38%, and 49% after 1, 3, and 5 years, respectively. Responders had a significantly lower weight and BMI Z-scores at initiation of anti-TNFα treatment in compared to non-responders (p=0.04 and 0.02 respectively). CONCLUSIONS Our long term cohort supports the current evidence on the effectiveness and safety of anti-TNFα treatment in children with IBD. Response to treatment was interestingly associated with lower weight and BMI.


Journal of Pediatric Gastroenterology and Nutrition | 2003

A comparison of budesonide and prednisone for the treatment of active pediatric Crohn disease

Arie Levine; Weizman Z; Efrat Broide; Raanan Shamir; Ron Shaoul; Avi Pacht; Gabriel Dinari; On A; Batia Weiss; Yoram Bujanover

Objectives Budesonide has been found effective in patients with mild and moderate Crohn disease and has been found to cause fewer side effects than prednisone. The use of oral budesonide has not been prospectively evaluated in children with Crohn disease. Therefore, the authors initiated a trial to compare remission and tolerance to budesonide and prednisone in children with mild or moderately active Crohn disease. Methods A prospective randomized open controlled 12-week trial was carried out comparing pH modified release budesonide, 9 mg, versus prednisone, 40 mg, in children with active mild to moderate pediatric Crohn disease. Results Thirty-three patients (20 boys and 13 girls; mean age, 14.3 years) enrolled and completed the study. The groups treated with budesonide and prednisone did not differ by age, onset of disease, location of disease, or disease activity. The remission rate at 12 weeks was 47% in the budesonide treatment group and 50% in the prednisone treatment group. Side effects occurred in 32% and 71% of patients treated with budesonide and prednisone, respectively (P < 0.05). Severity of cosmetic side effects was significantly lower in patients treated with budesonide (P < 0.01). Conclusions Remission rates for Crohn disease with budesonide and prednisone treatment in this study were similar. Pediatric patients treated with budesonide had significantly fewer side effects than patients treated with prednisone. Budesonide should be considered an alternative to prednisone in pediatric patients with mild to moderate disease activity.


The American Journal of Gastroenterology | 2004

NOD2/CARD15 genotype and phenotype differences between Ashkenazi and Sephardic Jews with Crohn's disease

Amir Karban; Matti Waterman; Carolien Panhuysen; Rivka Dresner Pollak; Shula Nesher; Lisa W. Datta; Batia Weiss; Alain Suissa; Raanan Shamir; Steven R. Brant; Rami Eliakim

OBJECTIVE:NOD2/CARD15 has been identified as a major susceptibility gene for Crohns disease (CD). Three mutations, Arg702Trp, Gly908Arg, and Leu1007fsinsC, are associated with CD. The incidence and prevalence rate of inflammatory bowel diseases is two- to four-fold higher in Ashkenazi Jews as compared to non-Jewish Caucasians. The aim of this study was to determine the significance of the NOD2/CARD15 mutations in Jewish CD patients in Israel, and more specifically, to compare the significance of the mutations to the expression of CD in the Ashkenazi and Sephardic Jewish populations.METHODS:Allele frequencies of the mutations were determined in 180 Jewish CD patients, 73 ulcerative colitis patients, and 159 ethnically matched controls. Variants were detected using allele-specific PCR and restriction enzyme digestion assay. Demographic and phenotypic characterizations of the CD patients were determined.RESULTS:The carrier rate of the three mutations in the entire Jewish Israeli CD cohort is 41.1%versus 10.7% in controls (p < 0.0001). The Ashkenazi Jewish CD patients have an increased carrier rate compared to Sephardic Jews (47.4%vs 27.45%, p= 0.034). Association analyses in Ashkenazi Jews reveal odds ratios of 10.5, 9, and 4.8 for carriage of Gly908Arg, Arg702Trp, and Leu1007fsinsC mutations, respectively. Significantly higher rates of smoking, family history of inflammatory bowel diseases, and extraintestinal manifestations were found among the Sephardic CD patients.CONCLUSIONS:NOD2/CARD15 CD-associated mutations confer increased risk mainly to the Ashkenazi Jewish CD patients in Israel. This suggests that NOD2/CARD15 mutations could contribute to the higher incidence and prevalence rates of CD among Ashkenazi Jews.


Journal of Crohns & Colitis | 2015

Infliximab-Related Infusion Reactions: Systematic Review

Lev Lichtenstein; Yulia Ron; Shmuel Kivity; Shomron Ben-Horin; Eran Israeli; Gerald Fraser; Iris Dotan; Yehuda Chowers; Ronit Confino-Cohen; Batia Weiss

Objective: Administration of infliximab is associated with a well-recognised risk of infusion reactions. Lack of a mechanism-based rationale for their prevention, and absence of adequate and well-controlled studies, has led to the use of diverse empirical administration protocols. The aim of this study is to perform a systematic review of the evidence behind the strategies for preventing infusion reactions to infliximab, and for controlling the reactions once they occur. Methods: We conducted extensive search of electronic databases of MEDLINE [PubMed] for reports that communicate various aspects of infusion reactions to infliximab in IBD patients. Results: We examined full texts of 105 potentially eligible articles. No randomised controlled trials that pre-defined infusion reaction as a primary outcome were found. Three RCTs evaluated infusion reactions as a secondary outcome; another four RCTs included infusion reactions in the safety evaluation analysis; and 62 additional studies focused on various aspects of mechanism/s, risk, primary and secondary preventive measures, and management algorithms. Seven studies were added by a manual search of reference lists of the relevant articles. A total of 76 original studies were included in quantitative analysis of the existing strategies. Conclusions: There is still paucity of systematic and controlled data on the risk, prevention, and management of infusion reactions to infliximab. We present working algorithms based on systematic and extensive review of the available data. More randomised controlled trials are needed in order to investigate the efficacy of the proposed preventive and management algorithms.


PLOS ONE | 2016

Clinical guidelines for management of bone health in Rett syndrome based on expert consensus and available evidence

Amanda Jefferson; Helen Leonard; Aris Siafarikas; Helen Woodhead; Sue Fyfe; Leanne M. Ward; Craig Munns; Kathleen J. Motil; Daniel C. Tarquinio; Jay R. Shapiro; Torkel B. Brismar; Bruria Ben-Zeev; Anne Marie Bisgaard; Giangennaro Coppola; Carolyn Ellaway; Michael Freilinger; Suzanne Geerts; Peter Humphreys; Mary Jones; Jane B. Lane; Gunilla Larsson; Meir Lotan; Alan K. Percy; M. Pineda; Steven A. Skinner; Birgit Syhler; Sue Thompson; Batia Weiss; Ingegerd Witt Engerström; Jenny Downs

Objectives We developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians. Methods An initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement. Items describe the clinical assessment of bone health, bone mineral density assessment and technique, and pharmacological and non-pharmacological interventions. Results Agreement was reached on 39 statements which were formulated from 41 statements and 11 questions. When assessing bone health in Rett syndrome a comprehensive assessment of fracture history, mutation type, prescribed medication, pubertal development, mobility level, dietary intake and biochemical bone markers is recommended. A baseline densitometry assessment should be performed with accommodations made for size, with the frequency of surveillance determined according to individual risk. Lateral spine x-rays are also suggested. Increasing physical activity and initiating calcium and vitamin D supplementation when low are the first approaches to optimizing bone health in Rett syndrome. If individuals with Rett syndrome meet the ISCD criterion for osteoporosis in children, the use of bisphosphonates is recommended. Conclusion A clinically significant history of fracture in combination with low bone densitometry findings is necessary for a diagnosis of osteoporosis. These evidence and consensus-based guidelines have the potential to improve bone health in those with Rett syndrome, reduce the frequency of fractures, and stimulate further research that aims to ameliorate the impacts of this serious comorbidity.


Inflammatory Bowel Diseases | 2004

NOD2/CARD15 mutations and presence of granulomas in pediatric and adult Crohn's disease

Ron Shaoul; Amir Karban; Batia Weiss; Shimon Reif; Dror Wasserman; Avi Pacht; Rami Eliakim; Joram Wardi; Haim Shirin; Eitan Wine; Esther Leshinsky-Silver; Arie Levine

Objectives:The etiology and mechanism leading to granuloma formation in patients with Crohn’s disease (CD) are presently unknown. The first susceptibility gene to be identified as a risk factor for CD is the NOD2/CARD15 gene on Chromosome 16. Mutations in NOD2 could affect the intracellular response to bacterial products and may eventually lead to granuloma formation. The association between NOD2 and granulomas has not been previously explored. We evaluated a possible association between NOD2 mutations and granuloma formation, and compared the prevalence of granulomas in both pediatric and adult cohorts. Methods:Patients were consecutively recruited through pediatric gastroenterology and adult gastroenterology programs. Patients were eligible if CD was confirmed, and they had undergone full colonoscopy with biopsy and/or surgical resection. Patients underwent genotyping for NOD2 disease-associated mutations. Results:A total of 230 patients were enrolled into the study, of whom 169 patients met all inclusion/exclusion criteria (Group 1, 77 patients [age range 1–16 years]; Group 2, 92 patients [age range 17–68 years]). Surgical resection was performed more often in adults (P < 0.005), and gastroscopy was performed more frequently in children (P < 0.001). Granulomas were found in 34% of the patients studied. The prevalence of granulomas did not differ by age, age group, or gender. A disease-associated NOD2 mutation was found in 37.8% of patients. Granulomas were found in 39% of patients with NOD2 mutations compared with 31% of those without NOD 2 mutations (difference was not significant). In addition, no difference was noted for the specific mutations. Conclusions:We did not find any correlation between NOD2 mutations and granuloma formation. The cause of granulomas in CD remains elusive.

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Yoram Bujanover

Boston Children's Hospital

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Yael Haberman

Cincinnati Children's Hospital Medical Center

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Arie Levine

Wolfson Medical Center

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Dror S. Shouval

Boston Children's Hospital

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Scott B. Snapper

Boston Children's Hospital

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