Athos Bousvaros

University of Massachusetts Boston, Boston, Massachusetts, United States

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Publications (172)940.34 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent data from mainly homogeneous European and African populations implicate a 140-bp region 5' to the transcriptional start site of LCT (the lactase gene) as a regulatory site for lactase persistence and nonpersistence. Because there are no studies of US nonhomogeneous populations, we performed genotype/phenotype analysis of the -13910 and -22018 LCT single nucleotide polymorphisms (SNPs) in New England children, mostly of European ancestry. Duodenal biopsies were processed for disaccharidase activities, RNA quantification by reverse transcription polymerase chain reaction (RT-PCR), allelic expression ratios by PCR, and genotyping and SNP analysis. Results were compared with clinical information. Lactase activity and mRNA levels, and sucrase-to-lactase ratios of enzyme activity and mRNA, showed robust correlations with genotype. None of the other LCT SNPs showed as strong a correlation with enzyme or mRNA levels as did -13910. Data were consistent, with the -13910 being the causal sequence variant instead of -22018. Four individuals heterozygous for -13910T/C had allelic expression patterns similar to individuals with -13910C/C genotypes; of these, 2 showed equal LCT expression from the 2 alleles and a novel variant (-13909C>A) associated with lactase persistence. The identification of -13910C/C genotype is likely to predict lactase nonpersistence, consistent with prior published studies. A -13910T/T genotype will frequently, but not perfectly, predict lactase persistence in this mixed European-ancestry population; a -13910T/C genotype will not predict the phenotype. A long, rare haplotype in 2 individuals with -13910T/C genotype but equal allele-specific expression contains a novel lactase persistence allele present at -13909.
    Journal of pediatric gastroenterology and nutrition. 02/2015; 60(2):182-91.
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    ABSTRACT: Adult studies suggest antibodies to infliximab (ATI) correlate with loss of response in inflammatory bowel disease but pediatric data are limited. We conducted a cross-sectional study of trough infliximab levels and ATI in 134 pediatric and young adult patients receiving infliximab. At the time serum was obtained demographics, disease phenotype, duration of infliximab therapy, use of combination therapy (methotrexate or 6-mercaptopurine with infliximab), and surgery were recorded. Assays were performed on 134 subjects currently receiving infliximab (85 male; mean age, 17.3 ± 4.3 years; 114 Crohn's disease and 20 ulcerative colitis). Infliximab use ranged from 12 days to 12 years: median 2.0 (interquartile range (1.1-4.3) years. Twenty-seven of 134 (20%) patients had ATI ≥5 U/mL. Of patients with ATI ≥5 U/mL, 59% had infliximab levels <5 μg/mL, compared with 14% of patients with ATI <5 U/mL (P < 0.001). Ten (7%) patients (9 Crohn's disease, 1 ulcerative colitis) underwent bowel resections after beginning infliximab infusions. Sixty percent who underwent surgery had ATI ≥12 U/mL; in contrast, only 8% of patients who did not undergo surgery had ATI ≥12 U/mL (P = 0.01). At the time of serum sampling, 50 (37%) patients were receiving combination therapy, compared with 84 (63%) on infliximab alone. Combination therapy at the time of serum sampling did not correlate with either increase infliximab levels or lower ATI compared with infliximab monotherapy. However, prior immunomodulator use was associated with lower antibody levels (P = 0.007). ATI correlates with reduction in infliximab level and a higher risk of surgery in patients with inflammatory bowel disease.
    Inflammatory Bowel Diseases 01/2015; · 5.12 Impact Factor
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    ABSTRACT: Oral methotrexate (MTX) administration avoids weekly injections, reduces costs and may improve quality of life of patients with Crohn's disease (CD), especially children. Routes of administration have never been systematically compared in CD. We aimed to compare effectiveness and safety of orally (PO) versus subcutaneously (SC) administered MTX in paediatric CD. 226 children with CD treated with oral or subcutaneous MTX were included in a multicentre, retrospective 1-year cohort study (62% boys, mean age 13.8±2.8 years, 88% previous thiopurines). 38 (17%) were initially commenced on oral, 98 (43%) started subcutaneous and switched to oral and 90 (40%) were treated with subcutaneous only. Matching and 'doubly robust' weighted regression models were based on the propensity score method, controlling for confounding-by-indication bias. 11/23 pretreatment variables were different between the groups, but the propensity score modelling successfully balanced the treatment groups. 76 children (34%) had sustained steroid-free remission with a difference that did not reach significance between the PO and the SC groups (weighted OR=1.72 (95% CI 0.5 to 5.9); p=0.52). There were no differences in need for treatment escalation (p=0.24), elevated liver enzymes (p=0.59) or nausea (p=0.85). Height velocity was lower in the PO group (p=0.006) and time to remission was delayed in the PO group (p=0.036; Fleming (0, 1) test). In this largest paediatric CD cohort to date, SC administered MTX was superior to PO, but only in some of the outcomes and with a modest effect size. Therefore, it may be reasonable to consider switching children in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Gut 11/2014; · 13.32 Impact Factor
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    ABSTRACT: Pediatric inflammatory bowel disease (IBD) is associated with high rates of depression. This study compared the efficacy of cognitive behavioral therapy (CBT) to supportive nondirective therapy (SNDT) in treating youth with comorbid IBD and depression.
    Journal of the American Academy of Child and Adolescent Psychiatry 07/2014; 53(7):726-35. · 6.97 Impact Factor
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    ABSTRACT: Pediatric patients with inflammatory bowel disease (IBD) have high rates of abdominal pain. The study aims were to (1) evaluate biological and psychological correlates of abdominal pain in depressed youth with IBD and (2) determine predictors of abdominal pain in Crohn's disease (CD) and ulcerative colitis (UC).
    Inflammatory Bowel Diseases 06/2014; · 5.48 Impact Factor
  • Athos Bousvaros
    Gastroenterology 06/2014; · 12.82 Impact Factor
  • Ying Lu, Athos Bousvaros
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    ABSTRACT: The vast majority of patients with inflammatory bowel disease (IBD) will receive immunosuppressive therapy at some point for their disease, whether for the short term (such as a course of corticosteroids) or long term (such as maintenance therapy with immunomodulators or biologics). The systemic immunosuppression places patients at increased risk for infections. Therefore, it is important that patients are up-to-date with immunizations to minimize vaccine-preventable infections. However, the literature shows that the rate of immunization in patients with IBD is low. Ideally, the vaccination status is checked at diagnosis, and patients are immunized with the vaccines they need. Drawing titers is helpful in cases in which vaccination history is unclear or to confirm that titers are at an adequate level in cases in which patients have been vaccinated. Current guidelines recommend that patients with IBD follow the same routine immunization schedule as healthy children, but patients should not be administered live vaccines if they are receiving immunosuppressive therapy. Therefore, it is ideal to administer any necessary vaccinations as early as possible, prior to starting immunosuppressive therapy. Patients may receive inactivated vaccines regardless of immunosuppressive status. The IBD literature suggests that inactivated vaccines are safe and do not worsen disease activity. In general, patients with IBD mount an immune response to vaccines, but the response may be lower if patients are receiving immunosuppressive therapy, especially tumor necrosis factor inhibitors.
    Gastroenterology & hepatology. 06/2014; 10(6):355-63.
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    ABSTRACT: Despite advances in medical therapies, many children with Crohn's disease (CD) will require bowel resection. Although previous registry studies have attempted to identify risk factors for surgery, the effect of immunomodulators and biologics (IMB) on surgical indications has not been well characterized. We reviewed a series of 125 children with CD who underwent bowel resection with reanastomosis between 1977 and 2011 and were followed up for at least 6 months. We compared patients who underwent surgery for perforating disease (abscess or internal fistula) and patients who were operated on for medically refractory or fibrostenosing disease. Between these 2 groups, we examined medications received before surgery. Other demographic and disease-specific covariates were examined. Of the 82 patients who received IMB before surgery, only 19 patients (23%) required surgery for a perforating complication of CD, whereas 63 patients (77%) required surgery for strictures or medically refractory disease. In contrast, of the 43 patients who did not receive IMB preoperatively, 20 patients (45%) developed a perforating complication and 23 patients (53%) required surgery for strictures or refractory disease. These differences across groups were significant, with a lower rate of operation for perforating disease among patients receiving preoperative IMB therapy (P = 0.007). In our surgical cohort, children with CD who were treated with IMB were less likely to have surgery for perforating disease. This finding raises the possibility that the administration of IMB in children who require surgery may be associated with a difference in disease behavior.
    Inflammatory Bowel Diseases 04/2014; · 5.12 Impact Factor
  • Brian P Regan, Athos Bousvaros
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    ABSTRACT: Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract of unknown etiology that frequently presents in the pediatric population. The evaluation of pediatric UC involves excluding infection, and a colonoscopy that documents the clinical and histologic features of chronic colitis. Initial management of mild UC is typically with mesalamine therapy for induction and maintenance. Moderate UC is often initially treated with oral prednisone. Depending on disease severity and response to prednisone, maintenance options include mesalamine, mercaptopurine, azathioprine, infliximab, or adalimumab. Severe UC is typically treated with intravenous corticosteroids. Corticosteroid nonresponders should either undergo a colectomy or be treated with second-line medical rescue therapy (infliximab or calcineurin inhibitors). The severe UC patients who respond to medical rescue therapy can be maintained on infliximab or thiopurine, but 1-year remission rates for such patients are under 50 %. These medications are discussed in detail along with the initial work-up and a treatment algorithm.
    Paediatric Drugs 04/2014; · 1.72 Impact Factor
  • Journal of pediatric gastroenterology and nutrition 02/2014; · 2.18 Impact Factor
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    ABSTRACT: An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investigation are highlighted.
    Clinical Infectious Diseases 02/2014; 58(3):309-18. · 9.42 Impact Factor
  • The Journal of pediatrics 01/2014; 164(1):4-5.e1. · 4.02 Impact Factor
  • Journal of pediatric gastroenterology and nutrition 01/2014; 58(1):130-8. · 2.18 Impact Factor
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    ABSTRACT: The association between Inflammatory bowel disease (IBD) and depression provides a unique opportunity to understand the relationship between systemic inflammation and depressive symptom profiles. Youth (n = 226) ages 9-17 years with co-morbid IBD and depression underwent psychiatric assessment and evaluation of IBD activity. Latent profile analysis (LPA) identified depressive subgroups based on similar responses to the Children's Depression Rating Scale-Revised (CDRS-R). Demographic factors, depression severity, anxiety, IBD activity, inflammatory markers, IBD-related medications, and illness perception were evaluated as predictors of profile membership. Mean age was 14.3 years; 75% had Crohn's disease; 31% were on systemic corticosteroids. Mean depressive severity was moderate whereas IBD activity, which reflects inflammation, was mild. LPA identified three subgroups: Profile-1 mild (75%) had diverse low-grade depressive symptoms and highest quality of life; Profile-2 somatic (19%) had severe fatigue, appetite change, anhedonia, decreased motor activity, and depressed mood with concurrent high dose steroid therapy and the highest IBD activity; and Profile-3 cognitive (6%) had the highest rates of self-reported depressive symptoms, ostomy placements, and anxiety with IBD symptoms in the relative absence of inflammation. Evidence was found for three depression profiles in youth with IBD and depression. Our analyses determined that patients with predominantly somatic or cognitive symptoms of depression comprised 25% of our cohort. These findings may be used to design subgroup-specific interventions for depression in adolescents with IBD and potentially other physical illnesses associated with systemic inflammation.
    Journal of pediatric gastroenterology and nutrition 12/2013; · 2.18 Impact Factor
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    ABSTRACT: Determine whether infliximab use and other potential predictors are associated with decreased prevalence and severity of depression in pediatric patients with Crohn's disease (CD). Five hundred and fifty (n = 550) youth aged 9-17 with biopsy-confirmed CD were consecutively recruited as part of a multicenter randomized-controlled trial. 499 patients met study criteria and were included in the analysis. At recruitment, each subject and a parent completed the Children's Depression Inventory (CDI). A child or parent CDI ≥ 12 was used to denote clinically significant depressive symptoms (CSDS). Child and parent CDI scores were summed to form total CDI (CDIT). Infliximab use, demographic information, steroid use, laboratory values, and Pediatric Crohn's Disease Activity Index (PCDAI) were collected as potential predictors of depression. Univariate regression models were constructed to determine relationships between predictors, CSDS, and CDIT. Stepwise multivariate regression models were constructed to predict the relationship between infliximab use and depression while controlling for other predictors of depression. Infliximab use was not associated with a decreased proportion of CSDS and CDIT after adjusting for multiple comparisons. CSDS and CDIT were positively associated with PCDAI, erythrocyte sedimentation rate, and steroid dose (p < 0.01) and negatively associated with socioeconomic status (p < 0.001). In multivariate models, PCDAI and socioeconomic status (SES), were the strongest predictors of depression. Disease activity and socioeconomic status are significant predictors of depression in youth with Crohn's disease.
    Journal of pediatric gastroenterology and nutrition 12/2013; · 2.18 Impact Factor
  • 60th Meeting of American Academy of Child and Adolescent Psychiatry; 10/2013
  • Cary M. Qualia, Athos Bousvaros
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    ABSTRACT: The number of children throughout the world being diagnosed with inflammatory bowel disease (IBD) is ever increasing, while recommendations regarding its diagnosis and treatment are changing rapidly. This review article aims to inform the reader of the latest advances in the field of pediatric IBD, emphasizing interesting and important new findings published over the past 12–18 months. Epidemiological findings, non-invasive testing modalities, frequently utilized treatment options, potential complications of therapy, and psychosocial concerns are all discussed herein.
    Current Pediatrics Reports. 09/2013;
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    ABSTRACT: The primary purpose of this study was to investigate the relationship between Pediatric Ulcerative Colitis Activity Index (PUCAI) and operative management. We also specifically evaluated those patients receiving tacrolimus for their disease. A retrospective review (1/06-1/11) identified ulcerative colitis patients (≤21 years old) undergoing restorative proctocolectomy with rectal mucosectomy and ileal pouch-anal anastomosis. Main outcomes included pre-operative PUCAI, combined versus staged procedure, and postoperative complications. Patients receiving tacrolimus within 3 months of surgical intervention were identified. PUCAI at tacrolimus induction and medication side effects were also noted. Sixty patients were identified. Forty-two (70%) underwent combined and 18 (30%) had staged procedures. Pre-operative PUCAI was lower for combined versus staged patients (p=<0.001). Furthermore, a higher pre-operative PUCAI strongly correlated with the likelihood of undergoing a staged procedure (p<0.001). Forty-four patients (73%) received tacrolimus. Significant improvement in their PUCAI was noted from induction to pre-operative evaluation (p<0.001). Minor and reversible side effects occurred in 46% of patients receiving tacrolimus, but complication rates were not significantly different. There is a very strong correlation between the PUCAI and the likelihood of undergoing a staged procedure. A significant improvement in PUCAI occurs following preoperative tacrolimus therapy.
    Journal of Pediatric Surgery 07/2013; 48(7):1540-5. · 1.31 Impact Factor
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    ABSTRACT: There is extensive evidence implicating the intestinal microbiota in inflammatory bowel disease [IBD], but no microbial agent has been identified as a sole causative agent. Bacteroidales are numerically dominant intestinal organisms that associate with the mucosal surface and have properties that both positively and negatively affect the host. To determine precise numbers and species of Bacteroidales adherent to the mucosal surface in IBD patients, we performed a comprehensive culture based analysis of intestinal biopsies from pediatric Crohn's disease [CD], ulcerative colitis [UC], and control subjects. We obtained biopsies from 94 patients and used multiplex PCR or 16S rDNA sequencing of Bacteroidales isolates for species identification. Eighteen different Bacteroidales species were identified in the study group, with up to ten different species per biopsy, a number higher than demonstrated using 16S rRNA gene sequencing methods. Species diversity was decreased in IBD compared to controls and with increasingly inflamed tissue. There were significant differences in predominant Bacteroidales species between biopsies from the three groups and from inflamed and uninflamed sites. Parabacteroides distasonis significantly decreased in inflamed tissue. All 373 Bacteroidales isolates collected in this study grew with mucin as the only utilizable carbon source suggesting this is a non-pathogenic feature of this bacterial order. Bacteroides fragilis isolates with the enterotoxin gene [bft], previously associated with flares of colitis, were not found more often at inflamed colonic sites or within IBD subjects. B. fragilis isolates with the ability to synthesize the immunomodulatory polysaccharide A [PSA], previously shown to be protective in murine models of colitis, were not detected more often from healthy versus inflamed tissue.
    PLoS ONE 06/2013; 8(6):e63686. · 3.53 Impact Factor
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    ABSTRACT: OBJECTIVES:: Pediatric inpatients with IBD are rarely considered for thromboprophylaxis due to concerns about safety and under-appreciation of thrombotic risk. We characterized thromboembolism (TE) in children and young adults with inflammatory bowel disease (IBD) at a single tertiary care hospital. METHODS:: We performed a retrospective review of inpatient billing database for all IBD admissions with colonic involvement and an anticoagulation database for thrombotic complications from 2006 to 2011. RESULTS:: Of 532 patients admitted with IBD with colonic involvement, ten (1.9%) had TE (nine venous, one arterial), two of whom had recurrent thrombosis. Many of the events resulted in considerable morbidity, including four cerebrovascular events and two pulmonary emboli. Established risk factors in IBD colitis inpatients with TE included: indwelling catheter (4/10), first-degree family member with TE (2/10), hereditary thrombophilia (3/10), smoking (1/10), oral contraceptive (1/5 females) and thalidomide (1/10). Additionally most (8/10) patients had acquired thrombophilia, mostly elevation of factor VIII and anticardiolipin antibodies. Patients with IBD and TE received therapeutic anticoagulation without significantly increased bleeding. Thrombus resolution was documented in seven cases, persistence in two cases and recurrence in two cases. CONCLUSIONS:: Pediatric inpatients hospitalized with IBD with colonic involvement have increased risk of TE, including complications of pulmonary embolism, recurrence, persistence, and indefinite long term anticoagulation. Therapeutic anticoagulation in IBD patients with active colitis appears safe. We identified both inherited thrombophilias and acquired risk factors in patients with IBD and TE. We currently use risk stratification and recommend prophylactic anticoagulation in high-risk patients.
    Journal of pediatric gastroenterology and nutrition 06/2013; · 2.18 Impact Factor

Publication Stats

4k Citations
940.34 Total Impact Points

Institutions

  • 2014
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1996–2014
    • Boston Children's Hospital
      • • Center for Inflammatory Bowel Disease
      • • Department of Psychiatry
      • • Division of Gastroenterology, Hepatology and Nutrition
      Boston, Massachusetts, United States
  • 2013
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 1996–2013
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2006–2012
    • IWK Health Centre
      Halifax, Nova Scotia, Canada
    • Brigham and Women's Hospital
      • Center for Brain Mind Medicine
      Boston, Massachusetts, United States
    • The Children’s Hospital of Eastern Ontario
      Ottawa, Ontario, Canada
    • Mayo Foundation for Medical Education and Research
      • Division of Gastroenterology and Hepatology
      Scottsdale, AZ, United States
  • 2008–2011
    • Connecticut Children's Medical Center
      Hartford, Connecticut, United States
    • The Ohio State University
      Columbus, Ohio, United States
  • 2010
    • Nationwide Children's Hospital
      Columbus, Ohio, United States
  • 2009
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
    • Albany Medical College
      Albany, New York, United States
  • 2007
    • Children's Hospital of Eastern Ontario
      • Department of Pediatrics
      Ottawa, Ontario, Canada
  • 1996–2007
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2002
    • Royal Free London NHS Foundation Trust
      Londinium, England, United Kingdom