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Miguel Regueiro

Publications and source records attributed to Miguel Regueiro.

14 recordsLinked to original sources
PubMed2006

A genome-wide association study identifies IL23R as an inflammatory bowel disease gene.

The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.

Alleles↗
PubMed2006

Infliximab for hospitalized patients with severe ulcerative colitis.

To evaluate the efficacy of infliximab in hospitalized ulcerative colitis (UC) patients refractory to intravenous corticosteroids. Treatment options for steroid-refractory UC patients are limited and include cyclosporine and colectomy. Although two recent studies (ACT I/II) demonstrate a benefit from infliximab in outpatients with moderate to severely active UC, the utility of infliximab in severe i.v. steroid-refractory UC is less clear. We report our open-label experience with infliximab in hospitalized UC patients at the University of Pittsburgh Medical Center. All hospitalized UC patients who had received infliximab were identified. Age, sex, extent of UC, duration of disease, concomitant medication, hospital course, and response to infliximab were recorded. Response to infliximab was defined as avoidance of colectomy and cessation of corticosteroids. There were 12 UC inpatients refractory to intravenous corticosteroids and subsequently treated with infliximab. Nine of the 12 patients (75%) failed to respond to infliximab and required a colectomy; median time to colectomy was 3 months. Three patients (25%) did respond to infliximab and were able to withdraw from corticosteroids. In this open-label analysis, infliximab was not effective for the majority of UC patients refractory to intravenous corticosteroids. Whether earlier use of infliximab would prevent the need for hospitalization and colectomy is uncertain.

Adult↗
PubMed2006

Medical management of left-sided ulcerative colitis and ulcerative proctitis: critical evaluation of therapeutic trials.

BACKGROUND: The goal of this work was to critically evaluate the published studies on the treatment of ulcerative proctitis (UP) and left-sided ulcerative colitis (L-UC). The results of this review provided the content for the accompanying treatment guidelines, Clinical Guidelines for the Medical Management of Left-sided Ulcerative Colitis and Ulcerative Proctitis: Summary Statement. METHODS: All English language articles published between 1995 and September 2005 were identified through a comprehensive literature search using OVID and PubMed. The quality of the data supporting or rejecting the use of specific therapies was categorized by a data quality grading scale. An "A+" grade was assigned to treatment supported by multiple high-quality randomized controlled trials with consistent results, whereas a "D" grade was given to therapy supported only by expert opinion. The therapeutic efficacy of a treatment was defined by its success in treating UP and L-UC compared with placebo. A medication was ranked as "excellent" if it was specifically studied for UP and L-UC and had consistently positive results compared with placebo or another agent. Quality and efficacy scores were agreed on by author consensus. RESULTS: For the acute treatment of UP or L-UC, the rectally administered corticosteroids and mesalazine (5-ASA), either alone or in combination with oral 5-ASAs, are the most effective therapy: evidence quality, A+; efficacy, excellent. Only rectally administered 5-ASA received an A+/excellent rating for maintenance of remission. Infliximab received an A+ grade for induction and maintenance of remission but only a "good" rating because the studies were performed in all UC, not specifically UP or L-UC. CONCLUSIONS: This critical evaluation of treatment provides a "report card" on medications available for the management of patients with UP and L-UC. The guidelines should provide a useful reference and supplement for physicians treating UC patients.

Adrenal Cortex Hormones↗
PubMed2006

Clinical guidelines for the medical management of left-sided ulcerative colitis and ulcerative proctitis: summary statement.

There are few published guidelines for the treatment of inflammatory bowel disease. Physicians choose therapy based on evidence-based data, peer and expert opinion, and personal experience. This article provides treatment guidelines for the induction and maintenance of ulcerative proctitis and left-sided colitis and the management of disease refractory to 5-aminosalicylic acid (5-ASA) compounds and corticosteroids The guidelines are derived from evidence-based data and, when lacking, expert opinion or the authors' experience. The comprehensive review of the literature is presented in the accompanying article, "The Medical Management of Left-Sided Ulcerative Colitis and Ulcerative Proctitis: Critical Evaluation of Therapeutic Trials". Rectally administered 5-ASA and corticosteroid suppositories are effective treatment for most ulcerative proctitis patients. Corticosteroid and 5-ASA enemas, which reach the splenic flexure of the colon, are recommended for patients with left-sided ulcerative colitis. The combination of rectally administered 5-ASA enemas and oral 5-ASA agents may afford better treatment of left-sided colitis and possibly prevent proximal extension of disease. Patients refractory to 5-ASAs and corticosteroids may require an immunomodulator or biological response modifier therapy. Those who have ongoing signs and symptoms of ulcerative proctitis and left-sided ulcerative colitis despite maximal medical therapy require a proctocolectomy.

Adrenal Cortex Hormones↗
PubMed2006

Systemic mastocytosis mimicking inflammatory bowel disease: A case report and discussion of gastrointestinal pathology in systemic mastocytosis.

Gastrointestinal (GI) symptoms are present in up to 80% of patients with systemic mastocytosis (SM). GI symptoms include mainly abdominal pain, diarrhea, nausea, and vomiting. It is believed that most of the GI symptoms are due to the secondary effect of mast cell mediators on the GI tract. Direct involvement of the GI tract by neoplastic mast cell infiltration has not been well documented. We report a case of SM that initially mimicked inflammatory bowel disease based on clinical, radiographic, endoscopic, and histopathologic findings. On routine histologic sections of small bowel and colonic mucosal biopsies, there was expansion of the lamina propria by mononuclear inflammatory cells, foci of erosions with associated acute inflammation, and evidence of chronic mucosal injury with architectural distortion and gland foreshortening. Only on repeat biopsies and with ancillary tests for mast cells was a diagnosis of SM made, with extensive involvement of the GI tract. This is the first reported case of SM presenting as and mimicking inflammatory bowel disease. It is critical that clinicians and pathologists are aware that neoplastic mast cells in patients with SM can infiltrate the mucosa throughout the GI tract and that this infiltration can lead to symptoms and findings that can mimic inflammatory bowel disease.

Colonoscopy↗
PubMed2006

Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort.

OBJECTIVES: Inflammatory bowel disease (IBD), comprising primarily of Crohn's disease (CD) and ulcerative colitis (UC), is increasingly prevalent in racial and ethnic minorities. This study was undertaken to characterize racial differences in disease phenotype in a predominantly adult population. METHODS: Phenotype data on 830 non-Hispanic white, 127 non-Hispanic African American, and 169 Hispanic IBD patients, recruited from six academic centers, were abstracted from medical records and compiled in the NIDDK-IBD Genetics Consortium repository. We characterized racial differences in family history, disease location and behavior, surgical history, and extraintestinal manifestations (EIMs) using standardized definitions. RESULTS: African American CD patients were more likely than whites to develop esophagogastroduodenal CD (OR = 2.8; 95% CI: 1.4-5.5), colorectal disease (OR = 1.9; 95% CI: 1.1-3.4), perianal disease (OR = 1.7; 95% CI: 1.03-2.8), but less likely to have ileal involvement (OR = 0.55; 95% CI: 0.32-0.96). They were also at higher risk for uveitis (OR = 5.5; 95% CI: 2.3-13.0) and sacroiliitis (OR = 4.0; 95% CI: 1.55-10.1). Hispanics had higher prevalence of perianal CD (OR = 2.9; 95% CI: 1.8-4.6) and erythema nodosum (3.3; 95% CI: 1.7-6.4). Among UC patients, Hispanics had more proximal disease extent. Both African American and Hispanic CD patients, but not UC patients, had lower prevalences of family history of IBD than their white counterparts. CONCLUSIONS: There are racial differences in IBD family history, disease location, and EIMs that may reflect underlying genetic variations and have important implications for diagnosis and management of disease. These findings underscore the need for further studies in minority populations.

Adult↗
PubMed2005

Cigarette smoking and age at diagnosis of inflammatory bowel disease.

OBJECTIVES: The incidence and age of onset of inflammatory bowel disease (IBD) appear to be changing. The aim of this study was to determine whether the prevalence of cigarette smoking differs among patients with Crohn's disease (CD) or ulcerative colitis (UC) at the time of diagnosis compared with the general population and whether smoking history is related to the type and age of IBD onset. METHODS: Prevalence rates of smoking at the time of IBD diagnosis were compared between patients with CD and UC from the IBD Center at the University of Pittsburgh Medical Center versus age-, gender-, and time period-adjusted rates in the Pennsylvania general population. Analyses also were stratified by gender and diagnoses before and after 40 years of age, i.e., early and late onset. RESULTS: There were 263 IBD patients (144 UC patients and 119 CD patients) seen in the IBD center between August 2000 and December 2002. The prevalence of active smoking was significantly higher at diagnosis in CD patients compared with the Pennsylvania general population (33% versus 24%, P = 0.04), particularly in those with CD onset at 40 years of age or later (47% versus 27%, P = 0.005). In contrast, smoking prevalence was significantly lower in UC patients than the general population (9% versus 28%, P < 0.0001), particularly among those with UC onset before the age of 40 years (6% versus 27%, P < 0.0001). Smoking cessation was associated with an approximate, but nonsignificant, 3-fold higher likelihood of late-onset UC compared with CD. CONCLUSIONS: Cigarette smoking is associated with the development of late-onset CD and is protective against developing UC at any age, particularly early onset. Former smoking is associated with a high likelihood of developing late-onset UC, but not CD.

Adult↗
PubMed2003

Treatment of perianal fistulizing Crohn's disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement.

Perianal fistulas occur in approximately 30% of patients with Crohn's disease (CD). Infliximab, a chimeric monoclonal antibody targeting human tumor necrosis factor alpha (TNF), is approved for the treatment of fistulizing CD. Although the initial response to infliximab is dramatic, the median duration of fistula closure is approximately 3 months, and repeated infusions are often required. An exam under anesthesia (EUA) by a surgeon allows for complete inspection of the fistula as well as incision and drainage of an abscess and placement of a seton. Our aim was to compare the rate of perianal fistula healing, relapse rate, and time to relapse in patients with fistulizing CD treated with infliximab alone or as an adjunct to surgical EUA with seton placement. Thirty-two consecutive patients with perianal fistulizing CD who completed at least 3 infusions with infliximab (5 mg/kg at 0, 2, 6 weeks) between October 1999 and October 2001 were analyzed. All patients had at least 3 months of follow-up after the third dose of infliximab. Response was defined as complete closure and cessation of drainage from the fistula. Patients with CD and perianal fistulas who had an EUA prior to infliximab infusions had a better initial response (100% vs. 82.6%, p = 0.014), lower recurrence rate (44% vs. 79%, p = 0.001), and longer time to recurrence (13.5 months vs. 3.6 months, p = 0.0001) compared with patients receiving infliximab alone. In conclusion, patients with fistulizing CD treated with infliximab are more likely to maintain fistula closure if treatment is preceded by EUA and seton placement.

Adolescent↗
PubMed2003

Infliximab for treatment of pyoderma gangrenosum associated with inflammatory bowel disease.

OBJECTIVES: Pyoderma gangrenosum is an immune-mediated inflammatory condition characterized by ulcerative skin lesions affecting 1-2% of patients with inflammatory bowel disease (IBD). Treatment includes wound care, antibiotics, corticosteroids, and immunomodulators. However, response to therapy varies, and many patients with pyoderma gangrenosum have disease that is refractory to these agents. The aim of this study was to assess the response of medically refractory pyoderma gangrenosum to infliximab. METHODS: This was a multicenter retrospective study of patients with IBD and medically refractory pyoderma gangrenosum treated with infliximab. Data collected included the following: baseline demographics; duration of IBD; history of bowel resection; duration of skin lesions; number, size, and location of pyoderma gangrenosum lesions; prior medications; dose and number of infliximab infusions; bowel activity before and after infliximab; pyoderma gangrenosum activity before and after infliximab therapy; time to response and time to healing of pyoderma gangrenosum lesions; recurrence of pyoderma gangrenosum after infliximab; corticosteroid taper; and adverse reactions to infliximab. RESULTS: There were 13 patients with moderate to severe pyoderma gangrenosum and IBD treated with infliximab. All patients demonstrated complete healing of the skin lesions. Three patients had a complete response to induction infliximab therapy and did not require additional treatment. Ten patients responded to induction infliximab and have maintained pyoderma gangrenosum healing with infusions every 4-12 wk. All patients receiving corticosteroids were able to discontinue them completely after institution of infliximab treatment. Infliximab was well tolerated; the only treatment-related adverse events were sunburn in one patient and an infusion reaction in another. CONCLUSIONS: Infliximab is a safe and effective treatment for IBD-associated pyoderma gangrenosum.

Adult↗
PubMed2002

Pathologic features of early inflammatory bowel disease.

Often the pathologic changes of IBD are subtle and may not be present in a proportion of biopsy specimens. In cases of early disease, the changes may be missed, and additional specimens should be taken after a period of time. Modifying factors, such as prebiopsy treatment and coexisting disease, should be considered. A forum to review cases and allow for communication between gastroenterologists and pathologists is especially useful for clinicopathologic correlation and assignment of a working diagnosis to each case. Careful attention to the pathologic features of early UC and CD would be most useful when evaluating new therapies for IBD.

Biomarkers↗
PubMed2002

The role of endoscopy in the evaluation of fistulizing Crohn's disease.

Fistulas in Crohn's disease are classified as internal fistulas, for example, enteroenteric, enterovesical, rectovaginal, and external fistulas, for example, enterocutaneous, perianal, and parastomal. Although radiographic contrast studies are superior to endoscopy for diagnosing fistulas, endoscopic procedures have a definite role in the evaluation and management of fistulizing Crohn's disease. Endoscopy allows for tissue sampling, and provides information regarding the extent and severity of gastrointestinal inflammation, and the presence of such complications as strictures and cancer. Preoperative colonoscopy has particular value in assessing an enterocolonic fistula, and has important implications regarding the type of surgery performed. Endoscopic therapy for Crohn's fistula is less certain, but may allow for dilation of associated strictures, and may someday serve as a better delivery system for targeted anticytokine and immunologically based therapy.

Crohn Disease↗
PubMed2002

Determination of thiopurine methyltransferase genotype or phenotype optimizes initial dosing of azathioprine for the treatment of Crohn's disease.

BACKGROUND: although azathioprine (AZA) is an effective immunomodulator in treating Crohn's disease, some patients develop leukopenia and risk severe infections. Thiopurine methyltransferase (TPMT) is an enzyme responsible for the metabolism of AZA, and its activity is inversely related to the risk of developing acute leukopenia. GOALS: the aim of this retrospective study is to determine whether initial AZA dosing based on TPMT genotype or phenotype alters the likelihood of developing acute leukopenia. STUDY: between January 2000 and February 2001, 71 patients with Crohn's disease considered for AZA therapy and with a recorded TPMT genotype or phenotype were identified using a comprehensive text-oriented database at the University of Pittsburgh Medical Center, Presbyterian Hospital, Pittsburgh, PA. The baseline demographics, TPMT genotype or phenotype, initial dose of oral AZA, subsequent white blood counts, and complications that necessitated discontinuation of therapy were evaluated. RESULTS: of the 63 patients with normal TPMT activity, 45 were started on 2 to 2.5 mg/kg/d of AZA, seven received doses less than 2 mg/kg/d, and 11 did not start AZA. Of the eight patients with intermediate TPMT activity, seven were started on 1 to 1.5 mg/kg/d of AZA, and one did not receive treatment. None of the patients that received AZA developed acute leukopenia (< 3,000/mm ). CONCLUSIONS: patients with Crohn's disease and normal TPMT activity who were started on high-dose AZA (2-2.5mg /kg/d) and patients with intermediate enzyme activity who were started on reduced doses of AZA did not develop acute leukopenia.

Adolescent↗