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Biomedical subjects

Edward V Loftus

Publications and source records attributed to Edward V Loftus.

At least 55 records · Page 3Linked to original sources
PubMed2004

Venous thromboembolism in inflammatory bowel disease.

OBJECTIVES: Venous thromboembolism has been associated with inflammatory bowel disease (IBD). We sought to describe the clinical features, acquired and congenital risk factors, and outcomes of venous thromboembolism in IBD. METHODS: All patients with confirmed IBD and deep venous thrombosis (DVT) or pulmonary embolism (PE) at our institution between 1991 and 2000 were identified. Medical records were abstracted for clinical features, risk factors, treatment, and outcomes. RESULTS: Fifty-nine ulcerative colitis (UC) patients (68% males) and 39 Crohn's disease (CD) patients (41% males) were identified. UC extent was pancolonic in 76%, and CD extent was ileocolonic in 56%, colonic in 23%, and ileal in 21%. Eighty percent of CD patients and 79% of UC patients had active disease. Thrombophilia was present in 33% of the 40 patients tested. Most patients (87%) had other risk factors for DVT/PE. Long-term treatment included warfarin alone (62%), warfarin and IVC filter (18%), and IVC filter alone (7%). Five CD patients (13%) had recurrent DVT/PE. Among the 16 UC patients who underwent proctocolectomy following DVT/PE, there were two recurrences (13%), similar to the three recurrences (10%) seen among the 29 patients who had intact colons. Mortality rate was 22% after a median follow-up of 1.8 yr. CONCLUSIONS: Venous thromboembolism is a serious complication of IBD that may lead to death. Thrombophilia evaluations have a relatively high diagnostic yield overall, although specific genetic abnormalities are individually uncommon. Other DVT/PE risk factors are usually present. Proctocolectomy is not protective of recurrent DVT/PE.

Adolescent↗
PubMed2004

The safety profile of infliximab in patients with Crohn's disease: the Mayo clinic experience in 500 patients.

BACKGROUND AND AIMS: The aim of this study was to evaluate the short- and long-term safety of infliximab in patients with Crohn's disease in clinical practice. METHODS: The medical records of 500 consecutive patients treated with infliximab at the Mayo Clinic were reviewed and abstracted for demographic features and adverse events. The likelihood of a causal relationship to infliximab for each adverse event was determined by calculating an intrinsic likelihood (imputability) score. RESULTS: The 500 patients received a median of 3 infusions and had a median follow-up of 17 months. Forty-three patients (8.6%) experienced a serious adverse event, of which 30 (6%) were related to infliximab. Acute infusion reactions occurred in 19 of 500 patients (3.8%). Serum sickness-like disease occurred in 19 of 500 patients and was attributed to infliximab in 14 (2.8%). Three patients developed drug-induced lupus. One patient developed a new demyelination disorder. Forty-eight patients had an infectious event, of which 41 (8.2%) were attributed to infliximab. Twenty patients had a serious infection: 2 had fatal sepsis, 8 had pneumonia (of which 2 cases were fatal), 6 had viral infections, 2 had abdominal abscesses requiring surgery, one had arm cellulitis, and one had histoplasmosis. Nine patients had a malignant disorder, 3 of which were possibly related to infliximab. A total of 10 deaths were observed. For 5 of these patients (1%), the events leading to death were possibly related to infliximab. CONCLUSIONS: Short- and long-term infliximab therapy is generally well tolerated. However, clinicians must be vigilant for the occurrence of infrequent but serious events, including serum sickness-like reaction, opportunistic infection and sepsis, and autoimmune disorders.

Adolescent↗
PubMed2004

Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences.

Although the incidence and prevalence of ulcerative colitis and Crohn's disease are beginning to stabilize in high-incidence areas such as northern Europe and North America, they continue to rise in low-incidence areas such as southern Europe, Asia, and much of the developing world. As many as 1.4 million persons in the United States and 2.2 million persons in Europe suffer from these diseases. Previously noted racial and ethnic differences seem to be narrowing. Differences in incidence across age, time, and geographic region suggest that environmental factors significantly modify the expression of Crohn's disease and ulcerative colitis. The strongest environmental factors identified are cigarette smoking and appendectomy. Whether other factors such as diet, oral contraceptives, perinatal/childhood infections, or atypical mycobacterial infections play a role in expression of inflammatory bowel disease remains unclear. Additional epidemiologic studies to define better the burden of illness, explore the mechanism of association with environmental factors, and identify new risk factors are needed.

Appendectomy↗
PubMed2004

Small intestinal adenocarcinoma in Crohn's disease: a case-control study.

BACKGROUND: Small bowel adenocarcinoma is an uncommon complication of Crohn's disease. We sought to describe the clinical features, outcomes, and risk factors of small bowel adenocarcinoma in Crohn's disease. METHODS: A centralized diagnostic index identified all patients with Crohn's disease with small bowel adenocarcinoma evaluated at our institution between 1976 and 2000, and the medical records were abstracted. Two controls with Crohn's disease were selected for each case, matched by gender and age. RESULTS: Nine cases (four males) were identified. The patients presented with abdominal pain (89%), obstruction (89%), and weight loss (78%). Cancer was located in the ileum in 8 patients (89%) and the jejunum in 1 patient (11%). All cases but 1 had either lymph node involvement or metastasis. All cases had surgery, with 1 receiving adjuvant chemotherapy. No significant risk factors were found. The mortality rates at 1 and 2 years were 42% and 61%. CONCLUSIONS: Small bowel adenocarcinoma is a rare complication of Crohn's disease that typically involves the ileum. Affected patients have symptomatic, advanced malignancies upon diagnosis. No significant risk factors were identified.

Adenocarcinoma↗
PubMed2004

Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study.

BACKGROUND: Genetic factors may play a role in determining the development of extraintestinal manifestations (EIMs) and autoimmune diseases (AD) in patients with inflammatory bowel disease (IBD). We sought to determine the association between EIMs and AD in patients with first-degree familial IBD and sporadic IBD. METHODS: All patients evaluated in the IBD Clinic at the Mayo Clinic between January and September 1999 were offered enrollment. One clinic patient who was matched on age, gender, and geographic area of residence to each case served as controls. Information regarding EIMs and AD was obtained from a questionnaire completed by all IBD patients and controls. The adjusted odds ratios (95% CIs) for EIM as a function of first-degree familial IBD compared with sporadic IBD and AD as a function of first-degree familial IBD compared with sporadic IBD were estimated with a matched one-to-one conditional logistic regression model. RESULTS: Two hundred forty-three patients with IBD (47 first-degree familial IBD, 196 sporadic IBD) were enrolled. Forty percent of IBD patients had one or more EIMs compared with 14% matched controls [p < 0.001; OR = 3.1 (95% CI: 1.8 to 5.2)]. A total of 259 of the 1122 IBD patients and their first-degree family members indicated one or more EIM diagnoses (23%). The association between "familial versus sporadic" status and any EIM diagnosis was not significant [p = 0.59, the odds for an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.2 (95% CI: 0.8 to 1.7)]. Ten percent of IBD patients had one or more AD diagnoses compared with 19% matched controls [p = 0.04; OR = 0.4 (95% CI: 0.1 to 0.96)]. A total of 153 of the 1122 IBD patients and their first-degree family members indicated one or more AD diagnoses (14%). The association between disease status ("familial or sporadic") versus any AD diagnosis was not significant [p = 0.68, the odds for any AD in an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.4 (95% CI: 0.9 to 2.3)]. CONCLUSIONS: There was a positive association between IBD status (patient vs control) versus EIM, but not AD. A significant positive association between disease type (familial or sporadic) versus either EIM or AD was not detected.

Adolescent↗
PubMed2004

The diagnostic yield of stool pathogen studies during relapses of inflammatory bowel disease.

GOALS: We sought to determine the yield of stool analysis for bacterial culture, ova and parasites, and Clostridium difficile toxin in suspected relapses of inflammatory bowel disease (IBD). BACKGROUND: The diagnostic yield of such stool studies has not been examined recently in the United States. STUDY: The medical records of consecutive IBD patients who underwent stool testing for relapses at our institution between July 1, 2000, and November 25, 2001, were abstracted for demographics, stool test results, recent antibiotic exposure, and hospitalization. RESULTS: Fifty-four patients were evaluated during 62 relapses with 99 stool samples. Twelve stool tests were positive. C. difficile accounted for the majority of positive tests (10/12). Of these, 9 (90%) were associated with antibiotic use in the prior month versus 10 (22%) in the C. difficile-negative group (P < 0.001). Hospitalization, prednisone use, or sulfasalazine use did not differ significantly with C. difficile status. Eight C. difficile-positive patients improved clinically with targeted antibiotic therapy. Two bacterial cultures (4%) were positive for Campylobacter jejuni and Plesiomonas shigelloides. CONCLUSION: Stool studies yielded a pathogen, mainly C. difficile, in 20% of the relapsing IBD patients. Antibiotic use was significantly associated with a positive C. difficile toxin. Toxin-positive patients improved clinically with targeted antibiotics.

Adult↗
PubMed2004

Early postoperative complications are not increased in patients with Crohn's disease treated perioperatively with infliximab or immunosuppressive therapy.

AIM: The aim was to determine whether the use of steroids, immunosuppressive agents, or infliximab prior to abdominal surgery for Crohn's disease is associated with an increased rate of early postoperative complications. METHODS: All patients who underwent abdominal surgery for Crohn's disease between October 1998 and December 2001 were identified. Medical records were abstracted for demographics, location and duration of disease, use of infliximab within 8 wk before and 4 wk after surgery, and dose and duration of corticosteroids, azathioprine/6-mercaptopurine, and methotrexate. Steroid use was defined as: high (intravenous or oral >/=40 mg/day), moderate (oral >/=20 mg/day for at least 2 months), low (oral <20 mg/day or oral >20 mg/day for <2 months), or none. Early (within 30 days postinfliximab) septic and nonseptic complications were identified. Septic complications included wound sepsis, intraabdominal, and extraabdominal infections. Nonseptic complications included Crohn's disease recurrence, small bowel obstruction, gastrointestinal bleeding, and thromboembolism. A logistic regression analysis assessed the association between perioperative therapy with infliximab, corticosteroids, or immunosuppressive therapy and subsequent occurrence of septic complications and separately overall complications. RESULTS: Two hundred and seventy patients were operated upon including 107 patients who received steroids (34 low dose, 34 moderate dose, 43 high dose), 105 patients who received immunosuppressives (64 azathioprine, 38 6-mercaptopurine, 4 methotrexate), and 52 who received infliximab. Forty-eight patients underwent urgent or emergent surgery and 222 underwent elective surgery. Septic complications occurred in 52 of 270 (19%) patients including wound sepsis in 28 (10%), anastomotic leak in 9 (3%), intraabdominal abscess in 5 (2%), and extraabdominal infections in 19 (7%). Nonseptic complications occurred in 18 of 270 (7%) patients. Preoperative use of high- or moderate-dose steroids, immunosuppressives, or infliximab was not associated with greater complication rates. No deaths occurred. CONCLUSION: Early complications after elective abdominal surgery for CD are not associated with steroid dose, immunosuppressive therapy, or infliximab use.

Adolescent↗
PubMed2004

An open-label study of the human anti-TNF monoclonal antibody adalimumab in subjects with prior loss of response or intolerance to infliximab for Crohn's disease.

BACKGROUND: We assessed the tolerability and clinical benefit of adalimumab, a human antibody to tumor necrosis factor (TNF), in patients with Crohn's disease who had previously received and responded to the chimeric anti-TNF antibody infliximab, but who no longer had a sustained response and/or tolerance to infliximab. METHODS: A total of 24 patients with Crohn's disease who had lost responsiveness or developed intolerance (acute or delayed infusion reactions) to infliximab were enrolled in a 12-wk uncontrolled trial and treated with subcutaneous adalimumab 80 mg at week 0 and then 40 mg every other week starting at week 2. After week 4, the dose could be escalated to 40 mg weekly in patients who did not achieve clinical remission, complete fistula closure, and complete steroid withdrawal. Outcome measures included the ability to tolerate adalimumab and clinical remission (defined as a Crohn's disease activity index (CDAI) score < or =150 points) and clinical response (defined as a decrease in the CDAI) > or =100 points) in patients who had a baseline CDAI score > or =220. RESULTS: None of the patients experienced acute or delayed hypersensitivity reactions during treatment with adalimumab (including 14 who previously experienced treatment-limiting acute hypersensitivity reactions and 6 who previously experienced delayed hypersensitivity reactions with infliximab). Of 17 patients with baseline CDAI scores > or =220: clinical remission occurred at weeks 4 and 12 in 2 (12%) and 5 (29%), respectively; and clinical response occurred in 7 (41%) and 10 (59%), respectively. Nineteen patients (79%) escalated their dose during weeks 4-6. CONCLUSIONS: Adalimumab is well tolerated and appears to be a clinically beneficial option for patients with Crohn's disease who have previously lost their response to, or cannot tolerate infliximab.

Adalimumab↗
PubMed2003

Microscopic colitis: epidemiology and treatment.

Microscopic colitis, a chronic diarrheal condition, is characterized by colonic intraepithelial lymphocytosis, expansion of the lamina propria with acute and chronic inflammatory cells, and preserved crypt architecture. These changes, in association with a thickened subepithelial collagen band, are termed collagenous colitis, whereas changes occurring without a thickened collagen band are classified as lymphocytic colitis. Population-based epidemiologic studies confirm that microscopic colitis is most frequently diagnosed in middle-aged or elderly women and that its incidence is rising. Although these disorders diminish patients' quality of life, they are not associated with an increased risk of colorectal cancer, and survival is not diminished. Clinical and histologic improvement after therapy have been noted in one randomized trial of bismuth subsalicylate and three randomized clinical trials of oral delayed-release budesonide. A treatment algorithm for microscopic colitis is proposed.

Chronic Disease↗
PubMed2003

Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community.

BACKGROUND & AIMS: The epidemiology of primary sclerosing cholangitis (PSC) in the United States is unknown. We report the incidence, clinical spectrum, and outcomes of PSC in Olmsted County, Minnesota. METHODS: Using the Rochester Epidemiology Project, a medical records linkage system in Olmsted County, Minnesota, we identified county residents with PSC, and the diagnosis was confirmed according to clinical, biochemical, radiographic, and histologic criteria. RESULTS: Twenty-two patients met diagnostic criteria for PSC in 1976-2000. The age-adjusted (to 2000 U.S. whites) incidence of PSC in men was 1.25 per 100,000 person-years (95% CI, 0.70 to 2.06) compared with 0.54 per 100,000 person-years (95% CI, 0.22 to 1.12) in women. The prevalence of PSC in 2000 was 20.9 per 100,000 men (95% CI, 9.5 to 32.4) and only 6.3 per 100,000 women (95% CI, 0.1 to 12.5). Seventy-three percent of cases had inflammatory bowel disease, the majority with ulcerative colitis. Survival among PSC patients was significantly less than expected for the Minnesota white population of similar age and gender (P < 0.001). CONCLUSIONS: These data represent the first population-based estimates of the incidence and prevalence of PSC in the United States. The incidence and prevalence of PSC were approximately one third of those previously described for primary biliary cirrhosis in the same population. Our data suggest that the prevalence of PSC in the United States, with its attendant medical burdens, is significantly greater than previously estimated.

Adult↗
PubMed2003

Risk of fracture in ulcerative colitis: a population-based study from Olmsted County, Minnesota.

BACKGROUND & AIMS: Osteopenia is common in patients with ulcerative colitis (UC), but less is known about fracture risk. Previously we were unable to demonstrate increased fractures in a population-based cohort with Crohn's disease. METHODS: Medical records of 273 Olmsted County, Minnesota residents initially diagnosed with UC in 1940-1993 were reviewed for evidence of subsequent fractures, as were records of a control cohort of county residents matched on age and gender. Cumulative fracture incidence after diagnosis was estimated by using the Kaplan-Meier method. The hazard ratio of fracture in cases relative to control subjects was estimated by Cox proportional hazards regression, which was also used to evaluate potential risk factors for fracture. RESULTS: Median follow-up was 13 years (range, 1 day-53 years). The cumulative incidence of any fracture from time of diagnosis was 40% at 25 years versus 42% in control subjects (P=0.615). The hazard ratio in cases compared to control subjects was 1.1 (95% confidence interval, 0.8-1.6) for any fracture and 1.3 (95% confidence interval, 0.6-2.8) for any osteoporotic fracture (hip, spine, or wrist as a result of moderate trauma). Other causes of secondary osteoporosis were associated with increased fracture risk, whereas estrogen use was protective. One hundred three cases received any corticosteroids (38%), and 34 (12%) had taken corticosteroids for 6 months or longer. Corticosteroids and bowel resection were not associated with fracture risk. CONCLUSIONS: In this population-based cohort of patients with UC, fracture risk was not elevated relative to matched community control subjects. Use of corticosteroids did not appear to significantly influence the risk of fracture.

Adolescent↗
PubMed2003

Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis.

BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) has shown effectiveness as a colon cancer chemopreventive agent in preclinical studies. In addition, a recent report suggests that it also may decrease the risk for developing colorectal dysplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We sought to evaluate the effect of UDCA on colorectal neoplasia in a group of patients with UC and PSC enrolled in a randomized, placebo-controlled trial. METHODS: From a prior, randomized, placebo-controlled trial of UDCA therapy in PSC at our center, we followed-up patients with concomitant UC to assess the effect of UDCA on the development of colorectal dysplasia and cancer as compared with placebo. RESULTS: Fifty-two subjects were followed-up for a total of 355 person-years. Those originally assigned to receive UDCA had a relative risk of 0.26 for developing colorectal dysplasia or cancer (95% confidence interval, 0.06-0.92; P = 0.034). Many of the patients originally assigned to the placebo group eventually received open-label UDCA. Assigning these patients to the UDCA group from the time they began active therapy did not change the magnitude of the protective effect (relative risk, 0.26; 95% confidence interval, 0.07-0.99; P = 0.049). CONCLUSIONS: UDCA significantly decreases the risk for developing colorectal dysplasia or cancer in patients with UC and PSC.

Adult↗
PubMed2003

Management of Crohn's disease of the ileoanal pouch with infliximab.

OBJECTIVES: The occurrence of Crohn's disease (CD) in a patient with an ileal-pouch anastomosis (IPAA) often results in severe morbidity and significant chance of reservoir loss. We report our experience of the use of infliximab in these patients. METHODS: Medical records of 26 patients with an IPAA and CD-related complications were reviewed. The median time between the IPAA and the diagnosis of CD was 4.5 yr (range 0.1-16 yr). The main reasons for changing the original ulcerative colitis diagnosis to CD were complex perianal or pouch fistulizing disease in 14 patients (54%), prepouch ileitis in five (19%), and both prepouch ileitis and complex fistula in seven (27%). Patients received one to three doses of infliximab over 8 wk as induction therapy. Subsequently the patients received a variable number of maintenance infusions. RESULTS: At a short term follow-up, 16/26 patients (62%) had a complete response, six of 26 (23%) had a partial response, and four of 26 (15%) had no response. Information regarding long term follow-up was available in 24 patients. After a median follow-up of 21.5 months (range 3-44 months), eight patients (33%) either had their pouch resected or had a persistent diverting ileostomy. The pouch was functional in 16/24 (67%) patients, with either good (n = 7) or acceptable (n = 7) clinical results in 14/24 (58%). Of those 14 patients, 11 were under long term, on demand, or systematic maintenance treatment with infliximab. CONCLUSIONS: Infliximab is beneficial in both the short and long term treatment of patients with an IPAA performed for a presumed diagnosis of ulcerative colitis who subsequently develop CD-related complications. Good pouch function requires long term treatment with infliximab in most patients.

Adolescent↗
PubMed2002

Epidemiology of inflammatory bowel disease.

The incidence of IBD has either continued to increase or has stabilized at a high rate in most developed countries, whereas the incidence continues to rise in regions where IBD had been less common. The prevalence has continued to increase as a result of a combination of previously rising incidence and improved survival. Regardless of the exact prevalence, the burden of disease in North America and Europe is significant. Studying the patterns of geographic variation and age and gender distribution may yield important clues to the cause of IBD.

Female↗
PubMed2002

Epstein-Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine.

BACKGROUND & AIMS: The use of azathioprine and 6-mercaptopurine for inflammatory bowel disease increased in the early 1990s. We sought to determine the effect of this change in therapy on the risk of lymphoma in patients with inflammatory bowel disease. METHODS: All patients with inflammatory bowel disease at a single tertiary care medical center who developed lymphoma between 1985-2000 were identified and the pathologic features of the lymphoma including presence of Epstein- Barr virus were determined. The patients were divided into two 8-year periods (1985-1992, 1993-2000) corresponding with the introduction of azathioprine and 6-mercaptopurine in 1993. RESULTS: Eighteen patients with lymphoma were identified, 6 between 1985-1992 and 12 between 1993-2000. Six of 18 lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine, all between 1993-2000. Seven patients developed Epstein-Barr virus-positive lymphoma (1 from 1985-1992, 6 from 1993-2000). Five of 7 Epstein-Barr virus-positive lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine compared with 1 of 11 Epstein-Barr virus-negative lymphomas (P = 0.01). Approximately 1200 patients with inflammatory bowel disease were treated with these agents between 1993-2000. CONCLUSIONS: Treatment of inflammatory bowel disease with azathioprine or 6-mercaptopurine appears to be associated with a small increased risk of Epstein-Barr virus-positive lymphoma.

Adult↗