William S. Harmsen

Risk Factors for Prosthetic Joint Infection: Case-Control Study

We conducted a matched case-control study to determine risk factors for the development of prosthetic joint infection. Cases were patients with prosthetic hip or knee joint infection. Controls were patients who underwent total hip or knee arthroplasty and did not develop prosthetic joint infection. A multiple logistic regression model indicated that risk factors for prosthetic joint infection were the development of a surgical site infection not involving the prosthesis (odds ratio [OR], 35.9; 95% confidence interval [CI], 8.3-154.6), a National Nosocomial Infections Surveillance (NNIS) System surgical patient risk index score of 1 (OR, 1.7; 95% CI, 1.2-2.3) or 2 (OR, 3.9; 95% CI, 2.0-7.5), the presence of a malignancy (OR, 3.1; 95% CI, 1.3-7.2), and a history of joint arthroplasty (OR, 2.0; 95% CI, 1.4-3.0). Our findings suggest that a surgical site infection not involving the joint prosthesis, an NNIS System surgical patient risk index score of 1 or 2, the presence of a malignancy, and a history of a joint arthroplasty are associated with an increased risk of prosthetic joint infection.

PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis

Background: Inflammatory bowel disease associated with primary sclerosing cholangitis (PSC-IBD) may have a high prevalence of rectal sparing, backwash ileitis, and colorectal neoplasia. Aims: To describe the clinical features and outcomes of PSC-IBD and compare these to a group of chronic ulcerative colitis (CUC) patients. Methods: The medical records of all patients with PSC-IBD evaluated at the Mayo Clinic Rochester between 1987 and 1992 were abstracted for information on endoscopic and histological features, colorectal neoplasia, surgery, and other clinical outcomes. Patients referred for colorectal neoplasia and those who did not undergo colonoscopy with biopsies were excluded. A control group of CUC patients matched for sex, duration of IBD at first clinic visit, and calendar year of first clinic visit was identified, and similar information was abstracted. Results: Seventy one PSC-IBD patients and 142 CUC patients without PSC were identified. Rectal sparing and backwash ileitis were more common in the PSC-IBD group (52% and 51%, respectively) than in controls (6% and 7%, respectively). Overall, colorectal neoplasia developed in 18 cases and 15 controls, including 11 cancers (seven cases and four controls). An increased risk of colorectal neoplasia or death was not detected in a matched analysis. Although the cumulative incidence of colorectal neoplasia was higher in cases (33%) than in controls (13%) at five years, this was of borderline statistical significance (p = 0.054, unmatched log rank test). Overall survival from first clinic visit was significantly worse among cases (79% v 97%) at five years (p<0.001, unmatched log rank test). Conclusion: PSC-IBD is frequently characterised by rectal sparing and backwash ileitis. Colorectal neoplasia develops in a substantial fraction and overall survival is worse. PSC-IBD may represent a distinct IBD phenotype.

Correlation of C-Reactive Protein With Clinical, Endoscopic, Histologic, and Radiographic Activity in Inflammatory Bowel Disease

Introduction: We sought to examine the relationship between C‐reactive protein (CRP) and clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease (IBD). Methods: All IBD patients at our institution between January 2002 and August 2003 who had a CRP, colonoscopy, and either small bowel follow‐through (SBFT) or CT enterography (CTE) performed within 14 days were identified. Clinical activity was assessed retrospectively through review of the medical record. Logistic regression was used in Crohns disease (CD) patients to estimate the odds ratio (OR) with 95% confidence intervals for an elevated CRP. Associations were assessed using Fisher exact test in ulcerative colitis (UC) patients due to small sample size. Results: One‐hundred four CD patients (46% males) and 43 UC and indeterminate colitis patients (44% males) were identified. In CD patients, moderate‐severe clinical activity (OR, 4.5; 95% CI, 1.1‐18.3), active disease at colonoscopy (OR, 3.5; 95% CI, 1.4‐8.9), and histologically severe inflammation (OR, 10.6; 95% CI; 1.1‐104) were all significantly associated with CRP elevation. Abnormal small bowel radiographic imaging was not significantly associated with CRP elevation. In UC patients, CRP elevation was significantly associated with severe clinical activity, elevation in sedimentation rate, anemia, hypoalbuminemia, and active disease at ileocolonoscopy, but not with histologic inflammation. Conclusions: CRP elevation in IBD patients is associated with clinical disease activity, endoscopic inflammation, severely active histologic inflammation (in CD patients), and several other biomarkers of inflammation, but not with radiographic activity.

Ulcerative colitis in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival

BACKGROUND There is significant geographic variation in the reported incidence of ulcerative colitis. AIMS To update the incidence and prevalence of ulcerative colitis in Olmsted County, Minnesota, examine temporal trends, and determine overall survival. PATIENTS All Olmsted County residents diagnosed with ulcerative colitis between 1940 and 1993 (incidence cases), and all residents with ulcerative colitis alive on 1 January 1991 (prevalence cases). METHODS Incidence and prevalence rates were adjusted using 1990 US census figures for whites. The effects of age, sex, and calendar year on incidence rates were evaluated using Poisson regression. Survival from diagnosis was compared with that expected for US north-central whites. RESULTS Between 1940 and 1993, 278 incidence cases were identified, for an adjusted incidence rate of 7.6 cases per 100 000 person years (95% confidence interval (CI), 6.7 to 8.5). On 1 January 1991, there were 218 residents with definite or probable ulcerative colitis, for an adjusted prevalence rate of 229 cases per 100 000 (95% CI, 198 to 260). Increased incidence rates were associated with later calendar years (p<0.002), younger age (p<0.0001), urban residence (p<0.0001), and male sex (p<0.003). Overall survival was similar to that expected (p>0.2). CONCLUSIONS The overall incidence rate of ulcerative colitis in Olmsted County increased until the 1970s, and remained stable thereafter. Incidence rates among men and urban residents were significantly higher. The prevalence rate in Rochester in 1991 was 19% higher than that in 1980. Overall survival was similar to that of the general population.

Prospective blinded evaluation of computed tomographic colonography for screen detection of colorectal polyps.

BACKGROUND & AIMS This study used a low lesion prevalence population reflective of the screening setting to estimate the sensitivity and specificity of computerized tomographic (CT) colonography for detection of colorectal polyps. METHODS This prospective, blinded study comprised 703 asymptomatic persons at higher-than-average risk for colorectal cancer who underwent CT colonography followed by same-day colonoscopy. Two of 3 experienced readers interpreted each CT colonography examination. RESULTS Overall lesion prevalence for adenomas >/=1 cm in diameter was 5%. Seventy percent of all lesions were proximal to the descending colon. With colonoscopy serving as the gold standard, CT colonography detected 34%, 32%, 73%, and 63% of the 59 polyps >/=1 cm for readers 1, 2, 3, and double-reading, respectively; and 35%, 29%, 57%, and 54% of the 94 polyps 5-9 mm for readers 1, 2, 3, and double-reading, respectively. Specificity for CT colonography ranged from 95% to 98% and 86% to 95% for >1 cm and 5-9-mm polyps, respectively. Interobserver variability was high for CT colonography with kappa statistic values ranging from -0.67 to 0.89. CONCLUSIONS In a low prevalence setting, polyp detection rates at CT colonography are well below those at colonoscopy. These rates are less than previous reports based largely on high lesion prevalence cohorts. High interobserver variability warrants further investigation but may be due to the low prevalence of polyps in this cohort and the high impact on total sensitivity of each missed polyp. Specificity, based on large numbers, is high and exhibits excellent agreement among observers.

Effect of Femoral Head Diameter and Operative Approach on Risk of Dislocation After Primary Total Hip Arthroplasty

BACKGROUND It has been postulated that use of a larger femoral head could reduce the risk of dislocation after total hip arthroplasty, but only limited clinical data have been presented as proof of this hypothesis. METHODS From 1969 to 1999, 21,047 primary total hip arthroplasties with varying femoral head sizes were performed at one institution. Patients routinely were followed at defined intervals and were specifically queried about dislocation. The operative approach was anterolateral in 9155 arthroplasties, posterolateral in 3646, and transtrochanteric in 8246. The femoral head diameter was 22 mm in 8691 of the procedures, 28 mm in 8797, and 32 mm in 3559. RESULTS One or more dislocations occurred in 868 of the 21,047 hips. The cumulative risk of first-time dislocation was 2.2% at one year, 3.0% at five years, 3.8% at ten years, and 6.0% at twenty years. The cumulative ten-year rate of dislocation was 3.1% following anterolateral approaches, 3.4% following transtrochanteric approaches, and 6.9% following posterolateral approaches. The cumulative ten-year rate of dislocation was 3.8% for 22-mm-diameter femoral heads, 3.0% for 28-mm heads, and 2.4% for 32-mm heads in hips treated with an anterolateral approach; 3.5% for 22-mm heads, 3.5% for 28-mm heads, and 2.8% for 32-mm heads in hips treated with a transtrochanteric approach; and 12.1% for 22-mm heads, 6.9% for 28-mm heads, and 3.8% for 32-mm heads in hips treated with a posterolateral approach. Multivariate analysis showed the relative risk of dislocation to be 1.7 for 22-mm compared with 32-mm heads and 1.3 for 28-mm compared with 32-mm heads. CONCLUSIONS In total hip arthroplasty, a larger femoral head diameter was associated with a lower long-term cumulative risk of dislocation. The femoral head diameter had an effect in association with all operative approaches, but the effect was greatest in association with the posterolateral approach.

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 Crohns disease is associated with an increased rate of early postoperative complications.METHODS:All patients who underwent abdominal surgery for Crohns 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 Crohns 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.

Risk factors associated with progression to intestinal complications of Crohn's disease in a population-based cohort

BACKGROUND AND AIMS We sought to assess the evolution of Crohns disease behavior in an American population-based cohort. METHODS Medical records of all Olmsted County, Minnesota residents who were diagnosed with Crohns disease from 1970 to 2004 were evaluated for their initial clinical phenotype, based on the Montreal Classification. The cumulative probabilities of developing structuring and/or penetrating complications were estimated using the Kaplan-Meier method. Proportional hazards regression was used to assess associations between baseline risk factors and changes in behavior. RESULTS Among 306 patients, 56.2% were diagnosed between the ages of 17 and 40 years. Disease extent was ileal in 45.1%, colonic in 32.0%, and ileocolonic in 18.6%. At baseline, 81.4% had nonstricturing nonpenetrating disease, 4.6% had stricturing disease, and 14.0% had penetrating disease. The cumulative risk of developing either complication was 18.6% at 90 days, 22.0% at 1 year, 33.7% at 5 years, and 50.8% at 20 years after diagnosis. Among 249 patients with nonstricturing, nonpenetrating disease at baseline, 66 changed their behavior after the first 90 days from diagnosis. Relative to colonic extent, ileal, ileocolonic, and upper GI extent were significantly associated with changes in behavior, whereas the association with perianal disease was barely significant. CONCLUSIONS In a population-based cohort study, 18.6% of patients with Crohns disease experienced penetrating or stricturing complications within 90 days after diagnosis; 50% experienced intestinal complications 20 years after diagnosis. Factors associated with development of complications were the presence of ileal involvement and perianal disease.

Esophageal Resection for Cancer of the Esophagus: Long-Term Function and Quality of Life

BACKGROUND Information on function and quality of life of long-term survivors after esophageal resection for carcinoma is limited. METHODS Between 1972 and 1990, 359 patients underwent esophagectomy for stage I or II esophageal carcinoma at Mayo Clinic. We evaluated long-term function and quality of life in 107 of these patients (81 men and 26 women) who survived 5 or more years. Median age at operation was 62 years (range, 30 to 81 years). The operation performed was an Ivor Lewis resection in 77 patients (72%), transhiatal esophagectomy in 14 (13%), extended esophagectomy in 4 (4%), thoracoabdominal esophagectomy in 4 (4%), and other in 8 (7%). Adenocarcinoma was present in 72 patients (67%), squamous cell carcinoma in 28 (26%), and other in 7 (7%). Thirty-four patients (32%) were in postsurgical stage I, 65 (61%) in stage IIA, and 8 (8%) in stage IIB. Median survival was 10.2 years (range, 5.0 to 23.2 years). Follow-up was complete for all patients. RESULTS Gastroesophageal reflux was present in 64 patients (60%), symptoms of dumping in 53 (50%), and dysphagia to solid food in 27 (25%). Seventeen patients (16%) were asymptomatic. Factors affecting late functional outcome were analyzed. Patients who had a cervical anastomosis had significantly fewer reflux symptoms (p < 0.05). Dumping syndrome occurred more frequently in younger patients (p < 0.05) and women (p < 0.01). Quality of life was assessed separately by the Medical Outcomes Study 36-Item Short-Form Health Survey and compared with the national norm. Scores measuring physical functioning were decreased (p < 0.01). Scores measuring ability to work, social interaction, daily activities, emotional dysfunction, perception of health, and levels of energy were similar. Mental health scores were higher (p < 0.05). CONCLUSIONS We conclude that long-term functional outcome after esophagectomy for esophageal carcinoma is affected by age, sex, and type of reconstruction. Quality of life as judged by the patients is similar to the national norm.

A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Etanercept in the Treatment of Alcoholic Hepatitis

BACKGROUND & AIMS Alcoholic hepatitis is a cause of major morbidity and mortality that lacks effective therapies. Both experimental and clinical evidence indicate that the multifunctional cytokine tumor necrosis factor-alpha (TNF-alpha) contributes to pathogenesis and clinical sequelae of alcoholic hepatitis. A pilot study demonstrated that the TNF-alpha-neutralizing molecule etanercept could be an effective treatment for patients with alcoholic hepatitis. METHODS Forty-eight patients with moderate to severe alcoholic hepatitis (Model for End-Stage Liver Disease score > or = 15) were enrolled and randomized to groups that were given up to 6 subcutaneous injections of either etanercept or placebo for 3 weeks. Primary study end points included mortality at 1- and 6-month time points. RESULTS There were no significant baseline differences between the placebo and etanercept groups in demographics or disease severity parameters including age, gender, and Model for End-Stage Liver Disease score. The 1-month mortality rates of patients receiving placebo and etanercept were similar on an intention-to-treat basis (22.7% vs 36.4%, respectively; OR, 1.8; 95% CI, 0.5-6.5). The 6-month mortality rate was significantly higher in the etanercept group compared with the placebo group (57.7% vs 22.7%, respectively; OR, 4.6; 95% CI, 1.3-16.4; P = .017). Rates of infectious serious adverse events were significantly higher in the etanercept group compared with the placebo group (34.6% vs 9.1%, respectively, P = .04). CONCLUSIONS In patients with moderate to severe alcoholic hepatitis, etanercept was associated with a significantly higher mortality rate after 6 months, indicating that etanercept is not effective for the treatment of patients with alcoholic hepatitis.