Impact of Obesity on the Management and Clinical Course of Patients with Inflammatory Bowel Disease.

BACKGROUND: Obesity has been linked with a proinflammatory state and the development of inflammatory diseases. Data on the clinical course and treatment of obese patients with inflammatory bowel disease (IBD) are limited. We used an institutional IBD registry to investigate the impact of obesity on IBD severity and treatment. METHODS: This was a retrospective analysis of prospectively collected data for 3 years (2009-2011). Patients with IBD were categorized by body mass index (BMI). IBD-related quality of life, biochemical markers of inflammation, comorbidities, health care utilization, and treatment were characterized. Obesity was defined as a BMI ≥30 (type I: 30-34.9, type II: 35-39.9, and type III ≥40). RESULTS: Among 1494 patients with IBD, 71.9% were above their ideal BMI and 31.5% were obese. Obesity was more common in ulcerative colitis compared with patients with Crohn's disease (P = 0.04). Obese class II and class III patients were predominantly female. Obesity in IBD was associated with female gender (P < 0.0001), diabetes mellitus (P < 0.001), hypertension (P < 0.001), hyperlipidemia (P < 0.001), poor quality of life (P < 0.0001), and increased rates of C-reactive protein elevation (P = 0.008). In logistic regression analysis, quality of life and C-reactive protein elevation were not independently correlated with obesity. There was no association between increasing BMI and annual prednisone use, emergency department visits, hospitalization, and surgery. Obesity was associated with lower milligrams per kilogram doses of purine analogs and biologics. CONCLUSIONS: Obesity in IBD is not associated with increased health care utilization and IBD-related surgeries. Optimal regimens for drug dosing in obese patients with IBD have yet to be defined.

Infliximab for Crohn's disease: the first 500 patients followed up through 2009.

BACKGROUND: The aim of this study was to assess the long-term usage patterns and safety of infliximab in patients with Crohn's disease in clinical practice. METHODS: The medical records of 492 unselected patients treated with infliximab at Mayo Clinic were reviewed and abstracted for demographic features, usage patterns, and adverse events. RESULTS: The patients received a median of seven infusions and had a median follow-up of 6.3 years. Twenty-eight patients (6 %) were lost to follow-up, 63 patients (13 %) had no clinical benefit, and 401 patients (80 %) had partial or complete response. Of the responding patients, 114 (28 %) received induction treatment only, 167 (42 %) received initial episodic treatment (62 switched to scheduled maintenance treatment of whom 32 [42 %] were still on infliximab at last follow-up), and 120 (30 %) received scheduled maintenance treatment (56 patients [32 %] still on infliximab at last follow-up). Three patients (0.6 %) developed septic shock and six patients (1.5 %) developed septicemia. One patient (0.2 %) developed Mycobacterium avium complex. Histoplasmosis occurred in three patients (0.6 %). The cumulative 10-year probability for developing cancer after infliximab was 9 %. Among the 31 patients developing malignancies (6 %), 15 (3 %) had solid tumors, 11 (2 %) had melanoma and non-melanoma skin cancers, three (0.6 %) had lymphomas (0.6 %), and two (0.4 %) had leukemia. Overall 10-year survival after the final course of infliximab was 94 %. Among the 28 deaths (6 %), nine occurred within 12 weeks of an infliximab infusion-two of these deaths were due to infections. CONCLUSIONS: Long-term follow-up of patients with Crohn's disease who were treated with infliximab initially between 1998 and 2002 showed persistence of therapy (due to clinical benefit) and an acceptable safety profile, despite the fact that less than one-third initially received three-dose induction followed by scheduled maintenance therapy. Infections and malignancy occurred at rates similar to those previously reported.

Rapamycin preserves renal function compared with cyclosporine A after ischemia/reperfusion injury.

OBJECTIVES: To determine the effect of cyclosporine and rapamycin administration on renal function after ischemia/reperfusion injury (I/R). Cyclosporine A has known nephrotoxic effects. Thus, cyclosporine therapy subsequent to I/R injury may further exacerbate graft dysfunction. Rapamycin is a newer agent that suppresses the immune system by a different mechanism. METHODS: Male Wistar rats (250 g) were anesthetized, and the suprarenal aorta was clamped for 40 minutes. The right kidney was removed. After recovery, the rats were divided into four groups: group 1, controls, no ischemia and no treatment (n = 10); group 2, ischemia with no treatment (n = 8); group 3, ischemia plus rapamycin (0.17 mg/kg/day gavage, n = 8); and group 4, ischemia plus cyclosporine A (30 mg/kg/day intraperitoneally, n = 9). The glomerular filtration rate was measured 5 to 7 days after I/R injury using urinary iohexol clearance. Data are expressed as the mean +/- SEM, and intergroup comparisons were made using one-way analysis of variance. RESULTS: The mean GFR value for the controls (no ischemia, no treatment) was 1.23 +/- 0.08 mL/min; for group 2 (ischemia, no treatment), it was 1.05 +/- 0.10 mL/min; for group 3 (ischemia plus rapamycin) 1.06 +/- 0.14 mL/min; and for group 4 (ischemia plus cyclosporine A) 0.44 +/- 0.06 mL/min (P <0.05 versus the other three groups). The mean arterial pressure was significantly lower in the ischemic rats treated with cyclosporine A (P <0.05 versus the other three groups). CONCLUSIONS: After I/R injury, rapamycin may preserve renal function compared with cyclosporine treatment, because it does not have a direct vasoconstrictor effect on the renal microcirculation.