Background
Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease (IBD) in a multicenter cohort of patients.
Methods
Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300mg) was administered at weeks 0, 2, 6 and 14. Efficacy was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment, along with C-reactive protein (CRP) and decrease of corticosteroid therapy. Clinical response was defined as decrease in HBI ≥ 3 and SCCAI ≥ 3 and remission as HBI ≤ 4, SCCAI ≤ 2 and physician assessment of response and remission.
Results
Our study included 172 patients (107 CD, 59 UC, 6 IBD-U, male 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had an ostomy and 9 an ileoanal pouch and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with ≥ 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14. Adverse events occurred in 10.5%.
Conclusions
VDZ is safe and well tolerated in refractory IBD patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials.
Four months of diet supplementation with fish oil in patients with inflammatory bowel disease resulted in reductions in rectal dialysate leukotriene B4 levels, improvements in histologic findings, and weight gain.
Rotaviruses infect epithelial cells of the small intestine, but the pathophysiology of the resulting severe diarrhea is incompletely understood. Histological damage to intestinal epithelium is not a consistent feature, and in vitro studies showed that intestinal cells did not undergo rapid death and lysis during viral replication. We show that rotavirus infection of Caco-2 cells caused disruption of tight junctions and loss of transepithelial resistance (TER) in the absence of cell death. TER declined from 300 to 22 Omega. cm(2) between 8 and 24 h after infection and was accompanied by increased transepithelial permeability to macromolecules of 478 and 4,000 Da. Distribution of tight junction proteins claudin-1, occludin, and ZO-1 was significantly altered during infection. Claudin-1 redistribution was notably apparent at the onset of the decline in TER. Infection was associated with increased production of lactate, decreased mitochondrial oxygen consumption, and reduced cellular ATP (60% of control at 24 h after infection), conditions known to reduce the integrity of epithelial tight junctions. In conclusion, these data show that rotavirus infection of Caco-2 intestinal cells altered tight junction structure and function, which may be a response to metabolic dysfunction.
We found that 5-ASA therapy is associated with higher 6-TGn levels in children and adults with IBD on 6-MP/AZA. TPMT inhibition may not explain this effect because 5-ASA exposure did not affect 6-MMP levels. The observed association of CD with higher 6-TGn levels is novel and needs to be verified in prospective studies.
An increasing amount of evidence suggests that enteric flora may have a role in the pathogenesis of inflammatory bowel disease (IBD). Patients with IBD appear to have an altered composition of luminal bacteria that may provide the stimulus for the chronic inflammation characterizing IBD. The suspected role of bacteria in the pathogenesis of IBD provides the rationale for using agents, such as antibiotics, that alter the intestinal flora. However, there remains much uncertainty about the optimal use of antibiotics in the treatment of Crohn's disease, ulcerative colitis, and pouchitis. This article reviews the literature and presents a clinical model for the use of antibiotics in IBD.
Oral qd dosing of STA 5326 for 4 weeks was well tolerated in doses up to 70 mg qd in patients with active moderate to severe Crohn's disease. Clinical activity was observed at qd doses of 28 mg and above.
If no physiologic benefit is expected with PEG placement (anorexia-cachexia syndrome), the health care team has no obligation to offer or perform an intervention. This same principle would apply if intervention improves physiologic states but has no effect on quality of life (e.g., permanent vegetative state). Small-bore feeding tubes are cost effective and relatively safe for enteral feedings of up to 6-8 weeks. This is especially pertinent in the population with acute neurological deficits, in which prognostication on extent of impairment is best estimated by communication with neurologist. In the geriatric population there is no proved benefit in weight gain or markers of nutrition (albumin, prealbumin) in patients with malnutrition due to impaired oral intake.
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