Updates in therapeutic drug monitoring in inflammatory bowel disease.

Biologics and immunomodulators (IMM) are generally considered the most effective therapies for the treatment of ulcerative colitis and Crohn's disease. However, despite the efficacy of these therapies, many patients either have a primary lack of response or a secondary loss of response to these medications. Therapeutic drug monitoring (TDM) is a systematic approach to managing such patients. In this review, we summarize the latest data on TDM, including reactive and proactive TDM, in patients with inflammatory bowel disease on biologics and/or IMM.

Endoscopy in inflammatory bowel disease: Role in diagnosis, management, and treatment.

Endoscopy plays a fundamental role in the diagnosis, management, and treatment of inflammatory bowel disease (IBD). Colonoscopy, flexible sigmoidoscopy, and esophagogastroduodenoscopy have long been used in the care of patients with IBD. As endoscopic technologies have progressed, tools such as endoscopic ultrasound, capsule endoscopy, and balloon-assisted enteroscopy have expanded the role of endoscopy in IBD. Furthermore, chromoendoscopy has enhanced our ability to detect dysplasia in IBD. In this review article, we will focus on the roles, indications, and limitations of these tools in IBD. We will also discuss the most commonly used endoscopic scoring systems, as well as special considerations in post-surgical patients. Lastly, we will discuss the role of endoscopy in the diagnosis and management of fistulae and strictures.

Histoplasma meets Crohn's disease: a rare case of new-onset ascites.

A 53-year-old man with Crohn's disease treated with adalimumab was hospitalised with abdominal pain, fatigue, fever and chills. CT scan of the abdomen showed chronic thickening of the terminal ileum and cecum and new-onset ascites. Further studies revealed weakly positive urine and serum histoplasma antigen. Laparoscopy revealed metastatic caking of the omentum and abdominal wall; peritoneal biopsy demonstrated organisms morphologically consistent with Histoplasma capsulatum No dissemination outside of the peritoneal cavity was evident. The patient completed 2 weeks of liposomal amphotericin B followed by oral itraconazole for 1 year. Adalimumab therapy was held for 10 weeks, then restarted. Presenting symptoms resolved following initiation of antifungal therapy. Follow-up MRI of his abdomen demonstrated resolution of ascites. To our knowledge, this is the first reported case of histoplasmosis presenting as peritonitis in a patient with Crohn's disease receiving antitumour necrosis factor-alpha (TNF-α) therapy. Many clinicians are aware that patients receiving anti-TNF-α therapy are at increased risk for histoplasmosis, but may fail to consider the diagnosis in the absence of lung involvement.

Medical Therapy for Inflammatory Bowel Disease.

Surgeons often care for patients with inflammatory bowel disease (IBD) who are receiving therapies that can include 5-ASA compounds, steroids, immunomodulators, and biologics. The goal of these agents is to suppress intestinal inflammation, ultimately improving the quality of life in patients afflicted with IBD. Traditionally, an acceptable therapeutic endpoint was the resolution of symptoms, defined as clinical remission. However, as a result of recent advances in therapy, clinicians can now strive to achieve more stringent endpoints, such as endoscopic or histologic remission. Many different classes of agents can be used, individually or in combination, to achieve mucosal healing.

Predisposing factors for positive D-Xylose breath test for evaluation of small intestinal bacterial overgrowth: a retrospective study of 932 patients.

AIM: To investigate, in the largest cohort to date, patient characteristics and associated risk factors for developing small intestinal bacterial overgrowth (SIBO) using the D-Xylose breath test (XBT). METHODS: We performed a retrospective cross-sectional study to analyze patient characteristics who underwent the XBT for evaluation of SIBO. Diagnostic testing with the XBT was performed based on a clinical suspicion for SIBO in patients with symptoms of bloating, abdominal pain, abdominal distension, weight loss, diarrhea, and/or constipation. Consecutive electronic medical records of 932 patients who completed the XBT at the University of Florida between 2005 and 2009 were reviewed. A two-way Analysis of Variance (ANOVA) was used to test for several associations including age, gender, and body mass index (BMI) with a +XBT. A two-way ANOVA was also performed to control for the differences and interaction with age and between genders. A similar analysis was repeated for BMI. Associations between medical conditions and prior surgical histories were conducted using the Mantel-Haenszel method for 2 by 2 contingency tables, stratified for gender. Reported odds ratio estimates reflect the odds of the prevalence of a condition within the +XBT group to that of the -XBT group. P values of less than 0.05 (two-sided) were considered statistically significant. RESULTS: In the 932 consecutive eligible subjects studied, 513 had a positive XBT. A positive association was found between female gender and a positive XBT (P = 0.0025), and females with a positive test were, on average, greater than 5 years older than those with a negative test (P = 0.024). The mean BMI of positive XBT subjects was normal (24.5) and significantly lower than the subjects with a negative XBT (29.5) (P = 0.0050). A positive XBT was associated with gastroesophageal reflux disease (GERD) (OR = 1.35; 95%CI: 1.02-1.80, P = 0.04), peptic ulcer disease (PUD) (OR = 2.61; 95%CI: 1.48-4.59, P < 0.01), gastroparesis (GP) (OR = 2.04; 95%CI: 1.21-3.41, P < 0.01) and steroid use (OR = 1.35; 95%CI: 1.02-1.80, P = 0.01). Irritable bowel syndrome, independent proton-pump inhibitor (PPI) usage, or previous abdominal surgery was not significantly associated with a positive XBT. No single subdivision by gender or PPI use was associated with a significant difference in the odds ratios between any of the subsets. CONCLUSION: Female gender, lower BMI, steroid use, PUD, GERD (independent of PPI use), and GP were more prevalent in patients with SIBO, determined by a positive XBT. Increasing age was associated with SIBO in females, but not in males.

Advanced therapy for inflammatory bowel disease: a guide for the primary care physician.

Primary care physicians care for patients with inflammatory bowel disease (IBD) who are receiving advanced therapies that include immunomodulator drugs (eg, azathioprine and methotrexate) and biologic therapy. These agents have significantly improved remission rates and the quality of life for patients suffering from IBD. However, patients taking these drugs need special care and counseling with regard to adverse effects, infection risk, cancer risk, and pregnancy. Newer treatment paradigms incorporate earlier use of biologic therapy, often in combination with immunomodulator drugs, to alter the natural course of the disease. Comprehensive care for these patients, including health maintenance, requires collaboration between primary care physicians and gastroenterologists. Despite their high cost, advanced therapies are likely to be cost-effective. This article discusses general concepts about azathioprine, 6-mercaptopurine, methotrexate, and common biologic drugs used in IBD.

The appropriate use of vaccines in patients with inflammatory bowel disease.

An increasing majority of patients with inflammatory bowel disease (IBD) will be placed on immunosuppressive medications, thus increasing their susceptibility to infections. Although many of these infections are preventable through the use of vaccinations, vaccines seem to be underutilized in IBD patients. This article reviews current immunization guidelines and makes evidence-based recommendations regarding the appropriate use of vaccinations for patients with IBD.

Hepatic portal venous gas due to cryptosporidiosis in a patient with acquired immunodeficiency syndrome.

Although the presence of hepatic portal venous gas (HPVG) on computed tomography (CT) is typically an ominous finding, HPVG may sometimes be less catastrophic. The clinical significance of HPVG is variable, and it depends primarily on the underlying pathology. We report a case of a patient with acquired immunodeficiency syndrome (AIDS) who was found to have HPVG on CT as a presumed result of gastrointestinal cryptosporidiosis, an association that, to our knowledge, has not been reported. This case illustrates another cause of HPVG that should be considered in patients with AIDS.

Risk of contrast-induced nephropathy in hospitalized patients with cirrhosis.

AIM: To evaluate the incidence of contrast-induced nephropathy (CIN) in cirrhotic patients and to identify risk factors for the development of CIN. METHODS: We performed a retrospective review of 216 consecutive patients with cirrhosis who underwent computed tomography (CT) with intravenous contrast at the University of Rochester between the years 2000-2005. We retrospectively examined factors associated with a high risk for CIN, defined as a decrease in creatinine clearance of 25% or greater within one week after receiving contrast. RESULTS: Twenty-five percent of our patients developed CIN, and 74% of these patients had ascites seen on CT. Of the 75% of patients who did not develop CIN, only 46% had ascites. The presence of ascites was a significant risk factor for the development of CIN (P = 0.0009, OR 3.38, 95% CI 1.55-7.34) in multivariate analysis. Patient age, serum sodium, Model for End-stage Liver Disease score, diuretic use, and the presence of diabetes were not found to be significant risk factors for the development of CIN. Of the patients who developed CIN, 11% developed chronic renal insufficiency, defined as a creatinine clearance less than baseline for 6 wk. CONCLUSION: Our results suggest that in hospitalized cirrhotic patients, especially those with ascites, the risk of CIN is substantial.

Utilizing intraluminal pressure gradients to predict esophageal clearance: a validation study.

BACKGROUND: Esophageal bolus clearance requires a preferential esophagogastric pressure gradient sustained for a sufficient period. We aimed to validate a high-resolution manometry (HRM) paradigm for predicting bolus clearance. METHODS: Twenty volunteers and 30 patients were studied with HRM during barium swallows with concurrent fluoroscopy. Simultaneous bolus domain pressure and esophagogastric junction (EGJ) obstruction pressure were plotted and flow permissive time was tallied during which the bolus domain pressure exceeded the EGJ obstruction pressure. Distal peristaltic integrity was assessed at incrementally increasing pressure isobaric contour thresholds from 15-40 mmHg. ROC analysis was performed to assess the sensitivity and specificity of cutoff values for flow permissive time and peristaltic amplitude for predicting incomplete clearance as verified fluoroscopically. RESULTS: Flow permissive time < or =2.5 s had a sensitivity of 86% and specificity of 92% for predicting incomplete clearance. In contrast, a 30-mmHg peristaltic amplitude had a sensitivity of only 48% and specificity of 88%. Incomplete clearance was variably attributable to functional EGJ obstruction, hiatus hernia, or impaired peristalsis. CONCLUSIONS: A detailed analysis of intraluminal pressure gradients in the distal esophagus and across the EGJ in the postdeglutitive period predicts esophageal bolus clearance with far greater accuracy than any threshold value of peristaltic amplitude.

Utilizing intraluminal pressure differences to predict esophageal bolus flow dynamics.

Successful esophageal emptying depends on the generation of a sustained intrabolus pressure (IBP) sufficient to overcome esophagogastric junction (EGJ) obstruction. Our aim was to develop a manometric analysis paradigm that describes the bolus driving pressure difference and the flow permissive time for esophageal bolus transit. Twenty normal subjects were studied with a 36-channel manometry assembly (1-cm spacing) during two 5- and one 10-ml barium swallows and concurrent fluoroscopy. Bolus domain pressure plots were generated by plotting bolus domain pressure (BDP) and EGJ relaxation pressure. BDP was defined as the pressure midway between the peristaltic ramp-up and the proximal margin of the EGJ. The flow permissive time was defined as the period where the BDP was > or = EGJ relaxation pressure. The mean BDP was 11.7 +/- 1.0 mmHg (SE), and the mean flow permissive time was 3.9 +/- 0.4 s for 5-ml swallows in normal controls. The mean BDP difference during flow was 4.0 +/- 1.0 mmHg. There was no significant difference in the fluoroscopic transit time and the flow permissive time calculated from the BDP plots (5 ml: fluoroscopy 3.4 +/- 0.2 s; BDP 3.9 +/- 0.4 s, P > 0.05). BDP plots provide a reliable measurement of IBP and its relationship with EGJ relaxation. The time available for flow can be readily delineated from this analysis, and the driving pressure responsible for flow can be accurately described and quantified. This may help predict abnormal bolus transit and the underlying mechanical properties of the EGJ.