Correlation of Probe-Based Confocal Laser Endomicroscopy (pCLE) and Mucosal Integrity Testing (MIT) with Epithelial Barrier Function and Presence of Gastroesophageal Reflux Disease (GERD).

INTRODUCTION: Epithelial barrier function (EBF) disruption is a key mechanism underlying gastroesophageal reflux disease (GERD). Our aim was to assess whether two novel technologies, probe-based confocal laser endomicroscopy (pCLE) and mucosal integrity testing (MIT), could assess EBF. METHODS: We prospectively enrolled patients undergoing upper endoscopy for refractory GERD or non-GERD conditions. Patients underwent esophagogastroduodenoscopy, pCLE, MIT, esophageal biopsy at 2 cm and 6 cm above the esophagogastric junction, and wireless pH testing. To assess EBF in vitro, biopsies were mounted in a mini-Ussing chamber, 1 ml of fluorescein was instilled on the mucosal side, and concentration of fluorescein on the serosal side was measured at 3 h. RESULTS: We enrolled 54 subjects (28 GERD, 26 non-GERD based on Lyon consensus criteria). In vivo permeability assessed by pCLE did not differ significantly between GERD vs. non-GERD patients and did not correlate with in vitro permeability. Mean MIT at 2 cm was lower in GERD compared to non-GERD (1914 vs. 3727 ohms). MIT correlated inversely with in vitro permeability at 2 cm and at 6 cm. Using a predictive model that used slope and intercept of MIT at 2 cm and 6 cm, sensitivity and specificity of MIT at identifying GERD was 76% and 72%, respectively. CONCLUSION: pCLE did not differentiate GERD vs non-GERD and did not correlate with EBF measured in vitro. MIT, on the other hand, may be more promising as it differentiated GERD vs non-GERD and correlated with EBF measured in vitro.

Depressive Symptoms Predict Anti-tumor Necrosis Factor Therapy Noncompliance in Patients with Inflammatory Bowel Disease.

BACKGROUND: Noncompliance in use of anti-tumor necrosis factor (anti-TNF) therapy in patients with moderate-to-severe inflammatory bowel disease (IBD) can be a factor in medication failure. Few studies have evaluated the contribution of depressive symptoms to medication noncompliance in anti-TNF therapies. METHODS: A retrospective chart review was performed in a single-center tertiary care IBD center for patients with Crohn's disease and ulcerative colitis starting anti-TNF therapy over a 2-year period. Medication noncompliance was defined as interruption of medication (not filling anti-TNF prescription if injectable or not getting infliximab infusion for 30 days beyond needed date for continuation) due to patient-driven circumstances. Depressive symptoms were evaluated at baseline using the well-validated Patient Health Questionnaire-9 (PHQ-9), with PHQ-9 ≥ 10 indicative of at least moderate depressive symptoms. Statistical analysis was performed using Cox proportional hazards regression controlling for age, sex, psychiatric history, and disease. RESULTS: A total of 246 patients (75 with ulcerative colitis, 171 with Crohn's disease) were started on anti-TNF therapy. Seventy-nine patients (32%) had a prior psychiatric diagnosis reported in the medical record. Thirty-three patients (13%) were noncompliant in follow-up. Sixty patients (24%) had at least moderate depressive symptoms at baseline (PHQ ≥ 10). Depressive symptoms at baseline were significantly associated with noncompliance in follow-up (hazards ratio 2.28, CI 1.1-4.6, p < 0.05). CONCLUSION: Depressive symptoms at baseline were associated with medication noncompliance of anti-TNF therapies at follow-up when controlling for age, sex, disease type, and history of psychiatric disease.

World Health Organization's Growth Reference Overestimates the Prevalence of Severe Malnutrition in Children with Sickle Cell Anemia in Africa.

Anthropometric indices are widely used to assess the health and nutritional status of children. We tested the hypothesis that the 2007 World Health Organization (WHO) reference for assessment of malnutrition in children with sickle cell anemia (SCA) overestimates the prevalence of severe malnutrition when compared to a previously constructed SCA-specific reference. We applied the WHO and SCA-specific references to children with SCA aged 5-12 years living in northern Nigeria (Primary Prevention of Stroke in Children with SCA in sub-Saharan Africa (SPRING) trial) to determine the difference in prevalence of severe malnutrition defined as body mass index (BMI) Z-score <-3 and whether severe malnutrition was associated with lower mean hemoglobin levels or abnormal transcranial Doppler measurements (>200 cm/s). A total of 799 children were included in the final analysis (median age 8.2 years (interquartile range (IQR) 6.4-10.4)). The application of the WHO reference resulted in lower mean BMI than the SCA-specific reference (-2.3 versus -1.2; p < 0.001, respectively). The use of the WHO reference when compared to the SCA-specific reference population also resulted in a higher prevalence of severe malnutrition (28.6% vs. 6.4%; p < 0.001). The WHO reference significantly overestimates the prevalence of severe malnutrition in children with SCA when compared to an SCA-specific reference. Regardless of the reference population, severe malnutrition was not associated with lower mean hemoglobin levels or abnormal transcranial Doppler (TCD) measurements.