Histologic response to steroids in eosinophilic esophagitis is dependent on delivery compound.

Topical steroids are commonly used in treatment of eosinophilic esophagitis (EoE), but currently there is lack of data to clarify most effective regimen. We aimed to study the achievement of histologic remission using the same dose of budesonide in two different delivery formulations. Patients with established EoE treated with pharmacy compounded budesonide capsule or budesonide Rincinol gel (both 3 mg twice daily) were studied retrospectively. Those with pre-treatment and post-treatment histologic assessment were included with main endpoint being histologic remission. 103 patients (62 gel, 41 capsule) were included, with higher rate of histologic remission with gel (84 vs. 59%, P=0.004). A subset of patients in both groups had lack of steroid response (<50% drop in eosinophils) (15% for gel, 32% for capsule). Formulation/delivery vehicle of steroid treatments to esophageal mucosa in EoE appears important for treatment efficacy, with budesonide gel having higher likelihood of histologic remission compared to budesonide capsules in our population. A truly steroid refractory group appears likely in our population. Larger, prospective studies may help clarify best regimen of topical steroids in EoE and may work to identify patients likely to benefit from alternative therapies.

Effectiveness and Safety of High- vs Low-Dose Swallowed Topical Steroids for Maintenance Treatment of Eosinophilic Esophagitis: A Multicenter Observational Study.

BACKGROUND & AIMS: Data evaluating efficacy of different doses of swallowed topical corticosteroids (STC) in the long-term management of eosinophilic esophagitis (EoE) are lacking. We assessed long-term effectiveness and safety of different STC doses for adults with EoE after achievement of histological remission. METHODS: We performed a retrospective multicenter study at five EoE referral centers (US and Switzerland). We analyzed data on 82 patients with EoE in histological remission and ongoing STC treatment with therapeutic adherence of ≥75% (58 males; mean age at diagnosis, 37.2±14.4 years). Patients were followed for a median of 2.2 years (interquartile range [IQR], 1.0-3.8 years). We collected data from 217 follow-up endoscopy visits. The primary endpoint was time to histological relapse. RESULTS: Histological relapse occurred in 67% of patients. Relapse rates were comparable in patients taking low dose (≤0.5 mg per day, n = 58) and high dose STC (>0.5 mg per day, n = 24) with 72 vs 54% (ns). However, histological relapse occurred significantly earlier with low dose STC (1.0 vs 1.8 years, P = .030). There was no difference regarding rates of and time to stricture formation for low vs high dose STC. Esophageal candidiasis was observed in 6% of patients (5% for low dose, 8% for high dose, ns). No dysplasia or mucosal atrophy was detected. CONCLUSION: Histological relapse frequently occurs in EoE despite ongoing STC treatment regardless of STC doses. However, relapse develops later in patients on high dose STC without an increase in side-effects. Doses higher than 0.5 mg/day may be considered for EoE maintenance treatment, but advantage over lower doses appears to be small.

Effect of Maintenance Therapy for Eosinophilic Esophagitis on Need for Recurrent Dilation.

BACKGROUND: Eosinophilic esophagitis is an inflammatory condition in which eosinophil infiltration leads to esophageal remodeling and stricturing, with dilation therapy often needed. Achieving histologic remission reduces the need for repeat dilation, although little is known about the effects of long-term maintenance therapy. AIMS: To further assess the relationship between short-term histologic remission and maintenance therapy on need for repeat dilation in eosinophilic esophagitis. METHODS: A total of 77 patients with eosinophilic esophagitis (59.7% male; mean age 41.6 years) seen at a single medical center from June 2000 to August 2017 were included. Information on history of dilation and therapy [proton pump inhibitors (PPIs), steroids, elimination diet] was collected. Mean follow-up was 164 weeks. Fifty-one patients achieved histologic remission and 42 of these remained on maintenance therapy (23 PPIs, 14 topical steroids, and 5 dietary therapy). Standard phone interview was completed in cases with lack of follow-up. Only patients who underwent esophageal dilation to ≥ 17 mm were included. RESULTS: A significantly lower proportion of patients on maintenance therapy required repeat dilation (12/42) compared with patients not on maintenance therapy (8/9) (hazard ratio 0.12; p < 0.001). Of patients who received maintenance therapy, 9.1% required re-dilation. The difference in need for repeat dilation in patients who achieved histologic remission on therapy (14/26) versus those who did not (20/51) was not significant (hazard ratio 1.34; p = 0.45). CONCLUSION: In a retrospective analysis of patients with eosinophilic esophagitis, we found that a significantly lower proportion who received maintenance therapy (PPIs, steroids, or dietary exclusions) required repeat dilation.

The promise of the gut microbiome as part of individualized treatment strategies.

Variability in disease presentation, progression and treatment response has been a central challenge in medicine. Although variability in host factors and genetics are important, it has become evident that the gut microbiome, with its vast genetic and metabolic diversity, must be considered in moving towards individualized treatment. In this Review, we discuss six broad disease groups: infectious disease, cancer, metabolic disease, cardiovascular disease, autoimmune or inflammatory disease, and allergic and atopic diseases. We highlight current knowledge on the gut microbiome in disease pathogenesis and prognosis, efficacy, and treatment-related adverse events and its promise for stratifying existing treatments and as a source of novel therapies. The Review is not meant to be comprehensive for each disease state but rather highlights the potential implications of the microbiome as a tool to individualize treatment strategies in clinical practice. Although early, the outlook is optimistic but challenges need to be overcome before clinical implementation, including improved understanding of underlying mechanisms, longitudinal studies with multiple data layers reflecting gut microbiome and host response, standardized approaches to testing and reporting, and validation in larger cohorts. Given progress in the microbiome field with concurrent basic and clinical studies, the microbiome will likely become an integral part of clinical care within the next decade.

The evolution of treatment and complications of esophageal food impaction.

Background: Esophageal food impaction is relatively common and increasing over time. Treatment ranges from medications to invasive endoscopic therapies. The endoscopic push technique has been advised against in favor of endoscopic retrieval for safety concerns. We sought to assess use patterns and safety of treatments for food impaction in a population-based retrospective review. Methods: A database of recorded esophageal food impactions in Olmsted County, MN, USA, from 1975-2011 was reviewed for patient demographics, treatment, and complications. Results: A total of 645 impactions occurred, with increasing incidence over time, peaking at 23.2 per year (2000-2004). Medications (almost exclusively glucagon) were successful in relieving impactions 34.5% of the time when trialed. Urgent endoscopy was common (74.0%), as was the need for endoscopic therapy (67.1%). Endoscopic therapy increased over time, with the endoscopic push technique becoming most common. Esophageal complications (deep mucosal injury or perforation) increased over time but remained rare (peak 11%). There was no difference in complications between push and retrieval techniques. Conclusions: The endoscopic push technique is safe in comparison to endoscopic retrieval in esophageal food impactions. While complications surrounding impaction have increased, they remain rare. Medication trials are reasonable, as long as they do not delay endoscopy, and may prevent the need for emergent endoscopy in one-third of cases.

Temporal changes in tolerance of uncertainty among medical students: insights from an exploratory study.

BACKGROUND: Physicians' tolerance of uncertainty (TU) is a trait potentially associated with desirable outcomes, and emerging evidence suggests it may change over time. Past studies of TU, however, have been cross-sectional and have not measured tolerance of the different, specific types of uncertainty that physicians confront. We addressed these limitations in a longitudinal exploratory study of medical students. METHODS: At the end of medical school (Doctor of Medicine degree) Years 1 and 4, a cohort of 26 students at a US medical school completed measures assessing tolerance of different types of uncertainty: 1) complexity (uncertainty arising from features of information that make it difficult to comprehend); 2) risk (uncertainty arising from the indeterminacy of future outcomes); and 3) ambiguity (uncertainty arising from limitations in the reliability, credibility, or adequacy of information). Change in uncertainty-specific TU was assessed using paired t-tests. RESULTS: Between Years 1 and 4, there was a significant decrease in tolerance of ambiguity (t=3.22, p=0.004), but no change in students' tolerance of complexity or risk. CONCLUSIONS: Tolerance of ambiguity--but not other types of uncertainty--decreases during medical school, suggesting that TU is a multidimensional, partially mutable state. Future studies should measure tolerance of different uncertainties and examine how TU might be improved.