Dilation-predominant approach versus routine care in patients with difficult-to-treat eosinophilic esophagitis: a retrospective comparison.

BACKGROUND: Little is known about esophageal dilation as a long-term treatment approach for eosinophilic esophagitis (EoE). We examined the impact of a "dilate and wait" strategy on symptom management and safety of patients with EoE. METHODS: This retrospective cohort study included two patient groups: those who underwent a dilation-predominant approach (≥ 3 dilations as sole therapy or for histologically refractory disease [> 15 eos/hpf]); and those who had routine care (< 3 dilations or histologic response). Group characteristics were compared and outcomes for the dilation-only group assessed. RESULTS: 53/205 patients (26 %) received the dilation-predominant strategy (total 408 dilations), predominantly for histologic treatment nonresponse (75 %). These patients were younger (33 vs. 41 years; P = 0.003), had a narrower baseline esophageal diameter (9.8 vs. 11.5 mm; P = 0.005), underwent more dilations (7.7 vs. 3.4; P < 0.001), but achieved a smaller final diameter (15.7 vs. 16.7 mm; P = 0.01) vs. routine care. With this strategy, 30 patients (57 %) had ongoing symptom improvement, with esophageal caliber change independently associated with symptom response (adjusted odds ratio 1.79, 95 % confidence interval 1.16-2.78); 26 (49 %) used the strategy as a bridge to clinical trials. Over a median follow-up of 1001 days (interquartile range 581-1710), no deaths or dilation-related perforations occurred, but there were nine emergency room visits, including one for post-dilation bleeding and four for food impaction. CONCLUSIONS: A dilation-predominant long-term treatment strategy allowed for symptom control or bridge to clinical trials for patients with difficult-to-treat EoE. Close follow-up and monitoring for complications are required.

Loss to Follow-Up and Health Care Utilization After Initial Diagnosis of Eosinophilic Esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic disease, but the extent of patient loss to follow-up (LTFU) and health care utilization has not been fully investigated. AIM: To determine frequency and predictors of LTFU and health care utilization in EoE patients. METHODS: In this retrospective cohort study, we extracted data from patients with a new diagnosis of EoE. Follow-up time for each patient was calculated as the time from the first diagnostic endoscopy to the last GI-related contact date in the medical record. Patients with and without LTFU were compared, and the volume of EoE-related health care interactions was recorded. RESULTS: Of 944 EoE cases, 249 (26%) met the definition for LTFU. Major reasons for LTFU were never being scheduled (45%) and inability to contact patients (40%). Factors independently associated with regular follow-up were having insurance (aOR 2.89; 95% CI 1.85-4.50), white race (aOR 2.16; 95% CI 1.37-3.41), and longer symptom length (aOR 1.04 per year; 95% CI 1.01-1.08). At the time of last contact, patients with follow-up had better symptom response (55% vs. 12%; p < 0.001), improved esophageal caliber (14.3 vs. 12.4 mm; p = 0.005), and more histologic response (45% vs. 4% at 15 eos/hpf; p < 0.001). Health care utilization was high, with an average of 4.6 endoscopies and 4.0 clinic visits over the follow-up period. CONCLUSIONS: LTFU of newly diagnosed EoE cases was common and associated with lack of insurance, non-white race, and shorter symptom duration. Those who followed up had high health care utilization but improved response rates. Strategies are needed to help decrease LTFU in EoE.

Peripheral eosinophilia and hypoalbuminemia are associated with a higher biopsy diagnostic yield for eosinophilic gastroenteritis.

BACKGROUND: Gastric and duodenal mucosa may appear normal in eosinophilic gastroenteritis (EGE). Adult gastroenterologists typically biopsy only in the setting of mucosal abnormalities or symptoms, while pediatric providers biopsy all patients. The biopsy yield of EGE has not been adequately evaluated. AIMS: To evaluate the biopsy yield of EGE in a pediatric cohort and assess predictors of increased biopsy yield. METHODS: We identified patients age 0-18 who underwent upper endoscopy. We recorded endoscopic findings, pathology, demographics, and clinical and laboratory characteristics. We identified EGE cases (>20 eosinophils per high-power field on stomach and/or duodenum biopsy). We compared characteristics between EGE and non-EGE cases, calculated biopsy diagnostic yield, and performed multivariate analysis for predictors of increased biopsy yield. RESULTS: In 509 patients (55.6% female, mean age 10.3 years, 69.7% white, 58.7% atopic), biopsy diagnostic yield for EGE was 1.2% (6/509) among all subjects, 7.7% (3/39) for those with peripheral eosinophilia (≥500 eos/uL), 9.1% (3/33) for those with hypoalbuminemia (<3.5 g/dL), and 25.0% (3/12) for those with peripheral eosinophilia and hypoalbuminemia. The odds of EGE were 27.8 (95% CI 3.3-231.8) times greater among those with peripheral eosinophilia. The mean total biopsy surface area and number of fragments was similar between patients with and without EGE. The area under the ROC curve for blood eosinophil counts and albumin level for predicting EGE was 0.926. CONCLUSIONS: The biopsy diagnostic yield for EGE is low but increases with peripheral eosinophilia and hypoalbuminemia. Patients with these features should have biopsies obtained, regardless of endoscopic appearance.

Clinical features and time trends associated with an endoscopically normal esophagus in active eosinophilic esophagitis.

BACKGROUND: A proportion of patients with active eosinophilic esophagitis (EoE) have a normal-appearing esophagus on esophagogastroduodenoscopy (EGD). We aimed to determine the associations between the baseline clinical features and the endoscopically normal esophagus in EoE, as well as time trends in reporting. METHODS: In this retrospective study of active EoE cases from 2002 - 2018, patients with and without esophageal endoscopic abnormalities were compared. Multivariable logistic regression identified the independent predictors of a normal EGD. The proportion of patients with a normal EGD was determined per year, and before and after the introduction of the first EoE guidelines and the EoE Endoscopic Reference Score (EREFS). RESULTS: Of 878 EoE patients, 101 (11.5 %) had an endoscopically normal esophagus; they were younger (8.3 vs. 25.4 years), had shorter median symptom duration before diagnosis (2.8 vs. 5.0 years), were less likely to have dysphagia (40 % vs. 76 %) or food impaction (8 % vs. 33 %), and more likely to have abdominal pain (37 % vs. 19 %) (P < 0.01 for all). On multivariable logistic regression, independent predictors of a normal esophagus were younger age (odds ratio [OR] 0.96, 95 % confidence interval [CI] 0.94 - 0.98), abdominal pain (OR 2.03, 95 %CI 1.13 - 3.67), and lack of dysphagia (OR 0.49, 95 %CI 0.26 - 0.93). The proportion of patients with a normal esophagus decreased from 21 % before the first EoE guidelines to 7 % (P < 0.01) after introduction of the EREFS. CONCLUSIONS: An endoscopically normal esophagus is seen in ~10 % of active EoE patients and should not preclude biopsies; younger age, abdominal pain, and lack of dysphagia are independent predictors. The proportion of normal EGDs decreased over time, suggesting improved recognition of endoscopic findings.

Psychiatric Comorbidities and Psychiatric Medication Use Are Highly Prevalent in Patients With Eosinophilic Esophagitis and Associate With Clinical Presentation.

OBJECTIVES: The prevalence of psychiatric disease in patients with eosinophilic esophagitis (EoE) is not fully characterized. We aimed to determine the prevalence of psychiatric disease and centrally acting medication use in a cohort of children and adults with EoE and evaluated whether psychiatric disease affects the EoE clinical presentation. METHODS: We conducted a retrospective study of newly diagnosed cases with EoE at the University of North Carolina from 2002 to 2018. Psychiatric comorbidities and relevant treatments were extracted from the medical records. The demographic and clinical features of patients with EoE with and without psychiatric diagnoses, and those with and without psychiatric medication use, were compared. RESULTS: Of 883 patients (mean age 26.6 years, 68% men, 79% white), 241 (28%) had a psychiatric comorbidity. The most common diagnosis was anxiety (23%) followed by depression (17%); 28% of patients were treated pharmacologically. There were 45 patients (5%) treated pharmacologically without a psychiatric diagnosis for chronic pain syndromes, insomnia, and/or epilepsy. Cases with EoE with a psychiatric diagnosis were more likely to be women, white, and 18 years or older and to have a longer symptom duration before diagnosis. DICUSSION: Psychiatric comorbidities were common in EoE, seen in a third of adults and more than 1 in 7 children, and with similar proportions receiving a prescription medication. These illnesses affected the EoE presentation because psychiatric comorbidities were more likely in older, female, and white patients with a longer duration of symptoms preceding diagnosis.

Relationship Between Housing Components and Development of Eosinophilic Esophagitis.

BACKGROUND: While the environment contributes to EoE pathogenesis, few environmental risk factors for EoE have been identified. AIM: To determine whether housing components such as exterior materials, heating systems, and house age are associated with EoE. METHODS: This case-control study used the UNC EoE clinicopathologic database to identify newly diagnosed EoE patients. Controls were patients without EoE who underwent endoscopy during the study time frame. Housing data were collected from publicly available online sources, and cases and controls were compared. The primary analysis was restricted to those living at their provided address at the time of diagnostic endoscopy. Multivariable logistical regression estimated associations after adjusting for potential confounders. RESULTS: Of 451 EoE cases and 2421 controls identified, the primary analysis included 158 cases and 769 controls. Compared to controls, EoE cases were more likely to have a house with a brick exterior (35% vs 26%; p = 0.04), gas heating (14% vs 8%; p = 0.06), or forced air (57% vs 45%; p = 0.009). In adjusted analysis, brick exterior was positively associated with EoE diagnosis [aOR 1.83 (95% CI 1.11-3.02)]. The average duration a patient lived in their house before EoE diagnosis was 7.2 ± 5.9 years, while symptom duration prior to diagnosis was 6.8 ± 8.4 years. CONCLUSION: EoE patients were more likely to have houses with a brick exterior, forced air, or gas heating, and brick exteriors were independently associated with EoE. Since symptoms generally started after moving into a house, housing-related environmental exposures may contribute to EoE disease development.

Rare Co-occurrence of Eosinophilic Esophagitis and Type 2B von Willebrand Disease: Implications for Endoscopic Surveillance and Esophageal Dilation.

Eosinophilic esophagitis (EoE) and type 2B von Willebrand disease (vWD) are both rare diseases, and the co-occurrence is unlikely. Patients with EoE often need recurrent endoscopic dilations and esophageal biopsies, and the safety of these procedures in the setting of bleeding disorders is not well described in the literature. We describe successful management strategies in a patient with co-existing EoE and type 2B vWD who required multiple dilations and biopsies. This approach might be used for patients with other esophageal disorders and type 2B vWD as well.

Precise Protein Photolithography (P3): High Performance Biopatterning Using Silk Fibroin Light Chain as the Resist.

Precise patterning of biomaterials has widespread applications, including drug release, degradable implants, tissue engineering, and regenerative medicine. Patterning of protein-based microstructures using UV-photolithography has been demonstrated using protein as the resist material. The Achilles heel of existing protein-based biophotoresists is the inevitable wide molecular weight distribution during the protein extraction/regeneration process, hindering their practical uses in the semiconductor industry where reliability and repeatability are paramount. A wafer-scale high resolution patterning of bio-microstructures using well-defined silk fibroin light chain as the resist material is presented showing unprecedent performances. The lithographic and etching performance of silk fibroin light chain resists are evaluated systematically and the underlying mechanisms are thoroughly discussed. The micropatterned silk structures are tested as cellular substrates for the successful spatial guidance of fetal neural stems cells seeded on the patterned substrates. The enhanced patterning resolution, the improved etch resistance, and the inherent biocompatibility of such protein-based photoresist provide new opportunities in fabricating large scale biocompatible functional microstructures.

Molecular gas clumps from the destruction of icy bodies in the ß Pictoris debris disk.

Many stars are surrounded by disks of dusty debris formed in the collisions of asteroids, comets, and dwarf planets, but is gas also released in such events? Observations at submillimeter wavelengths of the archetypal debris disk around ß Pictoris show that 0.3% of a Moon mass of carbon monoxide orbits in its debris belt. The gas distribution is highly asymmetric, with 30% found in a single clump 85 astronomical units from the star, in a plane closely aligned with the orbit of the inner planet, ß Pictoris b. This gas clump delineates a region of enhanced collisions, either from a mean motion resonance with an unseen giant planet or from the remnants of a collision of Mars-mass planets.

Biosorption of nickel in complex aqueous waste streams by cyanobacteria.

A study was undertaken to determined if a suitable biosorbent could be found for removal of nickel at low concentrations (< 20 parts per million [ppm]) from a chemically complex wastewater effluent generated by electroplating operations. Algae and cyanobacteria were chosen as candidate biosorbent materials because they are easy to grow and they have the ability to withstand processing into biosorbent materials. Several species were screened for nickel-biosorption capacity initially, and three species of cyanobacteria were selected for further study based on their performance in the scoping tests. When compared to live controls, autoclaving improved the binding capacities of all three species, but usually biosorption data from experiments with live cells were more consistent. None of the three species was able to bind nickel efficiently in actual effluent samples. Further experimentation indicated that sodium ions, which were present in high concentrations in the effluent, were interfering with the ability of the cells to bind nickel. Adsorption isotherm plots for biosorption of nickel by two species of Anabaena in NiCl2-deionized water solutions were prepared.

The role of phosphate esters in male fertility.

Spermatozoa do not achieve full maturation and fertilizing capacity until passage through the epididymis. During this time they also gain motility, although spermatozoa do not move until after ejaculation. The organic fraction of human seminal plasma contains phosphate esters, particularly glycerylphosphorylcholine (GPC), phosphorylcholine (PCh), and inorganic phosphate (Pi). GPC is found in relatively high concentrations in the semen of many male animals, including man. GPC is synthesized by the epithelial cells of the epididymis, apparently under androgenic control. Consequently, it has been suggested that GPC might be a useful indicator of epididymal function. We have measured GPC, Pi, and PCh in fresh and frozen semen samples, using phosphorus nuclear magnetic resonance (31P NMR). All samples were assayed for phosphate esters. It was found that PCh was totally hydrolized to Pi. The average ratio of GPC to total phosphate (TP = GPC + Pi) remained constant at a value of about 0.1 for sperm counts over 20 million/ml. The ratio for azoospermic specimens was 0.02 or less; the same results were obtained from vasectomy specimens. This finding indicates that most of the GPC comes from the epididymis. There was a significant correlation between motility, progression, and the GPC ratio. Poor motility and progression in the specimens were accompanied by low GPC ratios regardless of the sperm counts.