A biomarker panel predicts progression of Barrett's esophagus to esophageal adenocarcinoma.

Progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is uncommon but the consequences are serious. Predictors of progression are essential to optimize resource utilization. This study assessed the utility of a promising panel of biomarkers applicable to routine paraffin embedded biopsies (FFPE) to predict progression of BE to EAC in a large population-based, nested case-control study.We utilized the Amsterdam-based ReBus nested case-control cohort. BE patients who progressed to high-grade dysplasia (HGD)/EAC (n = 130) and BE patients who never progressed (n = 130) were matched on age, sex, length of the BE segment, and duration of endoscopic surveillance. All progressors had minimum 2 years of endoscopic surveillance without HGD/EAC to exclude prevalent neoplasia. We assessed abnormal DNA content, p53, Cyclin A, and Aspergillus oryzae lectin (AOL) in FFPE sections. We performed conditional logistic regression analysis to estimate odds ratio (OR) of progression based on biomarker status.Expert LGD (OR, 8.3; 95% CI, 1.7-41.0), AOL (3 vs. 0 epithelial compartments abnormal; OR, 3.6; 95% CI, 1.2-10.6) and p53 (OR, 2.3; 95% CI, 1.2-4.6) were independently associated with neoplastic progression. Cyclin A did not predict progression and DNA ploidy analysis by image cytometry was unsuccessful in the majority of cases, both were excluded from the multivariate analysis. The multivariable biomarker model had an area under the receiver operating characteristic curve of 0.73.Expert LGD, AOL, and p53 independently predict neoplastic progression in BE patients and are applicable to routine practice. These biomarkers can aid in selecting patients for endoscopic ablation or more intensive surveillance.

Late Recurrence of Barrett's Esophagus After Complete Eradication of Intestinal Metaplasia is Rare: Final Report From Ablation in Intestinal Metaplasia Containing Dysplasia Trial.

BACKGROUND & AIMS: The goal of treatment for Barrett's esophagus (BE) with dysplasia is complete eradication of intestinal metaplasia (CEIM). The long-term durability of CEIM has not been well characterized, so the frequency and duration of surveillance are unclear. We report results from a 5-year follow-up analysis of patients with BE and dysplasia treated by radiofrequency ablation (RFA) in the randomized controlled Ablation of Intestinal Metaplasia Containing Dysplasia (AIM) trial. METHODS: Participants for the AIM Dysplasia trial (18-80 years old) were recruited from 19 sites in the United States and had endoscopic evidence of non-nodular dysplastic BE ≤8 cm in length. Subjects (n = 127) were randomly assigned (2:1 ratio) to receive either RFA (entire BE segment ablated circumferentially) or a sham endoscopic procedure; patients in the sham group were offered RFA treatment 1 year later, and all patients were followed for 5 years. We collected data on BE recurrence (defined as intestinal metaplasia in the tubular esophagus) and dysplastic BE recurrence among patients who achieved CEIM. We constructed Kaplan-Meier estimates and applied parametric survival analysis to examine proportions of patients without any recurrence and without dysplastic recurrence. RESULTS: Of 127 patients in the AIM Dysplasia trial, 119 received RFA and met inclusion criteria. Of those 119, 110 (92%) achieved CEIM. Over 401 person-years of follow-up (mean, 3.6 years per patient; range, 0.2-5.8 years), 35 of 110 (32%) patients had recurrence of BE or dysplasia, and 19 (17%) had dysplasia recurrence. The incidence rate of BE recurrence was 10.8 per 100 person-years overall (95% CI, 7.8-15.0); 8.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI, 4.9-14.0), and 13.5 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 8.8-20.7). The incidence rate of dysplasia recurrence was 5.2 per 100 person-years overall (95% CI 3.3-8.2); 3.3 per 100 person-years among patients with baseline low-grade dysplasia (95% CI 1.5-7.2), and 7.3 per 100 person-years among patients with baseline high-grade dysplasia (95% CI 4.2-12.5). Neither BE nor dysplasia recurred at a constant rate. There was a greater probability of recurrence in the first year following CEIM than in the following 4 years combined. CONCLUSIONS: In this analysis of prospective cohort data from the AIM Dysplasia trial, we found BE to recur after CEIM by RFA in almost one third of patients with baseline dysplastic disease; most recurrences occurred during the first year after CEIM. However, patients who achieved CEIM and remained BE free at 1 year after RFA had a low risk of BE recurrence. Studies are needed to determine when surveillance can be decreased or discontinued; our study did not identify any BE or dysplasia recurrence after 4 years of surveillance.

Optimal Histologic Cutpoints for Treatment Response in Patients With Eosinophilic Esophagitis: Analysis of Data From a Prospective Cohort Study.

BACKGROUND AND AIMS: No prospective studies substantiate 15 eos/hpf as an appropriate endpoint for treatment of eosinophilic esophagitis (EoE). We aimed to determine a histologic cutpoint that identifies successful treatment of EoE by assessing symptomatic and endoscopic improvement. METHODS: We performed a prospective cohort study of 62 consecutive adult patients undergoing outpatient esophagogastroduodenoscopy at the University of North Carolina from 2009 through 2014. At diagnosis of EoE and after 8 weeks of standard treatment, symptom and endoscopic responses were measured using a visual analogue scale and an endoscopic severity score (ESS), and eosinophil counts were assessed. Receiver operator curves and logistic regression models evaluated the histologic threshold that best predicted symptomatic and endoscopic response. For symptoms, analysis was limited to patients without baseline esophageal dilation. RESULTS: The mean eosinophil count at diagnosis was 124 eos/hpf, falling to 35 eos/hpf after treatment. The mean visual analogue scale decreased from 3.4 at baseline to 1.7 after treatment, and the mean ESS decreased from 3 to 1.6. Twenty-nine patients had symptom responses (47%) and 34 had endoscopic responses (55%). Post-treatment eosinophil count thresholds of 8, 15, and 5 eos/hpf best predicted symptom, endoscopic and combined responses, respectively. On logistic regression, decreasing eosinophil count was significantly associated with the probability of symptomatic (P = .01) and endoscopic response (P < .001). CONCLUSIONS: In a prospective study of patients with EoE, we found that a cutpoint of <15 eos/hpf identifies most patients with symptom and endoscopic improvements, providing support for the current diagnostic threshold. A lower threshold (<5 eos/hpf) identifies most patients with a combination of symptom and endoscopic responses; this cutpoint might be used in situations that require a stringent histologic threshold.

Cost Utility Analysis of Topical Steroids Compared With Dietary Elimination for Treatment of Eosinophilic Esophagitis.

BACKGROUND & AIMS: Topical corticosteroids or dietary elimination are recommended as first-line therapies for eosinophilic esophagitis, but data to directly compare these therapies are scant. We performed a cost utility comparison of topical corticosteroids and the 6-food elimination diet (SFED) in treatment of eosinophilic esophagitis, from the payer perspective. METHODS: We used a modified Markov model based on current clinical guidelines, in which transition between states depended on histologic response simulated at the individual cohort-member level. Simulation parameters were defined by systematic review and meta-analysis to determine the base-case estimates and bounds of uncertainty for sensitivity analysis. Meta-regression models included adjustment for differences in study and cohort characteristics. RESULTS: In the base-case scenario, topical fluticasone was about as effective as SFED but more expensive at a 5-year time horizon ($9261.58 vs $5719.72 per person). SFED was more effective and less expensive than topical fluticasone and topical budesonide in the base-case scenario. Probabilistic sensitivity analysis revealed little uncertainty in relative treatment effectiveness. There was somewhat greater uncertainty in the relative cost of treatments; most simulations found SFED to be less expensive. CONCLUSIONS: In a cost utility analysis comparing topical corticosteroids and SFED for first-line treatment of eosinophilic esophagitis, the therapies were similar in effectiveness. SFED was on average less expensive, and more cost effective in most simulations, than topical budesonide and topical fluticasone, from a payer perspective and not accounting for patient-level costs or quality of life.

Six-Food Elimination Diet and Topical Steroids are Effective for Eosinophilic Esophagitis: A Meta-Regression.

BACKGROUND: Topical corticosteroids or six-food elimination diet is recommended as initial therapy for eosinophilic esophagitis (EoE). AIMS: We aimed to summarize published manuscripts that report outcomes of these therapies for EoE. METHODS: We performed a systematic review in MEDLINE, Web of Science, and Embase of published manuscripts describing topical fluticasone, topical budesonide, and six-food elimination diet as therapies for EoE. We conducted meta-analysis of symptom improvement and the change in peak mucosal eosinophil count, with heterogeneity between studies examined with meta-regression analysis. RESULTS: Systematic review yielded 51 articles that met inclusion criteria. Summary histologic response rates were 68.3% [95% prediction limits (PL) 16.2-96.0%] for fluticasone, 76.8% (95% PL 36.1-95.1%) for budesonide, and 69.0% (95% PL 31.9-91.4%) for six-food elimination diet. Corresponding decreases in eosinophil counts were 37.8 (95% PL 19.0-56.7), 62.5 (95% PL 125.6 to -0.67, and 44.6 (95% PL 26.5-62.7), respectively. Symptom response rates were 82.3% (95% PL 68.1-91.1%), 87.9% (95% PL 42.7-98.6%), and 87.3% (95% PL 64.5-96.3%), respectively. Meta-regression analyses decreased the initially large estimate of residual heterogeneity and suggested differences in histologic response rate associated with study populations' baseline eosinophil count and age. CONCLUSIONS: The literature describing topical corticosteroids and six-food elimination diet consists of small studies with diverse methods and population characteristics. Meta-analysis with meta-regression shows initial histologic and symptomatic response rates on the same order of magnitude for topical corticosteroids and six-food elimination diet, but heterogeneity of study designs prevents direct comparison of modalities.

Association Between Body Mass Index and Clinical and Endoscopic Features of Eosinophilic Esophagitis.

BACKGROUND: Because eosinophilic esophagitis (EoE) causes dysphagia, esophageal narrowing, and strictures, it could result in low body mass index (BMI), but there are few data assessing this. AIM: To determine whether EoE is associated with decreased BMI. METHODS: We conducted a prospective study at the University of North Carolina from 2009 to 2013 enrolling consecutive adults undergoing outpatient EGD. BMI and endoscopic findings were recorded. Incident cases of EoE were diagnosed per consensus guidelines. Controls had either reflux or dysphagia, but not EoE. BMI was compared between cases and controls and by endoscopic features. RESULTS: Of 120 EoE cases and 297 controls analyzed, the median BMI was lower in EoE cases (25 vs. 28 kg/m2, p = 0.002). BMI did not differ by stricture presence (26 vs. 26 kg/m2, p = 0.05) or by performance of dilation (26 vs. 27 kg/m2 for undilated; p = 0.16). However, BMI was lower in patients with narrow caliber esophagus (24 vs. 27 kg/m2, p < 0.001). EoE patients with narrow caliber esophagus also had decreased BMI compared to controls with narrow caliber esophagi (24 vs. 27 kg/m2, p = 0.001). On linear regression after adjustment for age, race, and gender, narrowing decreased BMI by 2.3 kg/m2 [95% CI -4.1, -0.6]. CONCLUSIONS: BMI is lower in EoE cases compared to controls, and esophageal narrowing, but not focal stricture, is associated with a lower BMI in patients with EoE. Weight loss or low BMI in a patient suspected of having EoE should raise concern for esophageal remodeling causing narrow caliber esophagus.

Effects of the Learning Curve on Efficacy of Radiofrequency Ablation for Barrett's Esophagus.

BACKGROUND & AIMS: Complete eradication of Barrett's esophagus (BE) often requires multiple sessions of radiofrequency ablation (RFA). Little is known about the effects of case volume on the safety and efficacy of RFA or about the presence or contour of learning curves for this procedure. METHODS: We collected data from the US RFA Patient Registry (from 148 institutions) for patients who underwent RFA for BE from July 2007 to July 2011. We analyzed the effects of the number of patients treated by individual endoscopists and individual centers on safety and efficacy outcomes of RFA. Outcomes, including stricture, bleeding, hospitalization, and complete eradication of intestinal metaplasia (CEIM), were assessed using logistic regression. The effects of center and investigator experience on numbers of treatment sessions to achieve CEIM were examined using linear regression. RESULTS: After we controlled for potential confounders, we found that as the experience of endoscopists and centers increased with cases, the numbers of treatment sessions required to achieve CEIM decreased. This relationship persisted after adjusting for patient age, sex, race, length of BE, and presence of pretreatment dysplasia (P < .01). Center experience was not significantly associated with overall rates of CEIM or complete eradication of dysplasia. We did not observe any learning curve with regard to risks of stricture, gastrointestinal bleeding, perforation, or hospitalization (P > .05). CONCLUSIONS: Based on analysis of a large multicenter registry, efficiency of the treatment, as measured by number of sessions needed to achieve CEIM, increased with case volume, indicating a learning curve effect. This trend began to disappear after treatment of approximately 30 patients by the center or individual endoscopist. However, there was no significant association between safety or efficacy outcomes and previous case volume.

Incidence of Esophageal Adenocarcinoma and Causes of Mortality After Radiofrequency Ablation of Barrett's Esophagus.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) is commonly used to treat Barrett's esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. METHODS: We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. RESULTS: Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. CONCLUSIONS: Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.

The extremely narrow-caliber esophagus is a treatment-resistant subphenotype of eosinophilic esophagitis.

BACKGROUND AND AIMS: Some patients with eosinophilic esophagitis (EoE) have an extremely narrow esophagus, but the characteristics of this group have not been extensively described. We aimed to characterize the narrow-caliber phenotype of EoE, determine associated risk factors, and identify differences in treatment response in this subgroup of patients. METHODS: This retrospective cohort study from 2001 to 2014 included subjects with a new diagnosis of EoE per consensus guidelines. Demographic, endoscopic, histologic, and treatment response data were extracted from medical records. An extremely narrow-caliber esophagus was defined when a neonatal endoscope was required to traverse the esophagus due to the inability to pass an adult endoscope. Patients with and without an extremely narrow-caliber esophagus were compared. Multivariable logistical regression was performed to assess treatment outcomes. RESULTS: Of 513 patients with EoE, 46 (9%) had an extremely narrow-caliber esophagus. These patients were older (33 vs 22 years; P < .01), had longer symptom duration (11 vs 3 years; P < .01), more dysphagia (98% vs 66%; P < .01), and food impactions (53% vs 31%; P < .01). Dilation was more common with extreme narrowing (69% vs 17%; P < .01). Patients with a narrow-caliber esophagus were more refractory to steroid treatment, with lower symptom (56% vs 85%), endoscopic (52% vs 76%), and histologic (33% vs 63%) responses (P < .01 for all), and these differences persisted after multivariate analysis. CONCLUSION: The extremely narrow-caliber esophagus is a more treatment-resistant subphenotype of EoE and is characterized by longer symptom duration and the need for multiple dilations. Recognition of an extremely narrow-caliber esophagus at diagnosis of EoE can provide important prognostic information.

The Six-Food Elimination Diet for Eosinophilic Esophagitis Increases Grocery Shopping Cost and Complexity.

The six-food elimination diet (SFED), where dairy, wheat, eggs, soy, nuts, and seafood are avoided, is an effective treatment for eosinophilic esophagitis (EoE). Patient-related costs of this approach, however, are unknown. We aimed to assess the cost of and ease of shopping for an SFED compared to an unrestricted diet. A dietitian with expertise in EoE generated menus meeting dietary requirements for a week's worth of meals for the SFED and an unrestricted diet. We compared prices and the number of missing items for both diets at standard and specialty grocery stores. The average weekly price of the SFED at a standard supermarket was $92.54 compared to $79.84 for an unrestricted diet (p = 0.0001). A patient shopping at a standard grocery store needed a higher proportion of items from a second store compared to an unrestricted diet (32 vs. 3 %, p = 0.0001). The prices of the SFED and unrestricted diet using a specialty supermarket were comparable ($106.47 vs. $105.96, p = 0.81), as was the percentage of items requiring a trip to a second store (6 vs. 2 % items, p = 0.03). Shopping at a specialty grocery store increased weekly grocery costs by $13.93 (p = 0.04) for the SFED and $26.12 (p = 0.03) for the unrestricted diet. In conclusion, for patients shopping at standard grocery stores, the cost of an SFED is higher, and an SFED requires more items from a second store. These differences disappear at specialty grocery stores, but costs were significantly higher. This cost and logistical burden can inform patients when selecting dietary therapy.

Predictors of response to steroid therapy for eosinophilic esophagitis and treatment of steroid-refractory patients.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is commonly treated with swallowed (topical) corticosteroids (tCS). However, few factors have been described that predict outcomes of steroid therapy. We aimed to identify factors associated with nonresponse to tCS and report outcomes of second-line treatment for patients with steroid-refractory EoE. METHODS: We performed a retrospective cohort study by using the University of North Carolina EoE Clinicopathologic Database to identify patients who received tCS for EoE from 2006 through 2013. Demographic, symptom, endoscopic, and histologic data were extracted from medical records. Immunohistochemistry was performed on archived biopsies. Responders and nonresponders to tCS were compared. RESULTS: Of 221 patients with EoE who received tCS, 71% had endoscopic improvement, 79% had symptomatic improvement, and 57% had histologic response (<15 eosinophils/high-power field). After multivariate logistic regression, esophageal dilation at the baseline examination predicted nonresponse (odds ratio, 2.9; 95% confidence interval, 1.4-6.3), and abdominal pain predicted response (odds ratio for nonresponse, 0.31; 95% confidence interval, 0.12-0.83); no other clinical features were predictive. On the basis of immunohistochemical analysis, higher baseline levels of tryptase (244 vs 157 mast cells/mm(2), P = .04) and eotaxin-3 (2425 vs 239 cells/mm(2), P = .02) were associated with steroid response, but levels of major basic protein were not. Among 27 steroid-refractory patients, a mean of 2 additional therapies were tried; only 48% of the patients eventually responded to any second-line therapy. CONCLUSIONS: On the basis of a retrospective analysis of a large group of patients with EoE, only 57% have a histologic response to steroid therapy. Baseline esophageal dilation and decreased levels of mast cells and eotaxin-3 predicted which patients would not respond to therapy. Combining clinical factors and immunohistochemistry might therefore be used to direct therapy.

Spatial predisposition of dysplasia in Barrett's esophagus segments: a pooled analysis of the SURF and AIM dysplasia trials.

OBJECTIVES: Surveillance endoscopy detects dysplasia within Barrett's esophagus (BE) and dictates treatment. Current biopsy regimens recommend uniformly spaced random biopsies. We assessed the distribution of dysplasia in BE to develop evidence-based biopsy regimens. METHODS: We performed analysis of the distribution of dysplasia within BE using pretreatment biopsy data from two randomized controlled trials (RCTs) of radiofrequency ablation for dysplastic BE: the SURF (Surveillance vs. Radiofrequency Ablation) trial and the AIM Dysplasia (Ablation of Intestinal Metaplasia (AIM) Containing Dysplasia) trial. We used generalized linear models with generalized estimating equations (GEE) to estimate prevalence differences for dysplasia depending on the standardized location of biopsies. We performed Monte Carlo simulation of biopsy regimens to estimate their yield for any dysplasia within segments. RESULTS: Dysplasia preferentially resides in the proximal-most half of the BE segment that is almost twice as likely to demonstrate dysplasia as the distal-most quartile. In pooled analysis, compared with the distal-most quarter, the prevalence difference in the proximal-most quarter was 22.6%, in the second proximal-most quarter 23.1%, and in the second distal-most quarter 15.3%. The best performing biopsy regimen in simulation studies acquired 8 biopsies in the most proximal cm of BE, 8 biopsies in the second cm, and 2 biopsies in each cm thereafter (q1cm: 8, 8, 2, 2…). A slightly simpler q2cm (every 2 cm) regimen (q2cm: 12, 12, 4…) was nearly as effective. CONCLUSIONS: The post hoc analysis of two RCTs reveals a substantially increased prevalence of dysplasia proximally in BE segments. Our simulations suggest an altered biopsy regimen could increase sensitivity of biopsies in short-segment BE by >30%.

Recurrent intestinal metaplasia after radiofrequency ablation for Barrett's esophagus: endoscopic findings and anatomic location.

BACKGROUND: Radiofrequency ablation (RFA) is a safe and effective treatment for Barrett's esophagus (BE) that results in high rates of complete eradication of intestinal metaplasia (CEIM). However, recurrence is common after CEIM, and surveillance endoscopy is recommended. Neither the anatomic location nor the endoscopic appearance of these recurrences is well-described. OBJECTIVE: Describe the location of histologic specimens positive for recurrence after CEIM and the testing performance of endoscopic findings for the histopathologic detection of recurrence. DESIGN: Retrospective cohort. SETTING: Single referral center. PATIENTS: A total of 198 patients with BE with at least 2 surveillance endoscopies after CEIM. INTERVENTIONS: RFA, EMR, surveillance endoscopy. MAIN OUTCOME MEASUREMENTS: The anatomic location and histologic grade of recurrence. RESULTS: In a mean 3.0 years of follow-up, 32 (16.2%; 95% confidence interval [CI], 11.0%-22.0%) patients had recurrence of disease, 5 (2.5%; 95% CI, 0.3%-4.7%) of whom progressed beyond their worst before-treatment histology. Recurrence was most common at or near the gastroesophageal junction (GEJ). Recurrence>1 cm proximal to the GEJ always was accompanied by endoscopic findings, and random biopsies in these areas detected no additional cases. The sensitivity of any esophageal sign under high-definition white light or narrow-band imaging for recurrence was 59.4% (42.4%, 76.4%), and the specificity was 80.6% (77.2%, 84.0%). LIMITATIONS: Single-center study. CONCLUSION: Recurrent intestinal metaplasia often is not visible to the endoscopist and is most common near the GEJ. Random biopsies>1 cm above the GEJ had no yield for recurrence. In addition to biopsy of prior EMR sites and of suspicious lesions, random biopsies oversampling the GEJ are recommended.

Dietary elimination therapy is an effective option for adults with eosinophilic esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is an immune-mediated disorder. Food elimination is an established treatment for children, but data in adults are limited. We aimed to determine the response of adults with EoE to dietary therapy. METHODS: This was a retrospective cohort study using the University of North Carolina EoE database from 2006 to 2012. Subjects were age 18 and older, had EoE by consensus guidelines, and had undergone dietary therapy either with a targeted elimination diet or a 6-food elimination diet (SFED). Outcomes were symptomatic, endoscopic, and histologic improvement. Demographic, endoscopic, symptomatic, and laboratory predictors of response to dietary therapy were assessed. RESULTS: Of 31 adults who underwent dietary therapy (mean age, 36 y; 48% male; 90% white; mean baseline eosinophil count, 78 eos/hpf), 22 had a targeted elimination diet and 9 had SFED. Symptoms improved in 71% (68% in targeted, 78% in SFED), and endoscopic appearance improved in 54% (53% in targeted, 56% in SFED). After dietary therapy, the mean eosinophil count decreased to 43 eos/hpf (P = .009). Eleven subjects (39%) responded with fewer than 15 eos/hpf (32% in targeted and 56% in SFED; P = .41). No clinical, endoscopic, or histologic factors predicted response to dietary therapy. Of the 11 responders, 9 underwent food re-introduction to identify trigger(s), and 4 (44%) reacted to dairy, 4 (44%) reacted to eggs, 2 (22%) reacted to wheat, 1 (11%) reacted to shellfish, 1 (11%) reacted to legumes, and 1 (11%) reacted to nuts. CONCLUSIONS: Dietary elimination is a successful treatment modality for adults with EoE. Further research should emphasize which factors can predict effective dietary therapy.

WSR-88D doppler radar detection of corn earworm moth migration.

Corn earworm (Lepidoptera: Noctuidae) (CEW) populations infesting one crop production area may rapidly migrate and infest distant crop production areas. Although entomological radars have detected corn earworm moth migrations, the spatial extent of the radar coverage has been limited to a small horizontal view above crop production areas. The Weather Service Radar (version 88D) (WSR-88D) continuously monitors the radar-transmitted energy reflected by, and radial speed of, biota as well as by precipitation over areas that may encompass crop production areas. We analyzed data from the WSR-88D radar (S-band) at Brownsville, Texas, and related these data to aerial concentrations of CEW estimated by a scanning entomological radar (X-band) and wind velocity measurements from rawinsonde and pilot balloon ascents. The WSR-88D radar reflectivity was positively correlated (r2=0.21) with the aerial concentration of corn earworm-size insects measured by a scanning X-band radar. WSR-88D radar constant altitude plan position indicator estimates of wind velocity were positively correlated with wind speed (r2=0.56) and wind direction (r2=0.63) measured by pilot balloons and rawinsondes. The results reveal that WSR-88D radar measurements of insect concentration and displacement speed and direction can be used to estimate the migratory flux of corn earworms and other nocturnal insects, information that could benefit areawide pest management programs. In turn, identification of the effects of spatiotemporal patterns of migratory flights of corn earworm-size insects on WSR-88D radar measurements may lead to the development of algorithms that increase the accuracy of WSR-88D radar measurements of reflectivity and wind velocity for operational meteorology.

Certification of vitamins and carotenoids in SRM 3280 multivitamin/multielement tablets.

A new multivitamin/multielement dietary supplement Standard Reference Material (SRM) has been issued by the National Institute of Standards and Technology (NIST), with certified and reference concentration values for 13 vitamins, 24 elements, and 2 carotenoids. The constituents have been measured by multiple analytical methods with data contributed by NIST and by collaborating laboratories. This effort included the first use of isotope dilution mass spectrometry for value assignment of both fat-soluble vitamins (FSVs) and water-soluble vitamins (WSVs). Excellent agreement was obtained among the methods, with relative expanded uncertainties for the certified concentration values typically ranging from <2% to 15% for vitamins.

Imino-bridged bisphosphaalkenes (2,4-diphospha-3-azapentadienes).

Deprotonation of aminophosphaalkenes (RMe(2)Si)(2)C=PN(H)(R') (R=Me, iPr; R'=tBu, 1-adamantyl (1-Ada), 2,4,6-tBu(3)C(6)H(2) (Mes*)) followed by reactions of the corresponding Li salts Li[(RMe(2)Si)(2)C=P(M)(R')] with one equivalent of the corresponding P-chlorophosphaalkenes (RMe(2)Si)(2)C=PCl provides bisphosphaalkenes (2,4-diphospha-3-azapentadienes) [(RMe(2)Si)(2)C=P](2)NR'. The thermally unstable tert-butyliminobisphosphaalkene [(Me(3)Si)(2)C=P](2)NtBu (4 a) undergoes isomerisation reactions by Me(3)Si-group migration that lead to mixtures of four-membered heterocyles, but in the presence of an excess amount of (Me(3)Si)(2)C=PCl, 4 a furnishes an azatriphosphabicyclohexene C(3)(SiMe(3))(5)P(3)NtBu (5) that gave red single crystals. Compound 5 contains a diphosphirane ring condensed with an azatriphospholene system that exhibits an endocylic P=C double bond and an exocyclic ylidic P((+))-C((-))(SiMe(3))(2) unit. Using the bulkier iPrMe(2)Si substituents at three-coordinated carbon leads to slightly enhanced thermal stability of 2,4-diphospha-3-azapentadienes [(iPrMe(2)Si)(2)C=P](2)NR' (R'=tBu: 4 b; R'=1-Ada: 8). According to a low-temperature crystal-structure determination, 8 adopts a non-planar structure with two distinctly differently oriented P=C sites, but (31)P NMR spectra in solution exhibit singlet signals. (31)P NMR spectra also reveal that bulky Mes* groups (Mes*=2,4,6-tBu(3)C(6)H(2)) at the central imino function lead to mixtures of symmetric and unsymmetric rotamers, thus implying hindered rotation around the P-N bonds in persistent compounds [(RMe(2)Si)(2)C=P](2)NMes* (11 a, 11 b). DFT calculations for the parent molecule [(H(3)Si)(2)C=P](2)NCH(3) suggest that the non-planar distortion of compound 8 will have steric grounds.