Pleural fluid metastasis of plasmacytoid urothelial carcinoma in comparison to micropapillary and conventional high-grade urothelial carcinoma: Cytologic and immuonohistochemical findings.

Plasmacytoid urothelial carcinoma (PUC) is a rare but clinically aggressive variant of high-grade urothelial carcinoma (HGUC). Cytological features include single plasmacytoid neoplastic cells with N:C ratio around 0.5, eccentric nuclei, nuclear hyperchromasia, irregular nuclear membrane, and vacuolated cytoplasm. Micropapillary urothelial carcinoma (MPUC) is another clinically aggressive variant of HGUC that shares some overlapping features of PUC. The diagnosis of these two aggressive variants in pleural effusions can be challenging due to features mimicking adenocarcinoma, unusual immunochemistry profile, and confusion with differential diagnoses, especially when pertinent clinical information is unavailable. We present report on one case each of pleural fluid metastasis of PUC and MPUC respectively, and compare the findings with that of a metastatic conventional HGUC originally thought to be metastatic adenocarcinoma. The diagnosis of PUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, and CD138, diminished or loss of E-cadherin membranous expression, negative expression for p63, p53, Epicam-BerEP4, Epicam-MOC31, and p120. The diagnosis of MPUC was confirmed with immunostain profile similar to that of PUC except positive stain for E-cadherin, p120, and p53. The diagnosis of HGUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, p63, Epicam-BerEP4 (focal weak), and Epicam-MOC31. Our cases of metastatic urothelial carcinoma showed features mimicking adenocarcinoma and others, especially the MPUC and HGUC were diagnosed without prior tissue diagnosis of urothelial carcinoma. This report emphasizes the cytohistological and immunohistochemical details of urothelial carcinoma involving effusion fluid and discusses potential pitfalls in diagnosis.

Immunotherapy- (Blinatumomab-) Related Lineage Switch of KMT2A/AFF1 Rearranged B-Lymphoblastic Leukemia into Acute Myeloid Leukemia/Myeloid Sarcoma and Subsequently into B/Myeloid Mixed Phenotype Acute Leukemia.

The presence of KMT2A/AFF1 rearrangement in B-lymphoblastic leukemia (B-ALL) is an independent poor prognostic factor and has been associated with higher rate of treatment failure and higher risk of linage switch under therapy. Blinatumomab has shown promising therapeutic results in refractory or relapsed B-ALL; however, it has potential risk of inducing lineage switch, especially in KMT2A/AFF1 rearranged B-ALL into acute myeloid leukemia and/or myeloid sarcoma. We report a 40-year-old female with KMT2A/AFF1-rearranged B-ALL that was refractory to conventional chemotherapy. Following administration of blinatumomab, she developed a breast mass proven to be myeloid sarcoma, in addition to bone marrow involvement by AML. Approximately six weeks after cessation of blinatumomab, a repeat bone marrow examination revealed B/myeloid MPAL.

Determination of esophageal eosinophil counts and other histologic features of eosinophilic esophagitis by pathology trainees is highly accurate.

Many studies of eosinophilic esophagitis (EoE) use expert pathology review, but it is unknown whether less experienced pathologists can reliably assess EoE histology. We aimed to determine whether trainee pathologists can accurately quantify esophageal eosinophil counts and identify associated histologic features of EoE, as compared with expert pathologists. We used a set of 40 digitized slides from patients with varying degrees of esophageal eosinophilia. Each of 6 trainee pathologists underwent a teaching session and used our validated protocol to determine eosinophil counts and associated EoE findings. The same slides had previously been evaluated by expert pathologists, and these results comprised the criterion standard. Eosinophil counts were correlated, and agreement was calculated for the diagnostic threshold of 15 eosinophils per high-power field as well as for associated EoE findings. Peak eosinophil counts were highly correlated between the trainees and the criterion standard (ρ ranged from 0.87 to 0.92; P<.001 for all). Peak counts were also highly correlated between trainees (0.75-0.91; P<.001), and results were similar for mean counts. Agreement was excellent for determining if a count exceeded the diagnostic threshold (κ ranged from 0.83 to 0.89; P<.001). Agreement was very good for eosinophil degranulation (κ = 0.54-0.83; P<.01) and spongiosis (κ = 0.44-0.87; P<.01) but was lower for eosinophil microabscesses (κ = 0.37-0.64; P<.01). In conclusion, using a teaching session, digitized slide set, and validated protocol, the agreement between pathology trainees and expert pathologists for determining eosinophil counts was excellent. Agreement was very good for eosinophil degranulation and spongiosis but less so for microabscesses.

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.

ß2-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study.

BACKGROUND: Despite the significant interest in ß2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95% confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy.

Estrogen and progesterone decrease let-7f microRNA expression and increase IL-23/IL-23 receptor signaling and IL-17A production in patients with severe asthma.

BACKGROUND: Women have an increased prevalence of severe asthma compared with men. IL-17A is associated with severe asthma and requires IL-23 receptor (IL-23R) signaling, which is negatively regulated by let-7f microRNA. OBJECTIVE: We sought to Determine the mechanism by which 17ß-estradiol (E2) and progesterone (P4) increase IL-17A production. METHODS: IL-17A production was determined by using flow cytometry in TH17 cells from women (n = 14) and men (n = 15) with severe asthma. Cytokine levels were measured by using ELISA, and IL-23R and let-7f expression was measured by using quantitative PCR in TH17-differentiated cells from healthy women (n = 13) and men (n = 14). In sham-operated or ovariectomized female mice, 17ß-E2, P4, 17ß-E2+P4, or vehicle pellets were administered for 3 weeks before ex vivo TH17 cell differentiation. Airway neutrophil infiltration and CXCL1 (KC) expression were also determined in ovalbumin (OVA)-challenged wild-type female recipient mice with an adoptive transfer of OVA-specific TH17 cells from female and male mice. RESULTS: In patients with severe asthma and healthy control subjects, IL-17A production was increased in TH17 cells from women compared with men. IL-23R expression was increased and let-7f expression was decreased in TH17-differentiated cells from women compared with men. In ovariectomized mice IL-17A and IL-23R expression was increased and Let-7f expression was decreased in TH17 cells from mice administered 17ß-E2+P4 compared with those administered vehicle. Furthermore, transfer of female OVA-specific TH17 cells increased acute neutrophil infiltration in the lungs of OVA-challenged recipient mice compared with transfer of male OVA-specific TH17 cells. CONCLUSIONS: 17ß-E2+P4 increased IL-17A production from TH17 cells, providing a potential mechanism for the increased prevalence of severe asthma in women compared with men.

A Clinical Prediction Tool Identifies Cases of Eosinophilic Esophagitis Without Endoscopic Biopsy: A Prospective Study.

OBJECTIVES: Eosinophilic esophagitis (EoE) is difficult to distinguish from gastroesophageal reflux (GERD) and other causes of dysphagia. We assessed the utility of a set of clinical and endoscopic features for predicting EoE without obtaining esophageal biopsies. METHODS: We prospectively enrolled consecutive adults undergoing outpatient upper endoscopy at the University of North Carolina from July 2011 through December 2013. Incident cases of EoE were diagnosed per consensus guidelines. Non-EoE controls had either GERD- or dysphagia-predominant symptoms. A predictive model containing clinical and endoscopic, but no histological, data was assessed. Receiver operator characteristic curves were constructed and the area under the curve (AUC) was calculated. RESULTS: A total of 81 EoE cases (mean age 38 years; 60% male; 93% white; 141 eosinophils per high-power field (eos/hpf)) and 144 controls (mean age 52, 38% male; 82% white; 3 eos/hpf) were enrolled. A combination of clinical (age, sex, dysphagia, food allergy) and endoscopic (rings, furrows, plaques, hiatal hernia) features was highly predictive of EoE. The AUC was 0.944, with sensitivity, specificity, and accuracy of 84, 97, and 92%. Similar values were seen after limiting controls to those with only reflux or dysphagia or to those with esophageal eosinophilia not due to EoE. CONCLUSIONS: We validated a set of clinical and endoscopic features to predict EoE with a high degree of accuracy and allow identification of those at very low risk of disease. Use of these predictors at the point-of-care will avoid the effort and expense of low-yield histological examinations for EoE.

Respiratory Severity Score Separates Upper Versus Lower Respiratory Tract Infections and Predicts Measures of Disease Severity.

Background: A respiratory severity score (RSS) describing acute respiratory illness (ARI) severity would be useful for research and clinical purposes. Methods: A total of 630 term infants presenting with ARI had their RSS measured. Results: RSS was higher in those with lower respiratory tract infection (LRTI) compared with those with upper respiratory infection (URI; LRTI 6.5 [4-8.5]; URI 1 [0-2], p<0.001) and in hospitalized infants compared with outpatients (hospitalized 6.5 [4-9]; outpatient 1 [0-3], p<0.001). Conclusions: RSS is higher in LRTI compared with URI and in hospitalized compared with nonhospitalized infants.

Utility of a Noninvasive Serum Biomarker Panel for Diagnosis and Monitoring of Eosinophilic Esophagitis: A Prospective Study.

OBJECTIVES: Noninvasive biomarkers would be valuable for diagnosis and monitoring of eosinophilic esophagitis (EoE). The aim of this study was to determine the utility of a panel of serum biomarkers for the diagnosis and management of EoE. METHODS: We conducted a prospective cohort study of consecutive adults undergoing outpatient esophagogastroduodenoscopy. Incident cases of EoE were diagnosed per consensus guidelines; controls had gastroesophageal reflux disease (GERD) or dysphagia and did not meet the EoE criteria. EoE cases were treated with topical steroids and had repeat endoscopy. Pre- and post-treatment serum samples were analyzed in a blinded manner for interleukin (IL)-4, IL-5, IL-6, IL-9, IL-13, transforming growth factor (TGF)-α, TGF-ß, tumor necrosis factor-α, eotaxin-1, -2, and -3, thymic stromal lymphopoietin (TSLP), major basic protein, and eosinophil-derived neurotoxin. Cases and controls were compared at baseline, and pre- and post-treatment assays were compared in cases. RESULTS: A total of 61 incident EoE cases and 87 controls were enrolled; 51 EoE cases had post-treatment serum analyzed. There were no significant differences in any of the biomarkers between EoE cases and controls at baseline. IL-13 and eotaxin-3 for cases and controls were 85 ± 160 vs. 43 ± 161 pg/ml (P=0.12) and 41 ± 159 vs. 21 ± 73 (P=0.30). There were no significant differences in assay values among cases before and after treatment. There were also no differences after stratification by atopic status or treatment response. CONCLUSIONS: A panel of inflammatory factors known to be associated with EoE pathogenesis were not increased in the serum, nor were they responsive to therapy. None of these biomarkers are likely candidates for a serum test for EoE. Histologic analysis for diagnosis and management of EoE continues to be necessary, and novel, less invasive, biomarkers are needed.

Distribution and variability of esophageal eosinophilia in patients undergoing upper endoscopy.

The variability of eosinophilic infiltrates in eosinophilic esophagitis is not well described. This study aimed to determine the distribution of esophageal eosinophilia and the utility of histologic cut-points for eosinophilic esophagitis diagnosis in subjects undergoing endoscopy. We performed a prospective study of adults undergoing outpatient endoscopy. Research protocol esophageal biopsies were obtained from all subjects. Incident cases of eosinophilic esophagitis were diagnosed per consensus guidelines. Biopsies were interpreted following a validated protocol, and maximum eosinophil counts (eosinophils per high-power field; eos/hpf) were determined. Histologic analyses were performed on a per-patient, per-biopsy, and per-hpf basis. There were 213 patients, yielding 923 esophageal biopsies with 4588 hpfs. Overall, 48 patients (23%), 165 biopsy fragments (18%), and 449 hpfs (10%) had ≥15 eos/hpf; most subjects had no or low levels of eosinophils. In the eosinophilic esophagitis cases, 119 biopsy fragments (63%) and 332 hpfs (36%) had ≥15 eos/hpf. There was a mean 104-fold difference between the lowest and highest hpf eosinophil count for the eosinophilic esophagitis patients; 85% of the biopsies from eosinophilic esophagitis cases also had at least one hpf with <15 eos/hpf. The cut-point of 15 eos/hpf had a sensitivity of 100% and a specificity of 96% for diagnosis of eosinophilic esophagitis. In conclusion, most patients have little to no esophageal eosinophilia. In patients with eosinophilic esophagitis, there was marked variability in the eosinophil counts by biopsy and by hpf within a given biopsy. Additionally, the 15 eos/hpf cut-point was highly sensitive and specific for eosinophilic esophagitis. Multiple esophageal biopsies from different locations should be obtained to optimize eosinophilic esophagitis diagnosis.

Markers of eosinophilic inflammation for diagnosis of eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia: a prospective study.

BACKGROUND & AIMS: Distinguishing between eosinophilic esophagitis (EoE), gastroesophageal reflux disease, and proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is challenging. We assessed whether immunohistochemical analysis of esophageal tissues for major basic protein (MBP), eotaxin-3, and tryptase can be used for diagnosis of EoE and to differentiate EoE from PPI-REE. METHODS: We conducted a prospective study of 196 consecutive adults who underwent outpatient endoscopy at the University of North Carolina from 2009 through 2012. Incident cases of EoE were diagnosed per consensus guidelines. Patients with gastroesophageal reflux disease or dysphagia served as controls. PPI-REE was defined as a symptomatic and histologic response to a PPI. Immunohistochemistry was performed to quantify MBP, eotaxin-3, and tryptase. The maximum density of epithelial staining was determined for each assay; levels were compared between EoE and control groups and then EoE and PPI-REE groups, and receiver operating characteristic curves were constructed. RESULTS: Esophageal tissues from patients with EoE (n = 50) had a median 951 MBP-positive cells/mm(2), whereas those from controls (n = 123) had a median 2 MBP-positive cells/mm(2) (P < .001). Samples from patients with EoE had a median 155 eotaxin-3-positive cells/mm(2), and those from controls (n = 123) had 18 eotaxin-3-positive cells/mm(2) (P < .001). Samples from patients with EoE had a median 249 tryptase-positive cells/mm(2), and those from controls (n = 123) had 11 tryptase-positive cells/mm(2) (P < .001). Levels of MBP, eotaxin-3, tryptase, and the combination of all 3 identified patients with EoE with area under the receiver operating characteristic curve values of 0.99, 0.94, 0.99, and 1.00. Analyses of only samples with eosinophil counts of 10-100 eosinophils per high-power field produced similar results. No marker distinguished EoE from PPI-REE. Esophageal tissues from patients with PPI-REE (n = 23) had 987 MBP-positive cells/mm(2) (P = .18, compared with EoE), 160 eotaxin-3-positive cells/mm(2) (P = .33), and 243 tryptase-positive cells/mm(2) (P = .28). CONCLUSIONS: Esophageal tissues from patients with EoE have substantially higher levels of MBP, eotaxin-3, and tryptase than controls on the basis of immunohistochemical analysis. Assays for the 3 markers identify patients with EoE with 100% accuracy but cannot distinguish EoE from PPI-REE.

Association between breast-feeding and severity of acute viral respiratory tract infection.

In a cross-sectional analysis of 629 mother-infants dyads, breast-feeding (ever vs. never) was associated with decreased relative odds of a lower versus upper respiratory tract infection (adjusted odds ratio: 0.64; 95% confidence interval: 0.42-0.99). There was not a significant association between breast-feeding and bronchiolitis severity score or length of hospital stay.

Gastroesophageal Reflux Disease Increases Infant Acute Respiratory Illness Severity, but not Childhood Asthma.

It is unknown whether gastroesophageal reflux disease (GERD) during infancy affects infant bronchiolitis severity or childhood asthma inception. Four hundred thirty-two infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection were studied. The primary exposure was the parental report of a previous GERD diagnosis. Outcomes included bronchiolitis severity at initial presentation and childhood asthma diagnosis at age 4. Infants with parentally reported GERD had a higher bronchiolitis severity score (range=0-12, clinically significant difference=0.5), indicating more severe disease, than infants without reported GERD (median 5.5 [interquartile range 3.5-9.0] among those with reported GERD versus 4.0 [1.0-7.0] among those without, P=0.005). This association persisted after adjusting for infant age, race, gender, and secondhand smoke exposure by a propensity score (adjusted odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14-3.46, P=0.02). The parental report of GERD during infancy was not associated with the parental report of asthma diagnosis at age 4. GERD during infancy may contribute to acute respiratory illness severity, but is not associated with asthma diagnosis at age 4. Future prospective studies are needed to confirm these findings.

Clinical and endoscopic characteristics do not reliably differentiate PPI-responsive esophageal eosinophilia and eosinophilic esophagitis in patients undergoing upper endoscopy: a prospective cohort study.

OBJECTIVES: Proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is a newly recognized entity that must be differentiated from eosinophilic esophagitis (EoE). Little is known about this condition. We aimed to determine the prevalence of PPI-REE and EoE in patients undergoing upper endoscopy and determine features that distinguish the two groups. METHODS: This prospective study conducted at the University of North Carolina from 2009 to 2011 enrolled consecutive adult patients undergoing outpatient upper endoscopy. Subjects had esophageal biopsies to quantify the maximum eosinophil count per high-power field (eos/hpf; hpf=0.24 mm(2)). If biopsies revealed ≥15 eos/hpf, subjects were treated with twice daily PPI for 8 weeks and endoscopy was repeated. If ≥15 eos/hpf persisted despite PPI therapy, EoE was diagnosed. If there were <15 eos/hpf, PPI-REE was diagnosed. The proportion of patients in each group was calculated, and patients with EoE and PPI-REE were compared. RESULTS: Of the 223 subjects enrolled, 173 had dysphagia and 50 did not. Of those with dysphagia, 66 (38%) had ≥15 eos/hpf. After the PPI trial, 40 (23%) were confirmed to have EoE, and 24 (14%) had PPI-REE. Of those without dysphagia, 2 (4%) had ≥15 eos/hpf, and after the PPI trial, 1 (2%) had EoE. Compared with EoE, PPI-REE patients were more likely to be older and male and less likely to have typical endoscopic findings of EoE. However, none of the individual factors was independently predictive of PPI-REE status on multivariable analysis. Similarly, although some endoscopic findings were differentially distributed between PPI-REE and EoE, none were significantly associated with disease status on multivariable analysis. CONCLUSIONS: Esophageal eosinophilia is common among patients undergoing esophagogastroduodenoscopy for dysphagia. Although EoE was seen in nearly a quarter of patients with dysphagia, PPI-REE was almost as common, and accounted for over one-third of those with ≥15 eos/hpf. No clinical or endoscopic features independently distinguished PPI-REE from EoE before the PPI trial.

Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years.

BACKGROUND: Prospective data on viral etiology and clinical characteristics of bronchiolitis and upper respiratory illness (URI) in infants are limited. METHODS: This prospective cohort enrolled previously healthy term infants during inpatient or outpatient visits for acute URI or bronchiolitis during September to May 2004 to 2008. Illness severity was determined using an ordinal bronchiolitis severity score. Common respiratory viruses were identified by real-time reverse-transcriptase polymerase chain reaction. RESULTS: Of 648 infants, 67% were enrolled during inpatient visits and 33% during outpatient visits. Seventy percent had bronchiolitis, 3% croup and 27% URI. Among infants with bronchiolitis, 76% had respiratory syncytial virus (RSV), 18% human rhinovirus (HRV), 10% influenza, 2% coronavirus, 3% human metapneumovirus and 1% parainfluenza virus. Among infants with croup, 39% had HRV, 28% parainfluenza virus, 28% RSV, 11% influenza, 6% coronavirus and none human metapneumovirus. Among infants with URI, 46% had HRV, 14% RSV, 12% influenza, 7% coronavirus, 6% parainfluenza virus and 4% human metapneumovirus. Individual viruses exhibited distinct seasonal, demographic and clinical expression. CONCLUSIONS: The most common infections among infants seeking care in unscheduled medical visits for URI or bronchiolitis were RSV and HRV. Demographic differences were observed between patients with different viruses, suggesting that host and viral factors play a role in phenotypic expression of viral illness.

Increased healthcare resource utilization for acute respiratory illness among Latino infants.

OBJECTIVE: To examine healthcare resource utilization for acute respiratory illness in Latino infants compared with other racial/ethnic groups. STUDY DESIGN: We studied 674 term-born, previously healthy infants brought in for an unscheduled healthcare visit for an acute respiratory illness. The predictor variable was infant race/ethnicity, and the primary outcome was healthcare resource utilization, adjusted for age and disease severity. RESULTS: The cohort was 14% Latino, 52% white, 22% African American, and 12% other race/ethnicity. More than one-third (37%) of the mothers of Latino infants were Spanish-speaking. The bronchiolitis severity score was higher (indicating more severe disease) in white infants (median, 6.0; IQR, 3.0-9.0 on a scale of 0-12) compared with Latino (median, 3.0; IQR, 1.0-6.0) and African American (median, 3.5; IQR, 1.0-6.0) infants (P < .001 for the comparison of all groups). Disease severity was similar in Latino and African American infants (P = .96). Latino infants were the most likely to receive antibiotics (58%, compared with 47% of whites and 34% of African Americans; P = .005) and to have body fluid cultures drawn. Latino infants also were more likely than African American infants to undergo chest radiography and respiratory virus rapid antigen testing (P ≤ .01). Latino infants from Spanish-speaking families had a higher rate of respiratory syncytial virus testing compared with those from English-speaking families (76% vs 51%; P = .016). CONCLUSION: Providers caring for Latino infants with acute respiratory illness ordered more antibiotics and diagnostic testing for this group, particularly compared with African Americans, even though the 2 groups had similar disease severity and socioeconomic disparities. Language barrier may be a possible explanation for these differences.

Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile.

BACKGROUND: EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management. METHODS: In this study, RNA expression profiling was performed on 326 macrodissected paraffin-embedded tissues including 204 cancers and, when available, adjacent non-malignant mucosa. Nanostring nCounter probes targeted 96 RNAs (20 viral, 73 human, and 3 spiked RNAs). RESULTS: In 182 tissues with adequate housekeeper RNAs, distinct profiles were found in infected versus uninfected cancers, and in malignant versus adjacent benign mucosa. EBV-infected gastric cancers expressed nearly all of the 18 latent and lytic EBV RNAs in the test panel. Levels of EBER1 and EBER2 RNA were highest and were proportional to the quantity of EBV genomes as measured by Q-PCR. Among protein coding EBV RNAs, EBNA1 from the Q promoter and BRLF1 were highly expressed while EBNA2 levels were low positive in only 6/14 infected cancers. Concomitant upregulation of cellular factors implies that virus is not an innocent bystander but rather is linked to NFKB signaling (FCER2, TRAF1) and immune response (TNFSF9, CXCL11, IFITM1, FCRL3, MS4A1 and PLUNC), with PPARG expression implicating altered cellular metabolism. Compared to adjacent non-malignant mucosa, gastric cancers consistently expressed INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, PTGS2 (COX2), BBC3, ICAM1, TNFSF9, SULF1, SLC2A1, TYMS, three collagens, the cell proliferation markers MYC and PCNA, and EBV BLLF1 while they lacked CDH1 (E-cadherin), CLDN18, PTEN, SDC1 (CD138), GAST (gastrin) and its downstream effector CHGA (chromogranin). Compared to lymphoepithelioma-like carcinoma of the uterine cervix, gastric cancers expressed CLDN18, EPCAM, REG4, BBC3, OLFM4, PPARG, and CDH17 while they had diminished levels of IFITM1 and HIF1A. The druggable targets ERBB2 (Her2), MET, and the HIF pathway, as well as several other potential pharmacogenetic indicators (including EBV infection itself, as well as SPARC, TYMS, FCGR2B and REG4) were identified in some tumor specimens. CONCLUSION: This study shows how modern molecular technology applied to archival fixed tissues yields novel insights into viral oncogenesis that could be useful in managing affected patients.

Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis.

We performed a randomized trial to compare nebulized and viscous topical corticosteroid treatments for eosinophilic esophagitis (EoE). Subjects with incident EoE (n = 25) received budesonide 1 mg twice daily, either nebulized and then swallowed (NEB) or as an oral viscous slurry (OVB), for 8 weeks. Baseline eosinophil counts for the NEB and OVB groups were 101 and 83 (P = .62). Posttreatment counts were 89 and 11 (P = .02). The mucosal medication contact time, measured by scintigraphy, was higher for the OVB group than the NEB group (P < .005) and was inversely correlated with eosinophil count (R = -0.67; P = .001). OVB was more effective than NEB in reducing numbers of esophageal eosinophils in patients with EoE. OVB provided a significantly higher level of esophageal exposure to the therapeutic agent, which correlated with lower eosinophil counts.