Eosinophilic esophagitis (EE) is an emerging disorder with a poorly understood pathogenesis. In order to define disease mechanisms, we took an empirical approach analyzing esophageal tissue by a genome-wide microarray expression analysis. EE patients had a striking transcript signature involving 1% of the human genome that was remarkably conserved across sex, age, and allergic status and was distinct from that associated with non-EE chronic esophagitis. Notably, the gene encoding the eosinophil-specific chemoattractant eotaxin-3 (also known as CCL26) was the most highly induced gene in EE patients compared with its expression level in healthy individuals. Esophageal eotaxin-3 mRNA and protein levels strongly correlated with tissue eosinophilia and mastocytosis. Furthermore, a single-nucleotide polymorphism in the human eotaxin-3 gene was associated with disease susceptibility. Finally, mice deficient in the eotaxin receptor (also known as CCR3) were protected from experimental EE. These results implicate eotaxin-3 as a critical effector molecule for EE and provide insight into disease pathogenesis.

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Collectively, these studies demonstrate cooperation between systemic CD4+ Th2-cell-mediated immunity and an enhanced eosinophil-CCR3/eotaxin-3 pathway in EE pathogenesis. Furthermore, the imbalanced Th2 immunity and increased CCR3 expression are reversible with disease remission.

BACKGROUND The purpose of our study was to perform a large cross-sectional study aimed at determining the postnatal growth pattern of the clavicle from birth to 18 years of age. METHODS We analyzed digital chest radiographs of a convenience sample of 961 individuals between birth and 18 years of age. Malrotated radiographs were excluded. Right and left clavicle lengths were measured in millimeters from the most lateral ossified border to the most medial ossified border of each clavicle. Study subjects were divided into 19 subgroups with the first group being labeled “birth to 11 months of age” followed by 1 year olds, 2 year olds, etc. Subjects were also grouped by gender. There was a minimum of 25 subjects in each group. RESULTS At 18 years of age the mean±SD clavicle length for females was 149±12 mm and for males it was 161±11 mm. Although a statistically significant difference (p=0.049) was noted between the length of right and left clavicles it was not clinically significant (0.036 mm). A steady growth rate was noted for both genders from birth to age 12 years (8.4 mm per yr). Above age 12 there were significant differences in the growth of the clavicles of girls (2.6 mm per yr) versus boys (5.4 mm per yr) (p<0.001). Our data suggest that females achieve 80% of their clavicle length by 9 years of age and boys by 12 years of age. CONCLUSION This cross-sectional study establishes that relatively little clavicle growth (20%) remains for girls beyond age 9 years and for boys beyond 12 years. The length of one clavicle may be properly judged by comparing it to the contralateral clavicle. CLINICAL RELEVANCE Remodeling of clavicle shaft fractures is currently believed to be proportional to growth remaining. Our study questions the capacity of the clavicle to re-establish normal length beyond the age thresholds we have identified.

Introduction Critically ill children with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT) are at increased risk of death. The selective cytopheretic device (SCD) promotes an immunomodulatory effect when circuit ionized calcium (iCa 2+ ) is maintained at <0.40 mmol/l with regional citrate anticoagulation (RCA). In a randomized trial of adult patients on CRRT, those treated with the SCD maintaining an iCa 2+ <0.40 mmol/l had improved survival/dialysis independence. We conducted a US Food and Drug Administration (FDA)–sponsored study to evaluate safety and feasibility of the SCD in 16 critically ill children. Methods Four pediatric intensive care units (ICUs) enrolled children with AKI and multiorgan dysfunction receiving CKRT to receive the SCD integrated post-CKRT membrane. RCA was used to achieve a circuit iCa 2+ level <0.40 mmol/l. Subjects received SCD treatment for 7 days or CKRT discontinuation, whichever came first. Results The FDA target enrollment of 16 subjects completed the study from December 2016 to February 2020. Mean age was 12.3 ± 5.1 years, weight was 53.8 ± 28.9 kg, and median Pediatric Risk of Mortality II was 7 (range 2–19). Circuit iCa 2+ levels were maintained at <0.40 mmol/l for 90.2% of the SCD therapy time. Median SCD duration was 6 days. Fifteen subjects survived SCD therapy; 12 survived to ICU discharge. All ICU survivors were dialysis independent at 60 days. No SCD-related adverse events (AEs) were reported. Conclusion Our data demonstrate that SCD therapy is feasible and safe in children who require CKRT. Although we cannot make efficacy claims, the 75% survival rate and 100% renal recovery rate observed suggest a possible favorable benefit-to-risk ratio.

MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P = .038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant.