Understanding and Improving Knowledge of Cancer Survivorship Care Among College Providers.

This study aimed to assess college providers' basic knowledge of the health risks of young adult cancer survivors (YAS) and related care guidelines and to determine whether an educational in-service is an effective platform for increasing college health providers' knowledge about survivorship care at a large university health center. During phase 1, staff from college health centers and office of disabilities in the Philadelphia area (n = 40 staff members from 24 colleges/universities) completed a needs assessment on their experiences with YAS and preferences for education and care coordination. During phase 2, a 1-h educational in-service, informed by results of the survey, was provided to 18 health center medical providers. While most providers indicated that YAS are at risk for chronic health conditions because of cancer treatment, nearly all were unfamiliar with the content of published long-term follow-up guidelines for cancer survivorship. Over half did not have knowledge of cancer survivorship services in their area. All respondents were interested in more education on cancer survivorship care. Attendees of the in-service increased their knowledge of survivorship follow-up guidelines, awareness of local survivorship resources, and comfort with caring for YAS at posttest relative to baseline. The in-service was highly acceptable to providers and feasible to implement. College providers had little baseline knowledge of cancer survivorship guidelines, but were motivated to obtain more information. Through an educational in-service, college health providers may be better equipped to provide acute and longitudinal survivorship care to a vulnerable population who are at risk for inadequate engagement in risk-based follow-up care.

Exome sequencing analysis reveals variants in primary immunodeficiency genes in patients with very early onset inflammatory bowel disease.

BACKGROUND & AIMS: Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed at 5 years of age or younger, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. METHODS: Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (age, 3 wk to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by postprocessing and variant calling. After functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency less than 0.1%, and scaled combined annotation-dependent depletion scores of 10 or less. We focused on genes associated with primary immunodeficiencies and related pathways. An additional 210 exome samples from patients with pediatric IBD (n = 45) or adult-onset Crohn's disease (n = 20) and healthy individuals (controls, n = 145) were obtained from the University of Kiel, Germany, and used as control groups. RESULTS: Four hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 coding exons totaling more than 1 Mbp of coding sequence, were selected from the whole-exome data. Our analysis showed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. CONCLUSIONS: In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the identification of previously unidentified IBD-associated variants.

Infliximab therapy in pediatric patients 7 years of age and younger.

BACKGROUND: Infliximab (IFX) is efficacious for induction and maintenance of remission in pediatric patients with moderate-to-severe inflammatory bowel disease (IBD). It has, however, not been studied in patients 7 years old and younger. Our aim was to characterize efficacy and safety of IFX therapy in this cohort. METHODS: This was a retrospective study of patients with IBD ages 7 years and younger, treated with IFX between 1999 and 2011. Medical records were reviewed for age of diagnosis, disease phenotype, therapy, surgery, IFX infusion dates, dose, and intervals. Outcome measures included physician global assessment, corticosteroid requirement, and adverse events. RESULTS: Thirty-three children (ages 2.4-7 years) were included. Twenty patients had Crohn disease, 4 had ulcerative colitis, and 9 had indeterminate colitis. Maintenance of IFX therapy at 1, 2, and 3 years was 36%, 18%, and 12%, respectively. Patients of age 5 years and younger had the lowest rates of maintenance of therapy at 25% at year 1, and 10% at years 2 and 3 combined. Nine percent of all of the patients demonstrated response measured by the physician global assessment and were steroid free at 1 year. There were 8 infusion reactions. There were no malignancies, serious infections, or deaths. CONCLUSIONS: IFX demonstrated a modest response rate and a low steroid-sparing effect in patients with IBD 7 years old and younger. Although this is a limited study, there appears to be a trend for decreased sustained efficacy with IFX in this age group, particularly in children 5 years old and younger, when compared with the previously published literature in older children.

Alterations of the Subgingival Microbiota in Pediatric Crohn's Disease Studied Longitudinally in Discovery and Validation Cohorts.

BACKGROUND: Oral manifestations are common in Crohn's disease (CD). Here we characterized the subgingival microbiota in pediatric patients with CD initiating therapy and after 8 weeks to identify microbial community features associated with CD and therapy. METHODS: Pediatric patients with CD were recruited from The Children's Hospital of Pennsylvania. Healthy control subjects were recruited from primary care or orthopedics clinic. Subgingival plaque samples were collected at initiation of therapy and after 8 weeks. Treatment exposures included 5-ASAs, immunomodulators, steroids, and infliximab. The microbiota was characterized by 16S rRNA gene sequencing. The study was repeated in separate discovery (35 CD, 43 healthy) and validation cohorts (43 CD, 31 healthy). RESULTS: Most subjects in both cohorts demonstrated clinical response after 8 weeks of therapy (discovery cohort 88%, validation cohort 79%). At week 0, both antibiotic exposure and disease state were associated with differences in bacterial community composition. Seventeen genera were identified in the discovery cohort as candidate biomarkers, of which 11 were confirmed in the validation cohort. Capnocytophaga, Rothia, and TM7 were more abundant in CD relative to healthy controls. Other bacteria were reduced in abundance with antibiotic exposure among CD subjects. CD-associated genera were not enriched compared with healthy controls after 8 weeks of therapy. CONCLUSIONS: Subgingival microbial community structure differed with CD and antibiotic use. Results in the discovery cohort were replicated in a separate validation cohort. Several potentially pathogenic bacterial lineages were associated with CD but were not diminished in abundance by antibiotic treatment, suggesting targets for additional surveillance.