Patients diagnosed with triple negative breast cancer (TNBC) have an increased risk of rapid metastasis compared to other subtypes. Predicting long-term survival post-chemotherapy in patients with ...TNBC is difficult, yet enhanced infiltration of tumor infiltrating lymphocytes (TILs) has been associated with therapeutic response and reduced risk of metastatic relapse. Immune biomarkers that predict the immune state of a tumor and risk of metastatic relapse pre- or mid-neoadjuvant chemotherapy are urgently needed to allow earlier implementation of alternate therapies that may reduce TNBC patient mortality. Utilizing a neoadjuvant chemotherapy trial where TNBC patients had sequential biopsies taken, we demonstrate that measurement of T-cell subsets and effector function, specifically CD45RO expression, throughout chemotherapy predicts risk of metastatic relapse. Furthermore, we identified the tumor inherent interferon regulatory factor IRF9 as a marker of active intratumoral type I and II interferon (IFN) signaling and reduced risk of distant relapse. Functional implications of tumor intrinsic IFN signaling were demonstrated using an immunocompetent mouse model of TNBC, where enhanced type I IFN signaling increased anti-tumor immunity and metastasis-free survival post-chemotherapy. Using two independent adjuvant cohorts we were able to validate loss of IRF9 as a poor prognostic biomarker pre-chemotherapy. Thus, IRF9 expression may offer early insight into TNBC patient prognosis and tumor heat, allowing for identification of patients that are unlikely to respond to chemotherapy alone and could benefit from further immune-based therapeutic intervention.
Nine years after child sexual abuse Swanston, Heather Y; Plunkett, Angela M; O’Toole, Brian I ...
Child abuse & neglect,
08/2003, Volume:
27, Issue:
8
Journal Article
Peer reviewed
Objective: During 1988–1990, 103 children presented to Child Protection Units (CPU) at two children’s hospitals in Sydney, Australia. Nine years later, the psychological adjustment of these young ...people (mean age=19.1 years,
SD=3.4 years; range=14–25 years) was compared with that of non-abused young people of similar age and gender to assess group differences and examine potential risk factors.
Method: At intake, data on the nature of the index sexual abuse, demographics and the family environment were collected by clinicians. A comparison group, of similar age and gender, was selected from schools in the catchment area of the CPUs. Six years after presentation for the abuse, records of the statutory child protection authority were checked to determine any further notifications for abuse and/or neglect. Nine years after intake, 49 of the abused young people and 68 of the non-abused young people and/or their parents were interviewed and assessed.
Results: The sexually abused young people performed more poorly than non-abused young people on psychometric tests of depression (
p=.001), self-esteem (
p<.001), anxiety (
p<.001), behavior (Child Behavior Checklist:
p=.01; Youth Self Report:
p=.01; Young Adult Self Report:
p<.001), and despair (
p=.001). They were also more likely to have a history of bingeing (
p=.002), self-inducing vomiting (
p=.02), smoking cigarettes (
p=.01), and using amphetamines (
p=.002), ecstasy (
p=.002) and cocaine (
p=.004). Potential risk factors were in two groups, family and child. Family factors: family functioning, parental drug/alcohol problems, mother’s sexual abuse history, mother’s depression and socio-economic status. Child factors: despair and hopefulness, number of negative life events, ratings of their father’s care, previous notifications for child sexual abuse and placements in out-of-home care by the statutory child protection authority. In the presence of other risk factors, child sexual abuse was a significant predictor of self-esteem, behavior and bingeing.
Conclusions: Rather than focusing only on the individual’s child sexual abuse, treatment may also need to address the family’s functioning and the individual’s feelings of despair.
Objectif: Durant les années 1988–1990, 103 enfants se sont présentés au service de la protection de l’enfance de deux hôpitaux pédiatriques de Sydney, en Australie. Neuf ans plus tard, on a comparé l’ajustement psychologique des ces jeunes (âge moyen=19,1 ans; variant de 14 à 25 ans) avec celui de jeunes du même âge et sexe qui n’ont pas été abusés, pour évaluer les différences dans ces deux groupes et examiner les facteurs de risques possibles.
Méthode: Les cliniciens ont colligé des renseignements sur les mauvais traitements, les données démographiques et le milieu familial au moment de la prise de contact. On a créé un groupe de comparaison composé de jeunes enrôlés dans des écoles environnantes. Six ans après le contact initial, on a consulté les dossiers de la protection de l’enfance afin de confirmer s’il y a eu des signalements subséquents. Neuf ans après la prise de contact, 49 victimes et 68 jeunes non abusés ainsi que/ou leurs parents ont été interviewés et évalués.
Résultats: Les jeunes qui ont été victimes d’abus sexuels démontrent des résultats moins favorables que les non victimes sur les tests psychométriques mesurant la dépression (
p=,001), l’estime de soi (
p=,001) le comportement (Child Behavior Checklist:
p=,01, Youth Self-Report:
p=,01; Young Adult Self-Report:
p<,001) et le désespoir (
p=,001). Les victimes étaient plus portés à avoir des fringales (
p=,002), à être boulimique (
p=,02), à fumer des cigarettes (
p=,01) et à prendre des amphétamines (
p=,002), la drogue extase (
p=,02) et la cocaı̈ne (
p=,004). Le risque potentiel se manifeste dans deux groupes: la famille et l’enfant. Les facteurs familiaux sont le fonctionnement de la famille, les problèmes de drogue et d’alcool des parents, la mère victime d’agressions sexuelles dans le passé, la dépression chez la mère et le statut socioéconomique. Les facteurs pour l’enfant sont le désespoir et l’espoir, bon nombre de vécus pénibles, la façon dont il cote les soins prodigués par le père, des signalements antérieurs d’agressions sexuelles et le placement en foyer d’accueil par les autorités de la protection de l’enfance. Lorsque d’autres facteurs de risque sont présents, les agressions sexuelles prédisent de façon importante l’estime de soi, le comportement et les fringales.
Conclusions: Plutôt que de se pencher seulement sur les agressions sexuelles de l’enfant, le traitement devra aussi s’orienter vers le fonctionnement familial et les sentiments de désespoir de l’individu.
Spanish-language abstract not available at time of publication.
Abstract Objective: To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. Design: Community based 13 ...month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. Subjects: 108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. Setting: Southampton and surrounding community. Main outcome measures: Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. Results: Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 1/min. The most commonly identified virus type was rhinovirus. Conclusions: This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children. Key messages Key messages In this study common cold viruses were found in 80-85% of reported exacerbations of asthma in children Rhinoviruses, which cause most common colds, accounted for two thirds of viruses detected Analysis of diary cards also showed large numbers of similar but less severe episodes that may also be viral in origin
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