Idiopathic granulomatous mastitis masquerading as carcinoma of the breast: a case report and review of the literature

BACKGROUND: Idiopathic granulomatous mastitis is an uncommon, benign entity with a diagnosis of exclusion. The typical clinical presentation of idiopathic granulomatous mastitis often mimics infection or malignancy. As a result, histopathological confirmation of idiopathic granulomatous mastitis combined with exclusion of infection, malignancy and other causes of granulomatous disease is absolutely necessary. CASE PRESENTATION: We present a case of a young woman with idiopathic granulomatous mastitis, initially mistaken for mastitis as well as breast carcinoma, and successfully treated with a course of corticosteroids. CONCLUSION: There is no clear clinical consensus regarding the ideal therapeutic management of idiopathic granulomatous mastitis. Treatment options include expectant management with spontaneous remission, corticosteroid therapy, immunosuppressive agents and extensive surgery for refractory cases

An exploratory analysis of the impact of family functioning on treatment for depression in adolescents.

This article explores aspects of family environment and parent-child conflict that may predict or moderate response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive behavioral therapy, their combination, or placebo. Outcomes were Week 12 scores on measures of depression and global impairment. Of 20 candidate variables, one predictor emerged: Across treatments, adolescents with mothers who reported less parent-child conflict were more likely to benefit than their counterparts. When family functioning moderated outcome, adolescents who endorsed more negative environments were more likely to benefit from fluoxetine. Similarly, when moderating effects were seen on cognitive behavioral therapy conditions, they were in the direction of being less effective among teens reporting poorer family environments

Prolonged Graft Survival in Older Recipient Mice Is Determined by Impaired Effector T-Cell but Intact Regulatory T-Cell Responses

Elderly organ transplant recipients represent a fast growing segment of patients on the waiting list. We examined age-dependent CD4+ T-cell functions in a wild-type (WT) and a transgenic mouse transplant model and analyzed the suppressive function of old regulatory T-cells. We found that splenocytes of naïve old B6 mice contained significantly higher frequencies of T-cells with an effector/memory phenotype (CD4+CD44highCD62Llow). However, in-vitro proliferation (MLR) and IFNγ-production (ELISPOT) were markedly reduced with increasing age. Likewise, skin graft rejection was significantly delayed in older recipients and fewer graft infiltrating CD4+T-cells were observed. Old CD4+ T-cells demonstrated a significant impaired responsiveness as indicated by diminished proliferation and activation. In contrast, old alloantigen-specific CD4+CD25+FoxP3+ T-cells demonstrated a dose-dependent well-preserved suppressor function. Next, we examined characteristics of 18-month old alloreactive T-cells in a transgenic adoptive transfer model. Adoptively transferred old T-cells proliferated significantly less in response to antigen. Skin graft rejection was significantly delayed in older recipients, and graft infiltrating cells were reduced. In summary, advanced recipient age was associated with delayed acute rejection and impaired CD4+ T-cell function and proliferation while CD4+CD25+FoxP3+ T-cells (Tregs) showed a well-preserved function

Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma

CD8+ T cell reactivity towards tumor mutation-derived neoantigens is widely believed to facilitate the antitumor immunity induced by immune checkpoint blockade (ICB). Here we show that broadening in the number of neoantigen-reactive CD8+ T cell (NART) populations between pre-treatment to 3-weeks post-treatment distinguishes patients with controlled disease compared to patients with progressive disease in metastatic urothelial carcinoma (mUC) treated with PD-L1-blockade. The longitudinal analysis of peripheral CD8+ T cell recognition of patient-specific neopeptide libraries consisting of DNA barcode-labelled pMHC multimers in a cohort of 24 patients from the clinical trial NCT02108652 also shows that peripheral NARTs derived from patients with disease control are characterised by a PD1+ Ki67+ effector phenotype and increased CD39 levels compared to bystander bulk- and virus-antigen reactive CD8+ T cells. The study provides insights into NART characteristics following ICB and suggests that early-stage NART expansion and activation are associated with response to ICB in patients with mUC

Erratum to:Effects of a physical activity and nutrition program in retirement villages: a cluster randomised controlled trial

Abstract Background This cluster randomised controlled trial aimed to determine if a 6- month home-based intervention could improve the physical activity and dietary behaviours of adults aged 60 to 80 years living in retirement villages located in Perth, Western Australia. Methods Participants (n = 363) from 38 retirement villages were recruited into the trial and allocated to the intervention (n = 197: 17 sites) or control (n = 166: 21 sites) group and were blinded. Previously validated instruments-Fat and Fibre Barometer and International Physical Activity Questionnaire, along with anthropometric measures (weight, height, waist and hip circumferences) and blood pressure were collected at baseline and 6 -month time period. Comparisons between intervention and control groups were undertaken pre- and post- intervention using univariate chi-square and t-tests. Multi-level mixed regression analyses were then conducted to ascertain the effects of the intervention on changes in the outcome variables over time and between groups. Results A total of 139 (70.5%) intervention and 141 (84.9%) control group participants completed the program and post-test assessments. The intervention group demonstrated significant increases in time (80 min more per week on average) devoted to moderate-intensity physical activity, engagement in strength exercises (from 23.7% to 48.2%), frequency of fruit consumed as well as fat avoidance and fibre intake scores, in addition to a 0.5 kg mean reduction in weight post program, whereas no apparent changes were observed in the control group. Mixed regression results further confirmed statistically significant improvements in weight loss (p < 0.05), engagement in strength exercises (p < 0.001) and fruit intake (p = 0.012) by the intervention participants at post-test relative to their controls. Conclusions Retirement offers a time to reassess lifestyle, and adopt positive health enhancing physical activity and dietary behaviours. This intervention was successful in improving weight, engagement in strength exercises, increasing levels of moderate-intensity physical activity and consumption of fruit among retirement village residents. Further investigation is needed on how to better engage retirement village managers in such programs. Trial registration Australia and New Zealand Clinical Trial Registry (ACTRN12612001168842) registered November 2, 2012

Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: Clinical and therapeutic implications

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. Methods We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. Results The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. Conclusions The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways

A pig model of acute Staphylococcus aureus induced pyemia

<p>Abstract</p> <p>Background</p> <p>Sepsis caused by <it>Staphylococcus aureus </it>constitutes an important cause of morbidity and mortality in humans, and the incidence of this disease-entity is increasing. In this paper we describe the initial microbial dynamics and lesions in pigs experimentally infected with <it>S. aureus</it>, with the aim of mimicking human sepsis and pyemia.</p> <p>Methods</p> <p>The study was conducted in anaesthetized and intravenously inoculated pigs, and was based on bacteriological examination of blood and testing of blood for IL-6 and C-reactive protein. Following killing of the animals and necropsy bacteriological and histological examinations of different organs were performed 4, 5 or 6 h after inoculation.</p> <p>Results</p> <p>Clearance of bacteria from the blood was completed within the first 2 h in some of the pigs and the highest bacterial load was recorded in the lungs as compared to the spleen, liver and bones. This probably was a consequence of both the intravenous route of inoculation and the presence of pulmonary intravascular macrophages. Inoculation of bacteria induced formation of acute microabscesses in the lungs, spleen and liver, but not in the kidneys or bones. No generalized inflammatory response was recorded, i.e. IL-6 was not detected in the blood and C-reactive protein did not increase, probably because of the short time course of the study.</p> <p>Conclusion</p> <p>This study demonstrates the successful induction of acute pyemia (microabscesses), and forms a basis for future experiments that should include inoculation with strains of <it>S. aureus </it>isolated from man and an extension of the timeframe aiming at inducing sepsis, severe sepsis and septic shock.</p