Bilateral, simultaneous pneumococcal septic arthritis of the knees: a normal immune system, an unknown source.

Pneumococcal septic arthritis is a rare clinical entity and is often associated with a systemic bacteraemia. A 60-year-old man was admitted with bilateral swollen, painful knees. He was feeling feverish with raised inflammatory markers. Joint aspiration yielded purulent fluid, which, when cultured, grew Streptococcus Pneumoniae bilaterally. The patient underwent repeated arthroscopic knee washouts and was treated with intravenous (IV) antibiotics. During his admission, various investigations and scans were undertaken to find an infective focus or signs of immunodeficiency; none were found. After 4 weeks of IV antibiotics and 4 knee washouts, the patient was discharged. We believe this is the only case documented of bilateral simultaneous pneumococcal septic arthritis of the knees in an immunocompetent patient with no extra-articular infective focus. This case exemplifies the importance of careful assessment of patients who present with bilateral swollen joints.

A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity.

INTRODUCTION: There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. METHODS: We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets. RESULTS: In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER + and HER2-/ER + tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. CONCLUSIONS: A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway.