Periodic monitoring of women at high risk for LE with BIS allows early detection and timely intervention for LE, which reduces the incidence of clinical LE from 36.4% to 4.4%. This may have implications for quality of life and health care costs.

Regulatory T cells (Tregs), including natural CD4+CD25+ Tregs and inducible IL-10 producing T regulatory type 1 (TR1) cells, maintain tolerance and inhibit autoimmunity. Recently, increased percentages of Tregs have been observed in the blood of septic patients, and ex vivo-activated Tregs were shown to prevent polymicrobial sepsis mortality. Whether endogenous Tregs contribute to sepsis outcome remains unclear. Polymicrobial sepsis, induced by cecal ligation and puncture, caused an increased number of splenic Tregs compared with sham-treated mice. Splenic CD4+CD25+ T cells from septic mice expressed higher levels of Foxp3 mRNA and were more efficient suppressors of CD4+CD25− T effector cell proliferation. Isolated CD4+ T cells from septic mice displayed increased intracellular IL-10 staining following stimulation, indicating that TR1 cells may also be elevated in sepsis. Surprisingly, Ab depletion of total CD4+ or CD4+CD25+ populations did not affect mortality. Furthermore, no difference in survival outcome was found between CD25 or IL-10 null mice and wild-type littermates, indicating that Treg or TR1-generated IL-10 are not required for survival. These results demonstrate that, although sepsis causes a relative increase in Treg number and increases their suppressive function, their presence does not contribute significantly to overall survival in this model.

Background The study purpose was to examine and compare the effect of the first 18 months anastrozole therapy on cognitive function in women with breast cancer. Methods This large, longitudinal cohort study was composed of postmenopausal women with early-stage breast cancer who receive chemotherapy-plus-anastrozole (n=114) or anastrozole alone (n=173) and a control group (n=110). Cognitive function was assessed before systemic therapy and at six, 12, and 18 months after therapy initiation and at comparable timepoints in controls. Results The chemotherapy-plus-anastrozole and anastrozole alone groups had poorer executive function than controls at nearly all timepoints (p<.0001 to p=.09). A pattern of deterioration in working memory and concentration was observed during the first six months of anastrozole therapy for the chemotherapy-plus-anastrozole (p<.0001; p<.0009 respectively) and anastrozole alone groups (p=.0008; p=.0002 respectively). This was followed by improved working memory and concentration from six to 12 months in both groups. The anastrozole alone group had a second decline in working memory and concentration from 12 to 18 months post-initiation of therapy (p<.0001; p=.02). Conclusion Women with breast cancer had poorer executive functioning from pre-therapy through the entire first 18 months of therapy. A pattern of decline in working memory and concentration with initial exposure to anastrozole was observed. Women receiving anastrozole alone had a second deterioration in working memory and concentration from 12 to 18 months post-therapy initiation. The longer term (> 18 months) effects of anastrozole on cognitive function remain to be determined.

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CD11c+ dendritic cells (DCs) are APCs that link innate and adaptive immunity. Although DCs are lost from spleen and lymph nodes in sepsis, their role in outcome remains unclear. Transgenic mice (B6.FVB-Tg.Itgax-DTR/EGFP.57Lan/J) expressing the diphtheria toxin (DT) receptor on the CD11c promoter (DCKO mice) received 4 ng/kg DT, which resulted in depletion of 88–95% of mature myeloid and lymphoid DCs, with less depletion (75%) of plasmacytoid DCs. Pretreatment of DCKO mice with DT resulted in reduced survival in sepsis compared with saline-pretreated DCKO mice (0 vs 54%; p &lt; 0.05) or DT-treated wild-type littermates (0 vs 54%; p &lt; 0.05). This increased mortality was not associated with either increased bacteremia or plasma cytokine concentrations. Intravenous injection of 107 wild-type DCs improved survival in DCKO mice (42 vs 0%; p = 0.05). These data confirm that DCs are essential in the septic response and suggest that strategies to maintain DC numbers or function may improve outcome.