Amanda M. Pugh

A Murine Model of Persistent Inflammation, Immune Suppression, and Catabolism Syndrome

Critically ill patients that survive sepsis can develop a Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS), which often leads to extended recovery periods and multiple complications. Here, we utilized a cecal ligation and puncture (CLP) method in mice with the goal of creating a model that concurrently displays all the characteristics of PICS. We observed that, after eight days, mice that survive the CLP develop persistent inflammation with significant myelopoiesis in the bone marrow and spleen. These mice also demonstrate ongoing immune suppression, as evidenced by the decreased total and naïve splenic CD4 and CD8 T cells with a concomitant increase in immature myeloid cells. The mice further display significant weight loss and decreased muscle mass, indicating a state of ongoing catabolism. When PICS mice are challenged with intranasal Pseudomonas aeruginosa, mortality is significantly elevated compared to sham mice. This mortality difference is associated with increased bacterial loads in the lung, as well as impaired neutrophil migration and neutrophil dysfunction in the PICS mice. Altogether, we have created a sepsis model that concurrently exhibits PICS characteristics. We postulate that this will help determine the mechanisms underlying PICS and identify potential therapeutic targets to improve outcomes for this patient population.

Burn injury alters the intestinal microbiome’s taxonomic composition and functional gene expression

Burn patients have a high risk of sepsis-related mortality even after surviving the initial injury. Immunosuppression increases the risk of sepsis after burn injury, as does the disruption of the intestinal epithelial barrier, which allows the translocation of bacteria and bacterial products into the circulation. The integrity of the intestinal epithelial barrier is largely maintained by the intestinal microbiota. Burn injury has been reported to result in significant changes in the intestinal microbiome composition. In this mouse study, we confirm these taxonomic differences in a full-thickness scald injury model using CF-1 mice. For the first time, we also address alterations in functional gene expression of the intestinal microbiota after burn injury to assess the microbiome’s physiological capabilities for overgrowth and pathogenic invasion: 38 pathways were differentially abundant between the sham and burn injury mice, including bacterial invasion of epithelial cells and gap- and adherens junction pathways.

Characteristics and diagnosis of pregnancy and lactation associated breast cancer: Analysis of a self-reported regional registry

BACKGROUND Pregnancy-associated breast cancer (PABC) is the most common malignancy in pregnancy. However due to its infrequent occurrence, PABC continues to be poorly understood. METHODS We performed a retrospective study using self-reported data from 1079 eligible women in a regional breast cancer registry. RESULTS The PABC cases were more likely than non-PABCs to be younger than age 35 and have nodal involvement at diagnosis. Despite diagnosis at a young age, there was not an association between PABC and family history. For method of diagnosis, PABC was found on self-exam, while non-PABCs were found on mammography. CONCLUSION In conclusion, PABC is rarely detected by mammography and diagnosis is highly dependent on detection during self-breast exam. Women who are or recently were pregnant should be encouraged to perform regular self-breast exams to report any changes for further evaluation. Patient and clinician education regarding risk and realities of PABC is essential.