Mapping and modeling human colorectal carcinoma interactions with the tumor microenvironment.

The initiation and progression of cancer are intricately linked to the tumor microenvironment (TME). Understanding the function of specific cancer-TME interactions poses a major challenge due in part to the complexity of the in vivo microenvironment. Here we predict cancer-TME interactions from single cell transcriptomic maps of both human colorectal cancers (CRCs) and mouse CRC models, ask how these interactions are altered in human tumor organoid (tumoroid) cultures, and functionally recapitulate human myeloid-carcinoma interactions in vitro. Tumoroid cultures suppress gene expression programs involved in inflammation and immune cell migration, providing a reductive platform for re-establishing carcinoma-immune cell interactions in vitro. Introduction of human monocyte-derived macrophages into tumoroid cultures instructs macrophages to acquire immunosuppressive and pro-tumorigenic gene expression programs similar to those observed in vivo. This includes hallmark induction of SPP1, encoding Osteopontin, an extracellular CD44 ligand with established oncogenic effects. Taken together, these findings offer a framework for understanding CRC-TME interactions and provide a reductionist tool for modeling specific aspects of these interactions.

Environmental transmission of Clostridium difficile: association between hospital room size and C. difficile Infection.

OBJECTIVE: To evaluate the association between hospital room square footage and acquisition of nosocomial Clostridium difficile infection (CDI). METHODS: A case-control study was conducted at a university hospital during the calendar year of 2011. Case patients were adult inpatients with nosocomial CDI. Control patients were hospitalized patients without CDI and were randomly selected and matched to cases in a 2:1 ratio on the basis of hospital length of stay in 3-day strata. A multivariate model was developed using conditional logistic regression to evaluate risk factors for nosocomial CDI. RESULTS: A total of 75 case patients and 150 control patients were included. On multivariate analyses, greater square footage of the hospital room was associated with a significantly increased risk of acquiring CDI (odds ratio for every 50 ft² increase, 3.00; 95% CI, 1.75-5.16; P<.001). Other factors associated with an increased risk of CDI were location in a single room (odds ratio, 3.43; 95% CI, 1.31-9.05; P=.01), malignant tumor (4.56; 1.82-11.4; P=.001), and receipt of cefepime (2.48; 1.06-5.82; P=.04) or immunosuppressants (6.90; 2.07-23.0; P=.002) within the previous 30 days. CONCLUSIONS: Greater room square footage increased the risk of acquisition of CDI in the hospital setting, likely owing to increased environmental contamination and/or difficulty in effective disinfection. Future studies are needed to determine feasible and effective cleaning protocols based on patient and room characteristics.