Publications

There is increasing evidence that the numerous mechanisms that regulate cell differentiation during normal development are also involved in tumorigenesis. In breast cancer, differentiation markers expressed by the primary tumor are routinely profiled to guide clinical decisions. Indeed, numerous studies have shown that the differentiation profile correlates with the metastatic potential of tumors. The transcription factor GATA3 has emerged recently as a strong predictor of clinical outcome in human luminal breast cancer. In the mammary gland, GATA3 is required for luminal epithelial cell differentiation and commitment, and its expression is progressively lost during luminal breast cancer progression as cancer cells acquire a stem cell-like phenotype. Importantly, expression of GATA3 in GATA3-negative, undifferentiated breast carcinoma cells is sufficient to induce tumor differentiation and inhibits tumor dissemination in a mouse model. These findings demonstrate the exquisite ability of a differentiation factor to affect malignant properties, and raise the possibility that GATA3 or its downstream genes could be used in treating luminal breast cancer. This review highlights our recent understanding of GATA3 in both normal mammary development and tumor differentiation.

The dermal-epidermal basement membrane zone is an important epithelial and stromal interface, consisting of an intricately organized collection of intracellular, transmembrane, and extracellular matrix proteins. The basement membrane zone has several main functions including acting as a permeability barrier, forming an adhesive interface between epithelial cells and the underlying matrix, and controlling cellular organization and differentiation. This article identifies key molecular players of the dermal-epidermal membrane zone, and highlights recent research studies that have identified structural and functional roles of these components in the context of various blistering, neoplastic, and developmental syndromes.

OBJECTIVE

This study evaluated the association between depression and hospitalization among geriatric home care patients.

METHODS

A sample of 477 patients newly admitted to home care over two years was assessed for depression. Bivariate and logistic regression analyses examined the likelihood of hospitalization during a 60-day home care episode.

RESULTS

The hospitalization rate was similar for the 77 depressed patients and 400 nondepressed patients (about 7%). However, mean time to hospitalization was 8.4 versus 19.5 days after start of care, respectively. Hospitalization risk was significantly higher for depressed patients during the first few weeks. A main effect for depression and a depression-by-time interaction was found when analyses controlled for medical comorbidity, cognitive status, age, gender, race, activities of daily living and instrumental activities of daily living, and referral to home care after hospitalization.

CONCLUSIONS

Depression appears to increase short-term risk of hospitalization for geriatric home care patients immediately after starting home care.

OBJECTIVE

Chronic diabetes mellitus (DM) is a known cause of multisystem injury. The effect of DM in acute critical illness may also be detrimental, but is not specifically known. We hypothesized that the preexisting diagnosis of DM is an independent risk factor for mortality in critically ill patients.

DESIGN

Parallel retrospective and prospective cohort study.

SETTING

Two large patient datasets were used: the retrospective University HealthSystem Consortium database (UHC) and the prospective Mayo Clinic Acute Physiology And Chronic Health Evaluation III critical care database (Mayo).

PATIENTS

Inclusion criteria were admission to an intensive care unit and age > or =18 yrs. Patients with diabetic ketoacidosis or hyperosmolar nonketotic coma were excluded. A total of 1,509,890 patients (including 143,078 deaths) in the UHC cohort and 36,414 patients (including 3562 deaths) in the Mayo cohort were included in the study analysis.

MEASUREMENTS AND MAIN RESULTS

The primary outcome was in-hospital mortality compared between patients with a history of DM and all other patients. Other outcomes included in-hospital mortality in prespecified subgroups. In the UHC dataset, patients with DM had a lower unadjusted odds ratio (0.90, 95% confidence interval 0.89-0.91, p < .001) and a lower adjusted effect on mortality (odds ratio 0.75, 0.74-0.76, p < .001) compared with that seen in patients without DM. In the Mayo dataset, patients with DM had a comparable unadjusted odds ratio (1.07, 0.97-1.17, p = NS) and a lower adjusted effect on mortality (odds ratio 0.88, 0.79-0.98, p = .022) compared with that seen in patients without DM. A lower mortality in diabetic patients held across multiple demographic subgroups, including patients who underwent coronary-artery bypass grafting (UHC data: unadjusted odds ratio 0.66, 0.62-0.71, p < .001).

CONCLUSIONS

Critically ill adults with DM do not have an increased mortality compared with that seen in patients without DM, and may have a decreased mortality. Further investigation needs to be done to determine the mechanism for this effect.