Implanted adipose progenitor cells as physicochemical regulators of breast cancer

Multipotent adipose-derived stem cells (ASCs) are increasingly used for regenerative purposes such as soft tissue reconstruction following mastectomy; however, the ability of tumors to commandeer ASC functions to advance tumor progression is not well understood. Through the integration of physical sciences and oncology approaches we investigated the capability of tumor-derived chemical and mechanical cues to enhance ASC-mediated contributions to tumor stroma formation. Our results indicate that soluble factors from breast cancer cells inhibit adipogenic differentiation while increasing proliferation, proangiogenic factor secretion, and myofibroblastic differentiation of ASCs. This altered ASC phenotype led to varied extracellular matrix (ECM) deposition and contraction thereby enhancing tissue stiffness, a characteristic feature of breast tumors. Increased stiffness, in turn, facilitated changes in ASC behavior similar to those observed with tumor-derived chemical cues. Orthotopic mouse studies further confirmed the pathological relevance of ASCs in tumor progression and stiffness in vivo. In summary, altered ASC behavior can promote tumorigenesis and, thus, their implementation for regenerative therapy should be carefully considered in patients previously treated for cancer.     

Enhancing Care for Hospitalized Older Adults with Cognitive Impairment: A Randomized Controlled Trial

Background

Approximately 40% of hospitalized older adults have cognitive impairment (CI) and are more prone to hospital-acquired complications. The Institute of Medicine suggests using health information technology to improve the overall safety and quality of the health care system.

Objective

Evaluate the efficacy of a clinical decision support system (CDSS) to improve the quality of care for hospitalized older adults with CI.

Design

A randomized controlled clinical trial.

Setting

A public hospital in Indianapolis.

Population

A total of 998 hospitalized older adults were screened for CI, and 424 patients (225 intervention, 199 control) with CI were enrolled in the trial with a mean age of 74.8, 59% African Americans, and 68% female.

Intervention

A CDSS alerts the physicians of the presence of CI, recommends early referral into a geriatric consult, and suggests discontinuation of the use of Foley catheterization, physical restraints, and anticholinergic drugs.

Measurements

Orders of a geriatric consult and discontinuation orders of Foley catheterization, physical restraints, or anticholinergic drugs.

Results

Using intent-to-treat analyses, there were no differences between the intervention and the control groups in geriatric consult orders (56% vs 49%, P = 0.21); discontinuation orders for Foley catheterization (61.7% vs 64.6%, P = 0.86); physical restraints (4.8% vs 0%, P = 0.86), or anticholinergic drugs (48.9% vs 31.2%, P = 0.11).

Conclusion

A simple screening program for CI followed by a CDSS did not change physician prescribing behaviors or improve the process of care for hospitalized older adults with CI.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-012-1994-8) contains supplementary material, which is available to authorized users.KEY WORDS: cognitive impairment, clinical trial, decision support, hospitalized elders     

Prevalence of, associations with, and prognostic value of tricuspid annular plane systolic excursion (TAPSE) among out-patients referred for the evaluation of heart failure

BackgroundPrevalence, predictors, and prognostic value of right ventricular (RV) function measured by the tricuspid annular plane systolic excursion (TAPSE) in patients with chronic heart failure (CHF) symptoms with a broad range of left ventricular ejection fraction (LVEF) are unknown.Methods and ResultsOf 1,547 patients, mean (±SD) age was 71 ± 11 years, 48% were women, median (interquartile range [IQR]) TAPSE was 18.5 (14.0–22.7) mm, mean LVEF was 47 ± 16%, 47% had LVEF ≤45% and 67% were diagnosed with CHF, defined as systolic (S-HF) if LVEF was ≤45% and as heart failure with preserved ejection fraction (HFPEF) if LVEF was >45% and treated with a loop diuretic. During a median (IQR) follow-up of 63 (41–75) months, mortality was 34%. In multivariable analysis, increasing age, N-terminal pro–B-type natriuretic peptide (NT-proBNP), New York Heart Association functional class, right atrial volume index, and transtricuspid pressure gradient; lower TAPSE, diastolic blood pressure, and hemoglobin; and atrial fibrillation (AF) or COPD were associated with an adverse prognosis. Receiver operating characteristic curve analysis identified a TAPSE of 15.9 mm as the best prognostic threshold (P = .0001); 47% of S-HF and 20% of HFPEF had a TAPSE of <15.9 mm. The main associations with a TAPSE <15.9 mm were higher NT-proBNP, presence of atrial fibrillation and presence of LV systolic dysfunction.ConclusionsIn patients with CHF, low values for TAPSE are common, especially in those with reduced LVEF. TAPSE, unlike LVEF, was an independent predictor of outcome.     

Toxicity and biomedical imaging of layered nanohybrids in the mouse

Layered nanohybrids (LNH) are a promising nonviral system allowing controlled drug and DNA delivery. In order to test the toxicity of LNH consisting of a magnesium/aluminum core, mice were subjected to subcutaneous, intraperitoneal, and intravenous injections of these nanoparticles at three doses. Intravenous injections resulted in 8% (1 out of 12) lethality at doses 100 micro l and 200 micro l of 6.96 x 10(- 4) M solution, while all mice survived after LNH administration by any other routes. Histopathological alterations were limited to mild localized inflammatory lesions in the lungs and the dermis after intravenous and subcutaneous administration, respectively. LNH labeled with Lucifer Yellow were readily detectable in both locations by fluorescent microscopy. To test their potential for intravital imaging, LNH-Lucifer Yellow were injected into the ovarian bursa and successfully visualized by multiphoton microscopy within the ovarian surface epithelial cells. In similar experiments, the ovary and the ovarian bursa were readily detectable by magnetic resonance imaging after administration of modified LNH, where aluminum was substituted for gadolinium. Taken together, these results demonstrate minimal in vivo toxicity of LNH and illuminate their potential as multifunctional nanoscale particles suitable for combination of intravital biomedical imaging with controlled drug release.