Calcium Administration Is Associated with Adverse Outcomes in Critically Ill Patients Receiving Parenteral Nutrition: Results from a Natural Experiment Created by a Calcium Gluconate Shortage.

STUDY OBJECTIVE: Parenteral calcium is frequently administered to critically ill patients. However, animal studies demonstrate that calcium administration during critical illness heightens inflammation and leads to shock, organ dysfunction, and mortality. We sought to evaluate the association between calcium administration and adverse outcomes in critically ill patients receiving parenteral nutrition (PN). DESIGN: Retrospective cohort examined before and during a calcium gluconate shortage. During the shortage, calcium was absent from PN, but calcium supplementation outside of PN was allowed. The shortage resulted in a natural experiment that included a group of patients who did not receive calcium. SETTING: Intensive care units (ICUs) in three teaching hospitals. PATIENTS: A total of 259 adults who received PN in the ICU for 48 hours or longer. MEASUREMENTS AND MAIN RESULTS: Patients were divided into quartiles based on amount of parenteral calcium received; the lowest quartile received no calcium. End points were in-hospital mortality, acute respiratory failure, new-onset shock, and a composite of any one of these end points. For patients not on mechanical ventilation or vasoactive support when PN started, logistic regression revealed that calcium administration was associated with mortality (odds ratio [OR] 2.48, 95% confidence interval [CI] 1.08-5.69), acute respiratory failure (OR 2.43, 95% CI 1.28-4.60), new-onset shock (OR 2.81, 95% CI 1.22-6.44), and the combined end point (OR 2.33, 95% CI 1.31-4.16). The odds of adverse outcomes increased as the calcium dose increased. CONCLUSION: Calcium administration correlated with adverse outcomes in critically ill patients receiving PN. The data suggest that administration of parenteral calcium to critically ill patients may be harmful.

Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status.

Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT.