Did a Goals-of-Care Discussion Happen? Differences in the Occurrence of Goals-of-Care Discussions as Reported by Patients,Clinicians, and in the Electronic Health Record

Context

Goals-of-care discussions are associated with improved end-of-life care for patients and therefore may be used as a process measure in quality improvement, research, and reimbursement programs.

Signalling pathways and mechanisms of protection in pre- and postconditioning: historical perspective and lessons for the future

Ischaemic pre- and postconditioning are potent cardioprotective interventions that spare ischaemic myocardium and decrease infarct size after periods of myocardial ischaemia/reperfusion. They are dependent on complex signalling pathways involving ligands released from ischaemic myocardium, G-protein-linked receptors, membrane growth factor receptors, phospholipids, signalling kinases, NO, PKC and PKG, mitochondrial ATP-sensitive potassium channels, reactive oxygen species, TNF-α and sphingosine-1-phosphate. The final effector is probably the mitochondrial permeability transition pore and the signalling produces protection by preventing pore formation. Many investigators have worked to produce a roadmap of this signalling with the hope that it would reveal where one could intervene to therapeutically protect patients with acute myocardial infarction whose hearts are being reperfused. However, attempts to date to show efficacy of such an intervention in large clinical trials have been unsuccessful. Reasons for this inability to translate successes in the experimental laboratory to the clinical arena are evaluated in this review. It is suggested that all patients with acute coronary syndromes currently presenting to the hospital and being treated with platelet P2Y₁₂ receptor antagonists, the current standard of care, are indeed already benefiting from protection from the conditioning pathways outlined earlier. If that proves to be the case, then future attempts to further decrease infarction will have to rely on interventions which protect by a different mechanism.     

Clinical study of tooth shade lightening from dentist-supervised, patient-applied treatment with two 10% carbamide peroxide gels

PURPOSE: Prescribed, patient-applied tooth lightening agents, or nightguard vital bleaching, typically utilizes a 10% carbamide peroxide agent applied during nocturnal hours. The purpose of this randomized double-blind study was to compare the amount of tooth color change in two groups of subjects using dentist-supervised, patient-applied 10% carbamide peroxide gel. MATERIALS AND METHODS: One group used Opalescence (Ultradent Products Inc., South Jordan, Utah) and the other NiteWhite Excel (Discus Dental, Inc., Los Angeles, California). Evaluation of tooth color for the six maxillary anterior teeth was done using a Vita shade guide at baseline, 1, 2, and 4 weeks. Subjects were instructed to apply the gel nocturnally using a custom-made soft tray 8 hours per day for 2 weeks. The 16 tabs of the shade guide were ranked according to value from darkest to lightest. The number (1-16) that correlated to the shade tab selected as the match for each tooth was the outcome variable. A Kruskal-Wallis one way analysis of variance on ranks was used. RESULTS: The test revealed no statistically significant difference between Opalescence and NiteWhite Excel for lightening the teeth (p = .807). The color change was still significant after 2 weeks without further bleaching activity. The baseline evaluation of the maxillary incisors and canines for all subjects, regardless of group, demonstrated a significant shade difference, with the canines being darker. This difference was not seen after 2 weeks of active bleaching or at the 4-week evaluation. CLINICAL SIGNIFICANCE: In this study comparing bleaching products, patients using Opalescence and NiteWhite Excel experienced a significant change in the color of their teeth relative to baseline values after 2 weeks of active treatment.     

Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice

Iatrogenic tumor cell implantation within surgical wounds can compromise curative cancer surgery. Adhesion of cancer cells, in particular colon cancer cells, is stimulated by exposure to increased extracellular pressure through a cytoskeleton-dependent signaling mechanism requiring FAK, Src, Akt, and paxillin. Mechanical stimuli during tumor resection may therefore negatively impact patient outcome. We hypothesized that perioperative administration of colchicine, which prevents microtubule polymerization, could disrupt pressure-stimulated tumor cell adhesion to surgical wounds and enhance tumor-free survival. Ex vivo treatment of Co26 and Co51 colon cancer cells with colchicine inhibited pressure-stimulated cell adhesion to murine surgical wounds and blocked pressure-induced FAK and Akt phosphorylation. Surgical wound contamination with pressure-activated Co26 and Co51 cells significantly reduced tumor-free survival compared with contamination with tumor cells under ambient pressure. Mice treated with pressure-activated Co26 and Co51 cells from tumors preoperatively treated with colchicine in vivo displayed reduced surgical site implantation and significantly increased tumor-free survival compared with mice exposed to pressure-activated cells from tumors not pretreated with colchicine. Our data suggest that pressure activation of malignant cells promotes tumor development and impairs tumor-free survival and that perioperative colchicine administration or similar interventions may inhibit this effect.     

Ovarian Cancer in BRCA Mutation Carriers: Improved Outcome After Intraperitoneal (IP) Cisplatin

Background

Ovarian cancer arising in women with BRCA mutations is known to have a more favorable outcome and to be more responsive to platinum-based regimens than in those without a hereditary background. We analyze our previously published intraperitoneal (IP) studies in relation to BRCA mutation status and update their outcomes.

Methods

Among 62 patients with ovarian cancer enrolled in IP platinum doublet studies in clinical trials (with etoposide (n = 18), with floxuridine (n = 30), and with topotecan (n = 14)), a deleterious BRCA mutation was eventually identified in 10 patients. The outcomes in these BRCA mutation carriers are described and compared with survival of others in respective trials.

Results

Ten patients that were confirmed to have BRCA mutations—all with high-grade and stages IIC to IV disease—survived a median of 10 years (range: 4–18+) after receiving IP cisplatin-based regimens. Two continue with no evidence of disease since their IP treatment, while four others remain alive with recurrences after 8, 9, 10, and 11 years, respectively.

Conclusions

This experience suggests that IP cisplatin leads to favorable long term outcomes in advanced ovarian cancer in women with defective homologous recombination (i.e., with deleterious BRCA mutations). Whether such cisplatin dose-intensification from IP relative to (intravenous) IV drug administration leads to superior results in these mutation carriers requires further study.