Anesthetic Management During Electroconvulsive Therapy in Children: A Systematic Review of the Available Literature.

Electroconvulsive therapy (ECT) is indicated in a myriad of pediatric psychiatric conditions in children, and its use is increasing. Literature on the clinical features salient to anesthetic care is lacking. The objective of this systematic review is to describe the available literature on the anesthetic considerations of pediatric ECT. Original publications were screened for inclusion criteria: (1) manuscript written in English; (2) persons under 18 years of age; and (3) use of ECT. Data tabulation included demographic information, details of anesthetic management and ECT procedure, and adverse events. The mean age was 15 years, 90% were 12-17 years of age, and no cases involving children <6 years of age were identified. The psychiatric diagnoses most commonly represented were major depressive disorder (n = 185) and schizophrenia/schizoaffective disorders (n = 187). ECT was also used to treat many neurological disorders. Medical comorbidities were reported in 16% of all cases. Common coexisting conditions included developmental delay (n = 21) and autism (n = 18). Primary ECT indications included severe psychosis (n = 190), symptoms refractory to pharmacotherapy (n = 154), and suicidality (n = 153). ECT courses per patient ranged from 2 to 156. Duration averaged 91.89 ± 144.3 seconds. The most commonly reported induction agents were propofol and methohexital, and the most commonly reported paralytic agent was succinylcholine. Reported adverse events included headache, nausea, sedation, and short-term amnesia, as well as rare cases of benign dysrhythmias and prolonged seizure. Negative perception and diminished access to care result in treatment delays; thus, these children present in an advanced state of disease. In examining the details of modern ECT performed in 592 children, no major anesthetic morbidity was identified. Further study should start with retrospective analysis of anesthesia data during ECT to compare various effects of anesthesia medications and technique on adverse events and outcomes.

Association of Metformin Use with Outcomes in Advanced Endometrial Cancer Treated with Chemotherapy.

There is increasing evidence that metformin, a commonly used treatment for diabetes, might have the potential to be repurposed as an economical and safe cancer therapeutic. The aim of this study was to determine whether stage III-IV or recurrent endometrial cancer patients who are using metformin during treatment with chemotherapy have improved survival. To test this we analyzed a retrospective cohort of subjects at two independent institutions who received chemotherapy for stage III-IV or recurrent endometrial cancer from 1992 to 2011. Diagnosis of diabetes, metformin use, demographics, endometrial cancer clinico-pathologic parameters, and survival duration were abstracted. The primary outcome was overall survival. The final cohort included 349 patients, 31 (8.9%) had diabetes and used metformin, 28 (8.0%) had diabetes but did not use metformin, and 291 (83.4%) did not have diabetes. The results demonstrate that the median overall survival was 45.6 months for patients with diabetes who used metformin compared to 12.5 months for patients with diabetes who did not use metformin and 28.5 months for patients without diabetes (log-rank test comparing the three groups P = 0.006). In a model adjusted for confounders, the difference in survival between the three groups remained statistically significant (P = 0.023). The improvement in survival among metformin users was not explained by better baseline health status or more aggressive use of chemotherapy. Overall, the findings in this retrospective cohort of endometrial cancer patients with stage III-IV or recurrent disease treated with chemotherapy indicate that patients with diabetes who were concurrently treated with metformin survived longer than patients with diabetes who did not use metformin.

Mesothelial cells promote early ovarian cancer metastasis through fibronectin secretion.

Ovarian cancer (OvCa) metastasizes to organs in the abdominal cavity, such as the omentum, which are covered by a single layer of mesothelial cells. Mesothelial cells are generally thought to be "bystanders" to the metastatic process and simply displaced by OvCa cells to access the submesothelial extracellular matrix. Here, using organotypic 3D cultures, we found that primary human mesothelial cells secrete fibronectin in the presence of OvCa cells. Moreover, we evaluated the tumor stroma of 108 human omental metastases and determined that fibronectin was consistently overexpressed in these patients. Blocking fibronectin production in primary mesothelial cells in vitro or in murine models, either genetically (fibronectin 1 floxed mouse model) or via siRNA, decreased adhesion, invasion, proliferation, and metastasis of OvCa cells. Using a coculture model, we determined that OvCa cells secrete TGF-ß1, which in turn activates a TGF-ß receptor/RAC1/SMAD-dependent signaling pathway in the mesothelial cells that promotes a mesenchymal phenotype and transcriptional upregulation of fibronectin. Additionally, blocking α5 or ß1 integrin function with antibodies reduced metastasis in an orthotopic preclinical model of OvCa metastasis. These findings indicate that cancer-associated mesothelial cells promote colonization during the initial steps of OvCa metastasis and suggest that mesothelial cells actively contribute to metastasis.

Statin therapy is associated with improved survival in patients with non-serous-papillary epithelial ovarian cancer: a retrospective cohort analysis.

AIM: To determine whether statin use is associated with improved epithelial ovarian cancer (OvCa) survival. METHODS: This is a single-institution retrospective cohort review of patients treated for OvCa between 1992 and 2013. Inclusion criteria were International Federation of Gynecology and Obstetrics (FIGO) stage I-IV OvCa. The primary exposures analyzed were hyperlipidemia and statin use. The primary outcomes were progression-free survival (PFS) and disease-specific survival (DSS). RESULTS: 442 patients met inclusion criteria. The cohort was divided into three groups: patients with hyperlipidemia who used statins (n = 68), patients with hyperlipidemia who did not use statins (n = 28), and patients without hyperlipidemia (n = 346). OvCa outcomes were evaluated. When we analyzed the entire cohort, we found no significant differences in PFS or DSS among the groups. The median PFS for hyperlipidemics using statins, hyperlipidemics not using statins, and non-hyperlipidemics was 21.7, 13.6, and 14.7 months, respectively (p = 0.69). Median DSS for hyperlipidemics using statins, hyperlipidemics not using statins, and non-hyperlipidemics was 44.2, 75.7, and 41.5 months, respectively (p = 0.43). These findings did not change after controlling for confounders. However, a secondary analysis revealed that, among patients with non-serous-papillary subtypes of OvCa, statin use was associated with a decrease in hazards of both disease recurrence (adjusted HR = 0.23, p = 0.02) and disease-specific death (adjusted HR = 0.23, p = 0.04). To augment the findings in the retrospective cohort, the histology-specific effects of statins were also evaluated in vitro using proliferation assays. Here, statin treatment of cell lines resulted in a variable level of cytotoxicity. CONCLUSION: Statin use among patients with non-serous-papillary OvCa was associated with improvement in both PFS and DSS.