Perillyl alcohol (POH) is a monoterpene that has been used orally for the treatment of systemic cancer. However, when used orally significant gastrointestinal side effects and lack of overall efficacy were documented. Recently, in a phase II trial in Brazil for the treatment of temozolomide (TMZ)-resistant malignant gliomas, POH was well tolerated when administered intranasally. The present study explores the effects and mechanisms of POH on TMZ-sensitive and TMZ-resistant glioma cells. In vitro studies showed that POH was cytotoxic to TMZ-resistant as well as TMZ-sensitive glioma cells, and this effect was independent of O 6 -methylguanine-DNA methyltransferase expression. POH induced cytotoxicity, in part, through the endoplasmic reticulum (ER) stress pathway as shown by the increased expression of glucose-regulated protein-78 (GRP78), activating transcription factor 3, and C/EBP-homologous protein. In addition, POH impeded survival pathways, such as mTOR and Ras. As well, POH reduced the invasive capacity of sensitive and resistant glioma cells. POH alone and/or in combination with other ER stress-inducing cytotoxic drugs (i.e., 2, 5-dimethyl-celecoxib, nelfinavir) further induced apoptosis in TMZ-sensitive and TMZ-resistant glioma cells. To show whether intranasal delivery of POH was effective for the treatment of TMZ-resistant gliomas, animals bearing intracranial tumors were given POH intranasally. Animals treated through intranasal administration of POH exhibited a decrease in tumor growth and an increase in survival. Our data show that POH is an effective anti-glioma cytotoxic agent for TMZ-resistant gliomas when administered intranasally.

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Firearm-related injuries types in hospitalized children are associated with age, race, and state level legislation. Accidents are most prevalent in young children, Whites, and states with lenient gun laws, while suicide attempts are more common in adolescents, Whites, and states with lenient gun laws. Suicide attempts are also associated with the greatest odds of in-hospital mortality. To address firearm violence, consideration should be given to legislation that promote safe gun storage behaviors and restrict firearm accessibility to children.

The American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial demonstrated no survival advantage for women with clinical T1–T2 invasive breast cancer with 1–2 positive sentinel lymph nodes (SLN) who received whole‐breast radiation, and no further axillary surgery when compared to women who did undergo axillary lymph node dissection (ALND). We used the National Cancer Database (NCDB) to study changes in utilization of ALND after the publication of this trial. NCDB was queried for female patients from 2012 to 2015 who met Z0011 criteria. Patients were divided into four groups based on Commission on Cancer facility accreditation. Outcome measures include the rate of ALND (nonadherence to Z0011) and the average number of nodes retrieved with ALND. 27,635 patients were identified, with no significant differences in T stage and receptor profiles between groups. Overall rate of ALND decreased from 34.0% in 2012 to 22.7% in 2015. Nonadherence was lowest in Academic Programs (decreasing from 30.1% in 2012 to 20.5% in 2015) and was highest in Community Cancer Programs (41.2% in 2012 to 29.1% in 2015). Median number of positive SLN did not differ between groups (p = .563). Median number of nodes retrieved on ALND decreased from 9 (IQR 5–14) in 2012 to 7 (IQR 4–12) in 2015 (p < .001). In patients who met the ACOSOG Z11 trial guidelines, rates of ALND have decreased over time. However, rates of nonadherence to Z0011 are significantly higher in Community Cancer Programs compared to Academic Programs.

BackgroundSurgical intervention for ischemic colitis is associated with significant postoperative morbidity and mortality. Predictive factors of adverse outcomes have been reported in the literature, but are based on small sample populations. We sought to identify risk factors for mortality after emergent colectomy for ischemic colitis using a clinical outcomes database.MethodsThe American College of Surgeons National Surgical Quality Improvement Project database was queried from 2010 to 2015 to identify emergent colectomies performed for ischemic colitis using Current Procedural Terminology and International Classification of Diseases, Ninth Revision codes. Univariate and multivariate logistic regression analysis was used to identify independent risk factors associated with increased risk of mortality.ResultsA total of 4548 patients undergoing emergent colectomies for ischemic colitis were identified. Overall, 30-day postoperative mortality was 25.3%. On univariate analysis, preoperative risk factors associated with a higher rate of mortality include dyspnea, functional status, ventilator dependency, history of chronic obstructive pulmonary disease, ascites, congestive heart failure exacerbation, hypertension, dialysis dependency, cancer, open wounds, chronic steroids, weight loss >10%, transfusions within 72 hours before surgery, septic shock and duration from hospital admission to surgery. Factors that were significant for mortality on logistic regression analysis include elderly age, poor functional status, multiple comorbidities, septic shock, blood transfusion, acute renal failure and the duration of time from hospital admission to surgery.ConclusionsPostoperative morbidity and mortality rates for ischemic colitis remain significantly high. Identification of risk factors may help patient selection for surgical interventions, and make informed decisions with patients and family members. Although it is certainly challenging, early diagnosis and prompt surgical intervention for patients with ischemic colitis may improve outcomes.Study type and level of evidenceTherapeutic/care management, level II