Over the last decade, there has been a shift in the focus of cancer therapy from conventional cytotoxic drugs to therapies more specifically directed to cancer cells. These novel therapies include immunotherapy, targeted therapy and precision medicine, each developed in great part with a goal of limiting collateral destruction of normal tissues, while enhancing tumor destruction. Although this approach is sound in theory, even new, specific therapies have some undesirable, ‘off target effects’, in great part due to molecular pathways shared by neoplastic and normal cells. One such undesirable effect is hyperglycemia, which results from either the loss of immune tolerance and autoimmune destruction of pancreatic β-cells or dysregulation of the insulin signaling pathway resulting in insulin resistance. These distinct pathogenic mechanisms lead to clinical presentations similar to type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. Both types of diabetes have been reported in patients across clinical trials, and data on the mechanism(s) for developing hyperglycemia, prevalence, prognosis and effect on cancer mortality is still emerging. With the rapidly expanding list of clinical indications for new cancer therapies, it is essential to understand the impact of their adverse effects. In this review, we focus on hyperglycemia and diabetes related to cancer therapies, describe what is known about mechanism(s) leading to dysregulated glucose metabolism and provide a guide to management of complex oncology patients with a new diagnosis of diabetes.
P ediatric neurosurgeons frequently perform emergency surgical procedures outside "regular" operating room hours due to the time-sensitive nature of disease processes and because delays in care may contribute to adverse outcomes. However, operating room staffing and hospital resource availability are variable outside of the conventional Monday through Friday work week.There is a growing body of literature that suggests increased rates of morbidity and mortality for a number of pediatric and adult conditions when patients present to the hospital on a weekend compared with weekdays. [1][2][3][4][5][6][7][8][11][12][13][14][15][16]19,20,[23][24][25] The "weekend effect" on pediatric neurosurgical procedures is unknown. Therefore, our primary aim was to abbreviation ASA = American Society of Anesthesiologists. obJect Several studies have indicated that the 30-day morbidity and mortality risks are higher among pediatric and adult patients who are admitted on the weekends. This "weekend effect" has been observed among patients admitted with and for a variety of diagnoses and procedures, including myocardial infarction, pulmonary embolism, ruptured abdominal aortic aneurysm, stroke, peptic ulcer disease, and pediatric surgery. In this study, morbidity and mortality outcomes for emergency pediatric neurosurgical procedures carried out on the weekend or after hours are compared with emergency surgical procedures performed during regular weekday business hours. methods A retrospective analysis of operative data was conducted. Between December 1, 2011, and August 20, 2014, a total of 710 urgent or emergency neurosurgical procedures were performed at Texas Children's Hospital in children younger than than 18 years of age. These procedures were then stratified into 3 groups: weekday regular hours, weekday after hours, and weekend hours. By cross-referencing these events with a prospectively collected morbidity and mortality database, the impact of the day and time on complication incidence was examined. Outcome metrics were compared using logistic regression models. results The weekday regular hours and after-hours (weekday after hours and weekends) surgery groups consisted of 341 and 239 patients and 434 and 276 procedures, respectively. There were no significant differences in the types of cases performed (p = 0.629) or baseline preoperative health status as determined by American Society of Anesthesiologists classifications (p = 0.220) between the 2 cohorts. After multivariate adjustment and regression, children undergoing emergency neurosurgical procedures during weekday after hours or weekends were more likely to experience complications (p = 0.0227). conclusions Weekday after-hours and weekend emergency pediatric neurosurgical procedures are associated with significantly increased 30-day morbidity and mortality risk compared with procedures performed during weekday regular hours.
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