The Association of Statin Use after Cancer Diagnosis with Survival in Pancreatic Cancer Patients: A SEER-Medicare Analysis

Background

Pancreatic cancer has poor prognosis and existing interventions provide a modest benefit. Statin has anti-cancer properties that might enhance survival in pancreatic cancer patients. We sought to determine whether statin treatment after cancer diagnosis is associated with longer survival in those with pancreatic ductal adenocarcinoma (PDAC).

Methods

We analyzed data on 7813 elderly patients with PDAC using the linked Surveillance, Epidemiology, and End Results (SEER) - Medicare claims files. Information on the type, intensity and duration of statin use after cancer diagnosis was extracted from Medicare Part D. We treated statin as a time-dependent variable in a Cox regression model to determine the association with overall survival adjusting for follow-up, age, sex, race, neighborhood income, stage, grade, tumor size, pancreatectomy, chemotherapy, radiation, obesity, dyslipidemia, diabetes, chronic pancreatitis and chronic obstructive pulmonary disease (COPD).

Results

Overall, statin use after cancer diagnosis was not significantly associated with survival when all PDAC patients were considered (HR = 0.94, 95%CI 0.89, 1.01). However, statin use after cancer diagnosis was associated with a 21% reduced hazard of death (Hazard ratio = 0.79, 95% confidence interval (CI) 0.67, 0.93) in those with grade I or II PDAC and to a similar extent in those who had undergone a pancreatectomy, in those with chronic pancreatitis and in those who had not been treated with statin prior to cancer diagnosis.

Conclusions

We found that statin treatment after cancer diagnosis is associated with enhanced survival in patients with low-grade, resectable PDAC.     

Thymic Atrophy and Apoptosis of CD4+CD8+ Thymocytes in the Cuprizone Model of Multiple Sclerosis

Previous studies on the degenerative animal model of multiple sclerosis suggested that the copper-chelator cuprizone might directly suppress T-cell functions. Peripheral T-cell function in the cuprizone model has already been explored; therefore, in the present study, we investigated, for the first time, how cuprizone feeding affects the thymus, the organ of T-cell maturation and selection. We found that even one week of cuprizone treatment induced significant thymic atrophy, affecting the cortex over the medulla. Fluorescent microscopy and flow-cytometric analyses of thymi from cuprizone- and vehicle-treated mice indicated that eradication of the cluster of the differentiation-4 (CD4)-CD8 double-positive T-cell subset was behind the substantial cell loss. This result was confirmed with CD3-CD4-CD8 triple-staining experiments. Ultrastructurally, we observed degraded as well as enlarged mitochondria, myelin-bodies, large lipid droplets, and large lysosomes in the thymi of cuprizone-treated mice. Some of these features were similar to those in physiological and steroid-induced accelerated aging. According to our results, apoptosis was mainly of mitochondrial origin mediated by both caspase-3- and apoptosis inducing factor-mediated mechanisms. Additionally, mitogen activated protein kinase activation and increased pro-apoptotic B cell lymphoma-2 family protein expression were the major underlying processes. Our results do not indicate a functional relationship between cuprizone-induced thymus involution and the absence of inflammatory responses or the selective demyelination observed in the cuprizone model. On the other hand, due to the reversible nature of cuprizone’s deleterious effects, the cuprizone model could be valuable in studying thymus regeneration as well as remyelination processes.     

Selection against Heteroplasmy Explains the Evolution of Uniparental Inheritance of Mitochondria

Why are mitochondria almost always inherited from one parent during sexual reproduction? Current explanations for this evolutionary mystery include conflict avoidance between the nuclear and mitochondrial genomes, clearing of deleterious mutations, and optimization of mitochondrial-nuclear coadaptation. Mathematical models, however, fail to show that uniparental inheritance can replace biparental inheritance under any existing hypothesis. Recent empirical evidence indicates that mixing two different but normal mitochondrial haplotypes within a cell (heteroplasmy) can cause cell and organism dysfunction. Using a mathematical model, we test if selection against heteroplasmy can lead to the evolution of uniparental inheritance. When we assume selection against heteroplasmy and mutations are neither advantageous nor deleterious (neutral mutations), uniparental inheritance replaces biparental inheritance for all tested parameter values. When heteroplasmy involves mutations that are advantageous or deleterious (non-neutral mutations), uniparental inheritance can still replace biparental inheritance. We show that uniparental inheritance can evolve with or without pre-existing mating types. Finally, we show that selection against heteroplasmy can explain why some organisms deviate from strict uniparental inheritance. Thus, we suggest that selection against heteroplasmy explains the evolution of uniparental inheritance.     

The effect of helmets on the risk of head and neck injuries among skiers and snowboarders: a meta-analysis

Background

The prevention of head injuries in alpine activities has focused on helmets. However, no systematic review has examined the effect of helmets on head and neck injuries among skiers and snowboarders.

Methods

We searched electronic databases, conference proceedings and reference lists using a combination of the key words “head injury or head trauma,” “helmet” and “skiing or snowboarding.” We included studies that used a control group; compared skiers or snowboarders with and without helmets; and measured at least one objectively quantified outcome (e.g., head injury, and neck or cervical injury).

Results

We included 10 case–control, 1 case–control/case-crossover and 1 cohort study in our analysis. The pooled odds ratio (OR) indicated that skiers and snowboarders with a helmet were significantly less likely than those without a helmet to have a head injury (OR 0.65, 95% confidence interval [CI] 0.55–0.79). The result was similar for studies that used controls without an injury (OR 0.61, 95% CI 0.36–0.92), those that used controls with an injury other than a head or neck injury (OR 0.63, 95% CI 0.52–0.80) and studies that included children under the age of 13 years (OR 0.41, 95% CI 0.27–0.59). Helmets were not associated with an increased risk of neck injury (OR 0.89, 95% CI 0.72–1.09).

Interpretation

Our findings show that helmets reduce the risk of head injury among skiers and snowboarders with no evidence of an increased risk of neck injury.Skiing and snowboarding are popular winter activities.¹ Estimates from numerous countries indicate that head injuries account for 9% to 19%, and neck injuries for 1% to 4%, of all injuries reported by ski patrols and emergency departments.^2–11 Rates of head and neck injuries have been reported between 0.09 and 0.46 per 1000 outings.¹² Head and neck injuries are disproportionately represented in cases of severe trauma, and traumatic brain injury is the leading cause of death and serious injury among skiers and snow-boarders.¹³ As far back as 1983, Oh and Schmid recommended mandatory helmet use for children while skiing.¹⁴Many studies of the relation between helmet use and head injuries among skiers and snowboarders have found a protective effect.^15–24 It has been suggested that the use of helmets may increase the risk of neck injury in a crash or fall.²⁵ This may be more evident among children because they have a greater head:body ratio than adults, and the additional size and weight of the helmet may increase the risk of neck injury in an otherwise routine fall.²⁶ We conducted a systematic review of the effect of helmets on head and neck injuries among skiers and snowboarders.