A randomized, double-blind, placebo-controlled trial assessing the impact of dexamphetamine on fatigue in patients with advanced cancer

Fatigue is very common in patients with cancer. Current guidelines suggest that psychostimulants are "reasonable to consider for severe fatigue." This randomized, double-blind, placebo-controlled trial investigated the hypothesis that dexamphetamine in fatigued patients with advanced cancer would produce a clinically significant improvement with minimal side effects. Fifty patients with advanced cancer, who were receiving palliative care, were randomized to dexamphetamine 10mg twice daily or placebo for eight days. Effectiveness was assessed using the Brief Fatigue Inventory and the McGill Quality-of-Life Questionnaire. The side effects were recorded. The results were analyzed on an intention-to-treat basis. The baseline demographics, fatigue levels, and quality-of-life scores were similar between the two arms. Patients were elderly, had impaired performance status (Eastern Cooperative Oncology Group score=3), and were taking a range of neurologically active medications. Thirty-nine patients completed the trial. There was a transient improvement in the fatigue levels on day 2, but no significant difference in fatigue (P=0.267) or quality of life (P=0.579) by the end of the study. Statistical modeling did not reveal any significant predictors of response to dexamphetamine. These results suggest that dexamphetamine 20mg daily, although well tolerated, does not significantly improve fatigue or quality of life in patients with advanced cancer, as measured by the selected instruments.     

Anestesia e doença de Alzheimer – Percepções atuais

Background and objectives

It has been speculated that the use of anesthetic agents may be a risk factor for the development of Alzheimer disease. The objective of this review is to describe and discuss pre‐clinical and clinical data related to anesthesia and this disease.

Palliative care and active disease management are synergistic in modern surgical oncology

Palliative care has long been described in medical literature but only recently is being discussed in the surgical domain. Mounting evidence suggests that early integration of palliative care improves patient outcomes and this is especially true of oncology patients. Thus, the pendulum is swinging toward recognizing that palliative care and active disease management are not mutually exclusive but rather synergistic in modern surgical oncology. Here we use a patient vignette to demonstrate the new challenges and possibilities in modern surgical oncology, we then discuss the historic perspective of palliative care and describe how the paradigm is shifting. Finally, we introduce a model that may be beneficial in conceptualizing this new way of thinking about and integrating palliative care into surgical oncology.     

Does Muscle Atrophy and Fatty Infiltration Plateau or Persist in Chronic Spinal Cord Injury?

Atrophy and fatty infiltration of lower extremity muscle after spinal cord injury (SCI) predisposes individuals to metabolic syndrome and related diabetes and cardiovascular disease. The objective of this study was to prospectively measure changes in muscle atrophy and fat content of distal lower extremity muscles and explore related factors in a cohort of adults with chronic SCI and diverse impairments. Muscle cross-sectional area and density were calculated from peripheral quantitative computed tomography scans of the 66% site of the calf from 70 participants with chronic SCI (50 male, mean age 49 years, C2-T12, American Spinal Injury Association Impairment Scale A-D) at study enrollment and annually for 2 years. Mixed-model repeated measures analysis of variance (rANOVA) examined longitudinal changes in muscle area and density, and regression analyses explored factors related to muscle changes using 16 potential correlates selected a priori. A high degree of individual variation in muscle area and density change was observed over 2 years (range: 8.5 to???22.6?cm²; 6.4 to??8.6?mg/cm³). Repeated measures analysis of variance revealed significant reductions in muscle area (estimated mean difference [95% confidence intervals] ?1.76 [?3.29?to ?0.23]) cm², p?=?0.025) and density (?1.04 [?1.94 to??0.14] mg/cm³, p?<?0.024); however, changes in area were not significant with outliers removed. Regression analyses explained a small proportion of the variability in muscle density change; however, none of the preselected variables were significantly related to changes in muscle density after post hoc sensitivity analyses. Lower extremity muscle size and fat content may not reach a “steady-state” after chronic SCI. Progressive atrophy and fatty infiltration of lower extremity muscle may have adverse implications for metabolic syndrome and cardiovascular disease risk and related mortality after chronic SCI.     

cIAP2 Is an Independent Signaling and Survival Factor during Mammary Lactational Involution and Tumorigenesis

Cellular inhibitor of apoptosis proteins-1 and -2 (cIAP1/2) are integral to regulation of apoptosis and signaling by the tumor necrosis factor (TNF) and related family of receptors. The expression of cIAP2 in tissues is typically low and considered functionally redundant with cIAP1, however cIAP2 can be activated by a variety of cellular stresses. Members of the TNFR family and their ligands have essential roles in mammary gland biology. We have found that cIAP2^?/? virgin mammary glands have reduced ductal branching and delayed lobuloalveogenesis in early pregnancy. Post-lactational involution involves two phases where the first phase is reversible and is mediated, in part, by TNFR family ligands. In cIAP2?/? mice mammary glands appeared engorged at mid-lactation accompanied by enhanced autophagic flux and decreased cIAP1 protein expression. Severely stretched myoepithelium was associated with BIM-EL expression and other indicators of anoikis. Within 24 h after forced or natural weaning, cIAP2^?/? glands had nearly completed involution. The TNF-related weak inducer of apoptosis (Tweak) which results in degradation of cIAP1 through its receptor, Fn14, began to increase in late lactation and was significantly increased in cIAP2^?/? relative to WT mice by 12 h post weaning accompanied by decreased cIAP1 protein expression. Carcinogen/progesterone-induced mammary tumorigenesis was significantly delayed in cIAP2^?/? mice and tumors contained high numbers of apoptotic cells. We conclude that cIAP2 has a critical role in the mammary gland wherein it prevents rapid involution induced by milk stasis-induced stress associated with Tweak activation and contributes to the survival of mammary tumor cells.