Physical Function and Quality of Life After Resection of Mobile Spine Chondrosarcoma.

Study Design:Retrospective cohort study. Objectives:(1) To assess patient-reported outcomes-physical function, pain, and quality of life-in patients who underwent resection of a mobile spine chondrosarcoma. (2) To assess complications (90 days), readmissions, reoperations, oncological outcomes, and neurologic status. Methods:Thirty-three patients with spinal conventional chondrosarcoma resection between 1984 and 2014 at one hospital were included. The primary outcome measures were-minimally 6 months after surgery-the EuroQol 5 Dimensions (EQ5D), PROMIS-Physical Function, PROMIS-Pain Intensity, and Oswestry (ODI) Disability Index, or Neck (NDI) Disability established in 14 out of 20 alive (70.0%) patients. Complications, readmission, reoperations, oncological outcomes, and neurological status were reported for the complete cohort of 33 patients. Results:After spine chondrosarcoma resection, patients (n = 14) reported worse physical function (median 43, range 22-61, P = .026), worse quality of life (median EQ5D 0.70, range 0.04-1, P = .022), and comparable pain intensity (median 47, range 31-56, P = .362) when compared with US general population values. The median NDI/ODI was 25 (range 0-72) indicating mild to moderate disability. Patients undergoing reoperation had worse patient-reported outcomes than those who did not. Eighteen (55.5%) out of 33 patients suffered complications (90 days), 14 (42.4%) had unplanned readmission, and 13 (39.4%) underwent reoperation. Intralesional resection was associated with increased readmission, reoperation, and recurrence rate. Conclusions:Chondrosarcoma affects quality of life and physical function and its treatment frequently results in complications and reoperations. Our findings can be used to inform future patients about expected outcomes

Cannabinoid CB1 Receptor Activation Mediates the Opposing Effects of Amphetamine on Impulsive Action and Impulsive Choice

It is well known that acute challenges with psychostimulants such as amphetamine affect impulsive behavior. We here studied the pharmacology underlying the effects of amphetamine in two rat models of impulsivity, the 5-choice serial reaction time task (5-CSRTT) and the delayed reward task (DRT), providing measures of inhibitory control, an aspect of impulsive action, and impulsive choice, respectively. We focused on the role of cannabinoid CB1 receptor activation in amphetamine-induced impulsivity as there is evidence that acute challenges with psychostimulants activate the endogenous cannabinoid system, and CB1 receptor activity modulates impulsivity in both rodents and humans. Results showed that pretreatment with either the CB1 receptor antagonist/inverse agonist SR141716A or the neutral CB1 receptor antagonist O-2050 dose-dependently improved baseline inhibitory control in the 5-CSRTT. Moreover, both compounds similarly attenuated amphetamine-induced inhibitory control deficits, suggesting that CB1 receptor activation by endogenously released cannabinoids mediates this aspect of impulsive action. Direct CB1 receptor activation by Δ9-Tetrahydrocannabinol (Δ9-THC) did, however, not affect inhibitory control. Although neither SR141716A nor O-2050 affected baseline impulsive choice in the DRT, both ligands completely prevented amphetamine-induced reductions in impulsive decision making, indicating that CB1 receptor activity may decrease this form of impulsivity. Indeed, acute Δ9-THC was found to reduce impulsive choice in a CB1 receptor-dependent way. Together, these results indicate an important, though complex role for cannabinoid CB1 receptor activity in the regulation of impulsive action and impulsive choice as well as the opposite effects amphetamine has on both forms of impulsive behavior

The Relationship between Impulsive Choice and Impulsive Action: A Cross-Species Translational Study

Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task) and impulsive action (five-choice serial reaction time task) paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT) and impulsive action (immediate and delayed memory task, IMT/DMT). Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action) and filled out the Barratt impulsiveness scale (BIS-11). Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1) self-reported impulsivity (BIS-11); (2) impulsive action (IMT/DMT and SST); (3) impulsive choice (DDT). This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology

Overview of the effects of CB1 receptor (ant)agonists on impulsive behavior found in this study.

<p>Arrows indicate the direction of the effects of CB1 receptor (ant)agonists on impulsivity relative to baseline or amphetamine-induced levels of impulsivity, whereby amphetamine alone increases and decreases impulsive action and choice as compared to baseline, respectively.</p><p>*SR141716A has under these conditions previously been found to reduce impulsivity in the 5-CSRTT (Pattij et al. 2007a). N.D. not determined.</p

Effects of the CB1 receptor antagonist/inverse agonist SR141716A (SR) on measures of attentional function, compulsivity, and motivation in the 5-CSRTT under conditions of normal or lengthened intertrial interval (ITI).

<p>In total n = 14 animals were included in the analyses and data depict mean±SEM.</p><p>*p<0.05 compared to respective Vehicle control.</p>+<p>p<0.05.</p>++<p>p<0.005 compared to respective ITI = 5 s control.</p

The CB receptor agonist Δ9-Tetrahydrocannabinol does not affect inhibitory control, but reduces impulsive choice.

<p>Effects of acute administration of Δ9-Tetrahydrocannabinol (THC) on the mean (± SEM) number of premature responses made in the 5-CSRTT (a,b) and effects of THC, SR141716A (SR), and their combination on the percentage preference for the larger, delayed reinforcer in the DRT (c,d). ITI: intertrial interval. In total <i>n</i> = 13−14 animals were included in the analyses. Drug doses are expressed as mg/kg. ^*<i>p</i><0.05 and ^**<i>p</i><0.005 versus Vehicle or Vehicle-Vehicle; ^#<i>p</i><0.05 compared to THC-Vehicle, ⁺⁺p<0.005 vs respective ITI 5 s control.</p

Effects of the CB1 receptor agonist Δ9-Tetrahydrocannabinol (THC) on measures of attentional function, compulsivity, and motivation in the 5-CSRTT under conditions of normal or lengthened intertrial interval (ITI).

<p>In total n = 13 animals were included in the analyses and data depict mean±SEM.</p>+<p><i>p</i><0.05.</p>++<p><i>p</i><0.005 compared to respective ITI = 5 s control.</p

Pretreatment with the CB1 receptor antagonist/inverse agonist SR141716A attenuates amphetamine-induced impulsive behaviors.

<p>Effects of acute administration of 0.5 mg/kg amphetamine (AMPH), SR141716A (SR), and their combination on the mean (± SEM) number of premature responses made in the 5-CSRTT (a,b) and percentage preference for the larger, delayed reinforcer in the DRT (c,d). ITI: intertrial interval. In total <i>n</i> = 13-14 animals were included in the analyses. Drug doses are expressed as mg/kg. ^**<i>p</i><0.005 versus respective Vehicle or Vehicle-Vehicle control; ^#<i>p</i><0.05 and ^##<i>p</i><0.005 compared to Amphetamine-Vehicle, ⁺⁺p<0.005 vs respective ITI 5 s control.</p

Effects of the CB1 receptor agonist Δ9-Tetrahydrocannabinol (THC) on measures of attentional function, compulsivity, and motivation in the 5-CSRTT.

<p>In total n = 13 animals were included in the analyses and data depict mean±SEM.</p><p><i>**p</i><0.005 versus Vehicle.</p