Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Postura da mão e imagética motora: um estudo sobre reconhecimento de partes do corpo Hand posture and motor imagery: a body-part recognition study

OBJETIVOS: Assim como a imagética motora, o reconhecimento de partes do corpo aciona representações somatosensoriais específicas. Essas representações são ativadas implicitamente para comparar o corpo com o estímulo. No presente estudo, investigou-se a influência da informação proprioceptiva da postura no reconhecimento de partes do corpo (mãos) e propõe-se a utilização dessa tarefa na reabilitação de pacientes neurológicos. MATERIAIS E MÉTODOS: Dez voluntários destros participaram do experimento. A tarefa era reconhecer a lateralidade de figuras da mão apresentada, em várias perspectivas e em vários ângulos de orientação. Para a figura da mão direita, o voluntário pressionava a tecla direita e para a figura da mão esquerda, a tecla esquerda. Os voluntários realizavam duas sessões: uma com as mãos na postura prona e outra com as mãos na postura supina. RESULTADOS: Os tempos de reação manual (TRM) eram maiores para as vistas e orientações, nas quais é difícil realizar o movimento real, mostrando que durante a tarefa, existe um acionamento de representações motoras para comparar o corpo com o estímulo. Além disso, existe uma influência da postura do sujeito em vistas e ângulos específicos. CONCLUSÕES: Estes resultados mostram que representações motoras são ativadas para comparar o corpo com o estímulo e que a postura da mão influencia esta ressonância entre estímulo e parte do corpo.<br>OBJECTIVE: Recognition of body parts activates specific somatosensory representations in a way that is similar to motor imagery. These representations are implicitly activated to compare the body with the stimulus. In the present study, we investigate the influence of proprioceptive information relating to body posture on the recognition of body parts (hands). It proposes that this task could be used for rehabilitation of neurological patients. METHODS: Ten right-handed volunteers participated in this experiment. The task was to recognize the handedness of drawings of a hand that were presented in different perspectives and several orientations. For drawings of a right hand, the volunteers pressed the right key, and for drawings of a left hand, they pressed the left key. The volunteers underwent two sessions: one with their hands in a prone posture and the other with their hands in a supine posture. RESULTS: The manual reaction time was longer for perspectives and orientations for which the real movement was difficult to achieve. This showed that, during the task, motor representations were activated to compare the body with the stimulus. Furthermore, the subject's posture had an influence in relation to specific perspectives and orientations. CONCLUSIONS: These results showed that motor representations are activated to compare the body with the stimulus, and that the position of the hand influences this resonance between the stimulus and the body part