ArteFill® Permanent Injectable for Soft Tissue Augmentation: I. Mechanism of Action and Injection Techniques

After more than 25 years of research and development, in October 2006 ArteFill® became the first and only permanent injectable wrinkle filler to receive FDA approval. ArteFill is a third-generation polymeric microsphere-based filler, following its predecessor Artecoll®, which was marketed outside the United States between 1994 and 2006. ArteFill is approved for the correction of nasolabial folds and has been used in over 15,000 patients since its U.S. market introduction in February 2007. No serious side effects have been reported to date according to the FDA’s MAUDE reporting database. ArteFill consists of polymethylmethacrylate (PMMA) microspheres (20% by volume), 30–50 μm in diameter, suspended in 3.5% bovine collagen solution (80% by volume) and 0.3% lidocaine. The collagen carrier is absorbed within 1 month after injection and completely replaced by the patient’s own connective tissue within 3 months. Each cc of ArteFill contains approximately six million microspheres and histological studies have shown that long-term wrinkle correction consists of 80% of the patient’s own connective tissue and 20% microspheres. The standard injection technique is subdermal tunneling that delivers a strand of ArteFill at the dermal–subdermal junction. This strand beneath a wrinkle or fold acts like a support structure that protects against further wrinkling and allows the diminished thickness of the dermis to recover to its original thickness

Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction – MiHeart/AMI study

Background: Myocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls. Methods: A sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 x 106 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo (saline with 5% autologous serum). Implications: Many phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required.Brazilian Ministry of Science and Technology (MCT)/The Financing Agency for Studies and Projects (FINEP

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.

Evidence for similar structural brain anomalies in youth and adult attention-deficit/hyperactivity disorder: a machine learning analysis

Attention-deficit/hyperactivity disorder (ADHD) affects 5% of children world-wide. Of these, two-thirds continue to have impairing symptoms of ADHD into adulthood. Although a large literature implicates structural brain differences of the disorder, it is not clear if adults with ADHD have similar neuroanatomical differences as those seen in children with recent reports from the large ENIGMA-ADHD consortium finding structural differences for children but not for adults. This paper uses deep learning neural network classification models to determine if there are neuroanatomical changes in the brains of children with ADHD that are also observed for adult ADHD, and vice versa. We found that structural MRI data can significantly separate ADHD from control participants for both children and adults. Consistent with the prior reports from ENIGMA-ADHD, prediction performance and effect sizes were better for the child than the adult samples. The model trained on adult samples significantly predicted ADHD in the child sample, suggesting that our model learned anatomical features that are common to ADHD in childhood and adulthood. These results support the continuity of ADHD’s brain differences from childhood to adulthood. In addition, our work demonstrates a novel use of neural network classification models to test hypotheses about developmental continuity

Estudo clínico da eficácia do bloqueio anestésico radicular transforaminal no tratamento da radiculopatia lombar Estudio clínico de la eficacia del bloqueo anestésico radicular transforaminal en el tratamiento de la radiculopatía lumbar Clinical study on the efficacy of transforaminal radicular block in lumbar radiculopathy treatment

OBJETIVO: O objetivo deste estudo é avaliar a eficácia da injeção transforaminal nos pacientes com dor radicular devido à hérnia de disco ou estenose foraminal lombar por meio de estudo prospectivo randomizado. MÉTODOS: Foram avaliados 61 pacientes com quadro de radiculopatia nos membros inferiores. Esses pacientes foram divididos em dois grupos escolhidos aleatoriamente. Desses, 32 foram submetidos à injeção de corticosteroides e 29 foram submetidos à injeção salina. O período de acompanhamento foi de 12 meses. Para avaliar os resultados aplicamos a Escala Analógica Visual de Dor (EAV) e o Índice Oswestry (ODI). RESULTADOS: Houve melhora significativa da intensidade de dor (p < 0,001) na primeira semana nas escalas EAV e ODI, em ambos os grupos estudados (corticosteroides e solução salina). Na observação após o terceiro mês, os dois grupos apresentaram resultados semelhantes. O uso do bloqueio transforaminal evidenciou-se um método eficaz para o tratamento da dor radicular aguda, e sem melhora da patologia se considerado a longo prazo. CONCLUSÃO: O bloqueio transforaminal é um excelente método com alta evidência para tratar a crise de dor radicular e ciática a curto prazo (menor que três meses), porém moderado a longo prazo (maior que seis meses).<br>OBJETIVO: El presente estudio tuvo como objetivo evaluar la eficacia de la inyección transforaminal en pacientes con dolor radicular, debido a la hernia discal lumbar o estenosis foraminal, mediante un estudio prospectivo y aleatorizado. MÉTODOS: Se analizó un total de 61 pacientes con cuadro de radiculopatía en miembros inferiores. Estos pacientes fueron divididos en dos grupos seleccionados al azar. De ellos, 31 fueron sometidos a inyecciones de corticoides y a 29 se les aplicaron inyecciones de suero fisiológico. El período de seguimiento fue de 12 meses. Para evaluar los resultados se les aplicó la Escala Visual Analógica del dolor (EAV) y el Índice de Oswestry (ODI, sigla en inglés). RESULTADOS: Hubo una mejora significativa en la intensidad del dolor (p <0,001) en la primera semana según las escalas VAS y ODI, en ambos grupos estudiados (corticosteroides y solución salina). La observación después del tercer mes, en ambos grupos, mostró resultados similares. El uso del bloqueo transforaminal mostró un método eficaz para el tratamiento del dolor radicular agudo, y no hubo mejoría en la enfermedad en el largo plazo. CONCLUSIÓN: El bloqueo transforaminal es un excelente método, con alta evidencia, para hacer frente a la crisis de dolor radicular y la ciática en el corto plazo (menos de 3 meses), pero tiene efecto moderado en el largo plazo (más de 6 meses).<br>OBJECTIVE: To assess the efficacy of corticosteroid injections in patients with sciatica due to lumbar disc herniation or lumbar foraminal stenosis by a prospective randomized study. METHODS: There were analyzed 61 patients with sciatica due to lumbar disc degeneration. These patients were divided into two groups randomly chosen to radicular blocks with saline solution or corticosteroids. Thirty-one of these patients were submitted to corticosteroids radicular block and 29 patients were submitted to saline solution radicular block with a follow-up of 12 months. Outcomes were evaluated by visual analogue scale (VAS) and Oswestry disability index (ODI). RESULTS: Statistical analysis showed improvement in pain reduction (p < 0.001) in the first week on ODI and VAS in the group with corticosteroid radicular block in comparison to the group with saline solution; however no statistical differences were observed after three months of follow-up. The transforaminal root block presents a good method for treatment of acute sciatica and showed no improvement in a long-term-follow-up. CONCLUSION: Transforaminal root block is an excellent method with high evidence to treat sciatica in short-term follow-up, but for long-term (more than six months) follow-up is just moderate