Estudo da interação polímero/cartilagem/osso utilizando poli (ácido lático-co-ácido glicólico) e poli (p-dioxanona) em condilo femural de coelhos Study of polymer/cartilage/bone interaction using poly(lactic acid-co-glycolic acid) and poly (p-dioxanona) in femoral condyle of rabbits

Os dispositivos biorreabsorvíveis são alternativas para fixação interna das fraturas. Durante o tratamento estes dispositivos mantêm a fixação e degradam-se gradualmente não necessitando de uma cirurgia de remoção, reduzindo o custo de tratamento quando comparadas aos dispositivos metálicos. O objetivo desse trabalho foi estudar a interação polímero/tecido utilizando pinos de PLGA e PDS após implantes em coelhos Nova Zelândia. Separou-se os animais em 3 grupos os quais foram sacrificados após 3, 6 e 12 semanas de implantação e o material obtido foi submetido à análise histológica. As análises histológicas com implantes de PLGA mostraram após 3 semanas a formação de um tecido com características mesenquimatosas e com 12 semanas a formação de uma estrutura óssea madura. Já nos implantes de PDS de 3 semanas houve uma maior invasão de tecido mesenquimal comparado ao PLGA e após 12 semanas, ocorreu uma degradação avançada, com tecido proliferativo mesenquimal e ósseo. Assim, concluiu-se que ocorreram resultados positivos à resposta tecidual/implante e foi relevante a observação da ausência de células responsáveis pela resposta inflamatória. As análises demonstraram que o copolímero de PLGA apresentou propriedades osteoindutivas mais adequadas que os de PDS, apresentando biocompatibilidade aceitável para aplicação ortopédica.<br>Bioresorbable devices are alternatives for internal fixation. During the treatment, those devices maintain the fixation, degrade gradually and eliminate the need for a remove surgery, decreasing the treatment cost when compared with metallic devices. The aim of this work was to study the interaction polymer/tissue interaction using pins of PLGA and PDS implanted in New Zealand rabbits. The animals were separated in 3 groups which were sacrificed after 3, 6 and 12 weeks after implantation, and the obtained material was submitted to histological analysis. Histological analysis with PLGA implants showed after 3 weeks, the growth of a tissue with mesenchimal characteristics, after 3 weeks, with formation of mature bone aready after 12 weeks. PDS implants after 3 weeks showed a bigger invasion of mesenchimal tissue compared to PLGA and after 12 weeks an advanced degradation occurred, with proliferation of mesenchimal and bone tissue formation. It is concluded that the results are highly positive, with the relevant absence of cells responsible for inflammatory response. Analysis showed that the copolymer PLGA has better ostoinductive properties than PDS, showing biocompatibility acceptable for orthopedics application

Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial

ImportanceLocoregionally advanced head and neck squamous cell cancer (HNSCC) is treated curatively; however, risk of recurrence remains high among some patients. The ERBB family blocker afatinib has shown efficacy in recurrent or metastatic HNSCC. ObjectiveTo assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves disease-free survival (DFS) in patients with HNSCC. Design, Setting, and ParticipantsThis multicenter, phase 3, double-blind randomized clinical trial (LUX-Head & Neck 2) studied 617 patients from November 2, 2011, to July 4, 2016. Patients who had complete response after CRT, comprising radiotherapy with cisplatin or carboplatin, with or without resection of residual disease, for locoregionally advanced high- or intermediate-risk HNSCC of the oral cavity, hypopharynx, larynx, or oropharynx were included in the study. Data analysis was of the intention-to-treat population. InterventionsPatients were randomized (2:1) to treatment with afatinib (40 mg/d) or placebo, stratified by nodal status (N0-2a or N2b-3) and Eastern Cooperative Oncology Group performance status (0 or 1). Treatment continued for 18 months or until disease recurrence, unacceptable adverse events, or patient withdrawal. Main Outcomes and MeasuresThe primary end point was DFS, defined as time from the date of randomization to the date of tumor recurrence or secondary primary tumor or death from any cause. Secondary end points were DFS at 2 years, overall survival (defined as time from the date of randomization to death), and health-related quality of life. ResultsA total of 617 patients were studied (mean [SD] age, 58 [8.4] years; 528 male [85.6%]). Recruitment was stopped after a preplanned interim futility analysis on July 4, 2016, on recommendation from an independent data monitoring committee. Treatment was discontinued. Median DFS was 43.4 months (95% CI, 37.4 months to not estimable) in the afatinib group and not estimable (95% CI, 40.1 months to not estimable) in the placebo group (hazard ratio, 1.13; 95% CI, 0.81-1.57; stratified log-rank test P=.48). The most common grade 3 and 4 drug-related adverse effects were acneiform rash (61 [14.8%] of 411 patients in the afatinib group vs 1 [0.5%] of 206 patients in the placebo group), stomatitis (55 [13.4%] in the afatinib group vs 1 [0.5%] in the placebo group), and diarrhea (32 [7.8%] in the afatinib group vs 1 [0.5%] in the placebo group). Conclusions and RelevanceThis study's findings indicate that treatment with afatinib after CRT did not improve DFS and was associated with more adverse events than placebo in patients with primary, unresected, clinically high- to intermediate-risk HNSCC. The use of adjuvant afatinib after CRT is not recommended. Trial RegistrationClinicalTrials.gov identifier: NCT01345669Experimentele farmacotherapi

Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries

Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($). Results: High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was$216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with$195 for low FiO2 leading to a −$11 (95$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was$1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this