Comparación de las propiedades de osteoconducción y osteointegración de una hidroxiapatita reabsorbible comercial con una hidroxiapatita reabsorbible sintetizada

ABSTRACT: The effects of two types of hydroxylapatite on bone synthesis and properties were evaluated. An osteoconductive resorbable hydroxyapatite (OseoU), synthesized at two different temperatures of calcination (Type A and Type B) was compared with a commercial mixture of hydroxyapatite (Osteogen®), commonly used in several surgical procedures involving bone loss. The synthesis was performed in the laboratories of the University of Antioquia by precipitating a mixture of calcium nitrate and ammonium phosphate. The products obtained and the commercial hydroxyapatite were characterized by scanning electron microscopy (SEM), X- ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and energy dispersive spectroscopy (EDS). Osteoconductive and osseointegration characteristics were measured according to the products ability to induce local cell differentiation into bone forming cells. These characteristics were evaluated in hydroxyapatite implants performed in 70 New Zealand breed rabbits distributed into seven groups of 10 animals each, tested at 7, 14, 21, 28, 42, 60 and 90 days after the surgical procedure. seven groups of 10 animals each, tested at 7, 14, 21, 28, 42, 60 and 90 days after the surgical procedure. The results showed that Osteogen® and OseoU have similar characteristics in terms of crystal structure, chemical composition and adsorption properties, but morphological differences regarding particle shape. The analysis of variance found no statistically significant differences for the histopathological variables evaluated in both hydroxyapatite groups (p>0.05), indicating that the hydroxyapatites synthesized at the University of Antioquia (OseoU) had the same results as the commercial hydroxyapatite.RESUMEN: En el presente artículo se evalúan las propiedades de osteoconducción y osteointegración de una hidroxiapatita reabsorbible (OseoU), procesada a dos temperaturas diferentes de calcinación (Tipo A y Tipo B), con el propósito de compararlas con un preparado comercial de hidroxiapatita (Osteogen®), utilizado para múltiples procedimientos quirúrgicos en los cuales se involucra la pérdida de tejido óseo. La síntesis se realizó en los laboratorios de la Universidad de Antioquia por el método de precipitación acuosa de la mezcla de nitrato de calcio y de fosfato de amonio. Los productos obtenidos y la hidroxiapatita comercial fueron caracterizados por microscopia electrónica de barrido (SEM), difracción de rayos X (DRX), espectroscopia de infrarrojo transformada de Fourier (FTIR) y espectrometría por energía dispersiva (EDS). Las características de osteoconducción y osteointegración fueron medidas de acuerdo a la capacidad de los productos para inducir la diferenciación de células locales a células formadoras de hueso. Dichas características, se evaluaron en implantes de hidroxiapatita realizados en 70 conejos de la raza Nueva Zelanda distribuidos en siete grupos de 10 animales cada uno, evaluados a los 7, 14, 21, 28, 42, 60 y 90 días de efectuado el procedimiento quirúrgico. Los resultados obtenidos demostraron que el OseoU y el Osteogen®, presentaron características similares en cuanto a la estructura cristalina, la composición química y la adsorción, con apreciables diferencias morfológicas con respecto a la forma de las partículas. Al realizar el análisis de varianza no se encontraron diferencias estadísticas significativas para las variables histopatológicas evaluadas en las dos hidroxiapatitas (p>0.05), indicando que las hidroxiapatitas sintetizadas en la Universidad de Antioquia (OseoU) tuvieron el mismo resultado que la hidroxiapatita comercial (Osteogen®) en la osteoconducción y la osteointegración del tejido óseo

Comparation of osteoconduction and osteointegration properties of a commercial reabsorbable hydroxypatitie with respect to a synthetyzed one

ABSTRACT: In the following article the effects of two types of hydroxiapatites on bone synthesis and properties were evaluated. One of them (OseoU) was synthesized at two different temperatures to compare it to a commercial mixture of hydroxiapatite (Osteogen®) commonly used in several surgical procedures in which loss of bone tissue is present. The synthesis was carried out in the laboratories of the Universidad de Antioquia by precipitating the mixture of calcium nitrate and ammonium phosphate. The final products and the commercial hydroxiapatite were characterized by sweeper electronic microscopy (SEM), X ray diffraction (XRD), Fourier transformed infrared spectroscopy (FTIR), and energy dispersed spectrometry (EDS). The properties of osteoconduction and osteointegration were measured according to the capacity of the products to induce the differentiation of local cells into bone forming cells. Such characteristics were evaluated in hydroxiapatite implants in 70 New Zealand breed rabbits distributed in seven groups, ten rabbits in each group, which were evaluated at days 7, 14, 21, 28, 42, 60 and 90 after the surgical procedure. The results demonstrated that the hydroxiapatites synthesized in the laboratories of the Universidad de Antioquia and the commercial hydroxiapatite showed similar characteristics in terms of the crystal structure, chemical composition and absorption properties with slight morphological differences in particle shape and size. Using variance analysis, no meaningful statistical differences were found between the histopathological variables evaluated in the several hydroxiapatite groups (p>0.05), indicating that results obtained with both the OseoU and the commercial hydroxiapatite equally affected bone synthesis and properties.RESUMEN: En el presente artículo se evalúan las propiedades de osteoconducción y osteointegración de una hidroxiapatita reabsorbible (OseoU), procesada a dos temperaturas diferentes de calcinación (Tipo A y Tipo B), con el propósito de compararlas con un preparado comercial de hidroxiapatita (Osteogen®), utilizado para múltiples procedimientos quirúrgicos en los cuales se involucra la pérdida de tejido óseo. La síntesis se realizó en los laboratorios de la Universidad de Antioquia por el método de precipitación acuosa de la mezcla de nitrato de calcio y de fosfato de amonio. Los productos obtenidos y la hidroxiapatita comercial fueron caracterizados por microscopia electrónica de barrido (SEM), difracción de rayos X (DRX), espectroscopia de infrarrojo transformada de Fourier (FTIR) y espectrometría por energía dispersiva (EDS). Las características de osteoconducción y osteointegración fueron medidas de acuerdo a la capacidad de los productos para inducir la diferenciación de células locales a células formadoras de hueso. Dichas características, se evaluaron en implantes de hidroxiapatita realizados en 70 conejos de la raza Nueva Zelanda distribuidos en siete grupos de 10 animales cada uno, evaluados a los 7, 14, 21, 28, 42, 60 y 90 días de efectuado el procedimiento quirúrgico. Los resultados obtenidos demostraron que el OseoU y el Osteogen®, presentaron características similares en cuanto a la estructura cristalina, la composición química y la adsorción, con apreciables diferencias morfológicas con respecto a la forma de las partículas. Al realizar el análisis de varianza no se encontraron diferencias estadísticas significativas para las variables histopatológicas evaluadas en las dos hidroxiapatitas (p > 0.05), indicando que las hidroxiapatitas sintetizadas en la Universidad de Antioquia (OseoU) tuvieron el mismo resultado que la hidroxiapatita comercial (Osteogen®) en la osteoconducción y la osteointegración del tejido óseo

Cilengitide combined with cetuximab and platinum-based chemotherapy as first-line treatment in advanced non-small-cell lung cancer (NSCLC) patients: results of an open-label, randomized, controlled phase II study (CERTO)

Background: This multicentre, open-label, randomized, controlled phase II study evaluated cilengitide in combination with cetuximab and platinum-based chemotherapy, compared with cetuximab and chemotherapy alone, as first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: Patients were randomized 1:1:1 to receive cetuximab plus platinum-based chemotherapy alone (control), or combined with cilengitide 2000 mg 1×/week i.v. (CIL-once) or 2×/week i.v. (CIL-twice). A protocol amendment limited enrolment to patients with epidermal growth factor receptor (EGFR) histoscore ≥200 and closed the CIL-twice arm for practical feasibility issues. Primary end point was progression-free survival (PFS; independent read); secondary end points included overall survival (OS), safety, and biomarker analyses. A comparison between the CIL-once and control arms is reported, both for the total cohorts, as well as for patients with EGFR histoscore ≥200. Results: There were 85 patients in the CIL-once group and 84 in the control group. The PFS (independent read) was 6.2 versus 5.0 months for CIL-once versus control [hazard ratio (HR) 0.72; P = 0.085]; for patients with EGFR histoscore ≥200, PFS was 6.8 versus 5.6 months, respectively (HR 0.57; P = 0.0446). Median OS was 13.6 for CIL-once versus 9.7 months for control (HR 0.81; P = 0.265). In patients with EGFR ≥200, OS was 13.2 versus 11.8 months, respectively (HR 0.95; P = 0.855). No major differences in adverse events between CIL-once and control were reported; nausea (59% versus 56%, respectively) and neutropenia (54% versus 46%, respectively) were the most frequent. There was no increased incidence of thromboembolic events or haemorrhage in cilengitide-treated patients. αvβ3 and αvβ5 expression was neither a predictive nor a prognostic indicator. Conclusions: The addition of cilengitide to cetuximab/chemotherapy indicated potential clinical activity, with a trend for PFS difference in the independent-read analysis. However, the observed inconsistencies across end points suggest additional investigations are required to substantiate a potential role of other integrin inhibitors in NSCLC treatment

Early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up : 2nd ESMO Consensus Conference on Lung Cancer.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease

2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer

To complement the existing treatment guidelines, ESMO organises consensus conferences to focus on specific issues. The 2nd ESMO Consensus Conference on Lung Cancer included 35 experts who met to address several questions on non-small-cell lung cancer (NSCLC). Recommendations were made with reference to grade of recommendation and level of evidence. This paper focuses on locally advanced diseas

2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

This manuscript provides recommendations for the diagnosis, treatment and follow-up of early stage non-small cell lung cancer developed during the 2nd ESMO Consensus Conference on Lung Cancer in May 201

2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease

This manuscript provides recommendations for first-line / second and further lines of treatment in advanced disease in non-small cell lung cancer (NSCLC). These recommendations were developed during the 2nd ESMO Consensus Conference on Lung Cancer in May 201

Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer

Background: Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation–positive advanced non–small-cell lung cancer (NSCLC). Methods: In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation–positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival. Results: The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%). Conclusions: Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation–positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.

<title language="por">Comparação das propriedades da osteocondução e osteointegração de uma hidroxiapatita reabsorvivel comercial sintetizada Comparación de las propiedades de osteoconducción y osteointegración de una hidroxiapatita reabsorbible comercial con una hidroxiapatita reabsorbible sintetizada

En el presente artículo se evalúan las propiedades de osteoconducción y osteointegración de una hidroxiapatita reabsorbible (OseoU), procesada a dos temperaturas diferentes de calcinación (Tipo A y Tipo B), con el propósito de compararlas con un preparado comercial de hidroxiapatita (Osteogen®), utilizado para múltiples procedimientos quirúrgicos en los cuales se involucra la pérdida de tejido óseo. La síntesis se realizó en los laboratorios de la Universidad de Antioquia por el método de precipitación acuosa de la mezcla de nitrato de calcio y de fosfato de amonio. Los productos obtenidos y la hidroxiapatita comercial fueron caracterizados por microscopia electrónica de barrido (SEM), difracción de rayos X (DRX), espectroscopia de infrarrojo transformada de Fourier (FTIR) y espectrometría por energía dispersiva (EDS). Las características de osteoconducción y osteointegración fueron medidas de acuerdo a la capacidad de los productos para inducir la diferenciación de células locales a células formadoras de hueso. Dichas características, se evaluaron en implantes de hidroxiapatita realizados en 70 conejos de la raza Nueva Zelanda distribuidos en siete grupos de 10 animales cada uno, evaluados a los 7, 14, 21, 28, 42, 60 y 90 días de efectuado el procedimiento quirúrgico. Los resultados obtenidos demostraron que el OseoU y el Osteogen®, presentaron características similares en cuanto a la estructura cristalina, la composición química y la adsorción, con apreciables diferencias morfológicas con respecto a la forma de las partículas. Al realizar el análisis de varianza no se encontraron diferencias estadísticas significativas para las variables histopatológicas evaluadas en las dos hidroxiapatitas (p>0.05), indicando que las hidroxiapatitas sintetizadas en la Universidad de Antioquia (OseoU) tuvieron el mismo resultado que la hidroxiapatita comercial (Osteogen®) en la osteoconducción y la osteointegración del tejido óseo.No presente estudo foram avaliadas as propriedades de ostecondução e osteointegração de uma hidroxiapatita reabsorvivel (OseoU), processada a duas temperaturas de calcinaçao (Tipo A e B), como propósito de serem comparadas com um produto comercial (Osteogen®), utilizado para múltiples procedimentos cirúrgicos nos quais se envolve a perda do tecido osso. Asíntese foi realizada nos laboratórios da Universidad de Antioquia pelo método de precipitação aquosa da mistura de nitrato de cálcio e fosfato de amônio. Os produtos obtidos e a hidroxiapatita comercial foram caracterizados por microscopia eletrônica de barrido (SEM), difração raios X (DRX), espectroscopia de infravermelho transformada de Fourier (FTIR) e espectrometria por energia dispersiva (EDS). As características de osteocondução e osteointegração foram mensuradas de acordo à capacidade dos produtos para induzir a diferenciação das células locais formadoras do osso. Estas características foram avaliadas em implantações de hidroxiapatita realizadas em 70 coelhos da raça Nova Zelândia distribuídos em sete grupos de 10 animais cada um, avaliados aos 7, 14, 21, 28, 42, 60 e 90 dias de efetuado o procedimento cirúrgico. Os resultados obtidos demonstraram que o OseoU e o Osteogen® apresentaram características similares em quanto à estrutura cristalina, a comparação química e à absorção, com apreciáveis diferenças morfológicas com respeito à forma das partículas. Ao realizar as análises de variâncias não foram encontradas diferencias estatísticas significativas para as variáveis histopatológicas avaliadas nas duas hidroxiapatitas (p>0.05), indicando que as hidroxiapatitas sintetizadas na Universidad de Antioquia (OseoU) tiveram o mesmo resultado que a hidroxiapatita comercial (Osteogen®) em osteocondução e osteointegração do tecido ósseo.In the following article the effects of two types of hydroxiapatites on bone synthesis and properties were evaluated. One of them (OseoU) was synthesized at two different temperatures to compare it to a commercial mixture of hydroxiapatite (Osteogen®) commonly used in several surgical procedures in which loss of bone tissue is present. The synthesis was carried out in the laboratories of the Universidad de Antioquia by precipitating the mixture of calcium nitrate and ammonium phosphate. The final products and the commercial hydroxiapatite were characterized by sweeper electronic microscopy (SEM), X ray diffraction (XRD), Fourier transformed infrared spectroscopy (FTIR), and energy dispersed spectrometry (EDS). The properties of osteoconduction and osteointegration were measured according to the capacity of the products to induce the differentiation of local cells into bone forming cells. Such characteristics were evaluated in hydroxiapatite implants in 70 New Zealand breed rabbits distributed in seven groups, ten rabbits in each group, which were evaluated at days 7, 14, 21, 28, 42, 60 and 90 after the surgical procedure. The results demonstrated that the hydroxiapatites synthesized in the laboratories of the Universidad de Antioquia and the commercial hydroxiapatite showed similar characteristics in terms of the crystal structure, chemical composition and absorption properties with slight morphological differences in particle shape and size. Using variance analysis, no meaningful statistical differences were found between the histopathological variables evaluated in the several hydroxiapatite groups (p>0.05), indicating that results obtained with both the OseoU and the commercial hydroxiapatite equally affected bone synthesis and properties