LÓPEZ-POUSA A., RIFÀ J., CASAS DE TEJERINA A., GONZÁLEZ-LARRIBA J.L., IGLESIAS C., GASQUET J.A. & CARRATO A. (2010) European Journal of Cancer Care Risk assessment model for first-cycle chemotherapy-induced neutropenia in patients with solid tumoursChemotherapy-induced neutropenia, the major dose-limiting toxicity of chemotherapy, is directly associated with concomitant morbidity, mortality and health-care costs. The use of prophylactic granulocyte colony-stimulating factors may reduce the incidence and duration of chemotherapy-induced neutropenia, and is recommended in high-risk patients. The objective of this study was to develop a model to predict first-cycle chemotherapy-induced neutropenia (defined as neutropenia grade ≥3, with or without body temperature ≥38°C) in patients with solid tumours. A total of 1194 patients [56% women; mean age 58 ± 12 years; 94% Eastern Cooperative Oncology Group (ECOG) status ≤1] with solid tumours were included in a multi-centre non-interventional prospective cohort study. A predictive logistic regression model was developed. Several factors were found to influence chemotherapy-induced neutropenia. Higher ECOG status values increased toxicity (ECOG 2 vs. 0, P= 0.003; odds ratio 3.12), whereas baseline lymphocyte (P= 0.011; odds ratio 0.67) and neutrophil counts (P= 0.026; odds ratio 0.90) were inversely related to neutropenia occurrence. Sex and treatment intention also significantly influenced chemotherapy-induced neutropenia (P= 0.012). The sensitivity and specificity of the model were 63% and 67% respectively, and the positive and negative predictive values were 17% and 94% respectively. Once validated, this model should be a useful tool for clinical decision making.

The ideal temporary implant should offer enough mechanical support to allow healing of the fracture and then biodegrade and be resorbed by metabolic mechanisms without causing any toxic effect. The aim of this research has been to simultaneously study in situ bone healing and the biodegradation of AZ31 Mg alloy as an osteosynthesis material. The in vivo study was carried out in AZ31 implants with and without Mg-fluoride coating inserted in un-fractured and fractured femurs of Wistar rats for long experimentation time, from 1 to 13 months, by means of computed tomography, histological and histomorphometric analysis. Tomography analysis showed the bone healing and biodegradation of AZ31 implants. The fracture is healed in 100% of the animals, and AZ31 maintains its mechanical integrity throughout the healing process. Biodegradation was monitored, quantifying the evolution of gas over time by 3D composition of tomography images. In all the studied groups, gas pockets disappear with time as a result of the diffusion process through soft tissues. Histomorphometric studies reveal that after 13 months the 46.32% of AZ31 alloy has been resorbed. The resorption of the coated and uncoated AZ31 implants inserted in fractured femurs after 1, 9 and 13 months does not have statistically significant differences. There is a balance between the biodegradation of AZ31 and bone healing which allows the use of AZ31 to be proposed as an osteosynthesis material.

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ResumenEn el presente trabajo se ha estudiado el comportamiento frente a la corrosión y la biocompatibilidad in vitro/in vivo de la aleación de magnesio AZ31, cuyas propiedades mecánicas son superiores a los requisitos mecánicos del hueso. La aleación en estado de recepción ha mostrado una cinética de corrosión no compatible con el crecimiento celular. Para mejorar su comportamiento, el material ha sido modificado superficialmente mediante tratamiento de conversión química en ácido fluorhídrico. La capa de fluoruro de magnesio generada tras este tratamiento mejora el comportamiento del material frente a la corrosión, permitiendo el crecimiento in vitro de células osteoblásticas sobre su superficie y la formación in vivo de una capa de nuevo tejido óseo muy compacta. Estos resultados permiten concluir que el recubrimiento de fluoruro de magnesio es necesario para que el material AZ31 pueda ser potencialmente aplicado como implante biodegradable y reabsorbible en reparaciones óseas. Palabras claveAZ31; Fluoruro de magnesio; Corrosión; Biocompatibilidad; In vitro/in vivo. Corrosion behaviour and in vitro/in vivo biocompatibility of surface-modified AZ31 alloy AbstractThe present work evaluates the corrosion behaviour and the in vitro/in vivo biocompatibility of the AZ31 magnesium alloy, which fulfills the mechanical requirements of bone. The corrosion kinetic of as-received AZ31 alloy was not compatible with the cell growth. To improve its performance, the AZ31 alloy was surface modified by a chemical conversion treatment in hydrofluoric acid. The magnesium fluoride layer generated by the surface treatment of AZ31 alloy enhances its corrosion behaviour, allowing the in vitro growth of osteoblastic cells over the surface and the in vivo formation of a highly compact layer of new bone tissue. These results lead to consider the magnesium fluoride coating as necessary for potential use of the AZ31 alloy as biodegradable and absorbable implant for bone repair. INTRODUCCIÓNLos materiales metálicos, como los aceros inoxidables o el titanio y sus aleaciones, son utilizados habitualmente como implantes temporales de osteosíntesis, en forma de placas y tornillos, debido a su elevada resistencia a la corrosión y adecuada biocompatibilidad en el organismo. No obstante, si estos implantes permanecen en el cuerpo durante un periodo prolongado de tiempo acaban liberando cationes metálicos [1] que pueden ser tóxicos para el organismo, siendo por ello conveniente su retirada en una segunda intervención quirúrgica una vez cumplida su misión de reparación. Este problema puede ser resuelto empleando implantes biodegradables y reabsorbibles, que gradualmente se disuelven y eliminan una vez conseguida la reparación ósea. En este contexto, el magnesio y sus aleaciones pueden ser biomateriales más idóneos que cualesquiera otros implantes, metá-licos o poliméricos, para aplicaciones relacionadas

AZ31 alloy has been tested as a biodegradable material in the form of endomedullary implants in female Wistar rat femurs. In order to evaluate the accumulation of potentially toxic elements from the biodegradation of the implant, magnesium (Mg), aluminium (Al), zinc (Zn), manganese (Mn) and fluorine (F) levels have been measured in different organs such as kidneys, liver, lungs, spleen and brain. Several factors that may influence accumulation have been taken into account: how long the implant has been in place, whether or not the bone is fractured, and the presence of an MgF2 protective coating on the implant. The main conclusions and the clinical relevance of the study have been that AZ31 endomedullary implants have a degradation rate of about 60% after 13 months, which is fully compatible with fracture consolidation. Neither bone fracture nor an MgF2 coating seems to influence the accumulation of trace elements in the studied organs. Aluminium is the only alloying element in this study that requires special attention. The increase in Al recovered from the sampled organs represents 3.95% of the amount contained in the AZ31 implant. Al accumulates in a statistically significant way in all the organs except the brain. All of this suggests that in long-term tests AZ31 may be a suitable material for osteosynthesis.