Neurotoxidad inducida por ifosfamida / Ifosfamide-induced neurotoxicity

Introducción: La ifosfamida es un agente alquilante utilizado para el tratamiento de enfermedades oncohematológicas. Entre sus eventos adversos agudos se encuentra la neurotoxicidad. Esta puede presentarse desde el inicio de la infusión hasta tres días después. El tratamiento consiste en suspender la administración y asegurar una adecuada hidratación. Objetivo: Describir eventos neurológicos asociados al uso de ifosfamida en pacientes pediátricos con enfermedades oncohematológicas. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo y transversal. Los datos se obtuvieron de historias clínicas de pacientes internados en el Hospital Garrahan que infundieron ifosfamida y desarrollaron síntomas neurológicos. Se analizaron edad, diagnóstico de base, dosis de ifosfamida, síntomas neurológicos y su relación con la infusión, tratamiento instaurado, exámenes complementarios y posibles factores de riesgo asociados. Resultados: Se registraron un total de catorce eventos neurológicos en doce pacientes, sin diferencia de sexo, con una mediana de edad de 9,5 años. La enfermedad de base más prevalente fue osteosarcoma. Las convulsiones fueron el síntoma más frecuente (50%), seguido de somnolencia y paresias. La combinación de ifosfamida y etopósido con/sin carboplatino se asoció en un 36% cada uno. El 64% desarrolló neurotoxicidad dentro de las primeras cuatro horas. Ningún paciente presentó alteraciones en los exámenes complementarios. Todos presentaron recuperación ad integrum. Conclusión: Este estudio brinda información acerca del tiempo de aparición de esta complicación, lo cual facilitará su detección precoz y tratamiento oportuno (AU)

Introduction: Ifosfamide is an alkylating agent used for the treatment of cancer. Among its acute adverse events is neurotoxicity. This can occur from the beginning of the infusion up to three days afterwards. Treatment consists of discontinuing administration and ensuring adequate hydration. Objective: To describe neurological events associated with the use of ifosfamide in children with cancer. Materials and methods: Observational, descriptive, retrospective, and cross-sectional study. Data were obtained from clinical records of patients admitted to the Garrahan Hospital who received ifosfamide infusion and developed neurological symptoms. Age, baseline diagnosis, ifosfamide dose, neurological symptoms and their relationship with the infusion, treatment, complementary tests, and possible associated risk factors were analyzed. Results: A total of fourteen neurological events were recorded in twelve patients, without difference in sex and with a median age of 9.5 years. The most prevalent underlying disease was osteosarcoma. Seizures were the most frequent symptom (50%), followed by drowsiness and paresis. The combination of ifosfamide and etoposide with/without carboplatin was associated in 36% each. Sixty-four percent developed neurotoxicity within the first four hours. None of the patients presented with abnormalities in the complementary examinations. All recovered ad integrum. Conclusion: This study provides information about the time of onset of this complication, which will facilitate its early detection and timely treatment (AU)

Avance de tuberosidad tibial con heteroimplante óseo para el tratamiento de ruptura de ligamento cruzado anterior en caninos / Advance of tibial tuberosity with bone heteroimplant for previous crossed ligament in canine

RESUMEN Las evaluaciones clínica y radiológica son técnicas que se emplean para el diagnóstico de ruptura de ligamento cruzado anterior (RLCA) y para la evaluación posoperatoria de cirugías correctivas. Se planteó como objetivo describir los resultados posoperatorios de la técnica avance de tuberosidad tibial en caninos con RLCA utilizando hueso de origen bovino conservado en glicerina al 98%. Fueron intervenidos 5 caninos con la patología y sin cambios radiológicos marcados en las columnas óseas relacionadas. El heteroim-plante óseo se cortó a manera de cuña y, para determinar su tamaño, se tuvo en cuenta la medida prequirúrgica que necesitaba la rodilla para alcanzar el ángulo de avance de la cresta tibial. Seguidamente se fijó al receptor local con implantes metálicos (agujas de Kirschner y alambre ortopédico). En el posoperatorio, se evaluaron por 90 días signos clínicos como claudicación, dolor al movimiento flexión-extensión e inflamación, según la circunferencia de la rodilla, y se evaluó por 120 días el ángulo de avance tibial y la radiopacidad del heteroimplante con respecto al hueso circunvecino (tuberosidad tibial y tibia caudal). El estudio estableció que los parámetros clínicos y radiológicos tienen un efecto estadísticamente significativo; sin embargo, la evaluación del ángulo de avance tibial no tiene un efecto significativo entre el paciente y los días posquirúrgicos. Durante el periodo de evaluación el heteroimplante óseo bovino demostró ser efectivo para estabilizar una rodilla con RLCA en caninos.

ABSTRACT The clinical and radiological evaluations are techniques used for the diagnosis of the anterior cruciate ligament rupture (LCAR) and the post-operatory assessment of corrective surgeries. It was proposed as an objective to describe the post-operatory results of the advance technique of tibial tuberosity in canines with LCAR using bovine bone conserved in 98% glycerin. Five canines were intervened and with no other radiological changed in the related bone columns. The bone heteroimplant was cut in a wedge-like manner and for its size it was taken into account the pre-operatory measurement that the knee needed to reach the advancement angle of the tibial crest. Next, the bone implant was fixated to the local receptor with metallic implants (Kirschner needles and orthopedic wire). In the post-op, the canines were evaluated for 90 days for clinical signs such as claudication, pain when flexing and extending and inflammation according to the knee circumference, and for 120 days the advancement angle of the tibia and the radiopacitry of the heteroimplant in relation to the surrounding bone. The trial established that the clinical and radiological parameters have a statistically significant effect; however, the evaluation of the tibial advancement angle does not have a significant effect between the patient and the post-operatory days. During the evaluation period, the heteroimplant bovine bone proved to be effective to stabilize the knee in canines with LCAR.

Osseointegração clínica-radiológica do compósito hidroxiapatita-lignina entre implante metálico e tecido ósseo em coelho / Clinical-radiographic osseointegration of hydroxyapatite-lignin composite between metallic implant and bone tissue in rabbit

Para avaliar o compósito hidroxiapatita-lignina na osseointegração entre implante metálico e o tecido ósseo, foram utilizados 20 coelhos adultos, nos quais foi realizada uma falha óssea na face lateral proximal de ambas as tíbias. Na tíbia esquerda, introduziu-se, no canal medular, um pino intramedular de Schanz revestido com o compósito em sua parte rosqueada, após o preenchimento daquele com 1000mg do compósito. A falha cortical foi preenchida com o compósito. O mesmo foi feito na tíbia direita, porém sem a utilização do compósito, servindo como controle. A avaliação clínica baseou-se na deiscência, claudicação, sensibilidade dolorosa e circunferência tibial. Foram realizadas radiografias imediatamente após a cirurgia e aos oito, 30, 60, 90 e 120 dias do pós-operatório. A maioria dos animais apresentou evolução clínica normal. Nas radiografias do grupo tratado, houve decréscimo da radiopacidade no defeito e no espaço medular até tornar-se semelhante à do osso circunvizinho, quadro inverso ao do grupo-controle. Conclui-se que o compósito hidroxiapatita-lignina não mostrou indícios clínicos de rejeição e que o tecido visualizado na altura da falha óssea e ao redor do pino intramedular tinha radiopacidade semelhante à do osso circunvizinho, o que sugere que o material promoveu a integração com o tecido ósseo.

This study evaluated a sinthetic hydroxyapatite-lignin composite for osseoingration between metallic implant and bone tissue. Twenty New Zealand rabbits were used. A defect was made a the proximal region of lateral surfaces of both tibias. An intramedullary pin was inserted in the medullary cavity of the left tibia after filling the cavity with 1,000mg of the composite and covering the thread part of the pin with the composite. The same procedure was made in control tibias without the composite. Clinical evaluation was based on inflammatory reaction, dehiscence, lameness, pain, and tibial circumference. Radiographs were made immediately after surgery and then on days eight, 30, 60, 90, and 120. Most of the animals presented normal clinical progression. Radiographies of treated group showed decrease in the defect and medullary cavity radiopacity to the same pattern of the surrounding bone, while the contrary happened in control group; but, in this group, the medullary cavity remained radioluscent at the last observation date. It can be concluded that the hydroxyapatite-lignin composite did not show clinical signs of rejection and that radiopacity of the tissue in the bone defect and surrounding the pin was similar to bone radiopacity, suggesting that the material promoted osseointegration.

Resposta tecidual ao compósito 50 por cento hidroxiapatita: 50 por cento poli-hidroxibutirato para substituição óssea em coelhos / Tissue response to the composite 50 percent hydroxyapatite: 50 percent polyhydroxybutyrate for bone substitution in rabbits

Avaliaram-se a biocompatibilidade, a osseointegração, a osseocondução e a biodegradação de compósitos de 50 por cento hidroxiapatita (HAP-91®) e 50 por cento poli-hidroxibutirato. O compósito foi implantado em defeitos ósseos em 12 coelhos (grupo experimental), sendo comparado a defeitos não preenchidos (grupo-controle, de igual número). Os parâmetros clínicos dor, claudicação, infecção, deiscência e edema foram avaliados nos primeiros oito dias após a cirurgia e aos 45 e 90 dias. Radiografias foram realizadas aos oito, 45 e 90 dias após a cirurgia em quatro animais por grupo que, em seguida, foram submetidos à eutanásia para coleta de amostras destinadas a análises histológica e histomorfométrica. Não ocorreram diferenças entre os grupos para todos os parâmetros clínicos. Radiografias demonstraram um compósito com radiopacidade semelhante à do osso vizinho e contato direto entre osso e compósito aos 45 e 90 dias. Diferença significativa foi observada entre a porcentagem dos tecidos ósseo e conjuntivo dentro do defeito nos dias oito, 45 e 90, assim como na interface aos 45 e 90 dias. Foram observadas projeções dos tecidos ósseo e conjuntivo no interior do compósito e sinais de biodegradação na ausência de infiltrado inflamatório. Pode-se concluir que o compósito é biocompatível, osseocondutor, biodegradável e se integra ao tecido ósseo.

The biocompatibility, osseointegration, osseoconductivity, and biodegradation of a 50-50 percent hydroxyapatite (HAP-91®)-polyhydroxybutyrate were evaluated. The composite was implanted in bone defects of 12 rabbits (experimental group), being compared to unfilled defects (control group, 12 animals). The clinical parameters of pain, lameness, infection, dehiscence, and edema were evaluated during the first eight days and on the 45th and 90th days after surgery. Radiographs were taken in four animals per group at 8, 45, and 90 days after surgery, when animals were euthanized to collect samples for histology and histomorphometry. Significant differences between groups for all clinical parameters were not observed. Radiographs showed a similar radiopacity of the composite and bone and their direct contact. More bone than connective tissue was found within the defect at 8, 45, and 90 days and at the interface on the 45th and 90th days. Projections of bone and connective tissue were seen inside the composite. Biodegradation signs became evident, with absence of inflammatory infiltrate. Data support that such composite is biocompatible, osseoconductive, biodegradable, and integrate to bone.