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Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.

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Objective To reproduce in an animal model the surgical technique of Masquelet used in the treatment of critical bone defects and to analyze the characteristics of the membrane formed around the bone cement. Methods A 10mm critical defect was created in the femoral shaft of 21 Sprague-Dawley rats. After resection of the central portion of the diaphysis, the defect was stabilized with a Kirschner wire introduced through the medullary canal and with the interposition of a bone cement spacer. After 2, 4, and 6 weeks of the surgical procedure, the animals were euthanized and evaluated on radiographs of the posterior limb regarding the size of the defect, alignment and stability of the osteosynthesis. The membranes formed around the spacer were subjected to histological analysis to assess thickness, connective tissue maturation and vascular density. Results Over time, the membranes initially made up of loose connective tissue were replaced by membranes represented by dense connective tissue, rich in thick collagen fibers. At six weeks, membrane thickness was greater (565 ± 208µm) than at four (186.9 ± 70.21µm, p = 0.0002) and two weeks (252.2 ± 55.1µm, p = 0.001). All membranes from the initial time showed foci of osteogenic differentiation that progressively reduced over time. Conclusion In addition to the structural and protective function of the membrane, its intrinsic biological characteristics can actively contribute to bone regeneration. The biological activity attributed by the presence of foci of osteogenesis confers to the membrane the potential of osteoinduction that favors the local conditions for the integration of the bone graft.

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Abstract Objective To reproduce in an animal model the surgical technique of Masquelet used in the treatment of critical bone defects and to analyze the characteristics of the membrane formed around the bone cement. Methods A 10mm critical defect was created in the femoral shaft of 21 Sprague-Dawley rats. After resection of the central portion of the diaphysis, the defect was stabilized with a Kirschner wire introduced through the medullary canal and with the interposition of a bone cement spacer. After 2, 4, and 6 weeks of the surgical procedure, the animals were euthanized and evaluated on radiographs of the posterior limb regarding the size of the defect, alignment and stability of the osteosynthesis. The membranes formed around the spacer were subjected to histological analysis to assess thickness, connective tissue maturation and vascular density. Results Over time, the membranes initially made up of loose connective tissue were replaced by membranes represented by dense connective tissue, rich in thick collagen fibers. At six weeks, membrane thickness was greater (565 ± 208μm) than at four (186.9 ± 70.21μm, p = 0.0002) and two weeks (252.2 ± 55.1μm, p = 0.001). All membranes from the initial time showed foci of osteogenic differentiation that progressively reduced over time. Conclusion In addition to the structural and protective function of the membrane, its intrinsic biological characteristics can actively contribute to bone regeneration. The biological activity attributed by the presence of foci of osteogenesis confers to the membrane the potential of osteoinduction that favors the local conditions for the integration of the bone graft.

Resumo Objetivo Reproduzir em modelo animal a técnica cirúrgica de Masquelet utilizada no tratamento de defeitos ósseos críticos e analisar as características da membrana formada em torno do cimento ósseo. Métodos Um defeito crítico de 10mm foi realizado na diáfise femoral de 21 ratos Sprague-Dawley. Após a ressecção da porção central da diáfise o defeito foi estabilizado com fio de Kirschner introduzido pelo canal medular e com a interposição de espaçador de cimento ósseo. Após 2, 4, e 6 semanas do procedimento cirúrgico os animais foram eutanasiados e avaliados em radiografias do membro posterior quanto ao tamanho do defeito, o alinhamento e a estabilidade da osteossíntese. As membranas formadas em torno do espaçador foram submetidas a análise histológica para avaliação da espessura, da maturação do tecido conjuntivo e da densidade vascular. Resultados Ao longo do tempo as membranas inicialmente constituídas por tecido conjuntivo frouxo foram substituídas por membranas representadas por tecido conjuntivo denso, rico em fibras colágenas espessas. Com seis semanas a espessura das membranas foi maior (565 ± 208μm) do que com quatro (186,9 ± 70,21μm, p = 0,0002) e duas semanas (252,2 ± 55,1μm, p = 0,001). Todas as membranas do tempo inicial apresentaram focos de diferenciação osteogênica que reduziram progressivamente ao longo do tempo. Conclusão Além da função estrutural e protetora da membrana, suas características biológicas intrínsecas podem contribuir ativamente para a regeneração óssea. A atividade biológica atribuída pela presença de focos de osteogênese confere à membrana potencial de osteoindução que favorece as condições locais para a integração do enxerto ósseo.

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Objectives To evaluate the factors that influence the outcome of osteosynthesis after closed reduction of the fracture of the femoral neck in young adult patients. Methods A retrospective study was conducted, reviewing the data of patients operated in a large orthopedic hospital from 2003 to 2011; a total of 81 patients met the inclusion criteria. The time interval between the fracture and the surgery, the initial fracture deviation, the quality of the reduction, and the placement of the implant were evaluated. Results The present study observed a strong relationship between the quality of the reduction and therapeutic success. The degree of the initial deviation and the time elapsed between the initial trauma and the osteosynthesis did not influence the surgical outcome regarding bone consolidation. The correct positioning of the implants was associated with a satisfactory evolution in the postoperative period. Conclusion The quality of the reduction and the positioning of the implants are factors that influence the results of osteosynthesis in fractures of the femoral neck in young adult patients.

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Abstract Objectives To evaluate the factors that influence the outcome of osteosynthesis after closed reduction of the fracture of the femoral neck in young adult patients. Methods A retrospective study was conducted, reviewing the data of patients operated in a large orthopedic hospital from 2003 to 2011; a total of 81 patients met the inclusion criteria. The time interval between the fracture and the surgery, the initial fracture deviation, the quality of the reduction, and the placement of the implant were evaluated. Results The present study observed a strong relationship between the quality of the reduction and therapeutic success. The degree of the initial deviation and the time elapsed between the initial trauma and the osteosynthesis did not influence the surgical outcome regarding bone consolidation. The correct positioning of the implants was associated with a satisfactory evolution in the postoperative period. Conclusion The quality of the reduction and the positioning of the implants are factors that influence the results of osteosynthesis in fractures of the femoral neck in young adult patients.

Resumo Objetivos Avaliar os fatores que influenciam o resultado da osteossíntese pela redução fechada da fratura do colo femoral nos pacientes jovens. Métodos Foi feito um estudo retrospectivo com revisão dos dados dos pacientes operados em um hospital ortopédico de grande porte, de 2003 a 2011, com um total de 81 pacientes que atenderam aos critérios de inclusão. O intervalo de tempo entre a fratura e a cirurgia, o desvio inicial da fratura, a qualidade da redução e o posicionamento dos implantes foram os fatores avaliados. Resultados O estudo encontrou forte relação entre a qualidade da redução e o sucesso terapêutico. O grau de desvio inicial e o tempo entre o trauma inicial e a osteossíntese não influenciaramo desfecho cirúrgico emrelação à consolidação óssea. O correto posicionamento dos implantes mostrou relação com a evolução satisfatória no pós-operatório dos pacientes. Conclusão A qualidade da redução e o posicionamento dos implantes são fatores que influenciamoresultadodaosteossíntesenafraturadocolodofêmurnopacienteadultojovem.

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OBJECTIVE: Percutaneous fixation of the acetabulum is a treatment option for select acetabular fractures. Intra-operative fluoroscopy is required, and despite various described imaging strategies, it is debatable as to which combination of fluoroscopic views provides the most accurate and reliable assessment of screw position. MATERIALS AND METHODS: Using five synthetic pelvic models, an experimental setup was created in which the anterior acetabular columns were instrumented with screws in five distinct trajectories. Five fluoroscopic images were obtained of each model (Pelvic Inlet, Obturator Oblique, Iliac Oblique, Obturator Oblique/Outlet, and Iliac Oblique/Outlet). The images were presented to 32 pelvic and acetabular orthopaedic surgeons, who were asked to draw two conclusions regarding screw position: (1) whether the screw was intra-articular and (2) whether the screw was intraosseous in its distal course through the bony corridor. RESULTS: In the assessment of screw position relative to the hip joint, accuracy of surgeon's response ranged from 52% (iliac oblique/outlet) to 88% (obturator oblique), with surgeon confidence in the interpretation ranging from 60% (pelvic inlet) to 93% (obturator oblique) (P < 0.0001). In the assessment of intraosseous position of the screw, accuracy of surgeon's response ranged from 40% (obturator oblique/outlet) to 79% (iliac oblique/outlet), with surgeon confidence in the interpretation ranging from 66% (iliac oblique) to 88% (pelvic inlet) (P < 0.0001). CONCLUSIONS: The obturator oblique and obturator oblique/outlet views afforded the most accurate and reliable assessment of penetration into the hip joint, and intraosseous position of the screw was most accurately assessed with pelvic inlet and iliac oblique/outlet views. EVIDENCE: Clinical Question.

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This study describes the occurrence of dogs naturally co-infected with Hepatozoon canis and two Leishmania species: L. infantum or L. braziliensis. Four dogs serologically diagnosed with Visceral Leishmaniasis were euthanized. Liver and spleen samples were collected for histopathological analysis and DNA isolation. H. canis meronts were observed in tissues from all four dogs. H. canis infection was confirmed by PCR followed by sequencing of a fragment of 18S rRNA gene. Leishmania detection and typing was confirmed by ITS1' PCR-RFLP and parasite burden was calculated using ssrRNA quantitative qPCR. A DPP - Dual Path platform test was performed. One out (Dog #2) of four animals was asymptomatic. Dogs #1 and #4 were infected by L. infantum and were DPP test positive. Dogs #2 and #3 were infected by L. braziliensis and were DPP test negative. Furthermore, visceral dissemination was observed in Dogs #2 and #3, since L. braziliensis was detected in liver and spleen samples. The visceral dissemination of L. braziliensis associated with systemic signs suggested that this co-infection could influence the parasite burden and disease progression.

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Abstract This study describes the occurrence of dogs naturally co-infected with Hepatozoon canis and two Leishmania species: L. infantum or L. braziliensis. Four dogs serologically diagnosed with Visceral Leishmaniasis were euthanized. Liver and spleen samples were collected for histopathological analysis and DNA isolation. H. canis meronts were observed in tissues from all four dogs. H. canis infection was confirmed by PCR followed by sequencing of a fragment of 18S rRNA gene. Leishmania detection and typing was confirmed by ITS1' PCR-RFLP and parasite burden was calculated using ssrRNA quantitative qPCR. A DPP - Dual Path platform test was performed. One out (Dog /2) of four animals was asymptomatic. Dogs /1 and /4 were infected by L. infantum and were DPP test positive. Dogs /2 and /3 were infected by L. braziliensis and were DPP test negative. Furthermore, visceral dissemination was observed in Dogs /2 and /3, since L. braziliensis was detected in liver and spleen samples. The visceral dissemination of L. braziliensis associated with systemic signs suggested that this co-infection could influence the parasite burden and disease progression.(AU)

Resumo O presente estudo descreve a ocorrência de coinfecção com Hepatozoon canis e duas espécies de Leishmania (L. infantum ou L. braziliensis) em cães. Quatro cães sorologicamente diagnosticados com leishmaniose visceral foram eutanasiados. Amostras do baço e fígado foram submetidas à histopatologia e extração de DNA. Merontes de H. canis foram observados nos quatro cães. A infecção por H. canis foi confirmada por PCR e sequenciamento de um fragmento do gene 18S rRNA. A infecção por Leishmania e tipagem foram realizadas por PCR-RFLP do região intergênica ITS1. A carga parasitária foi calculada pela qPCR quantitativa baseada no gene ssrRNA. O teste DPP - Dual Path platform foi realizado. Apenas o Cão /2 era assintomático. Os cães /1 e /4 estavam infectados com L. infantum e foram positivos no DPP. Os cães /2 e /3 estavam infectados com L. braziliensis e foram negativos no DPP. Além disso, visceralização foi observada nos cães /2 e /3, nos quais L. braziliensis foi detectada em amostras de baço e fígado. A visceralização da L. braziliensis associada a sinais clínicos sistêmicos sugerem que esta coinfecção pode ter influenciado na carga parasitária e progressão da doença.(AU)

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Abstract This study describes the occurrence of dogs naturally co-infected with Hepatozoon canis and two Leishmania species: L. infantum or L. braziliensis. Four dogs serologically diagnosed with Visceral Leishmaniasis were euthanized. Liver and spleen samples were collected for histopathological analysis and DNA isolation. H. canis meronts were observed in tissues from all four dogs. H. canis infection was confirmed by PCR followed by sequencing of a fragment of 18S rRNA gene. Leishmania detection and typing was confirmed by ITS1' PCR-RFLP and parasite burden was calculated using ssrRNA quantitative qPCR. A DPP - Dual Path platform test was performed. One out (Dog #2) of four animals was asymptomatic. Dogs #1 and #4 were infected by L. infantum and were DPP test positive. Dogs #2 and #3 were infected by L. braziliensis and were DPP test negative. Furthermore, visceral dissemination was observed in Dogs #2 and #3, since L. braziliensis was detected in liver and spleen samples. The visceral dissemination of L. braziliensis associated with systemic signs suggested that this co-infection could influence the parasite burden and disease progression.

Resumo O presente estudo descreve a ocorrência de coinfecção com Hepatozoon canis e duas espécies de Leishmania (L. infantum ou L. braziliensis) em cães. Quatro cães sorologicamente diagnosticados com leishmaniose visceral foram eutanasiados. Amostras do baço e fígado foram submetidas à histopatologia e extração de DNA. Merontes de H. canis foram observados nos quatro cães. A infecção por H. canis foi confirmada por PCR e sequenciamento de um fragmento do gene 18S rRNA. A infecção por Leishmania e tipagem foram realizadas por PCR-RFLP do região intergênica ITS1. A carga parasitária foi calculada pela qPCR quantitativa baseada no gene ssrRNA. O teste DPP - Dual Path platform foi realizado. Apenas o Cão #2 era assintomático. Os cães #1 e #4 estavam infectados com L. infantum e foram positivos no DPP. Os cães #2 e #3 estavam infectados com L. braziliensis e foram negativos no DPP. Além disso, visceralização foi observada nos cães #2 e #3, nos quais L. braziliensis foi detectada em amostras de baço e fígado. A visceralização da L. braziliensis associada a sinais clínicos sistêmicos sugerem que esta coinfecção pode ter influenciado na carga parasitária e progressão da doença.

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OBJECTIVE: Giant cell tumors are benign bone neoplasms that are relatively rare in adults and their biological behavior is still unpredictable. The incidence of local recurrence has presented variation between 0% and 65% in studies conducted worldwide, but few data are available on this complication in the Brazilian population. METHODS: Information on 155 patients with confirmed histological diagnoses of giant cell tumor who were treated in our institution's orthopedic oncology service between January 2000 and July 2014 was gathered. Demographic characteristics were evaluated and compared between patients who presented local recurrence during the clinical follow-up. RESULTS: Local recurrence was observed in 26 patients (16.7%), of whom 22 were female (84.6%). The most common site of local recurrence was the distal femur (38.4%). Eleven patients presented early recurrence, while 15 cases were diagnosed after 15 months, representing 42.3% and 57.7%, respectively. Metastases were identified in five patients (3.2%). CONCLUSION: Tumor-related factors did not show any increased incidence of local recurrence of giant cell tumors. Surgical treatment with an intralesional margin is a valid option for treating local recurrences and does not show any difference in disease-free survival in relation to other types of procedures. Clinical treatment is reserved for cases of unresectable tumors or when surgical treatment is impossible.

OBJETIVOS: O tumor de células gigantes (TCG) é uma neoplasia óssea benigna relativamente rara em adultos, porém seu comportamento biológico ainda é imprevisível. A incidência de recidiva local apresenta variação entre 0­65% em estudos internacionais, porém há poucos dados referentes a essa complicação em nossa população. MÉTODOS: Foram coletadas informações sobre 155 pacientes com diagnóstico histológico confirmado de TCG, acompanhados no serviço de oncologia ortopédica da nossa instituição, de janeiro de 2000 a julho de 2014. As características demográficas foram avaliadas e comparadas entre os pacientes que apresentaram recidiva local durante o seguimento clínico. RESULTADOS: Houve recidiva local em 26 pacientes (16,7%), dos quais 22 eram do sexo feminino (84,6%). A localização mais comum de recidiva local foi o fêmur distal (38,4%). Onze pacientes apresentaram recidiva precoce, enquanto 15 casos foram diagnosticados após 15 meses, o que representa, respectivamente, 42,3% e 57,7%. Metástases foram identificadas em cinco pacientes (3,2%). CONCLUSÃO: Os fatores relacionados ao tumor não evidenciaram aumento da incidência de recidiva local de tumor de células gigantes. O tratamento cirúrgico com margem intralesional é uma opção válida no tratamento de recidivas locais e não apresenta diferença de sobrevida livre de doença entre outros tipos de procedimentos. Tratamento clínico é reservado em casos de tumores irressecáveis ou impossibilidade de tratamento cirúrgico.