Republication of "First Metatarsophalangeal Joint Arthrodesis: Functional Outcomes Using 2 Different Fixation Techniques. Is More Expensive Better?"

Background: First metatarsophalangeal (MTP) joint arthrodesis can be fixed using either a dorsal plate or crossed screws. However, there is considerable difference in the cost of these implants, and it is not known if there is sufficient difference in outcome that might justify this cost difference. Our aim was to compare the functional results and patient satisfaction rates after first MTP joint arthrodesis in a group of patients using the same surgical technique except for the fixation devices. Methods: A prospective cohort of 27 patients who underwent first MTP joint fusion by the same surgeon using 2 crossed screws or a single screw with a dorsal plate was recruited over a 3-year period. Demographic information, patient satisfaction rates, complications, and union rates were evaluated. American Orthopaedic Foot & Ankle Society (AOFAS) and visual analog scale (VAS) scoring systems were used pre- and postoperatively to compare the functional outcomes. Thirty consecutive procedures (screws, n = 15; plate, n = 15) were performed. Age (55.8 ± 11.1 vs 63.3 ± 12.4 years for screws and plate respectively; P = .091) and female gender percentages (80% and 73%, P = .666) were similar between groups. Results: The overall union rate was 93% with no differences between groups. AOFAS and VAS scores improved significantly postoperatively for each technique, and no differences were found between the two in the improvement in AOFAS (42.4 ± 8.0 vs 44.3 ± 8.2, screws and plate respectively; P = .520) and VAS scores (66.0 ± 5.4 vs 69.0 ± 6.9;P = .195). The implant cost for screws was $40 and for dorsal plate, $328. Conclusions: First MTP joint fusion using either screws or plate fixation results in an improvement in AOFAS and VAS scores. Functional improvement and patient satisfaction did not differ between the 2 techniques, despite a considerable difference in cost between the two methods of fixation. Level of Evidence: Level III, prospective comparative study.

Human mesenchymal stromal cells do not promote recurrence of soft tissue sarcomas in mouse xenografts after radiation and surgery.

BACKGROUND: Mesenchymal stromal cells (MSCs) promote wound healing, including after radiotherapy (RT) and surgery. The use of MSCs in regenerative medicine in the context of malignancy, such as to enhance wound healing post-RT/surgery in patients with soft tissue sarcomas (STSs), requires safety validation. The aim of this study was to determine the effects of human MSCs on STS growth in vitro and local recurrence and metastasis in vivo. METHODS: Human primary STS and HT-1080 fibrosarcoma lines were transduced to express luciferase/eGFP (enhanced green fluorescent protein). Sarcoma cells were co-cultured or co-injected with bone marrow-derived MSCs for growth studies. Xenograft tumor models were established with STS lines in NOD/SCID/γcnull mice. To emulate a clinical scenario, subcutaneous tumors were treated with RT/surgery prior to MSC injection into the tumor bed. Local and distant tumor recurrence was studied using histology and bioluminescence imaging. RESULTS: MSCs did not promote STS proliferation upon co-culture in vitro, which was consistent among MSCs from different donors. Co-injection of MSCs with sarcoma cells in mice exhibited no significant tumor-stimulating effect, compared with control mice injected with sarcoma cells alone. MSC administration after RT/surgery had no effect on local recurrence or metastasis of STS. DISCUSSION: These studies are important for the establishment of a safety profile for MSC administration in patients with STS. Our data suggest that MSCs are safe in STS management after standard of care RT/surgery, which can be further investigated in early-phase clinical trials to also determine the efficacy of MSCs in reducing morbidity and to mitigate wound complications in these patients.

Denosumab, tratamiento alternativo en tumor óseo de células gigantes / Denosumab, an alternative treatment for giant cell tumor of bone

Introducción: el tumor óseo de células gigantes (TOCG) es un tumor benigno pero localmente agresivo. Se presenta en población joven y a nivel epifiso-metafisario. Está compuesto por una población celular estromal y otra multinucleada similar a los osteoclastos, donde se destaca la interacción RANK-RANKL (receptor del activador del factor nuclear kappa-B y su ligando, respectivamente). El anticuerpo monoclonal humano denosumab actúa inhibiendo específicamente RANKL, lo que evita la formación y activación de células multinucleadas. En la bibliografía se evidencia que denosumab tiene resultados alentadores como tratamiento adyuvante de algunos TOCG, generando planes terapéuticos con una menor morbimortalidad que los planteados previamente a la administración del anticuerpo. Material y método: se describe la primera experiencia terapéutica en Uruguay con dos pacientes menores de 40 años que consultaron por gonalgia de larga data, realizándose diagnóstico de TOCG estadio III de Campanacci, donde se realiza tratamiento con denosumab de forma protocolar valorando respuesta clínica, imagenológica, efectos adversos y modificación en plan terapéutico inicial. Resultados: se evidenció una respuesta clínica e imagenológica en los pacientes valorados. No se reportaron efectos adversos, logrando preservar la articulación afectada. Conclusiones: los resultados obtenidos son alentadores respecto al uso terapéutico de denosumab en los pacientes seleccionados. Esto permite considerar a denosumab dentro de las opciones terapéuticas de determinados pacientes con diagnóstico de TOCG.

Introduction: giant cell tumor of bone (GCTB) is a benign tumor, although it is locally aggressive. It arises mainly in young people at the epi-metaphyseal level. It consists of stromal cells and osteoclasts-like populations, where the RANK-RANKL (receptor activator of nuclear factor kappa-B and its ligand, respectively) stands out. Denosumab, the human monoclonal antibody, acts by specifically inhibiting RANKL, what prevents the formation and activation of multinucleate cells. The existing bibliography indicates denosumab has obtained encouraging results as adjuvant treatment for some GCTB, enabling therapeutic plans that have lower morbi-mortality rates than those applied prior to administration of the antibody. Method: the study describes the therapeutic experience of two patients younger than 40 years old, who consulted in Uruguay for long standing gonalgia. Campanacci Stage III GCTB was diagnosed, and denosumab treatment was initiated. Clinical response was assessed, as well as imaging response, adverse side effects and the modification of initial treatment. Results: clinical and imaging response was seen in the assessed patients. No adverse side effects were reported, and the affected joint was preserved. Conclusions: the results obtained are encouraging with regard to the therapeutic use of denosumab in the selected patients. This allows for denosumab to be regarded within the therapeutic options for certain patients with a diagnosis of GCTB.

Introdução: O tumor de células gigantes ósseo (TOCG) é um tumor benigno, porém agressivo. Apresenta-se em jovens localizando-se na metáfise e epífise dos ossos; compõe-se de uma população celular estromal e outra multinucleada similar aos osteoclastos, donde se destaca a interação RANK-RANKL (receptor do ativador do fator nuclear kappa-B e seu ligando, respectivamente). O anticorpo monoclonal humano denosumab age inibindo especificamente o RANKL, evitando a formação e a activação de células multinucleadas. A bibliografia mostra que o denosumab tem resultados animadores como tratamento adjuvante de alguns TOCG, com planos terapêuticos com menor morbimortalidade que os utilizados antes da administração do anticorpo. Material e método: descreve-se a primeira experiencia terapêutica no Uruguai com dois pacientes com menos de 40 anos que consultaram por gonalgia de longa data, realizando-se diagnóstico de TOCG estádio III de Campanacci; realizou-se tratamento com denosumab de acordo com o protocolo e avaliando a resposta clínica, a imagenología, os efeitos adversos e a modificação no esquema terapêutico inicial. Resultados: evidenciou-se uma resposta clínica e na imagenología nos pacientes avaliados. Não se informaram efeitos adversos, sendo possivel preservar a articulação afetada. Conclusões: os resultados obtidos são animadores com relação ao uso terapêutico do denosumab nos pacientes selecionados. Isto permite considerar o denosumab como opção terapêutica para determinados pacientes com diagnóstico de TOCG.

Tratamiento de las fracturas no articulares de los metacarpianos excluido el primer dedo. Revisión bibliográfica sistematizada / Treatment of non-articular metacarpal fractures excluding thumb

Las fracturas de los metacarpianos constituyen el 10% del total de las fracturas(¹) y representan un 30%-50% de las fracturas de la mano(²). La fractura del cuello del quinto metacarpiano es la más frecuente, también llamada Boxer fracture, corresponde al 20% de todas las fracturas de la mano. Para la gran mayoría de estas fracturas la literatura actual avala el tratamiento conservador, ya que son estables desde el principio o luego de una reducción cerrada(¹). Se calcula que apenas un 5% tienen indicación quirúrgica. El propósito de nuestra revisión bibliográfica fue establecer los diferentes criterios que se utilizan para tratar en forma quirúrgica o no las fracturas no articulares de los metacarpianos excluido el primer dedo. Para ello realizamos una revisión sistematizada de los últimos diez años en mayores de 18 años, obteniendo 19 artículos que cumplían con nuestros criterios de inclusión. Nuestra estrategia de análisis fue revisar las indicaciones terapéuticas, frecuencia y justificaciones. Esta revisión sistematizada se organiza en tres grupos de trabajos, aquellos que se ocupaban del tratamiento ortopédico, los que indicaban el tratamiento quirúrgico y los que comparaban los resultados de ambos tratamientos entre sí. De sus resultados se puede concluir que no existe una indicación quirúrgica universalmente recomendada, ya que la literatura carece de estudios con nivel de evidencia I o II que vayan en esa dirección. De nuestra revisión se extrae cuáles son las indicaciones quirúrgicas más frecuentemente aceptadas en la literatura. Destacándose la angulación dorsal mayor a 30 grados, la malrotación y el acortamiento, los cuales determinan secuelas graves como el crossfinger, la pérdida de extensión o de fuerza de prensión. Finalmente, al no existir un consenso y hasta no contar con la suficiente evidencia científica, la decisión de la estrategia terapéutica recae sobre el cirujano ortopedista, quien debe elegirla según su experiencia, teniendo en cuenta la personalidad de la fractura, los materiales disponibles y la literatura revisada que lo avale.

Abstract Metacarpal fractures constitute 10% of the total number of fractures(1) and they represent 30%-50% of hand fractures(2). Fracture of the fifth metacarpal neck is the most frequent one, also called Boxer fracture, corresponding to 20% of all hand fractures. Literature favors a conservative treatment for most of these fractures, since they are stable from the beginning or after a closed reduction. Our bibliographic review aims to define the different criteria used to treat extra-articular metacarpal fractures excluding the thumb, with or without surgery. To that end, we conducted a systematized review of the last 10 years in patients over 18 years old, obtaining 19 articles that met our inclusion criteria. Our analysis strategy was to review therapy indications, frequency and justification. Systematized revision was divided into three groups of work: those who dealt with orthopedic treatment, those who indicated surgical treatment and those who compared results between the two treatments. Results led to the conclusion that there is no surgical indication that is universally recommended, since literature lacks Level I or II studies on this matter. Our review reveals the most frequently accepted surgical indications in literature. Dorsal angulation exceeding 30 degrees, malrotation and shortening stand out, all of which result in severe sequelae such as crossfinger, loss of extension or grip strength. Last, there being no consensus and until there is enough scientific evidence, decisions on therapeutic strategies are to the orthopedic surgeon, which decision shall be based on their experience, considering the kind of fracture, materials available and reviewed literature that supports it.

Resumo As fraturas dos metacarpianos correspondem a 10% das fraturas em geral(1) e a 30%-50% das fraturas da mão(2). A fratura do colo do quinto metacarpiano, também conhecida como Boxer fracture, é a mais frequente - 20% das fraturas da mão. A literatura atual apoia o tratamento conservador para a grande maioria destas fraturas, pois são estáveis desde o começo ou depois de uma redução fechada(1). Calcula-se que apenas 5% tem indicação cirúrgica. O objetivo desta revisão bibliográfica foi identificar os diferentes critérios utilizados para tratar, cirurgicamente ou não, as fraturas não articulares dos metacarpianos excluindo o primeiro dedo. Realizamos una revisão sistemática da literatura científica dos últimos dez anos que incluíam pacientes maiores de 18 anos; 19 artigos foram selecionados por seguir os critérios de inclusão. A estratégia da análise foi revisar as indicações terapêuticas, frequência e justificativas. Os artigos foram organizados em três grupos: tratamento ortopédico, tratamento cirúrgico e os que comparavam os resultados de ambos os tratamentos. A análise dos resultados mostrou que não se pode concluir que exista una indicação cirúrgica universalmente recomendada, pois a literatura carece de estudos com níveis de evidencia I ou II que considerem esses aspectos. Entre as indicações cirúrgicas mais frequentemente aceitas na literatura se destacam a angulação dorsal maior a 30 graus, má rotação e encurtamento, que determinam sequelas graves como o crossfinger, a perda da extensão ou da força de preensão. Finalmente, como não existe um consenso e enquanto não houver suficiente evidencia científica, a decisão sobre a estratégia terapêutica cabe ao ortopedista, que deve basear-se em sua experiência, considerando as características da fratura, os materiais disponíveis e a literatura disponível.

Effects of radiation and surgery on healing of femoral fractures in a rat model.

Management of soft tissue sarcoma involves multimodality treatment, including surgery and radiotherapy. Pathologic fracture of the femur after such treatment in the thigh is one serious, late complication and nonunion rates of 80-90% are reported. We hypothesize that the combination of radiotherapy and periosteal stripping (during tumor resection) leads to greater impairment of the fracture repair process than either intervention alone. Female Wistar retired breeder rats were randomized into four treatment groups (control, radiotherapy, surgery, and combination of radiotherapy and surgery) and three end-points (21, 28, and 35 days post-fracture). Designated animals first underwent radiotherapy, followed by surgical stripping of the periosteum 3 weeks later and femoral fracture with fixation after another 3 weeks. Animals were sacrificed and fractures examined using microCT and histomorphometry. Simple transverse or short oblique femoral fractures were produced. By 35 days, control animals formed unions, periosteum-stripped animals formed hypertrophic non-unions and irradiated animals formed atrophic non-unions. Histomorphometry revealed an absence of chondroid and osteoid production in animals undergoing radiotherapy. The relative contribution of periosteal stripping to occurrence of non-union was statistically insignificant. Radiation prior to fracture reliably resulted in atrophic non-union in our model. The contribution of periosteal stripping was negligible.

Acetabular osteoid osteoma excision by controlled hip dislocation: a case report.

Osteoid osteoma of the acetabulum is rare and its treatment represents a challenge for the orthopedic surgeon. We report a case of a 12-year-old boy with osteoid osteoma in the acetabulum who was treated with a controlled hip dislocation and a gamma probe guide to facilitate excision. The diagnosis was confirmed by pathology. The patient was asymptomatic immediately after surgery and remained so at long-term follow-up.

Human mesenchymal stromal cells improve scar thickness without enhancing cardiac function in a chronic ischaemic heart failure model.

Few data address the role of human mesenchymal stromal cells (MSCs) in the management of chronic ischaemic heart failure. We assessed their effect in immune-deficient animals. MSCs were cultured from bone marrow of human volunteers. Non-obese diabetes severe combined immunodeficiency (NOD/SCID) gamma null mice were randomly assigned to intramyocardial injection of human MSCs or phosphate-buffered saline 4 weeks after induction of acute myocardial infarction (MI). Echocardiography was performed 4 weeks after MI and 1 and 4 weeks after injection. Donor cell chimerism was assessed by DNA for human Alu sequences 2 and 4 weeks after injection. Histological assessment and quantification of neovascularization were determined 4 weeks after treatment. Donor MSCs at frequencies of 0.006 and 0.001% were present 2 and 4 weeks after cell injection, respectively. The infarcted ventricular wall was significantly thicker in the cohort receiving MSCs compared with control mice. There was no difference in fractional shortening, left ventricular dimensions or scar area between the groups. Small vessel density was also similar between the groups. Human MSCs increased the thickness of the infarcted ventricular wall without improving cardiac function in this chronic ischaemic heart failure model. Further studies are required to assess the benefit of MSCs in this setting.

Stem cell research and clinical development in tendon repair.

Stem cells are one of the most fascinating areas in regenerative medicine today. They play a crucial role in development and regeneration and are defined as cells that continuously reproduce themselves while maintaining the ability to differentiate into various cell types. Stem cells are found at all developmental stages, from embryonic stem cells (ESCs) which differentiate into all cell types, to adult stem cells (ASCs) which are responsible for tissue regeneration. Studies using animal models have shown promising results following cell therapy for induced injury in musculoskeletal system, including tendon healing, but the results can be variable. Alternative sources for cell therapy in tendon pathology may include ESCs, ASCs (bone marrow, adipose tissue or tendon derived stem cells) or induced pluripotent stem cells (iPSCs). While ethical and safety concerns currently forbid clinical application of ESCs and iPSCs, initial clinical trials with ASCs are promising.

Mesenchymal stromal cells mediate a switch to alternatively activated monocytes/macrophages after acute myocardial infarction.

Given the established anti-inflammatory properties of mesenchymal stromal cells (MSCs), we investigated their effect on inflammatory cell infiltration of ischemic cardiac tissue and cardiac function. We employed two types of MSCs, human bone marrow-derived (BM) MSCs and human umbilical cord perivascular cells in an experimental acute myocardial infarction (MI) model with the immune-deficient NOD/SCID gamma null mouse. Cells were infused 48 h after induction of MI and mice assessed 24 h later (72 h after MI) for bone marrow (BM), circulating and cardiac tissue-infiltrating monocytes/macrophages. We showed that in the presence of either MSC type, overall macrophage/monocyte levels were reduced, including pro-inflammatory M1-type macrophages, while the proportion of alternatively activated M2-type macrophages was significantly increased in the circulation and heart but not the BM. Moreover, we found decreased expression of IL-1ß and IL-6, increased IL-10 expression and fewer apoptotic cardiomyocytes without changes in angiogenesis in the infarct area. Fractional shortening was enhanced 2 weeks after cell infusion but was similar to medium controls 16 weeks after MI. In vitro studies showed that BM MSCs increased the frequency of alternatively activated monocytes/macrophages, in part by MSC-mediated secretion of IL-10. Our data suggest a new mechanism for MSC-mediated enhancement of cardiac function, possibly via an IL-10 mediated switch from infiltration of pro-inflammatory to anti-inflammatory macrophages at the infarct site. Additional studies are warranted confirming the role of IL-10 and augmenting the anti-inflammatory effects of MSCs in cardiac regeneration.