RESUMO
The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. Here we report initial findings from the Beat AML programme on a cohort of 672 tumour specimens collected from 562 patients. We assessed these specimens using whole-exome sequencing, RNA sequencing and analyses of ex vivo drug sensitivity. Our data reveal mutational events that have not previously been detected in AML. We show that the response to drugs is associated with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA sequencing also revealed gene expression signatures, which predict a role for specific gene networks in the drug response. Collectively, we have generated a dataset-accessible through the Beat AML data viewer (Vizome)-that can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of AML.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Genoma Humano/genética , Genômica , Leucemia Mieloide Aguda/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A , Conjuntos de Dados como Assunto , Exoma/genética , Feminino , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Masculino , Terapia de Alvo Molecular , Proteínas Nucleares/genética , Nucleofosmina , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Análise de Sequência de RNA , Fatores de Processamento de Serina-Arginina/genéticaRESUMO
Patients who are diagnosed with osteosarcoma (OS) today receive the same therapy that patients have received over the last 4 decades. Extensive efforts to identify more effective or less toxic regimens have proved disappointing. As we enter a postgenomic era in which we now recognize OS not as a cancer of mutations but as one defined by p53 loss, chromosomal complexity, copy number alteration, and profound heterogeneity, emerging threads of discovery leave many hopeful that an improving understanding of biology will drive discoveries that improve clinical care. Under the organization of the Bone Tumor Biology Committee of the Children's Oncology Group, a team of clinicians and scientists sought to define the state of the science and to identify questions that, if answered, have the greatest potential to drive fundamental clinical advances. Having discussed these questions in a series of meetings, each led by invited experts, we distilled these conversations into a series of seven Provocative Questions. These include questions about the molecular events that trigger oncogenesis, the genomic and epigenomic drivers of disease, the biology of lung metastasis, research models that best predict clinical outcomes, and processes for translating findings into clinical trials. Here, we briefly present each Provocative Question, review the current scientific evidence, note the immediate opportunities, and speculate on the impact that answered questions might have on the field. We do so with an intent to provide a framework around which investigators can build programs and collaborations to tackle the hardest problems and to establish research priorities for those developing policies and providing funding.
Assuntos
Epigenômica , Genômica , Osteossarcoma/terapia , Pesquisa Translacional Biomédica , Criança , Humanos , Mutação/genética , Osteossarcoma/epidemiologia , Osteossarcoma/genética , Osteossarcoma/patologia , Proteômica , Proteína Supressora de Tumor p53/genéticaRESUMO
Aplastic anemia in the neonate is rare. We report a case of severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia. This report highlights the importance of considering SCID early in the evaluation of neonatal aplastic anemia prior to the development of infectious complications.
Assuntos
Anemia Aplástica , Imunodeficiência Combinada Severa , Anemia Aplástica/complicações , Anemia Aplástica/patologia , Anemia Aplástica/terapia , Humanos , Recém-Nascido , Masculino , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/patologia , Imunodeficiência Combinada Severa/terapiaRESUMO
BACKGROUND: Survival rates of patients with osteosarcoma have remained stagnant over the last thirty years. Better understanding of biology, new therapeutics, and improved biomarkers are needed. The Children's Oncology Group (COG) addressed this need by developing one of the largest osteosarcoma biorepositories ever, containing over 15,000 tumor and tissue samples from over 1,500 patients. PROCEDURE: The biology study P9851 and the banking study AOST06B1 has enrolled 1,787 patients (as of September, 2013). Clinical information was lacking on 510 patients on P9851, who were not enrolled on a concurrent therapeutic trial. The value of these specimens was diminished. The lack of statistical support available for biology projects slowed the analysis of several critical studies. The QuadW Foundation, CureSearch, and the COG formed the Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) to provide the infrastructure and address these needs by linking clinically annotated patient data to archived tissue samples and to develop biostatistical support for childhood sarcoma research. RESULTS: Originally 5.3% of samples from the 510 patients on P9851 not enrolled on a therapeutic study had full clinical annotation. The efforts of the CSBAO have linked clinical annotation to 90.8% of those specimens and provided statistical analyses to several studies that had used COG samples. As a result, 24 biology studies in osteosarcoma have been completed and published in peer-reviewed journals. CONCLUSIONS: These samples and in-silico data are available to the research community for basic and translational science projects to improve the biological understanding and treatment of patients affected by osteosarcoma.
Assuntos
Biomarcadores Tumorais/metabolismo , Bases de Dados Factuais , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Bancos de Tecidos , Adolescente , Adulto , Criança , Pré-Escolar , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Children with relapsed central nervous system (CNS tumors), neuroblastoma, sarcomas, and other rare solid tumors face poor outcomes. This prospective clinical trial examined the feasibility of combining genomic and transcriptomic profiling of tumor samples with a molecular tumor board (MTB) approach to make realtime treatment decisions for children with relapsed/refractory solid tumors. METHODS: Subjects were divided into three strata: stratum 1-relapsed/refractory neuroblastoma; stratum 2-relapsed/refractory CNS tumors; and stratum 3-relapsed/refractory rare solid tumors. Tumor samples were sent for tumor/normal whole-exome (WES) and tumor whole-transcriptome (WTS) sequencing, and the genomic data were used in a multi-institutional MTB to make realtime treatment decisions. The MTB recommended plan allowed for a combination of up to 4 agents. Feasibility was measured by time to completion of genomic sequencing, MTB review and initiation of treatment. Response was assessed after every two cycles using Response Evaluation Criteria in Solid Tumors (RECIST). Patient clinical benefit was calculated by the sum of the CR, PR, SD, and NED subjects divided by the sum of complete response (CR), partial response (PR), stable disease (SD), no evidence of disease (NED), and progressive disease (PD) subjects. Grade 3 and higher related and unexpected adverse events (AEs) were tabulated for safety evaluation. RESULTS: A total of 186 eligible patients were enrolled with 144 evaluable for safety and 124 evaluable for response. The average number of days from biopsy to initiation of the MTB-recommended combination therapy was 38 days. Patient benefit was exhibited in 65% of all subjects, 67% of neuroblastoma subjects, 73% of CNS tumor subjects, and 60% of rare tumor subjects. There was little associated toxicity above that expected for the MGT drugs used during this trial, suggestive of the safety of utilizing this method of selecting combination targeted therapy. CONCLUSIONS: This trial demonstrated the feasibility, safety, and efficacy of a comprehensive sequencing model to guide personalized therapy for patients with any relapsed/refractory solid malignancy. Personalized therapy was well tolerated, and the clinical benefit rate of 65% in these heavily pretreated populations suggests that this treatment strategy could be an effective option for relapsed and refractory pediatric cancers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02162732. Prospectively registered on June 11, 2014.
Assuntos
Neuroblastoma , Criança , Humanos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/etiologiaRESUMO
Immune checkpoint inhibition (ICI) is effective for replication-repair-deficient, high-grade gliomas (RRD-HGG). The clinical/biological impact of immune-directed approaches after failing ICI monotherapy is unknown. We performed an international study on 75 patients treated with anti-PD-1; 20 are progression free (median follow-up, 3.7 years). After second progression/recurrence (n = 55), continuing ICI-based salvage prolonged survival to 11.6 months (n = 38; P < 0.001), particularly for those with extreme mutation burden (P = 0.03). Delayed, sustained responses were observed, associated with changes in mutational spectra and the immune microenvironment. Response to reirradiation was explained by an absence of deleterious postradiation indel signatures (ID8). CTLA4 expression increased over time, and subsequent CTLA4 inhibition resulted in response/stable disease in 75%. RAS-MAPK-pathway inhibition led to the reinvigoration of peripheral immune and radiologic responses. Local (flare) and systemic immune adverse events were frequent (biallelic mismatch-repair deficiency > Lynch syndrome). We provide a mechanistic rationale for the sustained benefit in RRD-HGG from immune-directed/synergistic salvage therapies. Future approaches need to be tailored to patient and tumor biology. SIGNIFICANCE: Hypermutant RRD-HGG are susceptible to checkpoint inhibitors beyond initial progression, leading to improved survival when reirradiation and synergistic immune/targeted agents are added. This is driven by their unique biological and immune properties, which evolve over time. Future research should focus on combinatorial regimens that increase patient survival while limiting immune toxicity. This article is featured in Selected Articles from This Issue, p. 201.
Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioma , Humanos , Antígeno CTLA-4 , Glioma/tratamento farmacológico , Glioma/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Antineoplásicos/uso terapêutico , Imunoterapia , Microambiente TumoralRESUMO
Alveolar rhabdomyosarcoma (aRMS) is a very aggressive sarcoma of children and young adults. Our previous studies have shown that small molecule inhibition of Pdgfra is initially very effective in an aRMS mouse model. However, slowly evolving, acquired resistance to a narrow-spectrum kinase inhibitor (imatinib) was common. We identified Src family kinases (SFKs) to be potentiators of Pdgfra in murine aRMS primary cell cultures from mouse tumors with evolved resistance in vivo in comparison to untreated cultures. Treating the resistant primary cell cultures with a combination of Pdgfra and Src inhibitors had a strong additive effect on cell viability. In Pdgfra knockout tumors, however, the Src inhibitor had no effect on tumor cell viability. Sorafenib, whose targets include not only PDGFRA but also the Src downstream target Raf, was effective at inhibiting mouse and human tumor cell growth and halted progression of mouse aRMS tumors in vivo. These results suggest that an adaptive Src-Pdgfra-Raf-Mapk axis is relevant to PDGFRA inhibition in rhabdomyosarcoma.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Rabdomiossarcoma Alveolar/enzimologia , Rabdomiossarcoma Alveolar/patologia , Quinases raf/metabolismo , Quinases da Família src/metabolismo , Animais , Benzamidas , Benzenossulfonatos/farmacologia , Proliferação de Células , Mesilato de Imatinib , Camundongos , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Sorafenibe , Células Tumorais Cultivadas , Quinases da Família src/antagonistas & inibidoresRESUMO
Patients with t(17;19) acute lymphoblastic leukemia (ALL) have a dismal prognosis even with the most intensive current therapies that include stem cell transplant. We present the case of a patient with t(17;19)(q22;p13) gene rearranged B-cell precursor ALL whose lymphoblasts were found to have significant in vitro sensitivity to dasatinib. The patient tolerated the addition of dasatinib with combination therapy and remained in remission for over nine months until his recurrence. Therefore, future studies will be needed to interrogate whether dasatinib has any therapeutic benefit in children with t(17;19) B-cell precursor ALL.
Assuntos
Antineoplásicos/uso terapêutico , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 19 , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Tiazóis/uso terapêutico , Translocação Genética , Dasatinibe , Humanos , Técnicas In Vitro , Linfócitos/efeitos dos fármacos , MasculinoRESUMO
Open reduction with rigid internal fixation is the basic principle for surgical management in foot and ankle trauma. High-risk patients present a surgical dilemma for the foot and ankle surgeon because the possible complications are magnified in this patient population. Percutaneous fixation is a unique alternative for achieving anatomic stabilization without increased physical strain to the patient. The significant advantages of percutaneous fixation include minimizing damage to the vascular supply, maintaining and preserving a stable soft tissue envelope, and decreasing the potential risk for infection. This article provides an overview of percutaneous surgical fixation methods and their role in foot and ankle trauma for the high-risk patient.
Assuntos
Traumatismos do Tornozelo/cirurgia , Ossos do Pé/lesões , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Luxações Articulares/cirurgia , Traumatismos do Tornozelo/complicações , Traumatismos do Tornozelo/diagnóstico , Fraturas Ósseas/complicações , Fraturas Ósseas/diagnóstico , Humanos , Luxações Articulares/complicações , Luxações Articulares/diagnóstico , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
The prospective banking of osteosarcoma tissue samples to promote research endeavors has been realized through the establishment of a nationally centralized biospecimen repository, the Children's Oncology Group (COG) biospecimen bank located at the Biopathology Center (BPC)/Nationwide Children's Hospital in Columbus, Ohio. Although the physical inventory of osteosarcoma biospecimens is substantive (>15,000 sample specimens), the nature of these resources remains exhaustible. Despite judicious allocation of these high-value biospecimens for conducting sarcoma-related research, a deeper understanding of osteosarcoma biology, in particular metastases, remains unrealized. In addition the identification and development of novel diagnostics and effective therapeutics remain elusive. The QuadW-COG Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) has developed the High Dimensional Data (HDD) platform to complement the existing physical inventory and to promote in silico hypothesis testing in sarcoma biology. The HDD is a relational biologic database derived from matched osteosarcoma biospecimens in which diverse experimental readouts have been generated and digitally deposited. As proof-of-concept, we demonstrate that the HDD platform can be utilized to address previously unrealized biologic questions though the systematic juxtaposition of diverse datasets derived from shared biospecimens. The continued population of the HDD platform with high-value, high-throughput and mineable datasets allows a shared and reusable resource for researchers, both experimentalists and bioinformatics investigators, to propose and answer questions in silico that advance our understanding of osteosarcoma biology.
Assuntos
Pesquisa Biomédica , Neoplasias Ósseas , Simulação por Computador , Bases de Dados Factuais , Osteossarcoma , Bancos de Tecidos , Neoplasias Ósseas/metabolismo , Biologia Computacional , RNA Helicases DEAD-box/metabolismo , Humanos , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteínas de Membrana/metabolismo , Análise em Microsséries , Antígenos de Histocompatibilidade Menor/metabolismo , Modelos Biológicos , Osteossarcoma/metabolismo , RNA/metabolismo , Ubiquitina Tiolesterase/metabolismoRESUMO
Kinases are dysregulated in most cancers, but the frequency of specific kinase mutations is low, indicating a complex etiology in kinase dysregulation. Here, we report a strategy to rapidly identify functionally important kinase targets, irrespective of the etiology of kinase pathway dysregulation, ultimately enabling a correlation of patient genetic profiles to clinically effective kinase inhibitors. Our methodology assessed the sensitivity of primary leukemia patient samples to a panel of 66 small-molecule kinase inhibitors over 3 days. Screening of 151 leukemia patient samples revealed a wide diversity of drug sensitivities, with 70% of the clinical specimens exhibiting hypersensitivity to one or more drugs. From this data set, we developed an algorithm to predict kinase pathway dependence based on analysis of inhibitor sensitivity patterns. Applying this algorithm correctly identified pathway dependence in proof-of-principle specimens with known oncogenes, including a rare FLT3 mutation outside regions covered by standard molecular diagnostic tests. Interrogation of all 151 patient specimens with this algorithm identified a diversity of kinase targets and signaling pathways that could aid prioritization of deep sequencing data sets, permitting a cumulative analysis to understand kinase pathway dependence within leukemia subsets. In a proof-of-principle case, we showed that in vitro drug sensitivity could predict both a clinical response and the development of drug resistance. Taken together, our results suggested that drug target scores derived from a comprehensive kinase inhibitor panel could predict pathway dependence in cancer cells while simultaneously identifying potential therapeutic options.
Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica/métodos , Leucemia/enzimologia , Leucemia/genética , Proteínas Tirosina Quinases/genética , Algoritmos , Análise por Conglomerados , Humanos , Transdução de Sinais/genéticaRESUMO
UNLABELLED: Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the Janus-activated kinase (JAK) tyrosine kinase family, TYK2, and its downstream effector STAT1, in T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently showed TYK2 dependence in both T-ALL primary specimens and cell lines, and a small-molecule inhibitor of JAK activity induced T-ALL cell death. Activation of this TYK2-STAT1 pathway in T-ALL cell lines occurs by gain-of-function TYK2 mutations or activation of interleukin (IL)-10 receptor signaling, and this pathway mediates T-ALL cell survival through upregulation of the antiapoptotic protein BCL2. These findings indicate that in many T-ALL cases, the leukemic cells are dependent upon the TYK2-STAT1-BCL2 pathway for continued survival, supporting the development of molecular therapies targeting TYK2 and other components of this pathway. SIGNIFICANCE: In recent years, "pathway dependence" has been revealed in specific types of human cancer, which can be important because they pinpoint proteins that are particularly vulnerable to antitumor-targeted inhibition (so-called Achilles' heel proteins). Here, we use RNAi technology to identify a novel oncogenic pathway that involves aberrant activation of the TYK2 tyrosine kinase and its downstream substrate, STAT1, which ultimately promotes T-ALL cell survival through the upregulation of BCL2 expression
Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT1/metabolismo , TYK2 Quinase/metabolismo , Animais , Antineoplásicos/farmacologia , Células da Medula Óssea , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Interleucina-10/metabolismo , Janus Quinase 3/antagonistas & inibidores , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Piperidinas/farmacologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Interferência de RNA , Fator de Transcrição STAT1/genética , Transdução de Sinais , TYK2 Quinase/antagonistas & inibidores , TYK2 Quinase/genética , Tirfostinas/farmacologiaRESUMO
Numerous procedures have been described for a bunionette deformity. Choosing a specific osteotomy depends largely on the degree of the deformity and surgeon preference. The Scarfette osteotomy is a versatile procedure that addresses specific etiologic factors associated with bunionette deformities. The primary aim of this study is to show the versatility of the Scarfette osteotomy in varying degrees of bunionette deformities. A retrospective review of 50 cases was performed with a follow-up of 12 months. Objective information was obtained by measuring specific radiographic variables on preoperative and postoperative weight-bearing radiographs. Mean radiographic results are presented for the intermetatarsal 4-5 angle, lateral deviation angle, and fifth metatarsophalangeal angles postoperatively. The authors report short-term results of the Scarfette osteotomy in the correction of bunionette deformities. The Scarfette is a predictable and versatile osteotomy to correct varying degrees of bunionette deformities. The Scarfette is not technically demanding and allows early postoperative ambulation.
Assuntos
Joanete do Alfaiate/cirurgia , Osteotomia/métodos , Adolescente , Adulto , Idoso , Pinos Ortopédicos , Joanete do Alfaiate/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Adulto JovemRESUMO
The purpose of this study was to evaluate the effectiveness of a new minimally invasive technique using bipolar radiofrequency in the treatment of plantar fasciosis. A prospective study was performed on 10 patients with recalcitrant plantar fasciosis that failed conservative care. A percutaneous microtenotomy was performed unilaterally with a Topaz microdebrider. Outcome measures included visual analog scale, American Orthopaedic Foot & Ankle Society (AOFAS) Hindfoot and Midfoot Scale, and patient satisfaction assessment. All patients had statistical improvement in outcome measures at 6 months and 1 year. One patient developed recurrent heel pain at the 1-year mark. There were no postoperative complications. This minimally invasive technique is a viable surgical treatment option in patients with plantar fasciosis that failed conservative care.
Assuntos
Ablação por Cateter/instrumentação , Fasciíte Plantar/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Adulto , Idoso , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Satisfação do Paciente , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
First metatarsophalangeal (MTP) joint arthrodesis is a proven technique as a salvage procedure for many foot pathologies. Many studies have looked at joint preparation techniques, position of the fusion, and construct stability. In this retrospective study, the authors report the overall fusion rate after first MTP joint fusion with full immediate postoperative weightbearing. Forty-five first MTP arthrodeses were performed during the study period. Eight fusions were excluded, leaving 37 fusions for review. The overall fusion rate was 91.1%. The mean time to fusion was 69.0 +/- 37.6 days. Complications included 2 delayed unions (1 screw, 1 plate), 3 nonunions (1 screw, 2 plates), and 2 hardware removals (1 screw, 1 plate). Fixation stability is important to allow immediate postoperative weightbearing. A fusion rate of 91.1% was seen in a diversity of patients after first MTP fusion with immediate weightbearing.
Assuntos
Artrodese/métodos , Hallux Rigidus/cirurgia , Articulação Metatarsofalângica/fisiologia , Recuperação de Função Fisiológica/fisiologia , Suporte de Carga/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hallux Rigidus/diagnóstico por imagem , Hallux Rigidus/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Radiografia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
UNLABELLED: Expensive surgical implants can significantly add to the cost of a procedure. We performed a crude cost analysis to evaluate and compare the crossed screw technique versus dorsal plating for first metatarsophalangeal arthrodesis. First metatarsophalangeal arthrodeses performed over a 20-month period were selected. Exclusion criteria included diabetes, neuroarthropathy, revision surgery, or alternate fixation. Hospital records were reviewed for each case to determine implant charges. Patient charts and radiographs were also reviewed to determine time to fusion, delayed union/nonunion, revision surgery, or hardware removal. Fifty-five first metatarsophalangeal arthrodeses were performed during the study period. Ten fusions were excluded, leaving 45 fusions for review. The overall fusion rate was 91.1%. The average time to fusion in crossed screw versus plating technique was 73.2 +/- 32.5 days (range, 43 to 162) and 69.3 +/- 37.3 days (range, 44 to 238), respectively, and not statistically significant. The mean implant cost in the crossed screw versus dorsal plating technique was $374.05 +/- 76.3 (range, 278.72 to 530.00) and $603.57 +/- 234.7 (range, 543.40 to 1677.00) respectively and was strongly significant (P = .0002). Complications included 2 delayed unions (1 screw, 1 plate), 4 nonunions (1 screw, 3 plate), 2 revisions (1 screw, 1 plate), and 2 hardware removals (1 screw, 1 plate). SUMMARY: A cost comparison of crossed screws versus dorsal plate construct for first metatarsophalangeal arthrodesis is performed. No statistical difference was found in the time to fusion between the 2 constructs but there was strong statistical difference in hardware cost. This information may aid in the cost management of this procedure without compromising clinical results. ACFAS Level of Clinical Evidence: 2c.
Assuntos
Artrodese/economia , Artrodese/instrumentação , Placas Ósseas , Parafusos Ósseos , Articulação Metatarsofalângica/cirurgia , Análise Custo-Benefício , Feminino , Hallux Rigidus/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , CicatrizaçãoRESUMO
UNLABELLED: We retrospectively compared crescentic and Mau osteotomies used to treat a total of 39 cases of hallux abductovalgus. Follow-up was possible in 10 of the crescentic cases (mean 228 days) and 24 of the Mau cases (mean 245 days). Preoperatively, the mean first intermetatarsal and hallux abductus angles were 17.5 degrees and 35.4 degrees , respectively, in the crescentic group; and 16.6 degrees and 31.3 degrees , respectively, in the Mau group. Postoperatively, these same radiographic angles were 11.7 degrees and 18.9 degrees , respectively, in the crescentic group; and 9.8 degrees and 12.9 degrees , respectively, in the Mau group, and these differences were not statistically significant. Complications included metatarsus primus elevatus (crescentic 7, Mau 2), lesser metatarsal transfer lesion (crescentic 1, Mau 0), nonunion (crescentic 5, Mau 1), revisional surgery (crescentic 0, Mau 1), and transarticular hardware (crescentic 3, Mau 0). The incidence of complications in the crescentic group was 60%, whereas that in the Mau group was 37.5%; this difference was not statistically significant (P = .276). Analysis by the type of complication revealed statistically significant differences between the crescentic and Mau groups in regard to metatarsus primus elevatus (70% versus 8.3%, P = .001), transarticular hardware (30% versus 0%, P = .02), and nonunion (50% versus 4.2%, P = .006). In conclusion, crescentic and Mau osteotomies satisfactorily corrected the first intermetatarsal and hallux abductus angles in patients that fit our inclusion criteria, although the incidence of postoperative metatarsus primus elevatus, delayed union, and transarticular hardware placement, was higher in the crescentic osteotomy group. LEVEL OF CLINICAL EVIDENCE: 2.
Assuntos
Hallux Valgus/cirurgia , Ossos do Metatarso/cirurgia , Osteotomia/métodos , Adulto , Feminino , Deformidades do Pé , Hallux Valgus/diagnóstico por imagem , Humanos , Masculino , Articulação Metatarsofalângica , Pessoa de Meia-Idade , Osteotomia/instrumentação , Complicações Pós-Operatórias , Radiografia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
UNLABELLED: In our retrospective study, we report the objective results of the Mau osteotomy in the treatment of hallux valgus. We reviewed the results of 24 cases of moderate to severe hallux valgus deformities corrected with the Mau osteotomy of the first metatarsal combined with a distal soft-tissue procedure. Follow-up was possible in 24 cases. Preoperatively the mean hallux valgus and first intermetatarsal angles were 31.3 degrees and 16.6 degrees respectively, and were corrected postoperatively to an average of 13.00 degrees+/-7.15 degrees and 9.80 degrees+/-2.43 degrees respectively (P< .001). In the sagittal plane, the first metatarsal was shortened by an average of 2.00 mm. Two (8.3%) cases had dorsal elevation of the osteotomy fragment. Complications included 3 recurrences of the deformity, 1 frank nonunion, 8 dorsal cortical nonunions, 5 cases of undercorrection, and 1 case of broken hardware that was present in the nonunion that went on to revision. There were no superficial or deep infections, and no cases of transfer metatarsalgia were noted. In this series, the use of an oblique first metatarsal osteotomy with a dorsal shelf resulted in reliable and powerful correction of the first intermetatarsal angle in patients with moderate to severe hallux valgus. Particular attention should be paid to severe IM angles and the possibility of undercorrections. Despite ambulation postoperatively, the Mau osteotomy minimized dorsal malunion and the incidence of transfer metatarsalgia. LEVEL OF CLINICAL EVIDENCE: 4.