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CMAJ Open ; 9(2): E711-E717, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34162663


BACKGROUND: In Canada, decisions regarding osteoporosis pharmacotherapy are based on estimated 10-year risk of osteoporotic fracture. We aimed to determine how frequently 2 common approaches (Canadian Association of Radiologists and Osteoporosis Canada [CAROC] tool and Fracture Risk Assessment Tool [FRAX]) produced different estimates and to seek possible explanations for differences. METHODS: We conducted a cross-sectional chart review at a tertiary osteoporosis centre (Dr. David Hanley Osteoporosis Centre in Calgary). Included patients were women referred for consideration of osteoporosis pharmacotherapy who attended a consultation between 2016 and 2019 and whose charts contained 10-year osteoporotic fracture risk estimates using both the CAROC tool (based on bone mineral density [BMD] results) and FRAX (based on BMD results and clinically assessed fracture risk factors). Risk estimates provided on BMD reports (calculated with CAROC) and generated through osteoporosis clinic consultation (calculated with FRAX, including BMD) were categorized as low (< 10.0%), moderate (10.0%-19.9%) or high (≥ 20.0%). Estimates were considered discordant when they placed the patient in different risk categories. RESULTS: Of 190 patients evaluated, 99 (52.1%) had discordant risk estimates. Although a similar proportion were considered high risk by BMD reports using the CAROC tool (17.9%) and clinic charts using FRAX (19.5%), the 2 methods identified different patients as being high risk. Around the crucial high-risk (20.0%) treatment threshold, discordance was present in 37 patients (19.5%, 95% confidence interval [CI] 14.5%-25.7%); discordance around the moderate-risk (10.0%) threshold was present in 69 (36.3%, 95% CI 29.5%-43.2%) patients. Disagreement regarding fracture history between BMD reports and clinic charts was observed in 19.8% of patients. INTERPRETATION: Fracture risk estimates on BMD reports (using the CAROC tool) and those calculated in the clinical setting (using FRAX) frequently result in different risk classification. Osteoporosis treatment decisions may differ in up to half of patients depending on which estimate is used, highlighting the need for a consistent and accurate assessment process for fracture risk.

Osteoporose , Fraturas por Osteoporose , Sistemas de Informação em Radiologia/estatística & dados numéricos , Medição de Risco , Alberta/epidemiologia , Densidade Óssea , Tomada de Decisão Clínica , Estudos Transversais , Tratamento Farmacológico/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Avaliação de Resultados em Cuidados de Saúde , Seleção de Pacientes , Medição de Risco/métodos , Medição de Risco/normas , Medição de Risco/estatística & dados numéricos
Ann Thorac Surg ; 90(3): 979-85, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20732527


BACKGROUND: Wire cerclage closure of sternotomy is the standard of care despite evidence of pathologic sternal displacement (> 2 mm) during physiologic distracting forces (coughing). Postoperative functional recovery, respiration, pain, sternal dehiscence, and infection are influenced by early bone stability. This translational research report provides proof-of-concept (part A) and first-in-man clinical data (part B) with use of a triglyceride-based porous adhesive to rapidly enhance the stability of conventional sternal closure. METHODS: In part A, fresh human cadaver blocks were subjected to midline sternotomy and either conventional wire closure or modified adhesive closure. After 24 hours at 37 degrees C, using a biomechanical test apparatus, a step-wise increase in lateral distracting force simulated physiologic stress. Sternal displacement was measured by microdisplacement sensors. In part B, a selected clinical case series was performed and sternal perfusion assessed by serial single photon emission computed tomography imaging. RESULTS: Wire closure resulted in measurable bony displacement with increasing load. Pathologic displacement (> or = 2 mm) was observed in all regional segments at loads 400 newton (N) or greater. In contrast, adhesive closure completely eliminated pathologic displacement at forces 600 N or less (p < 0.001). In patients, adhesive closure was not associated with adverse events such as adhesive migration, embolization, or infection. There was excellent qualitative correlation between cadaver and clinical computed tomographic images. Sternal perfusion was not compromised by adhesive closure. CONCLUSIONS: This first-in-man series provides proof-of-concept indicating that a novel biologic bone adhesive is capable of rapid sternal fixation and complete elimination of pathologic sternal displacement under physiologic loading conditions. A randomized clinical trial is warranted to further define the potential risks and benefits of this innovative technique.

Cimentos Ósseos , Fios Ortopédicos , Óleo de Rícino , Polímeros , Esterno/cirurgia , Cadáver , Humanos , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Torácicos/métodos
Pediatr Hematol Oncol ; 27(3): 212-27, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20367265


Interference with the molecular mechanisms that generate tumor supportive niches in the bone microenvironment is a rational approach to inhibit the growth of hematological malignancies. However, the advancement of knowledge in this area has been slowed down by the lack of in vitro models to facilitate the screening of potential candidate agents. The rare cases of acute lymphoblastic leukemia (ALL) in children presenting with extensive bone involvement may represent an exaggerated form of some aspects of the normal tumor-bone interactions. Thus, these cases can provide insight into processes that are otherwise challenging to uncover. The authors describe the case of a 6-year-old child who presented with severe osteopenia that resolved at the time of leukemic remission. Compared to control sera, serum taken at disease presentation contained increased levels of a group of osteolytic cytokines and was effective in activating preosteoclast cells in culture. Based on these findings, the authors describe an experimental model to identify agents that would interfere with leukemia mediated osteolytic process.

Doenças Ósseas Metabólicas/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Pré-Escolar , Citocinas/sangue , Receptores ErbB/antagonistas & inibidores , Humanos , Masculino , Osteoclastos/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
J Biol Chem ; 279(35): 36621-4, 2004 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-15234968


For nearly 50 years, succinyl-CoA synthetase in animals was thought to be specific for guanine nucleotides. Recently, we purified and characterized both an ADP-forming succinyl-CoA synthetase from pigeon breast muscle and the GDP-forming enzyme from liver (Johnson, J. D., Muhonen, W. W., and Lambeth, D. O. (1998) J. Biol. Chem. 273, 27573-27579). Using the sequences of the pigeon enzymes as queries in BLAST searches, we obtained genetic evidence that both enzymes are expressed in a wide range of animal species (Johnson, J. D., Mehus, J. G., Tews, K., Milavetz, B. I., and Lambeth, D. O. (1998) J. Biol. Chem. 273, 27580-27586). Here we extend those observations by presenting data from Western and Northern blots and enzymatic assays showing that both proteins are widely expressed in mammals with the relative amounts varying from tissue to tissue. We suggest that both succinyl-CoA synthetases catalyze the reverse reaction in the citric acid cycle in which the ADP-forming enzyme augments ATP production, whereas the GDP-forming enzyme supports GTP-dependent anabolic processes. Widely accepted shuttle mechanisms are invoked to explain how transport of P-enolpyruvate across mitochondrial membranes can transfer high energy phosphate between the cytosol and mitochondrial matrix.

Succinato-CoA Ligases/biossíntese , Succinato-CoA Ligases/química , Difosfato de Adenosina/química , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Animais , Northern Blotting , Western Blotting , Mama/metabolismo , Membrana Celular/metabolismo , Columbidae , Citosol/metabolismo , Primers do DNA/farmacologia , Bases de Dados como Assunto , Feminino , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/metabolismo , Humanos , Fígado/metabolismo , Masculino , Camundongos , Mitocôndrias/metabolismo , Modelos Biológicos , Miocárdio/metabolismo , Ratos , Testículo/metabolismo , Distribuição Tecidual