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1.
Magn Reson Med ; 91(3): 896-910, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37755319

RESUMO

PURPOSE: To develop a 3D phase modulated UTE adiabatic T1ρ (PM-UTE-AdiabT1ρ ) sequence for whole knee joint mapping on a clinical 3 T scanner. METHODS: This new sequence includes six major features: (1) a magnetization reset module, (2) a train of adiabatic full passage pulses for spin locking, (3) a phase modulation scheme (i.e., RF cycling pair), (4) a fat saturation module, (5) a variable flip angle scheme, and (6) a 3D UTE Cones sequence for data acquisition. A simple exponential fitting was used for T1ρ quantification. Phantom studies were performed to investigate PM-UTE-AdiabT1ρ 's sensitivity to compositional changes and reproducibility as well as its correlation with continuous wave-T1ρ measurement. The PM-UTE-AdiabT1ρ technique was then applied to five ex vivo and five in vivo normal knees to measure T1ρ values of femoral cartilage, meniscus, posterior cruciate ligament, anterior cruciate ligament, patellar tendon, and muscle. RESULTS: The phantom study demonstrated PM-UTE-AdiabT1ρ 's high sensitivity to compositional changes, its high reproducibility, and its strong linear correlation with continuous wave-T1ρ measurement. The ex vivo and in vivo knee studies demonstrated average T1ρ values of 105.6 ± 8.4 and 77.9 ± 3.9 ms for the femoral cartilage, 39.2 ± 5.1 and 30.1 ± 2.2 ms for the meniscus, 51.6 ± 5.3 and 29.2 ± 2.4 ms for the posterior cruciate ligament, 79.0 ± 9.3 and 52.0 ± 3.1 ms for the anterior cruciate ligament, 19.8 ± 4.5 and 17.0 ± 1.8 ms for the patellar tendon, and 91.1 ± 8.8 and 57.6 ± 2.8 ms for the muscle, respectively. CONCLUSION: The 3D PM-UTE-AdiabT1ρ sequence allows volumetric T1ρ assessment for both short and long T2 tissues in the knee joint on a clinical 3 T scanner.


Assuntos
Menisco , Ligamento Patelar , Reprodutibilidade dos Testes , Articulação do Joelho/diagnóstico por imagem , Ligamento Cruzado Anterior/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
2.
Semin Musculoskelet Radiol ; 28(1): 62-77, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38330971

RESUMO

Magnetic resonance imaging (MRI) is increasingly used to evaluate the microstructural and compositional properties of bone. MRI-based biomarkers can characterize all major compartments of bone: organic, water, fat, and mineral components. However, with a short apparent spin-spin relaxation time (T2*), bone is invisible to conventional MRI sequences that use long echo times. To address this shortcoming, ultrashort echo time MRI sequences have been developed to provide direct imaging of bone and establish a set of MRI-based biomarkers sensitive to the structural and compositional changes of bone. This review article describes the MRI-based bone biomarkers representing total water, pore water, bound water, fat fraction, macromolecular fraction in the organic matrix, and surrogates for mineral density. MRI-based morphological bone imaging techniques are also briefly described.


Assuntos
Osso e Ossos , Imageamento por Ressonância Magnética , Humanos , Osso e Ossos/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Água/química , Minerais
3.
J Clin Densitom ; 25(4): 649-667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36280582

RESUMO

The 22nd Annual Santa Fe Bone Symposium (SFBS) was a hybrid meeting held August 5-6, 2022, with in-person and virtual attendees. Altogether, over 400 individuals registered, a majority of whom attended in-person, representing many states in the USA plus 7 other countries. The SFBS included 10 plenary presentations, 2 faculty panel discussions, satellite symposia, Bone Health & Osteoporosis Foundation Fracture Liaison Service Boot Camp, and a Project ECHO workshop, with lively interactive discussions for all events. Topics of interest included fracture prevention at different stages of life; how to treat and when to change therapy; skeletal health in cancer patients; advanced imaging to assess bone strength; the state of healthcare in the USA; osteosarcopenia; vitamin D update; perioperative bone health care; new guidelines for managing primary hyperparathyroidism; new concepts on bone modeling and remodeling; and an overview on the care of rare bone diseases, including hypophosphatasia, X-linked hypophosphatemia, tumor induced osteomalacia, osteogenesis imperfecta, fibrodysplasia ossificans progressiva, and osteopetrosis. The SFBS was preceded by the Santa Fe Fellows Workshop on Osteoporosis and Metabolic Bone Diseases, a collaboration of the Endocrine Fellows Foundation and the Osteoporosis Foundation of New Mexico. From the Workshop, 4 participating fellows were selected to give oral presentations at the bone symposium. These proceedings represent the clinical highlights of 2022 SFBS presentations and the discussions that followed, all with the aim of optimizing skeletal health and minimizing the consequences of fragile bones.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Fraturas por Osteoporose , Humanos , Absorciometria de Fóton , Osteoporose/tratamento farmacológico , Doenças Ósseas Metabólicas/terapia , Fraturas por Osteoporose/prevenção & controle
4.
BMC Cancer ; 21(1): 89, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482769

RESUMO

BACKGROUND: Giant cell tumor of bone (GCTB) is a rare osteoclastogenic stromal tumor. GCTB can rarely undergo malignant transformation. This post hoc analysis evaluated and classified malignancies in patients with GCTB who received denosumab. METHODS: This analysis was conducted on patients with pathologically confirmed GCTB and measurable active disease treated with denosumab 120 mg subcutaneously once every 4 weeks, with loading doses on study days 8 and 15, as part of a phase 2, open-label, multicenter study. We identified potential cases of malignancy related to GCTB through an independent multidisciplinary review or medical history, associated imaging or histopathologic reports, and disease course. The findings were summarized and no statistical analysis was performed. RESULTS: Twenty of five hundred twenty-six patients (3.8%) who received at least one dose of denosumab were misdiagnosed with GCTB that was later discovered to be malignancies: five primary malignant GCTB, five secondary malignant GCTB, four sarcomatous transformations, and six patients with other malignancies (giant cell-rich osteosarcoma, undifferentiated pleomorphic sarcoma, spindle cell sarcoma, osteogenic sarcoma, phosphaturic mesenchymal tumor of mixed connective tissue type, and fibrosarcoma/malignant fibrous histiocytoma). Many malignancies were present before denosumab was initiated (8 definitive cases, 7 likely cases), excluding potential involvement of denosumab in these cases. Signs associated with potential misdiagnoses of GCTB included poor mineralization with denosumab treatment, rapid relapse in pain, or a failure of the typical dramatic improvement in pain normally observed with denosumab. CONCLUSIONS: Although rare, GCTB can undergo malignant transformation, and rates in this study were consistent with previous reports. Signs of poor mineralization or lack of response to denosumab treatment may warrant close monitoring. TRIAL REGISTRATION: clinicaltrials.gov , ( NCT00680992 ). Registered May 20, 2008.


Assuntos
Biomarcadores Tumorais/análise , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Feminino , Seguimentos , Tumor de Células Gigantes do Osso/metabolismo , Tumor de Células Gigantes do Osso/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto Jovem
5.
J Cell Biochem ; 118(2): 361-365, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27357060

RESUMO

Our laboratory pioneered patient-derived orthotopic xenograft (PDOX) mouse models using surgical orthotopic implantation (SOI). PDOX models are patient-like, in contrast to the ectopic subcutaneous-transplant cancer models. In the present study, we demonstrate that an undifferentiated pleomorphic soft-tissue sarcoma (UPS-STS) PDOX model acquired bright RFP-expressing stroma through one passage in red fluorescent protein (RFP) transgenic mice, which upon passage to non-colored nude mice was non-invasively imageable. A PDOX nude mouse model of UPS-STS was established in the biceps femoris of nude mice. After the tumors grew to a diameter of 10 mm, the tumors were subsequently passaged to RFP transgenic mice, and after tumor growth were then passaged to non-transgenic nude mice. Tumors were divided into small fragments and transplanted in the biceps femoris at each passage. The OV100 Small Animal Fluorescence Imaging System and FV1000 laser scanning confocal microscope were used to image RFP fluorescence in the UPS-STS PDOX models. UPS-STS PDOX tumors, previously grown in RFP transgenic nude mice for only one passage, had very bright fluorescence and after passage to non-transgenic nude mice maintained the bright fluorescence and were non-invasively imageable. FV1000 confocal imaging revealed diffusely distributed bright RFP stromal cells in the PDOX tumor, both in RFP transgenic mice and after passage to non-transgenic mice. These results demonstrate a powerful method to make the PDOX UPS-STS model brightly fluorescent for non-invasive imaging, as well as for confocal microscopy of individual stromal cells associated with the tumor. The RFP-labeled UPS PDOX has the potential to rapidly screen for novel effective agents for individual patients, including stroma-targeting drugs, whereby the stromal cells are a visual target. J. Cell. Biochem. 118: 361-365, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Rastreamento de Células/métodos , Proteínas Luminescentes/biossíntese , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Sarcoma/metabolismo , Sarcoma/patologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Humanos , Proteínas Luminescentes/genética , Camundongos , Camundongos Nus , Camundongos Transgênicos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/genética , Sarcoma/tratamento farmacológico , Sarcoma/genética , Proteína Vermelha Fluorescente
6.
J Clin Densitom ; 20(2): 134-152, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28185765

RESUMO

The Santa Fe Bone Symposium is an annual meeting of healthcare professionals and clinical researchers that details the clinical relevance of advances in knowledge of skeletal diseases. The 17th Santa Fe Bone Symposium was held in Santa Fe, New Mexico, USA, on August 5-6, 2016. The program included plenary lectures, oral presentations by endocrinology fellows, meet-the-professor sessions, and panel discussions, all aimed to provide ample opportunity for interactive discussions among all participants. Symposium topics included recent developments in the translation of basic bone science to patient care, new clinical practice guidelines for postmenopausal osteoporosis, management of patients with disorders of phosphate metabolism, new and emerging treatments for rare bone diseases, strategies to enhance fracture healing, and an update on Bone Health Extension for Community Healthcare Outcomes, using a teleconferencing platform to elevate the level of knowledge of healthcare professionals in underserved communities to deliver best practice care for skeletal diseases. The highlights and important clinical messages of the 2016 Santa Fe Bone Symposium are provided herein by each of the faculty presenters.


Assuntos
Absorciometria de Fóton , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Fraturas por Osteoporose/tratamento farmacológico , Fósforo/sangue , Doenças Raras/tratamento farmacológico , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/diagnóstico por imagem , Catepsina K/antagonistas & inibidores , Doença Crônica , Denosumab/uso terapêutico , Descoberta de Drogas , Consolidação da Fratura , Humanos , Hiperfosfatemia/sangue , Hiperfosfatemia/tratamento farmacológico , Hipofosfatemia/sangue , Hipofosfatemia/diagnóstico , Hipofosfatemia/tratamento farmacológico , Hipofosfatemia/etiologia , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Guias de Prática Clínica como Assunto , Ligante RANK/metabolismo , Doenças Raras/sangue , Doenças Raras/genética , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Pesquisa Translacional Biomédica
7.
AJR Am J Roentgenol ; 207(3): 517-25, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27224836

RESUMO

OBJECTIVE: The purpose of this article is to review the current guidelines and recommendations for percutaneous image-guided treatment of musculoskeletal tumors. CONCLUSION: With the ongoing technologic advances, it is essential that the musculoskeletal interventionalist is familiar with the current tools and techniques available for the treatment of soft-tissue and bone tumors. Fortunately, many of these tools are readily available in a standard interventional radiology department and can be easily applied to the musculoskeletal system.


Assuntos
Neoplasias Ósseas/terapia , Doenças Musculoesqueléticas/terapia , Radiografia Intervencionista , Ultrassonografia de Intervenção , Técnicas de Ablação , Corticosteroides/uso terapêutico , Humanos , Injeções , Guias de Prática Clínica como Assunto , Tomografia Computadorizada por Raios X
8.
J Oral Maxillofac Surg ; 74(12): 2403-2408, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27376180

RESUMO

PURPOSE: The risk of developing concomitant medication-related osteonecrosis of the jaw (MRONJ) in patients who have sustained an atypical femoral fracture (AFF) in association with parental administration of a bisphosphonate osteoclastic inhibitor medication for malignant disease is unclear. Published data were searched to determine the prevalence of these concomitant adverse medication events, if any. MATERIALS AND METHODS: A systematic review of published case series in the PubMed database was undertaken to ascertain the prevalence of patients having a concomitant history of AFF and MRONJ. The data were analyzed to provide prevalence rates of these events from the literature. RESULTS: Two case series were identified that delineated the risk (25 and 33%, respectively) of concomitant development of MRONJ and AFF in recipients of parenteral bisphosphonate medication administered for malignant disease. CONCLUSION: The published data suggest that approximately 30% of patients receiving parenteral bisphosphonates and having sustained an AFF could develop comorbid MRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Fraturas Espontâneas/induzido quimicamente , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas do Fêmur/complicações , Fraturas Espontâneas/complicações , Humanos , Injeções Intravenosas , Prevalência , Fatores de Risco
9.
J Imaging Inform Med ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548992

RESUMO

We proposed an end-to-end deep learning convolutional neural network (DCNN) for region-of-interest based multi-parameter quantification (RMQ-Net) to accelerate quantitative ultrashort echo time (UTE) MRI of the knee joint with automatic multi-tissue segmentation and relaxometry mapping. The study involved UTE-based T1 (UTE-T1) and Adiabatic T1ρ (UTE-AdiabT1ρ) mapping of the knee joint of 65 human subjects, including 20 normal controls, 29 with doubtful-minimal osteoarthritis (OA), and 16 with moderate-severe OA. Comparison studies were performed on UTE-T1 and UTE-AdiabT1ρ measurements using 100%, 43%, 26%, and 18% UTE MRI data as the inputs and the effects on the prediction quality of the RMQ-Net. The RMQ-net was modified and retrained accordingly with different combinations of inputs. Both ROI-based and voxel-based Pearson correlation analyses were performed. High Pearson correlation coefficients were achieved between the RMQ-Net predicted UTE-T1 and UTE-AdiabT1ρ results and the ground truth for segmented cartilage with acceleration factors ranging from 2.3 to 5.7. With an acceleration factor of 5.7, the Pearson r-value achieved 0.908 (ROI-based) and 0.945 (voxel-based) for UTE-T1, and 0.733 (ROI-based) and 0.895 (voxel-based) for UTE-AdiabT1ρ, correspondingly. The results demonstrated that RMQ-net can significantly accelerate quantitative UTE imaging with automated segmentation of articular cartilage in the knee joint.

10.
Geriatr Orthop Surg Rehabil ; 14: 21514593231216553, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38832288

RESUMO

Introduction: There are limited data on the management of bone health, including bone mineral density (BMD) evaluation and osteoporosis (OP) treatment, in patients undergoing elective orthopaedic surgeries. Methods: This was a retrospective cohort study using administrative claims data from Symphony Health, PatientSource for patients aged ≥50 years with documented kyphoplasty/vertebroplasty (KP/VP), total knee arthroplasty (TKA), and total hip arthroplasty (THA). Risk stratification to identify patients at very high risk for fracture (VHRFx) was based on clinical practice guideline recommendations to the extent information on variables of interest were available from the claims database. Results: A total of 251 919 patients met inclusion criteria: KP/VP (31 018), TKA (149 849), and THA (71 052). The majority were female (80.3%) with a mean (SD) age of 68.5 (7.5) years. Patients undergoing KP/VP were older and had a greater comorbidity burden associated with risk for falls, mobility issues, muscle weakness, and respiratory and cardiovascular diseases. In the 6 months before surgery, 11.8% of patients were tested and/or received treatment for OP. Patients undergoing KP/VP were more likely to be tested and/or treated (17.5%) than patients undergoing TKA (11.0%) or THA (10.9%). Overall, men had a lower rate of testing and/or treatment than women (4.6% vs 13.5%). In the 12 months before surgery, patients with an OP diagnosis and at VHRFx (30.8%) had a higher rate of treatment and/or testing than those without OP (11.5%), or those without OP but with a fracture in the year preceding surgery (10.2%). Conclusions: Bone health management is suboptimal in patients undergoing elective orthopaedic surgeries and is worse in men than in women. Proper management of OP before and after surgery may improve outcomes.

11.
Cell Tissue Res ; 347(3): 545-52, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21626290

RESUMO

Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH(1-34)) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH(1-34) has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction osteogenesis. These studies have demonstrated that intermittent PTH(1-34) treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH(1-34) has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH(1-34) treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH(1-34) treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the appropriate patient population for PTH(1-34) therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH(1-34) therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications) and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering.


Assuntos
Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Hormônio Paratireóideo/farmacologia , Engenharia Tecidual/métodos , Cicatrização/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Humanos , Pesquisa Translacional Biomédica
12.
Clin Orthop Relat Res ; 469(8): 2225-36, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21279487

RESUMO

BACKGROUND: Patients with impaired bone quality who suffer a fragility fracture face substantial challenges in both their short- and long-term care. In addition to poor bone quality, many of these patients have multiple medical comorbidities that alter their surgical risk and affect their ultimate functional recovery. Some medical issues can contribute to the altered bone quality and must be addressed to prevent future fractures. QUESTIONS/PURPOSES: This review summarizes the modifications in perioperative management and fracture fixation in patients with common fragility fractures who have impaired bone quality. It also summarizes the postoperative diagnosis and treatment of secondary causes of impaired bone quality in these patients. METHODS: We performed a PubMed search, and literature published after 2000 was prioritized, with the exception of benchmark clinical trial studies published before 2000. RESULTS: Patients with altered bone quality require rapid perioperative management of multiple medical comorbidities. Implant selection in patients with poor quality bone should permit early weightbearing, and constructs should maximize surface area contact with the remaining bone. Long-term diagnosis and treatment of other disease states contributing to poor bone quality (vitamin D deficiency/insufficiency, hypothyroidism, hyperthyroidism, hyperparathyroidism, Cushing's disease, and hypogonadism) must occur to minimize the chances of future fractures. CONCLUSIONS: Recognition of patients with impaired bone quality and proper treatment of their special needs in both the short and long term are essential for their best opportunity for maximal functional recovery and prevention of future fractures.


Assuntos
Fraturas por Osteoporose/epidemiologia , Osso e Ossos/fisiopatologia , Comorbidade , Demência/epidemiologia , Comunicação Atrioventricular/diagnóstico , Comunicação Atrioventricular/epidemiologia , Fraturas do Fêmur/epidemiologia , Fraturas do Fêmur/cirurgia , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Humanos , Fraturas do Úmero/epidemiologia , Fraturas do Úmero/cirurgia , Hipertireoidismo/epidemiologia , Hipotireoidismo/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Fraturas por Osteoporose/cirurgia , Assistência Perioperatória , Deficiência de Vitamina D/epidemiologia , Suporte de Carga
13.
Gait Posture ; 88: 167-173, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098401

RESUMO

BACKGROUND: Despite the proximal tibia being a common site of primary malignant bone tumors, there is limited information about gait function following proximal tibial tumor resection and endoprosthetic reconstruction (PTR). RESEARCH QUESTION: What is the impact of PTR on gait and quality of life? METHODS: This was a cross-sectional study of patients ≥18 years old who were ≥2 years post-PTR compared to a control group of similar age and sex distribution. Eighteen participants (9 PTR, 9 Control) were recruited. Gait spatial-temporal data, joint kinematics and kinetics were collected at preferred and fast walking speeds. Community walking cadence, health-related quality of life (SF-36) and knee joint torque were assessed. Comparisons were performed using one-way ANOVAs with Bonferroni corrections for multiple comparisons. Nonparametric tests were used for data not normally distributed. RESULTS: Mean age was 31 years for each group (PTR range = 18-42 yrs, Control range = 18-44 yrs). Compared to both control and nonsurgical limbs, the surgical limb exhibited significantly decreased % single limb support time, reduced heel rise during terminal stance and an absence of normally occurring knee flexion angles, extensor moments and power generation during initial double limb support. Additionally, a reduced peak plantar flexor moment was found for the surgical as compared to the control limb. The number of gait abnormalities increased during fast walking. Significantly reduced surgical knee extensor torque on isokinetic testing and weakness of the knee and ankle on clinical examination support gait findings. During community walking, the number of low frequency strides was an average of 5.3 % greater for the PTR group (p <  0.05). Norm-based PTR group SF-36 component scores were within normal values (53.4 physical, 56.5 mental). SIGNIFICANCE: Gait abnormalities were consistent with ankle muscle resection and transposition and knee extensor mechanism disruption. Despite these deficits, walking speed and quality of life were relatively normal.


Assuntos
Neoplasias Ósseas , Tíbia , Adolescente , Adulto , Fenômenos Biomecânicos , Neoplasias Ósseas/cirurgia , Estudos Transversais , Marcha , Humanos , Articulação do Joelho/cirurgia , Qualidade de Vida , Tíbia/cirurgia , Caminhada , Adulto Jovem
14.
Spine (Phila Pa 1976) ; 46(5): 277-284, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33038190

RESUMO

STUDY DESIGN: This was a subanalysis of an international, multicenter, open-label study. OBJECTIVE: The aim of this study was to assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.gov: NCT00680992). SUMMARY OF BACKGROUND DATA: Standard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (e.g., skull, spine). METHODS: Adults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120 mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3). RESULTS: Overall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and five in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% confidence interval [CI], 0.0-6.2) at year 1 and 7.4% (95% CI, 2.1-12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these, one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts). CONCLUSION: Results from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population.Level of Evidence: 2.


Assuntos
Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/diagnóstico por imagem , Tumor de Células Gigantes do Osso/tratamento farmacológico , Sacro/diagnóstico por imagem , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/cirurgia , Estudos de Coortes , Terapia Combinada/métodos , Feminino , Tumor de Células Gigantes do Osso/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Sacro/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , Resultado do Tratamento , Adulto Jovem
15.
Med Phys ; 48(6): 3262-3372, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33908045

RESUMO

PURPOSE: The goal of this study was to predict soft tissue sarcoma response to radiotherapy (RT) using longitudinal diffusion-weighted MRI (DWI). A novel deep-learning prediction framework along with generative adversarial network (GAN)-based data augmentation was investigated for the response prediction. METHODS: Thirty soft tissue sarcoma patients who were treated with five-fraction hypofractionated radiation therapy (RT, 6Gy×5) underwent diffusion-weighted MRI three times throughout the RT course using an MR-guided radiotherapy system. Pathologic treatment effect (TE) scores, ranging from 0-100%, were obtained from the post-RT surgical specimen as a surrogate of patient treatment response. Patients were divided into three classes based on the TE score (TE ≤ 20%, 20% < TE < 90%, TE ≥ 90%). Apparent diffusion coefficient (ADC) maps of the tumor from the three time points were combined as 3-channel images. An auxiliary classifier generative adversarial network (ACGAN) was trained on 20 patients to augment the data size. A total of 15,000 synthetic images were generated for each class. A prediction model based on a previously described VGG-19 network was trained using the synthesized data, validated on five unseen validation patients, and tested on the remaining five test patients. The entire process was repeated seven times, each time shuffling the training, validation, and testing datasets such that each patient was tested at least once during the independent test stage. Prediction performance for slice-based prediction and patient-based prediction was evaluated. RESULTS: The average training and validation accuracies were 86.5% ± 1.6% and 84.8% ± 1.8%, respectively, indicating that the generated samples were good representations of the original patient data. Among the seven rounds of testing, slice by slice prediction accuracy ranged from 81.6% to 86.8%. The overall accuracy of the independent test sets was 83.3%. For patient-based prediction, 80% was achieved in one round and 100% was achieved in the remaining six rounds. The mean accuracy was 97.1%. CONCLUSION: This study demonstrated the potential to use deep learning to predict the pathologic treatment effect from longitudinal DWI. Accuracies of 83.3% and 97.1% were achieved on independent test sets for slice-based and patient-based prediction respectively.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Imagem de Difusão por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Sarcoma/diagnóstico por imagem , Sarcoma/radioterapia
16.
Curr Osteoporos Rep ; 8(1): 28-33, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20425088

RESUMO

Teriparatide is a drug currently approved for treating patients with osteoporosis who are at high risk for future fracture. In the treatment of osteoporosis, teriparatide works as an anabolic agent stimulating bone formation throughout the skeleton by principally enhancing osteoblast-derived bone formation relative to osteoclast-derived bone resorption. The net effect is increased bone mass. For patients with a fracture, a similar process of increased bone formation is required transiently at the fracture site for repair. Teriparatide has been investigated in animal models and in patients as a potential agent to enhance fracture repair. In addition, evidence that teriparatide enhances chondrogenesis has generated interest in using the agent for articular cartilage repair. Research is currently underway to understand the effects teriparatide may have on mesenchymal stem cells, and on other effects that have been reported anecdotally in patients using the drug for osteoporosis care, including the healing of fracture nonunions and a decreased incidence of back pain. We review the current animal and human reports available on the uses of teriparatide in musculoskeletal diseases beyond osteoporosis.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Consolidação da Fratura/efeitos dos fármacos , Doenças Musculoesqueléticas/tratamento farmacológico , Teriparatida/uso terapêutico , Animais , Dor nas Costas/tratamento farmacológico , Reabsorção Óssea , Cartilagem/efeitos dos fármacos , Humanos , Osteoporose/tratamento farmacológico
17.
J Spinal Disord Tech ; 23(2): 151-5, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20051918

RESUMO

STUDY DESIGN: Case Report. OBJECTIVE: To report on the treatment of 3 cases of painful delayed unions of type III odontoid fractures with teriparatide. SUMMARY OF BACKGROUND DATA: Fractures of the C2 vertebra, also known as odontoid fractures, are an important subset of cervical spine fractures. Type III odontoid fractures pass through predominately cancellous bone of C2. Generally accepted treatment is external immobilization with either a rigid collar or a halo vest for 8 to 12 weeks. We report 3 patients who, despite external immobilization, developed painful delayed unions of type III odontoid fractures. Teriparatide is a novel anabolic drug therapy for osteoporosis. It has been shown to stimulate osteoblasts, enhance bone connectivity, increase endosteal cortical thickness, and improve bone mineral content. The drug is given through subcutaneous injection of 20 microg/d for between 6 weeks and 2 years. We treated these 3 patients with teriparatide. Each was informed that details of their case would be submitted for publication. METHODS: Retrospective case analysis. RESULTS: All 3 patients experienced both rapid clinical improvement and computed tomography evidence of fracture union. CONCLUSION: These 3 cases represent relatively uncommon clinical scenarios in which type III odontoid fractures in osteoporotic women failed to unite with external immobilization over several months. The patients presented for follow-up with substantial, activity-limiting neck pain. All 3 were begun on teriparatide doses therapeutic for osteoporosis, and all 3 experienced both remarkable resolution of chronic neck pain and computed tomography-confirmed union of the fractures.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Processo Odontoide/efeitos dos fármacos , Fraturas da Coluna Vertebral/tratamento farmacológico , Teriparatida/administração & dosagem , Cicatrização/efeitos dos fármacos , Idoso de 80 Anos ou mais , Regeneração Óssea/fisiologia , Esquema de Medicação , Fixadores Externos , Feminino , Humanos , Injeções Subcutâneas , Cervicalgia/tratamento farmacológico , Cervicalgia/etiologia , Cervicalgia/fisiopatologia , Processo Odontoide/diagnóstico por imagem , Processo Odontoide/patologia , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Osteoporose/prevenção & controle , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Cicatrização/fisiologia
18.
JBJS Case Connect ; 10(2): e0221, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649098

RESUMO

CASE: A 78-year-old woman who underwent reverse total shoulder arthroplasty (RTSA) for proximal humerus fracture developed a Type-3 acromial stress fracture, resulting in increased pain and decreased function 9 months post-op. She was managed nonoperatively with adjunctive teriparatide (FORTEO), and after a 4-month course, she had regained excellent motion and achieved union. CONCLUSION: Teriparatide is a viable adjunct in treating patients nonoperatively with acromial stress fractures after RTSA.


Assuntos
Acrômio/lesões , Artroplastia do Ombro/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Fraturas de Estresse/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Teriparatida/uso terapêutico , Idoso , Artroplastia do Ombro/métodos , Feminino , Fraturas de Estresse/diagnóstico por imagem , Humanos , Radiografia , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/cirurgia
19.
Surgery ; 168(6): 980-986, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33008615

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in reduced performance of elective surgeries and procedures at medical centers across the United States. Awareness of the prevalence of asymptomatic disease is critical for guiding safe approaches to operative/procedural services. As COVID-19 polymerase chain reaction (PCR) testing has been limited largely to symptomatic patients, health care workers, or to those in communal care centers, data regarding asymptomatic viral disease carriage are limited. METHODS: In this retrospective observational case series evaluating UCLA Health patients enrolled in pre-operative/pre-procedure protocol COVID-19 reverse transcriptase (RT)-PCR testing between April 7, 2020 and May 21, 2020, we determine the prevalence of COVID-19 infection in asymptomatic patients scheduled for surgeries and procedures. RESULTS: Primary outcomes include the prevalence of COVID-19 infection in this asymptomatic population. Secondary data analysis includes overall population testing results and population demographics. Eighteen of 4,751 (0.38%) patients scheduled for upcoming surgeries and high-risk procedures had abnormal (positive/inconclusive) COVID-19 RT-PCR testing results. Six of 18 patients were confirmed asymptomatic and had positive test results. Four of 18 were confirmed asymptomtic and had inconclusive results. Eight of 18 had positive results in the setting of recent symptoms or known COVID-19 infection. The prevalence of asymptomatic COVID-19 infection was 0.13%. More than 90% of patients had residential addresses within a 67-mile geographic radius of our medical center, the median age was 58, and there was equal male/female distribution. CONCLUSION: These data demonstrating low levels (0.13% prevalence) of COVID-19 infection in an asymptomatic population of patients undergoing scheduled surgeries/procedures in a large urban area have helped to inform perioperative protocols during the COVID-19 pandemic. Testing protocols like ours may prove valuable for other health systems in their approaches to safe procedural practices during COVID-19.


Assuntos
Centros Médicos Acadêmicos/estatística & dados numéricos , Doenças Assintomáticas/epidemiologia , COVID-19/epidemiologia , Procedimentos Cirúrgicos Eletivos , Pandemias , Assistência Perioperatória/estatística & dados numéricos , SARS-CoV-2 , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
20.
Phys Med Biol ; 65(17): 175006, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32554891

RESUMO

The objective of this study was to explore radiomics features from longitudinal diffusion-weighted MRIs (DWIs) for pathologic treatment effect prediction in patients with localized soft tissue sarcoma (STS) undergoing hypofractionated preoperative radiotherapy (RT). Thirty patients with localized STS treated with preoperative hypofractionated RT were recruited to this longitudinal imaging study. DWIs were acquired at three time points using a 0.35 T MRI-guided radiotherapy system. Treatment effect score (TES) was obtained from the post-surgery pathology as a surrogate of treatment outcome. Patients were divided into two groups based on TES. Response prediction was first performed using a support vector machine (SVM) with only mean apparent diffusion coefficient (ADC) or delta ADC to serve as the benchmark. Radiomics features were then extracted from tumor ADC maps at each of the three time points. Logistic regression and SVM were constructed to predict the TES group using features selected by univariate analysis and sequential forward selection. Classification performance using SVM with features from different time points and with or without delta radiomics were evaluated. Prediction performance using only mean ADC or delta ADC was poor (area under the curve (AUC) < 0.7). For the radiomics study using features from all time points and corresponding delta radiomics, SVM significantly outperformed logistic regression (AUC of 0.91 ± 0.05 v.s. 0.85 ± 0.06). Prediction AUC values using single or multiple time points without delta radiomics were all below 0.74. Including delta radiomics of mid- or post-treatment relative to the baseline drastically boosted the prediction. In this work, an SVM model was built to predict the TES using radiomics features from longitudinal DWI. Based on this study, we found that use of mean ADC, delta ADC, or radiomics features alone was not sufficient for response prediction, and including delta radiomics features of mid- or post-treatment relative to the baseline can optimize the prediction of TES, a pathologic and clinical endpoint.


Assuntos
Imagem de Difusão por Ressonância Magnética , Período Pré-Operatório , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/radioterapia , Área Sob a Curva , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecidos Moles/cirurgia , Máquina de Vetores de Suporte , Resultado do Tratamento
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