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1.
Sports Health ; 12(2): 114-115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32058855
2.
Bone ; 130: 115118, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31678490

RESUMO

Osteogenesis imperfecta (OI) is a rare and severe skeletal dysplasia marked by low bone mass and poor bone quality which is especially burdensome during childhood. Since clinical trials for pediatric OI are difficult, there is a widespread reliance on genetically modified murine models to understand the skeletal effects of emerging therapeutics. However a common model does not yet exist to understand how patient-specific genotype may influence treatment efficacy. Recently, sclerostin antibody (SclAb) has been introduced as a novel putative anabolic therapy for diseases of low bone mass, but effects in pediatric patients remain unexplored. In this study, we aim to establish a direct xenograft approach using OI patient-derived bone isolates which retain patient-specific genetic defects and cells residing in their intrinsic extracellular environment to evaluate the bone-forming effects of SclAb as a bridge to clinical trials. OI and age matched non-OI patient bone typically discarded as surgical waste during corrective orthopaedic procedures were collected, trimmed and implanted subcutaneously (s.c.) on the dorsal surface of 4-6-week athymic mice. A subset of implanted mice were evaluated at short (1 week), intermediate (4 week), and long-term (12 week) durations to assess bone cell survival and presence of donor bone cells in order to determine an appropriate treatment duration. Remaining implanted mice were randomly assigned to a two or four-week SclAb-treated (25mg/kg s.c. 2QW) or untreated control group. Immunohistochemistry determined osteocyte and osteoblast donor/host relationship, TRAP staining quantified osteoclast activity, and TUNEL assay was used to understand rates of bone cell apoptosis at each implantation timepoint. Longitudinal changes of in vivo µCT outcomes and dynamic histomorphometry were used to assess treatment response and ex vivo µCT and dynamic histomorphometry of host femora served as a positive internal control to confirm a bone forming response to SclAb. Human-derived osteocytes and lining cells were present up to 12 weeks post-implantation with nominal cell apoptosis in the implant. Sclerostin expression remained donor-derived throughout the study. Osterix expression was primarily donor-derived in treated implants and shifted in favor of the host when implants remained untreated. µCT measures of BMD, TMD, BV/TV and BV increased with treatment but response was variable and impacted by bone implant morphology (trabecular, cortical) which was corroborated by histomorphometry. There was no statistical difference between treated and untreated osteoclast number in the implants. Host femora confirmed a systemic bone forming effect of SclAb. Findings support use of the xenograft model using solid bone isolates to explore the effects of novel bone-targeted therapies. These findings will impact our understanding of SclAb therapy in pediatric OI tissue through establishing the efficacy of this treatment in human cells prior to extension to the clinic.

3.
6.
Am J Sports Med ; 47(9): 2067-2076, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307223

RESUMO

BACKGROUND: Nearly three-quarters of anterior cruciate ligament (ACL) injuries occur as "noncontact" failures from routine athletic maneuvers. Recent in vitro studies revealed that repetitive strenuous submaximal knee loading known to especially strain the ACL can lead to its fatigue failure, often at the ACL femoral enthesis. HYPOTHESIS: ACL failure can be caused by accumulated tissue fatigue damage: specifically, chemical and structural evidence of this fatigue process will be found at the femoral enthesis of ACLs from tested cadaveric knees, as well as in ACL explants removed from patients undergoing ACL reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: One knee from each of 7 pairs of adult cadaveric knees were repetitively loaded under 4 times-body weight simulated pivot landings known to strain the ACL submaximally while the contralateral, unloaded knee was used as a comparison. The chemical and structural changes associated with this repetitive loading were characterized at the ACL femoral enthesis at multiple hierarchical collagen levels by employing atomic force microscopy (AFM), AFM-infrared spectroscopy, molecular targeting with a fluorescently labeled collagen hybridizing peptide, and second harmonic imaging microscopy. Explants from ACL femoral entheses from the injured knee of 5 patients with noncontact ACL failure were also characterized via similar methods. RESULTS: AFM-infrared spectroscopy and collagen hybridizing peptide binding indicate that the characteristic molecular damage was an unraveling of the collagen molecular triple helix. AFM detected disruption of collagen fibrils in the forms of reduced topographical surface thickness and the induction of ~30- to 100-nm voids in the collagen fibril matrix for mechanically tested samples. Second harmonic imaging microscopy detected the induction of ~10- to 100-µm regions where the noncentrosymmetric structure of collagen had been disrupted. These mechanically induced changes, ranging from molecular to microscale disruption of normal collagen structure, represent a previously unreported aspect of tissue fatigue damage in noncontact ACL failure. Confirmatory evidence came from the explants of 5 patients undergoing ACL reconstruction, which exhibited the same pattern of molecular, nanoscale, and microscale structural damage detected in the mechanically tested cadaveric samples. CONCLUSION: The authors found evidence of accumulated damage to collagen fibrils and fibers at the ACL femoral enthesis at the time of surgery for noncontact ACL failure. This tissue damage was similar to that found in donor knees subjected in vitro to repetitive 4 times-body weight impulsive 3-dimensional loading known to cause a fatigue failure of the ACL. CLINICAL RELEVANCE: These findings suggest that some ACL injuries may be due to an exacerbation of preexisting hierarchical tissue damage from activities known to place larger-than-normal loads on the ACL. Too rapid an increase in these activities could cause ACL tissue damage to accumulate across length scales, thereby affecting ACL structural integrity before it has time to repair. Prevention necessitates an understanding of how ACL loading magnitude and frequency are anabolic, neutral, or catabolic to the ligament.

7.
Sports Health ; 11(5): 440-445, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31265352

RESUMO

BACKGROUND: "Research-ready" evidence platforms that link sports data with anonymized electronic health records (EHRs) or other data are important tools for evaluating injury occurrence in response to changes in games, training, rules, and other factors. While there is agreement that high-quality data are essential, there is little evidence to guide data curation. HYPOTHESIS: We hypothesized that an EHR used in the course of clinical care and curated for research readiness can provide a robust evidence platform. Our purpose was to describe the data curation used for active injury surveillance by the National Football League (NFL). STUDY DESIGN: Dynamic cohort study. LEVEL OF EVIDENCE: Level 2. METHODS: Players provide informed consent for research activities through the collective bargaining process. A league-wide EHR is used to record injuries that come to the attention of the teams' athletic trainers and physicians, NFL medical spotters, or unaffiliated neurotrauma consultants. Information about football activities and injuries are linkable by player, setting, and event to other sports-related data, including game statistics and game-day stadium quality measures, using a unique player identification designed to protect player privacy. Ongoing data curation is used to review data completeness and accuracy and is adjusted over time in response to findings. RESULTS: The core data curation activities include monthly injury summaries to team staff, queries to resolve incomplete reporting, and periodic external checks. Experiences derived from producing more than 100 reports per year on diverse topics are used to update coding training and related guidance documents in response to missing data or inconsistent coding that is observed. Roughly 20% more injuries were recorded for the same "reportable" injuries after switching from targeted reporting to an EHR. CONCLUSION: Research-ready databases need systematic curation for quality and completeness, along with related action plans. More injuries were reported through EHR than through targeted reporting. CLINICAL RELEVANCE: Evidence-driven decision-making thrives on reliable data fine-tuned through systematic use, review, and ongoing adjustments to the curation process.


Assuntos
Traumatismos em Atletas/diagnóstico , Registros Eletrônicos de Saúde , Futebol Americano/lesões , Estudos de Coortes , Curadoria de Dados , Humanos , Armazenamento e Recuperação da Informação , Medicina Esportiva
9.
J Orthop Res ; 37(9): 1910-1919, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31042312

RESUMO

Postnatal development and the physiological loading response of the anterior cruciate ligament (ACL) complex (ACL proper, entheses, and bony morphology) is not well understood. We tested whether the ACL-complex of two inbred mouse strains that collectively encompass the musculoskeletal variation observed in humans would demonstrate significant morphological differences following voluntary cage-wheel running during puberty compared with normal cage activity controls. Female A/J and C57BL/6J (B6) 6-week-old mice were provided unrestricted access to a standard cage-wheel for 4 weeks. A/J-exercise mice showed a 6.3% narrower ACL (p = 0.64), and a 20.1% more stenotic femoral notch (p < 0.01) while B6-exercise mice showed a 12.3% wider ACL (p = 0.10), compared with their respective controls. Additionally, A/J-exercise mice showed a 5.3% less steep posterior medial tibial slope (p = 0.07) and an 8.8% less steep posterior lateral tibial slope (p = 0.07), while B6-exercise mice showed a 9.8% more steep posterior medial tibial slope (p < 0.01) than their respective controls. A/J-exercise mice also showed more reinforcement of the ACL tibial enthesis with a 20.4% larger area (p < 0.01) of calcified fibrocartilage distributed at a 29.2% greater depth (p = 0.02) within the tibial enthesis, compared with their controls. These outcomes suggest exercise during puberty significantly influences ACL-complex morphology and that inherent morphological differences between these mice, as observed in their less active genetically similar control groups, resulted in a divergent phenotypic outcome between mouse strains. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1910-1919, 2019.

11.
Sports Health ; 11(4): 306-315, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30951444

RESUMO

BACKGROUND: Persistent quadriceps weakness and activation failure are common in individuals with anterior cruciate ligament (ACL) reconstruction. A growing body of evidence indicates that this chronic quadriceps dysfunction could be partly mediated due to reduced corticospinal excitability. However, current rehabilitation approaches do not directly target corticospinal deficits, which may be critical for restoring optimal clinical outcomes after the surgery. This case study tested the feasibility of operant conditioning of torque responses evoked by transcranial magnetic stimulation (TMS) to improve quadriceps function after ACL reconstruction. HYPOTHESIS: Operant conditioning of motor evoked torque responses would improve quadriceps strength, voluntary activation, and corticospinal excitability. STUDY DESIGN: Case study and research report. LEVEL OF EVIDENCE: Level 5. METHODS: A 24-year-old male with an ACL reconstruction (6 months postsurgery) trained for 20 sessions (2-3 times per week for 8 weeks) to increase his TMS-induced motor evoked torque response (MEP torque) of the quadriceps muscles using operant conditioning principles. Knee extensor strength, voluntary quadriceps muscle activation, and quadriceps corticospinal excitability were evaluated at 3 time points: preintervention (pre), 4 weeks (mid), and immediately after the intervention (post). RESULTS: The participant was able to successfully condition (ie, increase) the quadriceps MEP torque after 1 training session, and the conditioned MEP torque gradually increased over the course of 20 training sessions to reach about 500% of the initial value at the end of training. The participant's control MEP torque values and corticospinal excitability, which were measured outside of the conditioning paradigm, also increased with training. These changes were paralleled by improvements in knee extensor strength and voluntary quadriceps muscle activation. CONCLUSION: This study shows that operant conditioning of MEP torque is a feasible approach to improving quadriceps corticospinal excitability and quadriceps function after ACL reconstruction and encourages further testing in a larger cohort of ACL-reconstructed individuals. CLINICAL RELEVANCE: Operant conditioning may serve as a potential therapeutic adjuvant for ACL rehabilitation.


Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/reabilitação , Condicionamento Operante , Potencial Evocado Motor , Futebol Americano/lesões , Força Muscular , Músculo Quadríceps/fisiologia , Estimulação Magnética Transcraniana , Estudos de Viabilidade , Humanos , Joelho/fisiologia , Masculino , Medidas de Resultados Relatados pelo Paciente , Tratos Piramidais/fisiologia , Torque , Adulto Jovem
12.
SAGE Open Med Case Rep ; 7: 2050313X18823476, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30719315

RESUMO

Fibular hemimelia is a rare congenital malformation that is commonly associated with other lower limb abnormalities. This is a unique case of a bicruciate ligament, anterior cru ciate ligament/posterior cruciate ligament (ACL/PCL) deficiency in a 6-year-old female with fibular hemimelia in which we describe an ACL reconstruction using autograft-allograft hybrid technique. This case focuses on the technical aspects of an ACL reconstruction using a physeal-sparing technique with a hybrid ACL graft in a pediatric patient with fibular hemimelia. When evaluating patients with fibular hemimelia, it is important to consider implications of treatment in a stepwise manner as this condition commonly presents with other abnormalities that will most likely require multiple procedures, including limb lengthening.

14.
Sports Health ; 11(2): 115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30789815
15.
J Pediatr Orthop ; 39(2): 55-58, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28234731

RESUMO

BACKGROUND: Although studies have shown increased rates of chondral injury with delayed surgical treatment of pediatric anterior cruciate ligament (ACL) injuries, it is unknown if this is related to a delay in diagnosis and appropriate activity restrictions. The purpose of this study was to determine if the time from injury to diagnosis, time from diagnosis to reconstruction, and preoperative activity level correlate with the degree of cartilage injury seen intraoperatively. METHODS: A retrospective review of skeletally immature patients who underwent ACL reconstruction was performed. Patients were stratified based on the time from injury to diagnosis (≤6 vs. >6 wk), diagnosis to surgery (≤6 vs. >6 wk), and injury to surgery (≤12 vs. >12 wk). Weight-bearing status, brace usage, athletic participation, and meniscus tears were characterized as binary variables. Articular cartilage injury was graded on a scale of 0 to 3. Differences between groups were analyzed using the χ test. RESULTS: In total, 91 subjects with mean age of 13 years (range, 9 to 16 y) were included. In total, 71% were diagnosed within 6 weeks of injury and 40% underwent surgery within 6 weeks of diagnosis. No differences were found in the presence of medial or lateral meniscus tears or the grade of articular cartilage damage when groups were analyzed by time from injury to diagnosis, diagnosis to surgery, and injury to surgery (P>0.05 in all cases). When stratified by weight-bearing status, brace status, and athletic activity, there were no significant differences between groups for meniscal tears or cartilage injury in any compartment (P>0.05). CONCLUSIONS: Diagnosis of ACL rupture within 6 weeks of injury and surgical reconstruction within 6 weeks of diagnosis or 12 weeks of injury do not appear to affect the rate of cartilage injury in skeletally immature patients. Weight-bearing status, brace use, and participation in athletic activities between the time of injury and diagnosis also did not impact the rate of intra-articular injury following ACL tear. LEVEL OF EVIDENCE: Level IV.


Assuntos
Lesões do Ligamento Cruzado Anterior/diagnóstico , Reconstrução do Ligamento Cruzado Anterior/métodos , Ligamento Cruzado Anterior/diagnóstico por imagem , Diagnóstico Tardio , Meniscos Tibiais/diagnóstico por imagem , Lesões do Menisco Tibial/diagnóstico , Tempo para o Tratamento , Adolescente , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Braquetes , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/lesões , Cartilagem Articular/cirurgia , Criança , Feminino , Humanos , Masculino , Meniscos Tibiais/cirurgia , Estudos Retrospectivos , Lesões do Menisco Tibial/cirurgia , Fatores de Tempo
17.
Sports Health ; 10(5): 396-397, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30153103
18.
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