RESUMO
Fibrillin microfibrils are ubiquitous elements of extracellular matrix assemblies that play crucial roles in regulating the bioavailability of growth factors of the transforming growth factor beta superfamily. Recently, several "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS) proteins were shown to regulate fibrillin microfibril function. Among them, ADAMTS17 is the causative gene of Weill-Marchesani syndrome (WMS) and Weill-Marchesani-like syndrome, of which common symptoms are ectopia lentis and short stature. ADAMTS17 has also been linked to height variation in humans; however, the molecular mechanisms whereby ADAMTS17 regulates skeletal growth remain unknown. Here, we generated Adamts17-/- mice to examine the role of Adamts17 in skeletogenesis. Adamts17-/- mice recapitulated WMS, showing shorter long bones, brachydactyly, and thick skin. The hypertrophic zone of the growth plate in Adamts17-/- mice was shortened, with enhanced fibrillin-2 deposition, suggesting increased incorporation of fibrillin-2 into microfibrils. Comprehensive gene expression analysis of growth plates using laser microdissection and RNA sequencing indicated alteration of the bone morphogenetic protein (BMP) signaling pathway after Adamts17 knockout. Consistent with this, phospho-Smad1 levels were downregulated in the hypertrophic zone of the growth plate and in Adamts17-/- primary chondrocytes. Delayed terminal differentiation of Adamts17-/- chondrocytes, observed both in primary chondrocyte and primordial metatarsal cultures, and was prevented by BMP treatment. Our data indicated that Adamts17 is involved in skeletal formation by modulating BMP-Smad1/5/8 pathway, possibly through inhibiting the incorporation of fibrillin-2 into microfibrils. Our findings will contribute to further understanding of disease mechanisms and will facilitate the development of therapeutic interventions for WMS.
Assuntos
Proteínas ADAMTS/fisiologia , Proteínas Morfogenéticas Ósseas/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Transdução de Sinais , Proteínas ADAMTS/genética , Animais , Proteínas Morfogenéticas Ósseas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Fibrilina-2/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microfibrilas/metabolismo , Músculo Esquelético/patologia , Pele/fisiopatologia , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Proteína Smad8/metabolismo , Síndrome de Weill-Marchesani/metabolismo , Síndrome de Weill-Marchesani/patologia , Síndrome de Weill-Marchesani/veterináriaRESUMO
In the published article, the Fig. 4a was published incorrectly.
RESUMO
BACKGROUND: Surgery for intertrochanteric fractures using intramedullary hip nails (IHNs) is among the most common surgical procedures in the orthopedic field. Although IHNs provide good overall outcomes, they sometimes cause complications, such as loss of reduction and cut-out. Here, we investigated the usefulness of IHNs with an anterior offset (Best Fit Nail® [BFN]) in maintaining fragment reduction and ensuring proper lag screw position compared with conventional non-offset nails (Proximal Femoral Nail Antirotation® [PFNA]), using postoperative computed tomography (CT). METHODS: Fifty consecutive patients with intertrochanteric fractures who underwent surgery with BFNs (BFN group) and 50 patients who underwent surgery with PFNAs (PFNA group) were retrospectively analyzed. Indices evaluated by postoperative CT were displacement distance of proximal fragment relative to distal fragment, reduction status (intramedullary, anatomical, and extramedullary types), lag screw direction, and angle between lag screw and femoral neck axis (deviation angle). RESULTS: Median [interquartile range] displacement distance was significantly smaller in the BFN group (0 [0, 0] mm) compared with the PFNA group (5.2 [3.6, 7.1] mm) (p<0.001). Reduction status was significantly better in the BFN group (anatomical type, 40 cases; intramedullary type, in 9 cases, and extramedullary type in 1 case) than in the PFNA group (anatomical type, 6 cases; intramedullary type, 43 cases; extramedullary type, 1 case) (p<0.001). Deviation of lag screw direction was observed in significantly fewer cases in the BFN group (20 cases; 40%) compared with the PFNA group (36 cases; 72%). Lag screw deviation angle was significantly smaller in the BFN group (-0.71°±4.0°) compared with the PFNA group (6.9°±7.1°). No adverse events related to surgery were observed in either group. CONCLUSIONS: Intertrochanteric fracture surgery using offset BFNs exhibited significantly smaller displacement distance, better reduction status, and higher frequency of no deviation with central lag screw position, compared with surgery using non-offset PFNAs.
Assuntos
Fixação Intramedular de Fraturas , Fraturas do Quadril , Humanos , Pinos Ortopédicos , Estudos Retrospectivos , Resultado do Tratamento , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Fraturas do Quadril/etiologia , Fixação Intramedular de Fraturas/métodos , Parafusos Ósseos/efeitos adversosRESUMO
BACKGROUND CONTEXT: Dural tear represents a common complication of microendoscopic spine surgery that may lead to postoperative sequelae including insufficient decompression, cerebrospinal fluid fistula, intracranial hypotension, and subdural/intraparenchymal bleeding. The gold standard to manage intraoperative dural tears is primary repair. However, the downside of conversion to open surgery can be detrimental. Therefore, understanding the most appropriate strategy for microendoscopic dural repair and its impact on postoperative outcomes is of importance. PURPOSE: The purpose of this study was to investigate the incidence of dural tears in patients undergoing microendoscopic lumbar surgery and to elucidate their influence on surgical outcomes whenever proper repair is accomplished microendoscopically without conversion to open surgery. STUDY DESIGN/SETTING: A retrospective multicenter cohort study of prospectively enrolled patients using a propensity-matched analysis. PATIENT SAMPLE: A total of 922 consecutive patients underwent microendoscopic surgery of the lumbar spine between February and December 2012 in the three institutions belonging to our study group. OUTCOME MEASURES: Outcome measures included the Numeric Rating Scale for back and leg pain, Oswestry Disability Index, Japanese Orthopaedic Association score, Short Form-36, and a patients' satisfaction scale. METHODS: All incidental dural tears were repaired by microendoscopic suture of the dura mater from inside to outside using double-arm needles and/or by fibrin glue coverage without being converted to open surgery. Surgical outcomes were compared between patients with and without dural tears using a propensity-matched analysis. RESULTS: Microendoscopic discectomy for lumbar disc herniation was performed on 474 patients, whereas microendoscopic laminectomy and posterior lumbar interbody fusion for lumbar canal stenosis were performed on 271 and 177 patients, respectively. Dural tears occurred in 49 (5.3%) patients. Of these, 23 (2.5%) patients required suture repair, whereas the rest received a fibrin patch for a pinhole tear, all of which were successfully performed under microendoscopy. Six hundred (65.1%) patients responded pre- and postoperatively to the questionnaire. Of them, the responses of 38 patients with dural tears were compared with those of 38 matched patients. No significant differences in any outcome measures were observed between the two groups. CONCLUSIONS: In conclusion, all dural tears in our cases were managed without conversion to open surgery and did not influence surgical outcomes.
Assuntos
Discotomia/efeitos adversos , Dura-Máter/lesões , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Complicações Intraoperatórias/epidemiologia , Laminectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Dura-Máter/cirurgia , Feminino , Humanos , Complicações Intraoperatórias/etiologia , Região Lombossacral/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , CicatrizaçãoRESUMO
STUDY DESIGN: An experimental study to develop a mouse model of lumbar intervertebral disc degeneration (IDD). OBJECTIVE: The aim of this study was to develop a mouse lumbar IDD model using surgically induced instability and to compare the findings of this model to those in human IDD. SUMMARY OF BACKGROUND DATA: Previously, various kinds of inducers have been used to reproduce IDD in experimental animals; however, there is yet no standard mouse lumbar IDD model without direct injury to intervertebral disc. METHODS: A total number of 59 C57BL/6J male mice at 8 weeks old were used. Instability of lumbar spine was induced by surgical resection of posterior elements, including facet joints, supra- and interspinous ligaments. We then analyzed time course changes in radiographical (nâ=â17) and histological analyses (nâ=â42), and compared these findings with those in human IDD. RESULTS: Radiographical analyses showed that the disc height began to decrease in the first 2 weeks after the surgery, and the decrease continued throughout 12 weeks. Bone spurs at the vertebral rims were observed in the late stage of 8 and 12 weeks after the surgery. Histological analyses showed that the disorder of the anterior anulus fibrosus (AF) was initially obvious, followed by posterior shift and degeneration of the nucleus pulposus (NP). Proteoglycan detected in inner layer of AF and periphery of NP was decreased after 8 weeks. Immunohistochemistry displayed the increase of type I and X collagen, and matrix metalloproteinase 13 in the anterior AF. CONCLUSION: Surgical resection of posterior elements of mouse lumbar spine resulted in reproducible IDD. Because the present procedure does not employ direct injury to intervertebral disc and the radiological and histological findings are compatible with those in human IDD, it may contribute to further understanding of the native pathophysiology of IDD in future. LEVEL OF EVIDENCE: N/A.
Assuntos
Modelos Animais de Doenças , Degeneração do Disco Intervertebral/metabolismo , Instabilidade Articular/metabolismo , Vértebras Lombares/metabolismo , Vértebras Lombares/cirurgia , Animais , Degeneração do Disco Intervertebral/diagnóstico por imagem , Instabilidade Articular/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
STUDY DESIGN: A retrospective cross-sectional study. OBJECTIVE: The aim of this study was to assess the prevalence and natural course of calcification of the transverse ligament of the atlas (TLA) in healthy subjects and to investigate the relationship between the calcified lesion and clinical factors. SUMMARY OF BACKGROUND DATA: The prevalence and etiology of TLA calcification in healthy individuals remain uncertain. METHODS: We enrolled 1136 participants undergoing computed tomography (CT) scans in their routine medical checkups. The calcified lesion of the TLA was classified into two types: type 1, thin calcifications (<2âmm) and type 2, curvilinear lesions (>2âmm). We evaluated the natural course of the lesion and compared each clinical variable among subjects with and without TLA calcifications after adjusting for age and sex using propensity score matching techniques. RESULTS: TLA calcification was present in 40 participants (3.5%; 31 males and 9 females; mean age, 65.3 years), and the frequency increased with age (Pâ=â0.001). Both types 1 and 2 calcifications were observed in 26 (65%) and 14 cases (35%), with mean ages of 63.0 and 69.4 years (Pâ=â0.033), respectively. Of these, 37 (93%) underwent another medical checkup afterward, and the morphological changes were further assessed. Five cases (14%) showed enlargement [one case (4%) in type 1 vs. four cases (33%) in type 2], whereas six cases (16%) had disappearance or decrease [six cases (24%) in type 1 vs. 0 cases in type 2, which was statistically significant (Pâ=â0.019)]. A one-to-one propensity score matching analysis revealed no significant differences in clinical variables among subjects with and without TLA calcifications. CONCLUSION: The prevalence of the TLA calcification was not rare in normal subjects. Our results suggest that the calcified lesion could be morphologically changed on a yearly basis and may be associated with the normal aging process. LEVEL OF EVIDENCE: 3.
Assuntos
Calcinose/epidemiologia , Doenças do Tecido Conjuntivo/epidemiologia , Ligamentos Articulares , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas/epidemiologia , Articulação Atlantoccipital , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Doenças do Tecido Conjuntivo/diagnóstico por imagem , Doenças do Tecido Conjuntivo/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE Interbody fusion cages are widely used to achieve initial fixation and secure spinal fusion; however, there are certain technique-related complications. Although anterior cage dislodgement can cause major vascular injury, the incidence is extremely rare. Here, the authors performed a review of anterior cage dislodgement following posterior lumbar interbody fusion (PLIF) surgery. METHODS The authors retrospectively reviewed the cases of 4625 patients who had undergone PLIF at 6 institutions between December 2007 and March 2015. They investigated the incidence and causes of surgery-related anterior cage dislodgement, salvage mechanisms, and postoperative courses. RESULTS Anterior cage dislodgement occurred in 12 cases (0.26%), all of which were caused by technical errors. In 9 cases, excessive cage impaction resulted in dislodgement. In 2 cases, when the cage on the ipsilateral side was inserted, it interacted and pushed out the other cage on the opposite side. In 1 case, the cage was positioned in an extreme lateral and anterior part of the intervertebral disc space, and it postoperatively dislodged. In 3 cases, the cage was removed in the same operative field. In the remaining 9 cases, CT angiography was performed postoperatively to assess the relationship between the dislodged cage and large vessels. Dislodged cages were conservatively observed in 2 cases. In 7 cases, the cage was removed because it was touching or compressing large vessels, and an additional anterior approach was selected. In 2 patients, there was significant bleeding from an injured inferior vena cava. There were no further complications or sequelae associated with the dislodged cages during the follow-up period. CONCLUSIONS Although rare, iatrogenic anterior cage dislodgement following a PLIF can occur. The authors found that technical errors made by experienced spine surgeons were the main causes of this complication. To prevent dislodgement, the surgeon should be cautious when inserting the cage, avoiding excessive cage impaction and ensuring cage control. Once dislodgement occurs, the surgeons must immediately address this difficult complication. First, the possibility of a large vessel injury should be considered. If the patient's vital signs are stable, the surgeon should continue with the surgery without cage removal and perform CT angiography postoperatively to assess the cage location. Blind maneuvers should be avoided when the surgical site cannot be clearly viewed. When the cage compresses or touches the aortic artery or vena cava, it is better to remove the cage to avoid late-onset injury to major vessels. When the cage does not compress or touch vessels, its removal is controversial. The risk factors associated with performing another surgery should be evaluated on a case-by-case basis.
Assuntos
Fixadores Internos , Vértebras Lombares/cirurgia , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral/instrumentação , Idoso , Idoso de 80 Anos ou mais , Angiografia por Tomografia Computadorizada , Feminino , Seguimentos , Humanos , Incidência , Vértebras Lombares/irrigação sanguínea , Vértebras Lombares/diagnóstico por imagem , Masculino , Erros Médicos , Pessoa de Meia-Idade , Falha de Prótese/etiologia , Estudos Retrospectivos , Terapia de Salvação , Doenças da Coluna Vertebral/diagnóstico por imagem , Doenças da Coluna Vertebral/epidemiologia , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologiaRESUMO
To overcome serious clinical problems caused by large bone defects, various approaches to bone regeneration have been researched, including tissue engineering, biomaterials, stem cells and drug screening. Previously, we developed a free-standing biodegradable polymer nanosheet composed of poly(L-lactic acid) (PLLA) using a simple fabrication process consisting of spin-coating and peeling techniques. Here, we loaded recombinant human bone morphogenetic protein-2 (rhBMP-2) between two 60-nm-thick PLLA nanosheets, and investigated these sandwich-type nanosheets in bone regeneration applications. The PLLA nanosheets displayed constant and sustained release of the loaded rhBMP-2 for over 2months in vitro. Moreover, we implanted the sandwich-type nanosheets with or without rhBMP-2 into critical-sized defects in mouse calvariae. Bone regeneration was evident 4weeks after implantation, and the size and robustness of the regenerated bone had increased by 8weeks after implantation in mice implanted with the rhBMP-2-loaded nanosheets, whereas no significant bone formation occurred over a period of 20weeks in mice implanted with blank nanosheets. The PLLA nanosheets loaded with rhBMP-2 may be useful in bone regenerative medicine; furthermore, the sandwich-type PLLA nanosheet structure may potentially be applied as a potent prolonged sustained-release carrier of other molecules or drugs. STATEMENTS OF SIGNIFICANCE: Here we describe sandwich-type poly(L-lactic acid) (PLLA) nanosheets loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a novel method for bone regeneration. Biodegradable 60-nm-thick PLLA nanosheets display strong adhesion without any adhesive agent. The sandwich-type PLLA nanosheets displayed constant and sustained release of the loaded rhBMP-2 for over 2months in vitro. The nanosheets with rhBMP-2 markedly enhanced bone regeneration when they were implanted into critical-sized defects in mouse calvariae. In addition to their application for bone regeneration, PLLA nanosheets may be useful for various purposes in combination with various drugs or molecules, because they displays excellent capacity as a sustained-release carrier.
Assuntos
Proteína Morfogenética Óssea 2 , Regeneração Óssea/efeitos dos fármacos , Membranas Artificiais , Nanoestruturas , Poliésteres , Crânio , Animais , Proteína Morfogenética Óssea 2/química , Proteína Morfogenética Óssea 2/farmacologia , Masculino , Camundongos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Osteogênese/efeitos dos fármacos , Poliésteres/química , Poliésteres/farmacologia , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , Crânio/lesões , Crânio/metabolismo , Crânio/patologiaRESUMO
STUDY DESIGN: Retrospective case series. OBJECTIVE: To clarify how preoperative global sagittal imbalance influences outcomes in patients with cervical compression myelopathy undergoing cervical laminoplasty. SUMMARY OF BACKGROUND DATA: The influence of sagittal balance on outcomes of cervical laminoplasty remains uncertain. METHODS: The authors retrospectively reviewed data of 106 patients who underwent double-door cervical laminoplasty between 2004 and 2011 and investigated the influence of the C7 sagittal vertical axis (SVA) on outcome scores. Primary outcomes used were Japanese Orthopedic Association (JOA) scores, Numerical Rating Scale for neck or arm pain, the Short Form 36 Health Survey (physical and mental component summary scores ), and the Neck Disability Index (NDI). RESULTS: Ninety-two patients with complete data were eligible for inclusion. The preoperative C7 SVA was ≤5âcm in 64 patients (69.6%) andâ>â5âcm in 28 (30.4%). We compared each parameter by the magnitude of spinal sagittal balance (preoperative C7 SVAâ>â5âcm vs. C7 SVA ≤ 5âcm) after adjusting for age via the least square mean analysis because the average age was significantly higher in patients with C7 SVAâ>â5âcm. As for the radiographic parameters, both C2-7 SVA and C7 SVA were larger in patients when the C7 SVA wasâ>â5âcm. Numerical Rating Scale for postoperative arm pain, postoperative JOA scores, and both pre- and postoperative physical component summary and NDI were worse in patients with C7 SVAâ>â5âcm; however, the JOA score recovery rate and changes in physical component summary and NDI were not significantly different. CONCLUSION: Postoperative functional outcome scores were significantly lower in patients with C7 SVAâ>â5âcm, although the improvement after cervical laminoplasty was not greatly affected. The involvement of global sagittal balance and cervical regional alignment should be considered in evaluating surgical outcomes for patients undergoing cervical laminoplasty. LEVEL OF EVIDENCE: 4.