RESUMO
PURPOSE: The purpose of this study was to evaluate the benefits of collaborative management between orthopedic surgery and WOC nurses in patients undergoing resection of subcutaneous sarcomas. DESIGN: Retrospective case-control study. SUBJECTS AND SETTING: The sample comprised 25 patients who underwent wide resection for soft tissue sarcoma, followed by 2-stage split-thickness skin grafting. Data collection occurred between January 2015 and April 2021 in a university hospital based in Kagoshima, Japan. For comparison, we categorized these patients into 2 groups: intervention group participants were managed by an orthopedic surgeon and a WOC nurse; nonintervention group members were managed without WOC nurse participation. METHODS: Patient background and treatment-related information was retrospectively collected from medical records and compared between the WOC nurse intervention group and the nonintervention group, including maximum tumor diameter, surgical time, maximum skin defect diameter, length of hospital stay, and time from surgery to complete wound healing. RESULTS: The average length of hospital stay was significantly shorter in the WOC nurse intervention group compared with the nonintervention group (38.3 days, SD = 8.0 vs 47.1 days, SD = 10.2; P = .023). CONCLUSION: Collaborative wound management with a WOC nurse resulted in a shorter hospital length of stay when compared to traditional management with WOC nurse involvement. Based on these findings, we assert that WOC nurses provide an important bridge between postoperative wound management in patients undergoing resection of subcutaneous sarcomas.
Assuntos
Cirurgiões Ortopédicos , Estomia , Sarcoma , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Sarcoma/cirurgiaRESUMO
Hypothalamic aging is considered to be critical for systemic aging, and the accumulation of "exhausted glial cells" in the hypothalamus may contribute to brain dysfunction. In this study, we used normal aging mice and investigated aging-specific transcriptional identities of microglia and astrocytes in the hypothalamus. We confirmed that normal aging promoted anxiety, induced impairment of motor coordination and reduced physical strength of muscle in mice. To investigate the senescence of hypothalamic glial cells, we isolated CD11b-positive microglia and ACSA-2-positive astrocytes from the hypothalamus of aged mice using magnetic-activated cell sorting (MACS). The mRNA level of p16INK4A was dramatically increased in the hypothalamic microglia of aged mice compared to young mice. Furthermore, the expression of programmed cell death 1 (PD-1) as well as A1-like astrocyte mediators in the hypothalamic microglia was dramatically induced by aging, indicating that normal aging may produce PD-1-enriched "exhausted microglia" in the hypothalamus. Furthermore, neuroinflammatory A1-like reactive astrocytes with a p16INK4A-positive senescent state were predominantly detected in the hypothalamus of aged mice. Exhausted microglia were also detected in the prefrontal cortex of aged mice, whereas astrocytic neuroinflammation was milder than that observed in the hypothalamus, even with p16INK4A-positive senescence. These results suggest that the production of PD-1-enriched exhausted and senescent microglia and neuroinflammatory A1-like reactive astrocytes in the hypothalamus may partly contribute to aging-related emotional and physical dyscoordination.
Assuntos
Envelhecimento/metabolismo , Astrócitos/metabolismo , Senescência Celular , Hipotálamo/metabolismo , Microglia/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Envelhecimento/patologia , Animais , Astrócitos/patologia , Antígeno CD11b/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Emoções , Hipotálamo/patologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Microglia/patologia , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Desempenho Psicomotor , Teste de Desempenho do Rota-RodRESUMO
Undifferentiated pleomorphic sarcoma (UPS) is the second most frequent soft tissue sarcoma. Because of its resistance to chemotherapy, UPS patients are treated with surgical resection and complementary radiotherapy. However, since standard chemotherapy has not been established, unresectable or metastatic cases result in a poor prognosis. Therefore, the identification of a more effective therapy for UPS patients is needed. The development and progression of malignant tumors involve epigenetic alterations, and histone deacetylases (HDAC) have become a promising chemotherapeutic target. In this study, we investigated the potential effects and mechanisms of an HDAC inhibitor, LBH589, in UPS cells. We confirmed that LBH589 exhibits potent antitumor activities in four human UPS cell lines (GBS-1, TNMY-1, Nara-F, and Nara-H) and IC50 values ranged from 7 to 13 nM. A mouse xenograft model showed that LBH589 treatment effectively suppressed tumor growth. FACS analysis showed that LBH589 induced apoptosis and G2/M cell cycle arrest. Among apoptosis-related proteins, the expressions of Bcl-2 and Bcl-xL were decreased and the expression of Bak and Bim increased. Among cell cycle-related proteins, reductions of CDK1, p-CDK1, cyclin B1, Aurora A, and Aurora B were observed after LBH589 treatment. RNA microarray identified the FOS-like antigen 1 (FOSL1) gene as a downregulated gene in response to LBH589 in UPS cells. While knockdown of FOSL1 decreased UPS cell proliferation, overexpression induced cell proliferation. Our results show that LBH589 could be a promising chemotherapeutic agent in the treatment of UPS and downregulation of the FOSL1 gene could be the new molecular target of UPS treatment.
Assuntos
Regulação para Baixo , Inibidores de Histona Desacetilases/administração & dosagem , Panobinostat/administração & dosagem , Proteínas Proto-Oncogênicas c-fos/genética , Sarcoma/tratamento farmacológico , Animais , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Inibidores de Histona Desacetilases/farmacologia , Humanos , Concentração Inibidora 50 , Camundongos , Panobinostat/farmacologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Undifferentiated pleomorphic sarcoma (UPS) is the second most common soft tissue sarcoma. For patients with unresectable or metastatic disease, chemotherapies are considered, but in many cases they are not curative. There is a need to identify specific molecular dysregulations that can be therapeutic targets. We focused on neurotensin receptor 1 (NTSR1), which belongs to the G-protein-coupled receptor. NTSR1 expression was upregulated in specimens from patients with UPS. Real-time polymerase chain reaction showed that expression of NTSR1 messenger RNA was 5- to 7-fold increased in UPS cells compared with myoblasts. Western blot showed a high expression of NTSR1 protein in UPS cell lines. Knockdown of NTSR1 prevented UPS cell proliferation and invasion. We confirmed that SR48692, an inhibitor of NTSR1, exhibited antitumor activities in UPS cells. The combination index showed that SR48692 and standard chemotherapeutic drugs prevented UPS cell proliferation synergistically. Mouse xenograft models showed that SR48692 inhibited extracellular signal-regulated kinase phosphorylation and enhanced the response to standard chemotherapeutic drugs. Inhibition of NTSR1 improved the effect of standard chemotherapeutic drugs for UPS. SR48692 may be a new drug for targeted UPS therapy.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Receptores de Neurotensina/genética , Sarcoma/genética , Regulação para Cima/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Panobinostat/farmacologia , Pirazóis/farmacologia , Quinolinas/farmacologia , Receptores de Neurotensina/antagonistas & inibidores , Receptores de Neurotensina/metabolismo , Sarcoma/tratamento farmacológico , Sarcoma/metabolismo , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Recently, we reported highly active transforming growth factor (TGF)-ß and bone morphogenetic protein (BMP) signaling in human chondrosarcoma samples and concurrent downregulation of paternally expressed gene 10 (PEG10). PEG10 expression was suppressed by TGF-ß signaling, and PEG10 interfered with the TGF-ß and BMP-SMAD pathways in chondrosarcoma cells. However, the roles of PEG10 in bone tumors, including chondrosarcoma, remain unknown. Here, we report that PEG10 promotes SW1353 chondrosarcoma cell growth by preventing TGF-ß1-mediated suppression. In contrast, PEG10 knockdown augments the TGF-ß1-induced motility of SW1353 cells. Individually, TGF-ß1 and PEG10 siRNA increase AKT phosphorylation, whereas an AKT inhibitor, MK2206, mitigates the effect of PEG10 silencing on cell migration. SW1353 cell invasion was enhanced by BMP-6, which was further increased by PEG10 silencing. The effect of siPEG10 was suppressed by inhibitors of matrix metalloproteinase (MMP). BMP-6 induced expression of MMP-1, -3, and -13, and PEG10 lentivirus or PEG10 siRNA downregulated or further upregulated these MMPs, respectively. PEG10 siRNA increased BMP-6-induced phosphorylation of p38 MAPK and AKT, whereas the p38 inhibitor SB203580 and MK2206 diminished SW1353 cell invasion by PEG10 siRNA. SB203580 and MK2206 impeded the enhancing effect of PEG10 siRNA on the BMP-6-induced expression of MMP-1, -3, and -13. Our findings suggest dual functions for PEG10: accelerating cell growth by suppressing TGF-ß signaling and inhibiting cell motility and invasion by interfering with TGF-ß and BMP signaling via the AKT and p38 pathways, respectively. Thus, PEG10 might be a molecular target for suppressing the aggressive phenotypes of chondrosarcoma cells.
Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Neoplasias Ósseas/patologia , Movimento Celular , Condrossarcoma/metabolismo , Condrossarcoma/patologia , Proteínas/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Proteínas Reguladoras de Apoptose , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA , Inativação Gênica , Humanos , Metaloproteinase 1 da Matriz/metabolismo , Invasividade Neoplásica , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Ligação a RNA , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Apparent diffusion coefficient (ADC) histogram analyses have been used to differentiate tumor grades and predict therapeutic responses in various anatomic sites with moderate success. PURPOSE: To determine the ability of diffusion-weighted imaging (DWI) with a whole-tumor ADC histogram analysis to differentiate benign peripheral neurogenic tumors (BPNTs) from soft tissue sarcomas (STSs). STUDY TYPE: Retrospective study, single institution. SUBJECTS: In all, 25 BPNTs and 31 STSs. FIELD STRENGTH/SEQUENCE: Two-b value DWI (b-values = 0, 1000s/mm2 ) was at 3.0T. ASSESSMENT: The histogram parameters of whole-tumor for ADC were calculated by two radiologists and compared between BPNTs and STSs. STATISTICAL TESTS: Nonparametric tests were performed for comparisons between BPNTs and STSs. P < 0.05 was considered statistically significant. The ability of each parameter to differentiate STSs from BPNTs was evaluated using area under the curve (AUC) values derived from a receiver operating characteristic curve analysis. RESULTS: The mean ADC and all percentile parameters were significantly lower in STSs than in BPNTs (P < 0.001-0.009), with AUCs of 0.703-0.773. However, the coefficient of variation (P = 0.020 and AUC = 0.682) and skewness (P = 0.012 and AUC = 0.697) were significantly higher in STSs than in BPNTs. Kurtosis (P = 0.295) and entropy (P = 0.604) did not differ significantly between BPNTs and STSs. DATA CONCLUSION: Whole-tumor ADC histogram parameters except kurtosis and entropy differed significantly between BPNTs and STSs. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
RESUMO
BACKGROUND: The suture-bridge (SB) method has recently become the mainstream means of repairing full-thickness rotator cuff tears. However, in some patients the deep and superficial layers have moved in different directions because of delamination of their rotator cuffs. In such cases, a simple suture (double-layer, double-row [DD] method) is used to repair the superficial and deep layers separately. The purpose of this study was to analyze the clinical outcomes and re-tear rates of the DD and SB methods, with patients selected according to the condition of their torn cuffs. METHODS: We retrospectively registered 74 patients with full-thickness rotator cuff tears that had been repaired arthroscopically, 35 shoulders by the DD and 39 by the SB method. Mean ages were 66.1 years in the DD and 62.9 years in the SB group. We evaluated clinical status before and after surgery (Japanese Orthopedic Association [JOA] scores) and re-tear rate. The Wilcoxon signed-ranks test was used to compare JOA scores and active ROM between before and after surgery in each group. Mann-Whitney's U test was used for comparing JOA scores, active ROM, re-tear rates, size of tear, duration of follow-up, sex, and presence of subscapular muscle repair between the DD and SB groups. A hazard ratio of less than 5% was considered to denote significance. RESULTS: JOA scores improved significantly in the DD and SB groups from preoperative means of 63.4 and 63.3 points, respectively, to postoperative means of 91.8 and 92.1 points, respectively. The active flexural ROM improved significantly from means of 110.1° and 100.0°, respectively, to postoperative means of 142.3° and 142.7°, respectively; the differences between groups were not significant. Re-tear occurred in 5.9% of the DD (two of 34 shoulders) and 7.9% of the SB group (three of 38 shoulders); its incidence did not differ significantly between the two groups. CONCLUSIONS: Both the DD and SB methods achieve satisfactory clinical outcomes that do not differ significantly. Our results suggest that careful selection of operative method on the basis of the delamination pattern in patients undergoing RCT may reduce the re-tear rate after utilizing the SB method.
Assuntos
Artroscopia , Lesões do Manguito Rotador/cirurgia , Manguito Rotador/cirurgia , Técnicas de Sutura , Adulto , Idoso , Artroscopia/efeitos adversos , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/fisiopatologia , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/fisiopatologia , Técnicas de Sutura/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Here we report a rare case of lumbar spine epidural abscess and facet joint septic arthritis caused by Streptococcus agalactiae, which had spread to the iliopsoas muscles, leading to urine retention. CASE PRESENTATION: A 68-year-old woman with low back pain experienced a sudden onset of bilateral lower limb weakness, it was followed 14 days later by urine retention. At consultation, magnetic resonance imaging and identification of serum ß-hemolytic streptococci provided a diagnosis of Streptococcus agalactiae infection. She was started on antibiotics. Despite diminishing signs of inflammation, preoperative MRI showed an epidural mass at T12-L4 compressing the cord and involving the paravertebral muscles as well. Group B beta-hemolytic streptococci were detected in both urine and blood. Because of bilateral lower limb weakness and urine retention, T12-L4 hemilaminectomy was performed. The L3/L4 intertransverse ligament resected and abscess drained. Histopathology revealed that inflammatory cells had invaded the facet joint. Group B beta-hemolytic streptococci were identified, confirming the diagnosis. The patient continued with the antibiotics postoperatively, and her health rapidly improved. CONCLUSION: Lumbar spine epidural abscess and facet joint septic arthritis caused by Streptococcus agalactiae is a clinical emergency, with significant morbidity and mortality especially with delayed diagnosis. A delay in both diagnosis and aggressive treatment can lead to not only severe neurological deficit but also to septicaemia, multiorgan failure, and even death.
Assuntos
Artrite Infecciosa/microbiologia , Abscesso Epidural/microbiologia , Vértebras Lombares/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/isolamento & purificação , Articulação Zigapofisária/microbiologia , Idoso , Antibacterianos/uso terapêutico , Artrite Infecciosa/diagnóstico por imagem , Artrite Infecciosa/terapia , Abscesso Epidural/diagnóstico por imagem , Abscesso Epidural/terapia , Feminino , Humanos , Dor Lombar/etiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Imageamento por Ressonância Magnética , Abscesso do Psoas/diagnóstico por imagem , Abscesso do Psoas/microbiologia , Abscesso do Psoas/terapia , Doenças da Coluna Vertebral/diagnóstico por imagem , Doenças da Coluna Vertebral/microbiologia , Doenças da Coluna Vertebral/terapia , Infecções Estreptocócicas/terapia , Retenção Urinária/etiologia , Articulação Zigapofisária/diagnóstico por imagem , Articulação Zigapofisária/cirurgiaRESUMO
BACKGROUND: Langerhans cell histiocytosis (LCH) is categorized into three types, which include single-system single-site (SS-s), single-system multiple-site (SS-m) and multisystem (MS). The most commonly affected site in LCH is bone, and the bony lesion of SS-s LCH has a good prognosis. The bony lesion of SS-s LCH has been thought to regress spontaneously. Although treatments such as curettage, direct injection of corticosteroids, and chemotherapy have been performed, regular follow-up is the first line of treatment for the bony lesion of SS-s LCH. For preventing orthopedic sequelae, strict and appropriate follow-up should be performed, but the appropriate period and method of follow-up has not yet been established. METHODS: In the present study, we retrospectively analyzed a series of 7 cases of patients with SS-s LCH with a bony lesion treated in the Department of Orthopedic Surgery at Kagoshima University Hospital (Kagoshima, Japan) from 2006 to 2015. RESULTS: The bony lesion regressed spontaneously in all patients. Factors such as location, size, preoperative C-reactive protein (CRP) value, standardized uptake (SUV) value of positron emission tomography (PET), age, sex and direct steroid injection were not related to the clinical course. Temporary expansion of the lesion occurred in 3 patients and a temporary worsening of pain occurred in 1 patient during the follow-up period. These events occurred within 6 weeks after biopsy. CONCLUSION: Careful follow-up and the use of an appropriate orthosis can lead to a good clinical course for the bony lesion of SS-s LCH. Future research should seek to determine the appropriate follow-up period.
Assuntos
Doenças Ósseas/etiologia , Doenças Ósseas/terapia , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/diagnóstico por imagem , Imagem Multimodal/métodos , Adolescente , Biópsia por Agulha , Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/fisiopatologia , Criança , Pré-Escolar , Tomada de Decisão Clínica , Terapia Combinada , Feminino , Seguimentos , Histiocitose de Células de Langerhans/patologia , Humanos , Imuno-Histoquímica , Japão , Imageamento por Ressonância Magnética/métodos , Masculino , Metilprednisolona/administração & dosagem , Aparelhos Ortopédicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Medição de Risco , Estudos de Amostragem , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: This study aimed to identify and compare risk factors for surgical site infection (SSI) and non-surgical site infections (non-SSIs), particularly urinary tract infection (UTI), after spine surgery. METHODS: We retrospectively reviewed 825 patients (median age 59.0 years (range 33-70 years); 442 males) who underwent spine surgery at Kagoshima University Hospital from January 2009 to December 2014. Patient parameters were compared using the Mann-Whitney U and Fisher's exact tests. Risk factors associated with SSI and UTI were analyzed via the multiple logistic regression analysis. P < 0.05 was considered statistically significant. RESULTS: SSI occurred in 14 of 825 cases (1.7 %), and non-SSI occurred in 23 of 825 cases (2.8 %). Most non-SSIs were UTIs (20 of 23 cases, 87.0 %). In the 14 patients with SSI, UTI occurred before SSI onset in one patient, and after SSI onset in two patients. UTI onset before SSI was not a risk factor for SSI. Multiple logistic regression analysis indicated that common risk factors for SSI and UTI were operation time (P = 0.0019 and 0.0162, respectively) and ASA classification 3 (P = 0.0132 and 0.0356, respectively). The 1 week post-operative C-reactive protein (CRP) level was a risk factor for UTI (P = 0.0299), but not for SSI (P = 0.4996). CONCLUSIONS: There was no relationship between SSI and symptomatic UTI after spine surgery. Risk factors for post-operative SSI and UTI were operative time and ASA classification 3; 1 week post-operative CRP was a risk factor for UTI only.
Assuntos
Procedimentos Ortopédicos , Coluna Vertebral/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Infecções Urinárias/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Although most patients achieve favorable results following bipolar hip hemiarthroplasty (BHA), some experience rapid migration of the prosthesis. We retrospectively reviewed 18 patients with BHA that necessitated revision. METHODS: We examined soft tissues obtained from periprosthetic lesions. In total, 18 patients with pain and acetabular migration of the BHA prosthesis were included. The patients were divided into a polymorphonuclear leukocyte (PMN)-positive (≥5 PMNs per high-power field [HPF]) and PMN-negative (<5 PMNs/HPF) group. RESULTS: Pathological findings showed that 11 patients were PMN-positive, which was indicative of infection. All patients in the PMN-positive group showed no polyethylene particles or foreign body giant cells, while all patients in the PMN-negative group showed polyethylene debris or foreign body giant cells (p < 0.001). BHA survival, C-reactive protein (CRP) levels, and the Japanese Orthopaedic Association (JOA) hip score were significantly different between the PMN-positive and PMN-negative group (p < 0.01). A BHA survival cut-off value of 3270 days was diagnostic for PMN positivity (sensitivity: 100%; specificity: 100%). The cut-off values for CRP and the JOA hip score were 0.43 mg/dl and 56 points, respectively. Four of 11 PMN-positive patients showed no clinical symptoms of infection (asymptomatic PMN-positive group). BHA survival, CRP levels, and JOA hip scores were significantly different between the asymptomatic PMN-positive and PMN-negative group (p < 0.05). A BHA survival cut-off of 3270 days was diagnostic for asymptomatic PMN positivity (sensitivity: 100%; specificity: 100%). The cut-off values for CRP and the JOA hip score were 0.43 mg/dl and 57 points, respectively. CONCLUSION: Our findings suggest that some portion of rapid BHA prosthesis migration is caused by mild infection. Careful pathological examination should be performed to identify infection before removal of the BHA prosthesis in patients who develop migration within 9 years.
Assuntos
Artroplastia de Quadril/efeitos adversos , Hemiartroplastia/efeitos adversos , Falha de Prótese/efeitos adversos , Falha de Prótese/etiologia , Infecções Relacionadas à Prótese/complicações , Infecções Relacionadas à Prótese/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Prótese de Quadril/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Femoral bone remodeling in response to stress shielding induces periprosthetic bone loss. Computerized finite element analysis (FEA) is employed to demonstrate differences in initial stress distribution. However, FEA is often performed without considering the precise sites at which the stem was fixed. We determined whether FEA reflects mid-term radiological examination exactly as predicted following long-term stress shielding. METHODS: Femur-stem fixation sites were evaluated radiologically according to the location of spot welds in two anatomical cementless stem designs. Based on mid-term radiological results, four femur-stem bonding site conditions were defined as: (Condition A) no bonding; (Condition B) bonding within the 10 mm area proximal to the distal border of the porous area; (Condition C) bonding of the entire porous area; and (Condition D) bonding of the entire femoral stem, prior to conducting FEA analysis. Furthermore, we radiographically evaluated mid- and long-term stress shielding, and measured bone mineral density of the femur 10 years after total hip arthroplasty. RESULTS: Spot welds appeared frequently around the border between the porous and smooth areas. FEA showed that, based on mid-term radiological evaluation, von Mises stress was reduced in condition B in the area proximal to the femur-stem bonding sites for both stem designs compared with condition A (no bonding). Conversely, von Mises stress at all areas of the femur-stem bonding sites in conditions C and D was higher than that in condition A. With respect to stress shielding progression, there was no significant difference between the two types of stem designs. However, stress shielding progressed and was significantly higher in the presence of spot welds (p = 0.001). In both stem designs, bone mineral density in zone VII was significantly lower than that in the contralateral hips. CONCLUSIONS: These results indicate that FEA based on mid-term radiological evaluation may be helpful to predict the influence of long-term stress shielding more precisely.
Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/instrumentação , Remodelação Óssea , Reabsorção Óssea/diagnóstico por imagem , Prótese de Quadril/efeitos adversos , Absorciometria de Fóton , Adulto , Idoso , Densidade Óssea , Reabsorção Óssea/etiologia , Feminino , Fêmur , Análise de Elementos Finitos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Estresse MecânicoRESUMO
Allograft bone is a widely used as a convenient tool for reconstructing massive bone defects in orthopedic surgery. However, allografts are associated with the risk of viral disease transmission. One of the viruses transmitted in this manner is human T-lymphotropic virus type 1 (HTLV-1), which is found worldwide but is unevenly distributed. The southwestern parts of Japan are a highly endemic for HTLV-1. We investigated the HTLV-1 seroprevalence in candidate allograft donors at the regional bone bank in Kagoshima, Japan during its first 5 years of service. Between 2008 and 2012, we collected 282 femoral heads at the Kagoshima regional bone bank from living donors with osteoarthritis of the hip joint. Among the 282 candidate donors, 32 donors (11.3 %) were seropositive for anti-HTLV-1 antibody; notably, this prevalence is higher than that reported for blood donors in this area. Additionally, to determine if HTLV-1 genes are detectable after processing, we examined the bone marrow of the femoral heads from seropositive donors by conducting PCR assays. Our results confirm the existence of viral genes following the heat treatment processing of the femoral heads. Therefore, it is important to inactivate a virus completely by heat-treatment. Together, our findings highlight the importance of HTLV-1 screening at bone banks, particularly in HTLV-1-endemic areas such as southwest Japan.
Assuntos
Transplante Ósseo , Infecções por HTLV-I/diagnóstico , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos/virologia , Doadores de Sangue , Transplante Ósseo/efeitos adversos , Feminino , Cabeça do Fêmur/virologia , Infecções por HTLV-I/sangue , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/transmissão , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Doadores de TecidosRESUMO
Giant cell tumor of the bone is a benign, but locally aggressive, primary bone tumor of unknown origin. It most commonly occurs in the long bones and is only rarely found in the phalangeal bones, such as the distal phalanx of the foot. In our review of English-language published studies, only 4 other cases of giant cell tumor involving the distal phalangeal bone of the foot had been reported to date. We report a case of giant cell tumor arising in the distal phalanx of the fourth toe in a 28-year-old female. Although bisphosphonate therapy was administered, the tumor showed highly aggressive behavior with ulceration of the overlying skin, and the patient underwent phalangeal amputation 1.5 months after diagnosis.
Assuntos
Neoplasias Ósseas/diagnóstico , Tumor de Células Gigantes do Osso/diagnóstico , Falanges dos Dedos do Pé/diagnóstico por imagem , Adulto , Neoplasias Ósseas/cirurgia , Feminino , Tumor de Células Gigantes do Osso/cirurgia , Humanos , Falanges dos Dedos do Pé/cirurgiaRESUMO
Although bone morphogenic protein (BMP) signaling promotes chondrogenesis, it is not clear whether BMP-induced chondrocyte maturation is cell-autonomously terminated. Loss of function of Smpd3 in mice results in an increase in mature hypertrophic chondrocytes. Here, we report that in chondrocytes the Runx2-dependent expression of Smpd3 was increased by BMP-2 stimulation. Neutral sphingomyelinase 2 (nSMase2), encoded by the Smpd3 gene, was detected both in prehypertrophic and hypertrophic chondrocytes of mouse embryo bone cartilage. An siRNA for Smpd3, as well as the nSMase inhibitor GW4869, significantly enhanced BMP-2-induced differentiation and maturation of chondrocytes. Conversely, overexpression of Smpd3 or C2-ceramide, which mimics the function of nSMase2, inhibited chondrogenesis. Upon induction of Smpd3 siRNA or GW4869, phosphorylation of both Akt and S6 proteins was increased. The accelerated chondrogenesis induced by Smpd3 silencing was negated by application of the Akt inhibitor MK2206 or the mammalian target of rapamycin inhibitor rapamycin. Importantly, in mouse bone culture, GW4869 treatment significantly promoted BMP-2-induced hypertrophic maturation and calcification of chondrocytes, which subsequently was eliminated by C2-ceramide. Smpd3 knockdown decreased the apoptosis of terminally matured ATDC5 chondrocytes, probably as a result of decreased ceramide production. In addition, we found that expression of hyaluronan synthase 2 (Has2) was elevated by a loss of Smpd3, which was restored by MK2206. Indeed, expression of Has2 protein decreased in nSMase2-positive hypertrophic chondrocytes in the bones of mouse embryos. Our data suggest that the Smpd3/nSMase2-ceramide-Akt signaling axis negatively regulates BMP-induced chondrocyte maturation and Has2 expression to control the rate of endochondral ossification as a negative feedback mechanism.
Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Condrócitos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Proto-Oncogênicas c-akt/metabolismo , Esfingomielina Fosfodiesterase/genética , Animais , Células Cultivadas , Condrócitos/citologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Interferência de RNA , Transdução de Sinais , Esfingomielina Fosfodiesterase/metabolismoRESUMO
Human immunodeficiency virus type 1 enhancer-binding protein 3 (Hivep3) suppresses osteoblast differentiation by inducing proteasomal degradation of the osteogenesis master regulator Runx2. In this study, we tested the possibility of cooperation of Hivep1, Hivep2, and Hivep3 in osteoblast and/or chondrocyte differentiation. Microarray analyses with ST-2 bone stroma cells demonstrated that expression of any known osteochondrogenesis-related genes was not commonly affected by the three Hivep siRNAs. Only Hivep3 siRNA promoted osteoblast differentiation in ST-2 cells, whereas all three siRNAs cooperatively suppressed differentiation in ATDC5 chondrocytes. We further used microarray analysis to identify genes commonly down-regulated in both MC3T3-E1 osteoblasts and ST-2 cells upon knockdown of Hivep3 and identified asparagine-linked glycosylation 2 (Alg2), which encodes a mannosyltransferase residing on the endoplasmic reticulum. The Hivep3 siRNA-mediated promotion of osteoblast differentiation was negated by forced Alg2 expression. Alg2 suppressed osteoblast differentiation and bone formation in cultured calvarial bone. Alg2 was immunoprecipitated with Runx2, whereas the combined transfection of Runx2 and Alg2 interfered with Runx2 nuclear localization, which resulted in suppression of Runx2 activity. Chondrocyte differentiation was promoted by Hivep3 overexpression, in concert with increased expression of Creb3l2, whose gene product is the endoplasmic reticulum stress transducer crucial for chondrogenesis. Alg2 silencing suppressed Creb3l2 expression and chondrogenesis of ATDC5 cells, whereas infection of Alg2-expressing virus promoted chondrocyte maturation in cultured cartilage rudiments. Thus, Alg2, as a downstream mediator of Hivep3, suppresses osteogenesis, whereas it promotes chondrogenesis. To our knowledge, this study is the first to link a mannosyltransferase gene to osteochondrogenesis.
Assuntos
Diferenciação Celular/fisiologia , Condrócitos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Manosiltransferases/biossíntese , Osteoblastos/metabolismo , Osteogênese/fisiologia , Transporte Ativo do Núcleo Celular/fisiologia , Animais , Linhagem Celular , Núcleo Celular/genética , Núcleo Celular/metabolismo , Condrócitos/citologia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Proteínas de Ligação a DNA/genética , Estresse do Retículo Endoplasmático/fisiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Manosiltransferases/genética , Camundongos , Osteoblastos/citologiaRESUMO
Aberrant activation of the Hedgehog (Hh) pathway has been reported in several malignancies. We previously demonstrated that knockdown of GLI2 inhibited proliferation of osteosarcoma cells through regulation of the cell cycle. In this study, we analyzed the function of GLI2 in the pathogenesis of osteosarcoma metastasis. Immunohistochemical studies showed that GLI2 was overexpressed in patient osteosarcoma specimens. Knockdown of GLI2 inhibited migration and invasion of osteosarcoma cells. In contrast, the forced expression of constitutively active GLI2 in mesenchymal stem cells promoted invasion. In addition, xenograft models showed that knockdown of GLI2 decreased lung metastasis of osteosarcomas. To examine clinical applications, we evaluated the efficacy of arsenic trioxide (ATO), which is a Food and Drug Administration-approved antitumor drug, on osteosarcoma cells. ATO treatment suppressed the invasiveness of osteosarcoma cells by inhibiting the transcriptional activity of GLI2. In addition, the combination of Hh inhibitors including ATO, vismodegib and GANT61 prevented migration and metastasis of osteosarcoma cells. Consequently, our findings suggested that GLI2 regulated metastasis as well as the progression of osteosarcomas. Inhibition of the GLI2 transcription may be an effective therapeutic method for preventing osteosarcoma metastasis.
Assuntos
Neoplasias Ósseas/patologia , Fatores de Transcrição Kruppel-Like/fisiologia , Proteínas Nucleares/fisiologia , Osteossarcoma/secundário , Adolescente , Adulto , Animais , Trióxido de Arsênio , Arsenicais/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Criança , Feminino , Proteínas Hedgehog/fisiologia , Humanos , Fatores de Transcrição Kruppel-Like/análise , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Invasividade Neoplásica , Proteínas Nucleares/análise , Proteínas Nucleares/antagonistas & inibidores , Óxidos/farmacologia , Proteína Gli2 com Dedos de ZincoRESUMO
BACKGROUND: Well-differentiated liposarcoma (WDL)/atypical lipomatous tumor (ALT) is considered a low-grade malignancy that rarely metastasizes but should be carefully followed because recurrence or dedifferentiation may occur. It is recognized that WDL and ALT are essentially synonymous, describing lesions that are identical both morphologically and karyotypically, and that site-specific variations in behavior relate only to surgical resectability. Preoperative differential diagnosis between lipoma and ALT has been well studied because their clinical and image characteristics are very similar. We evaluated the factors that may differentiate ALTs from lipomas, and validated a tentative scoring system for the diagnosis of the 2 tumor types. METHODS: Forty-eight lipomas and 12 ALTs were included. The mean age, location and depth of the tumor as well as the compartment were not significantly different between the 2 groups. To evaluate the vascularity of the tumors, the average number of intratumoral vessels on pathological sections was calculated and compared between cases of lipoma and ALT. RESULTS: The tumor size was significantly larger in ALT cases than in lipoma cases (P < 0.001). Magnetic resonance imaging (MRI) revealed septal structures in 91.6% of ALTs, whereas 20.8% of lipomas showed septa. Contrast enhancement in MRI was found significantly more often in ALTs (81.2%) than in lipomas (18.8%) (P < 0.001). We created a "ALT score" to discriminate between lipoma and ALT (0-6 points). ALT cases gave significantly higher point values (average 5.1 points) than lipoma cases (average 1.7 points) (P < 0.001). We found a significantly increased number of vessels in cases of ALT than in cases of lipoma (P = 0.001). CONCLUSIONS: Our ALT score may help surgeons to differentiate a suspected ALT from a lipoma and could recommend a marginal resection in cases of suspected ALT. Increased intratumoral vascularity in ALT is reflected in the MRI findings and may play a key role in the acquisition of a malignant phenotype in adipocytic tumors.
Assuntos
Lipoma/irrigação sanguínea , Imageamento por Ressonância Magnética , Neovascularização Patológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Diferenciação Celular , Diagnóstico Diferencial , Estudos de Viabilidade , Feminino , Humanos , Lipoma/classificação , Lipoma/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Carga TumoralRESUMO
BACKGROUND: Most bone tumors that occur in the clavicle are malignant. A few giant cell tumors (GCTs) of the clavicle have been reported; however, the most appropriate operative method for this tumor has never been discussed. CASE PRESENTATION: A 54-year-old man noticed enlargement of the proximal aspect of the right clavicle. A plain X-ray revealed lytic change and ballooning of the proximal end of the right clavicle. The tumor was isointense on T1-weighted magnetic resonance images and showed a mixture of low- and high-intensity areas on T2-weighted images without extension to the surrounding soft tissues. Bone scintigraphy showed strong accumulation (normal/tumor ratio, 2.31), and positron emission tomography revealed strong uptake of fluorine-18-2-fluoro-2-deoxy-d-glucose (SUVmax, 6.0) in the proximal part of the right clavicle. Because we could not completely exclude malignancy, an open biopsy was performed. Pathologically, the tumor comprised mononuclear stromal cells and multinuclear giant cells, resulting in a diagnosis of a GCT of the bone. Although curettage may be considered for such lesions (Campanacci grade II), we chose resection to minimize the chance of recurrence. The tumor was resected en-bloc with the proximal half of the clavicle. No postoperative shoulder disproportion was observed, and full range of motion of the right shoulder was maintained. The patient was satisfied with the surgical outcome (Musculoskeletal Tumor Society score of 96 %). He returned to his original job as a land and house investigator without any signs of recurrence for 1 year after surgery. CONCLUSIONS: Although GCT of the bone rarely occurs in the clavicle, the typical X-ray findings demonstrated in the present case are helpful for a correct diagnosis. Although en-bloc resection without reconstruction is appropriate for GCTs in expendable bones, there has been much discussion about shoulder function after total claviculectomy. Considering the importance of the function of the clavicle, which is to support the scapula through the acromioclavicular joint, we preserved the muscle attachments of the deltoid, trapezius, and pectoralis major. Because both the oncological and functional outcomes were satisfactory, we recommend preservation of as much of the clavicle as possible in patients with clavicular bone tumors.
Assuntos
Neoplasias Ósseas/cirurgia , Clavícula/cirurgia , Tumor de Células Gigantes do Osso/cirurgia , Osteotomia/métodos , Fenômenos Biomecânicos , Biópsia , Neoplasias Ósseas/patologia , Clavícula/patologia , Clavícula/fisiopatologia , Meios de Contraste , Fluordesoxiglucose F18 , Tumor de Células Gigantes do Osso/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Amplitude de Movimento Articular , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Osteoporosis is a complication of rheumatoid arthritis (RA). We identified risk factors for osteoporosis during treatment with biologics. METHODS: Femoral neck bone mineral density (BMD) was measured in 186 patients with biologics-treated RA. We compared the characteristics of those with BMD ≥70% of young adult mean (YAM) and those with BMD <70% of YAM, and undertook multivariable logistic regression analysis to identify risk factors for bone loss. RESULTS: Mean age and disease duration, the proportion of females, scores in the Modified Health Assessment Questionnaire and history of vertebral fracture were significantly greater in the BMD <70% of YAM group, but body mass index (BMI) was significantly lower in the BMD <70% of YAM group. There was no significant difference between the groups in terms of other biomarkers of RA activity, the proportion treated with methylprednisolone, or the duration or choice of biologics. The proportions of patients treated with anti-osteoporosis drugs and parathyroid hormone were significantly higher in the BMD <70% of YAM group. In the multivariable analysis, advanced age, female, longer disease duration, history of past thoracic or lumbar vertebral fracture, higher Steinbrocker classification and lower BMI were significant factors for BMD <70% of YAM. DISCUSSION: We identified risk factors for bone loss in patients with RA treated with biologics. Before suppression of disease activity by biologics, bone loss might already be advanced. CONCLUSIONS: We recommend that patients with RA who possess these risk factors be considered for earlier and more intense treatment to prevent bone loss, as well as addressing RA disease progression.