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PURPOSE: This study proposes a process for detecting slices with bone marrow edema (BME), a typical finding of axSpA, using MRI scans as the input. This process does not require manual input of ROIs and provides the results of the judgment of the presence or absence of BME on a slice and the location of edema as the rationale for the judgment. METHODS: First, the signal intensity of the MRI scans of the sacroiliac joint was normalized to reduce the variation in signal values between scans. Next, slices containing synovial joints were extracted using a slice selection network. Finally, the BME slice detection network determines the presence or absence of the BME in each slice and outputs the location of the BME. RESULTS: The proposed method was applied to 86 MRI scans collected from 15 hospitals in Japan. The results showed that the average absolute error of the slice selection process was 1.49 slices for the misalignment between the upper and lower slices of the synovial joint range. The accuracy, sensitivity, and specificity of the BME slice detection network were 0.905, 0.532, and 0.974, respectively. CONCLUSION: This paper proposes a process to detect the slice with BME and its location as the rationale of the judgment from an MRI scan and shows its effectiveness using 86 MRI scans. In the future, we plan to develop a process for detecting other findings such as bone erosion from MR scans, followed by the development of a diagnostic support system.
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Osteogenesis imperfecta (OI) is a heterogeneous disorder characterised by bone fragility. Herein, we report a case of OI diagnosed after subchondral insufficiency fracture (SIF) of bilateral femoral heads. A 37-year-old woman was referred to Saitama Medical University Hospital due to left hip pain without any trauma that lasted for 2 months. She was subsequently diagnosed with SIF of the left femoral head. After 3 months, she further developed SIF of the right hip without any trauma. Magnetic resonance imaging of the bilateral hips showed linear low-signal changes of the subchondral bone and bone marrow oedema of the femoral head on T2-weighted coronal and sagittal images, diagnosing of both SIFs. The bone mineral density was 0.851 g/cm2 (T-score, -1.3) at the lumbar spine, 0.578 g/cm2 (T-score, -1.9) at the right femoral neck, and 0.582 g/cm2 (T-score, -1.9) at the left femoral neck. Considering that the patient had multiple histories of fracture, blue sclera, and mild bilateral sensorineural hearing loss, she satisfied the diagnostic criteria for OI. Genetic testing revealed a mutation in COL1A1 (NM_000088.3, c.3806G>A: p. Trp1269*). After 7 months of conservative therapy, her symptoms improved. After 4 years, both hips were pain-free with no evidence of osteoarthritis progression. OI can result in insufficiency fractures due to bone fragility in adolescence and adulthood or later, and none of the cases of OI, except for the current case, were diagnosed as a result of bilateral SIF.
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Fracturas por Estrés , Osteogénesis Imperfecta , Humanos , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/diagnóstico , Femenino , Adulto , Fracturas por Estrés/diagnóstico , Fracturas por Estrés/etiología , Imagen por Resonancia Magnética , Cabeza Femoral/patología , Cabeza Femoral/lesiones , Densidad Ósea , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , MutaciónRESUMEN
Histone lysine methylation is thought to play a role in the pathogenesis of rheumatoid arthritis (RA). We previously reported aberrant expression of the gene encoding mixed-lineage leukemia 1 (MLL1), which catalyzes methylation of histone H3 lysine 4 (H3K4), in RA synovial fibroblasts (SFs). The aim of this study was to elucidate the involvement of MLL1 in the activated phenotype of RASFs. SFs were isolated from synovial tissues obtained from patients with RA or osteoarthritis (OA) during total knee joint replacement. MLL1 mRNA and protein levels were determined after stimulation with tumor necrosis factor α (TNFα). We also examined changes in trimethylation of H3K4 (H3K4me3) levels in the promoters of RA-associated genes (matrix-degrading enzymes, cytokines, and chemokines) and the mRNA levels upon small interfering RNA-mediated depletion of MLL1 in RASFs. We then determined the levels of H3K4me3 and mRNAs following treatment with the WD repeat domain 5 (WDR5)/MLL1 inhibitor MM-102. H3K4me3 levels in the gene promoters were also compared between RASFs and OASFs. After TNFα stimulation, MLL1 mRNA and protein levels were higher in RASFs than OASFs. Silencing of MLL1 significantly reduced H3K4me3 levels in the promoters of several cytokine (interleukin-6 [IL-6], IL-15) and chemokine (C-C motif chemokine ligand 2 [CCL2], CCL5, C-X-C motif chemokine ligand 9 [CXCL9], CXCL10, CXCL11, and C-X3-C motif chemokine ligand 1 [CX3CL1]) genes in RASFs. Correspondingly, the mRNA levels of these genes were significantly decreased. MM-102 significantly reduced the promoter H3K4me3 and mRNA levels of the CCL5, CXCL9, CXCL10, and CXCL11 genes in RASFs. In addition, H3K4me3 levels in the promoters of the IL-6, IL-15, CCL2, CCL5, CXCL9, CXCL10, CXCL11, and CX3CL1 genes were significantly higher in RASFs than OASFs. Our findings suggest that MLL1 regulates the expression of particular cytokines and chemokines in RASFs and is associated with the pathogenesis of RA. These results could lead to new therapies for RA.
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Artritis Reumatoide , N-Metiltransferasa de Histona-Lisina , Proteína de la Leucemia Mieloide-Linfoide , Membrana Sinovial , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Artritis Reumatoide/genética , Células Cultivadas , Quimiocinas/metabolismo , Quimiocinas/genética , Citocinas/metabolismo , Fibroblastos/metabolismo , Regulación de la Expresión Génica , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Histonas/metabolismo , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Proteína de la Leucemia Mieloide-Linfoide/genética , Osteoartritis/metabolismo , Osteoartritis/patología , Osteoartritis/genética , Regiones Promotoras Genéticas , ARN Mensajero/metabolismo , ARN Mensajero/genética , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Background: Patients with bilateral lower limb deep venous thrombosis (DVT) have a higher risk of pulmonary thromboembolism (PTE) and mortality than patients with unilateral lower limb DVT. Preoperative dilatation of the soleal vein (SV) diameter is a predictor of postoperative DVT. The purpose of this study is to investigate the cutoff value for SV diameter as a risk factor for VTE development. Materials and methods: The authors examined 274 patients with unilateral THA who met the inclusion criteria in a retrospective study. The mean age of the patients was 65.7±11.2 years, with 70 males and 204 females. Bilateral lower limb vein ultrasonography was performed preoperatively and ~1 week after THA. The frequency and localization of DVT were investigated in postoperative ultrasonography. The patients were divided into three groups: no DVT (non-DVT), unilateral lower limb DVT (Uni-DVT), and bilateral lower limb DVT (Bi-DVT). The three groups were compared in terms of preoperative venous vessel maximum diameter. Results: There were 62 patients (22.6%) who had postoperative DVT. There are no symptomatic PTE patients. DVT was found in 44 patients (16.0%) of the Uni-DVT group and 18 patients (6.6%) of the Bi-DVT group. The SV maximum diameter was 6.41±1.79 mm in the non-DVT group, 7.06±2.13 mm in the Uni-DVT group, and 8.06±2.26 mm in the Bi-DVT group, with a significant difference (P=0.001) between the non-DVT and Bi-DVT groups. In the Bi-DVT group, the cutoff value for preoperative SV maximum diameter was 6.75 mm (95% CI: 0.625-0.831; P=0.001; sensitivity, 77.8%; specificity, 60.4%; area under the curve, 0.728). Conclusions: In THA, preoperative ultrasonography with a maximum SV diameter of 6.75 mm or greater was the risk of bilateral DVT leading to fatal PTE is increased.
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BACKGROUND BCOR: CCNB3 sarcoma is a rare mesenchymal tumor that was formerly included in the undifferentiated/unclassified sarcoma group and was recently reclassified as one of undifferentiated small round cell sarcomas with a genetically distinct subtype in the WHO 2020 classification. Because of its rarity, still not much is known, especially about its clinical features. CASE REPORT A 15-year-old boy presented with almost 1-year intermittent thigh pain. On the first visit, a pathologic fracture of the femur and a big mass expanding through the femoral cortex with lobular shape and homogenous appearance were recognized on radiography and magnetic resonance imaging. Plain radiography, which was taken 6 months before at a local clinic, showed an expansion and thickening of the right proximal femoral shaft. Biopsy specimen of the lesion revealed a proliferation of round to spindle tumor cells with diffuse and strong immunohistochemical nuclear positivity for BCOR and CCNB3. Under the diagnosis of BCOR::CCNB3 sarcoma of the femur, a chemotherapy based on a protocol of Ewing sarcoma, followed by a wide resection and total femoral replacement surgery, were conducted. The effect of chemotherapy was favorable, showing no microscopic residual tumor. Although postoperative chemotherapy was not completed because of a minor infection detected on the surgical site, the patient was doing well, without any recurrence, for 26 months. CONCLUSIONS BCOR: CCNB3 sarcoma of the bone is a quite rare tumor with much lower incidence than Ewing sarcoma. Notable clinical characteristics of the current case were a 1-year-long symptomatic period and homogenous appearance on MRI.
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Sarcoma de Ewing , Sarcoma , Neoplasias de los Tejidos Blandos , Masculino , Humanos , Adolescente , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/patología , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Biomarcadores de Tumor , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Ciclina BRESUMEN
OBJECTIVES: To develop an illustrative tool presenting visualized rheumatoid arthritis (RA) symptoms using pictures to promote a better understanding between patients and physicians. METHODS: The tool named 'Okomarigoto Sheet' was developed through an Internet survey of patients with RA and certified rheumatologists by repeated in-person interviews. RESULTS: An Internet survey on the reality of communication between patients with RA and physicians in 200 patients and 200 certified rheumatologists revealed various local and systemic symptoms of RA and difficulties in sharing those symptoms between patients and physicians during a short consultation. Interviews from patients and certified rheumatologists suggested that illustrations of symptoms would be helpful for better communication between them; therefore, an illustrative tool presenting visualized RA symptoms was drafted. The draft illustrations were refined through multiple rounds of interviews with the patients. The final version of the tool was discussed and evaluated at a joint meeting of patients and rheumatologists. CONCLUSIONS: A picture sheet presenting RA symptoms was developed. Future prospective studies should evaluate the usefulness of the sheet in clinical practice to promote better communication between patients and physicians.
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PURPOSE: We devised a low-concentration brachial plexus block (LCBB) that allows for intraoperative, active motion by blocking only sensory nerves. This study evaluated the efficacy of the LCBB. METHODS: Thirty-eight patients (14 men and 24 women; mean age, 60.0 years) underwent surgery with the LCBB. An ultrasound-guided supraclavicular brachial plexus block with 30-40 mL of 0.6 mg/ml ropivacaine hydrochloride hydrate was performed approximately 2 hours before starting the surgery. A local anesthetic (LA) was administered as a local infiltration if the intraoperative pain relief was locally insufficient. The surgery was performed using a tourniquet as usual, which was released for approximately 1 minute when there was a requirement to check for intraoperative, active motion. We recorded the waiting time required between LCBB administration and surgery, the total surgery time, the total tourniquet time, the number of patients administered an LA, the total LA volume (1% lidocaine equivalent), and the muscle strength at intraoperative, active motion (evaluated by manual muscle testing and categorized as ≥grade 4 or ≤grade 3). RESULTS: The mean waiting time was 137.0 minutes, the mean surgery time was 124.6 minutes, and the mean tourniquet time was 70.6 minutes. In 2 patients, the anesthetic effect was not achieved, and we switched to other methods of anesthesia (1 patient was switched to an intravenous, regional anesthesia; 1 patient was switched to a standard brachial plexus block). Excluding those 2 cases, the mean LA volume was 8.7 mL among 22 cases (61.1%), and 33 cases (91%) had manual muscle testing of ≥grade 4. In 36 of 38 cases (94.7%), surgery could be performed by LCBB. CONCLUSIONS: Although an LCBB may require additional LA, it is a useful anesthesia method that allows intraoperative active motion and tourniquet use. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
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OBJECTIVE: This nationwide study aimed to reveal the prevalence of ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-ax SpA), and the positivity rate of human leukocyte antigen (HLA) among such patients in Japan. METHODS: The first survey was conducted in 2221 randomly selected facilities (26.3%) in September 2018, where the patients with AS/nr-ax SpA were taken care of from January to December 2017. We estimated the total number of these patients using response and extraction rates. A second survey was conducted in 117 facilities (49.8%) to assess for HLA-B27 positivity rate and clinical features. RESULTS: The estimated total numbers of the patients with AS and nr-ax SpA were 3200 (95% confidence interval [CI]: 2400-3900) and 800 (530-1100), suggesting that the prevalence values of AS and nr-ax SpA in general population were 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively. Although 55.5% (76/137) of patients with AS were HLA-B27-positive, those whose age of onset was estimated to be over 50 years tended to undergo less HLA-B27 testing. CONCLUSION: This study revealed the lower prevalence of AS/nr-ax SpA in Japan, compared to those in other countries. Further studies are required to reveal the association of HLA-B27 with the clinical features.
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Espondiloartritis Axial , Espondiloartritis Axial no Radiográfica , Espondiloartritis , Espondilitis Anquilosante , Antígeno HLA-B27 , Humanos , Japón/epidemiología , Persona de Mediana Edad , Prevalencia , Espondiloartritis/diagnóstico por imagen , Espondiloartritis/epidemiología , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/epidemiología , Encuestas y CuestionariosRESUMEN
Importance: The optimal management for acute traumatic cervical spinal cord injury (SCI) is unknown. Objective: To determine whether early surgical decompression results in better motor recovery than delayed surgical treatment in patients with acute traumatic incomplete cervical SCI associated with preexisting canal stenosis but without bone injury. Design, Setting, and Participants: This multicenter randomized clinical trial was conducted in 43 tertiary referral centers in Japan from December 2011 through November 2019. Patients aged 20 to 79 years with motor-incomplete cervical SCI with preexisting canal stenosis (American Spinal Injury Association [ASIA] Impairment Scale C; without fracture or dislocation) were included. Data were analyzed from September to November 2020. Interventions: Patients were randomized to undergo surgical treatment within 24 hours after admission or delayed surgical treatment after at least 2 weeks of conservative treatment. Main Outcomes and Measures: The primary end points were improvement in the mean ASIA motor score, total score of the spinal cord independence measure, and the proportion of patients able to walk independently at 1 year after injury. Results: Among 72 randomized patients, 70 patients (mean [SD] age, 65.1 [9.4] years; age range, 41-79 years; 5 [7%] women and 65 [93%] men) were included in the full analysis population (37 patients assigned to early surgical treatment and 33 patients assigned to delayed surgical treatment). Of these, 56 patients (80%) had data available for at least 1 primary outcome at 1 year. There was no significant difference among primary end points for the early surgical treatment group compared with the delayed surgical treatment group (mean [SD] change in ASIA motor score, 53.7 [14.7] vs 48.5 [19.1]; difference, 5.2; 95% CI, -4.2 to 14.5; P = .27; mean [SD] SCIM total score, 77.9 [22.7] vs 71.3 [27.3]; P = .34; able to walk independently, 21 of 30 patients [70.0%] vs 16 of 26 patients [61.5%]; P = .51). A mixed-design analysis of variance revealed a significant difference in the mean change in ASIA motor scores between the groups (F1,49 = 4.80; P = .03). The early surgical treatment group, compared with the delayed surgical treatment group, had greater motor scores than the delayed surgical treatment group at 2 weeks (mean [SD] score, 34.2 [18.8] vs 18.9 [20.9]), 3 months (mean [SD] score, 49.1 [15.1] vs 37.2 [20.9]), and 6 months (mean [SD] score, 51.5 [13.9] vs 41.3 [23.4]) after injury. Adverse events were common in both groups (eg, worsening of paralysis, 6 patients vs 6 patients; death, 3 patients vs 3 patients). Conclusions and Relevance: These findings suggest that among patients with cervical SCI, early surgical treatment produced similar motor regain at 1 year after injury as delayed surgical treatment but showed accelerated recovery within the first 6 months. These exploratory results suggest that early surgical treatment leads to faster neurological recovery, which requires further validation. Trial Registration: ClinicalTrials.gov Identifier: NCT01485458; umin.ac.jp/ctr Identifier: UMIN000006780.
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Médula Cervical/lesiones , Vértebras Cervicales/lesiones , Descompresión Quirúrgica/estadística & datos numéricos , Traumatismos de la Médula Espinal/cirugía , Tiempo de Tratamiento/estadística & datos numéricos , Adulto , Anciano , Médula Cervical/cirugía , Vértebras Cervicales/cirugía , Tratamiento Conservador/estadística & datos numéricos , Descompresión Quirúrgica/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Desempeño Psicomotor , Recuperación de la Función , Traumatismos de la Médula Espinal/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The self-cinching stitch has been verified to have high mechanical strength. The mechanical strength of combining transosseous rotator cuff repair (RCR) and the self-cinching stitch in the lateral row is unknown. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the biomechanical properties of transosseous RCR combined with the cinch stitch in the lateral row. We hypothesized that this construct would have better mechanical strength than would transosseous repair using a vertical cinch stitch or simple stitch. STUDY DESIGN: Controlled laboratory study. METHODS: Rotator cuff tears were simulated in 48 porcine shoulder specimens. The tears were repaired using 1 of 6 repair configurations: 2-simple stitch transosseous repair alone (group 2TO), with a vertical cinch stitch (group 2TO-VC), or with a horizontal cinch stitch (group 2TO-HC) or 4-simple stitch transosseous repair alone (group 4TO), with a vertical cinch stitch (group 4TO-VC), or with a horizontal cinch stitch (group 4TO-HC). All specimens were set at a 45° angle from the footprint and underwent cyclic loading from 10 to 160 N for 200 cycles, followed by a load-to-failure test at 10 mm/min. RESULTS: During cyclic loading, all specimens in group 2TO and half of the specimens in group 2TO-VC failed by suture pullout. In the other groups, none of the specimens failed before 200 cycles. The yield load in group 2TO-HC was significantly greater than that in group 2TO-VC (261.43 vs 219.54 N, respectively; P < .05). There were significant differences between groups 4TO-HC and 4TO with regard to elongation (3.92 vs 5.68 mm, respectively), yield load (304.04 vs 246.94 N, respectively), and linear stiffness (63.44 vs 52.28 N/mm, respectively) (P < .01 for all). Group 4TO-HC also had shorter elongation and a superior yield load and linear stiffness compared with group 2TO-HC (P < .05 for all), and group 4TO-VC had shorter elongation and a stronger maximum load to failure and yield load than did group 2TO-VC (P < .05 for all). CONCLUSION: Increasing the number of medial simple stitches can prevent suture pullout. Adding the horizontal cinch stitch to the lateral row in transosseous repair can further improve biomechanical properties through a self-cinching mechanism. CLINICAL RELEVANCE: Transosseous RCR with a horizontal cinch stitch in the lateral row may reduce the retear rate.
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AIM: Patients with skeletal metastasis from prediagnosed primary malignancy sometimes have concurrent oncologic emergency (OE) during the first visit. This study aims to investigate the types of OEs and treatment outcome in such patients. METHODS: We have experienced 359 patients with skeletal metastasis from unknown primary malignancy. Among them, 130 patients required immediate admission for OE treatment (OE group), 229 patients had no OE and did not required immediate admission (non-OE group). RESULTS: The recognized types of OE were spinal cord compression in 60 patients, cancer pain in 30, hypercalcemia in 19, delirium in 16, deep vein thrombosis in 13, acute renal failure in 6, respiratory failure in 3, gastrointestinal hemorrhage in 3, and disseminated intravascular coagulation in 1. The overall 5-year survival rates were 28% and 37% in the OE and non-OE groups, respectively (P < 0.001). The multivariate analysis revealed that delirium (hazard ratio 4.2; 95% confidence interval, 1.6-12.5; P < 0.005) and respiratory failure (hazard ratio 22.6; 95% confidence interval, 4.5-92.8; P < 0.001) were significant prognostic factors in patients with OEs, whereas other OEs did not confer a significant risk for patient outcomes. CONCLUSION: In this study, OE was observed in as many as 36% of patients with skeletal metastasis from unknown primary malignancy. Delirium and respiratory failure were only two significant prognostic risk factors, which suggest that many of the OEs in untreated advanced cancer patients have probable chance to resolve. Early detection followed by appropriate treatment of such OEs is recommended.
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OBJECTIVE: We have previously reported that stimulation of mouse bone marrow-derived macrophages with tumor necrosis factor (TNF) and interleukin-6 (IL-6) induces differentiation of osteoclast-like cells. We undertook this study to clarify the characterization and function of human TNF and IL-6-induced osteoclasts using peripheral blood collected from patients with rheumatoid arthritis (RA) and healthy donors. METHODS: Peripheral blood monocytes were cultured with a combination of TNF and IL-6, TNF alone, IL-6 alone, or with RANKL, and their bone resorption ability was evaluated. Expression levels of NFATc1, proinflammatory cytokines, and matrix metalloproteinase 3 were analyzed. The effects of NFAT inhibitor and JAK inhibitor were examined. Furthermore, the relationship between the number of TNF and IL-6-induced osteoclasts or RANKL-induced osteoclasts differentiated from peripheral blood mononuclear cells (PBMCs) in patients with RA and the modified total Sharp score (mTSS) or whole-body bone mineral density (BMD) was examined. RESULTS: Peripheral blood monocytes stimulated with a TNF and IL-6-induced osteoclasts were shown to demonstrate the ability to absorb bone matrix. Cell differentiation was not inhibited by the addition of osteoprotegerin. Stimulation with a combination of TNF and IL-6 promoted NFATc1 expression, whereas the NFAT and JAK inhibitors prevented TNF and IL-6-induced osteoclast formation. Expression levels of IL1ß, TNF, IL12p40, and MMP3 were significantly increased in TNF and IL-6-induced osteoclasts, but not in RANKL-induced osteoclasts. The number of TNF and IL-6-induced osteoclasts differentiated from PBMCs in patients with RA positively correlated with the mTSS, whereas RANKL-induced osteoclast numbers negatively correlated with the whole-body BMD of the same patients. CONCLUSION: Our results demonstrate that TNF and IL-6-induced osteoclasts may contribute to the pathology of inflammatory arthritis associated with joint destruction, such as RA.
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Artritis Reumatoide/inmunología , Resorción Ósea/inmunología , Interleucina-6/inmunología , Osteoclastos/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Anciano , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/metabolismo , Densidad Ósea , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/metabolismo , Estudios de Casos y Controles , Citocinas/efectos de los fármacos , Citocinas/inmunología , Citocinas/metabolismo , Femenino , Humanos , Subunidad p40 de la Interleucina-12/efectos de los fármacos , Subunidad p40 de la Interleucina-12/inmunología , Subunidad p40 de la Interleucina-12/metabolismo , Interleucina-1beta/efectos de los fármacos , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo , Interleucina-6/farmacología , Masculino , Metaloproteinasa 3 de la Matriz/efectos de los fármacos , Metaloproteinasa 3 de la Matriz/inmunología , Metaloproteinasa 3 de la Matriz/metabolismo , Persona de Mediana Edad , Factores de Transcripción NFATC/efectos de los fármacos , Factores de Transcripción NFATC/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteogénesis/inmunología , Ligando RANK/metabolismo , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
INTRODUCTION: The objective of this study was to quantitatively evaluate the effects of daily teriparatide on rheumatoid arthritis patients using predicted bone strength (PBS) assessed by quantitative computed tomography-based finite-element analysis (QCT/FEA) and using bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA), and to prospectively investigate clinical determinants associated with PBS and BMD increases. MATERIALS AND METHODS: Participants comprised 39 patients (mean age, 69 years; disease activity score assessing 28 joints with CRP, 3.0; previous vertebral fractures, 82%) enrolled in this study. BMD by DXA and PBS by QCT/FEA of lumbar spine (LS) and proximal femur were measured at baseline, and after 6 and 12 months. In the groups showing increases in these values, variables that may have affected these increases were evaluated using univariate logistic regression analysis. RESULTS: Daily teriparatide treatment significantly increased not only LS BMD, but also LS PBS in RA patients with osteoporosis after both 6 and 12 months of treatment. Increases in N-terminal type I procollagen propeptide (PINP) at 1 and 3 months were significantly associated with increased LS PBS at 12 months according to univariate logistic regression analysis. The threshold value for increased PINP at 1 month for increased PBS at 12 months was 75 µg/L. CONCLUSIONS: Increased LS PBS at 12 months was predicted by increased PINP at 1 month from baseline.
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Artritis Reumatoide/tratamiento farmacológico , Análisis de Elementos Finitos , Teriparatido/uso terapéutico , Absorciometría de Fotón , Anciano , Área Bajo la Curva , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/fisiopatología , Biomarcadores/sangre , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Remodelación Ósea/efectos de los fármacos , Esquema de Medicación , Femenino , Humanos , Modelos Logísticos , Masculino , Teriparatido/farmacologíaRESUMEN
OBJECTIVES: Synovial fibroblasts (SFs) are one of the major components of the inflamed synovium in rheumatoid arthritis (RA). We aimed to gain insight into the pathogenic mechanisms of SFs through elucidating the genetic contribution to molecular regulatory networks under inflammatory condition. METHODS: SFs from RA and osteoarthritis (OA) patients (n=30 each) were stimulated with eight different cytokines (interferon (IFN)-α, IFN-γ, tumour necrosis factor-α, interleukin (IL)-1ß, IL-6/sIL-6R, IL-17, transforming growth factor-ß1, IL-18) or a combination of all 8 (8-mix). Peripheral blood mononuclear cells were fractioned into five immune cell subsets (CD4+ T cells, CD8+ T cells, B cells, natural killer (NK) cells, monocytes). Integrative analyses including mRNA expression, histone modifications (H3K27ac, H3K4me1, H3K4me3), three-dimensional (3D) genome architecture and genetic variations of single nucleotide polymorphisms (SNPs) were performed. RESULTS: Unstimulated RASFs differed markedly from OASFs in the transcriptome and epigenome. Meanwhile, most of the responses to stimulations were shared between the diseases. Activated SFs expressed pathogenic genes, including CD40 whose induction by IFN-γ was significantly affected by an RA risk SNP (rs6074022). On chromatin remodelling in activated SFs, RA risk loci were enriched in clusters of enhancers (super-enhancers; SEs) induced by synergistic proinflammatory cytokines. An RA risk SNP (rs28411362), located in an SE under synergistically acting cytokines, formed 3D contact with the promoter of metal-regulatory transcription factor-1 (MTF1) gene, whose binding motif showed significant enrichment in stimulation specific-SEs. Consistently, inhibition of MTF1 suppressed cytokine and chemokine production from SFs and ameliorated mice model of arthritis. CONCLUSIONS: Our findings established the dynamic landscape of activated SFs and yielded potential therapeutic targets associated with genetic risk of RA.
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Artritis Reumatoide , Leucocitos Mononucleares , Animales , Linfocitos T CD8-positivos/metabolismo , Células Cultivadas , Citocinas/metabolismo , Fibroblastos/metabolismo , Humanos , Leucocitos Mononucleares/metabolismo , Ratones , Membrana Sinovial/metabolismoRESUMEN
Non-radiographic axial spondyloarthritis (nr-axSpA) is a subgroup of axial spondyloarthritis (axSpA) without fulfilling the modified New York criteria of sacroiliac joint radiographs for ankylosing spondylitis (AS). AS and nr-axSpA share various demographic and clinical features and disease burden, although sex and objective inflammatory findings such as elevated serum C-reactive protein level are slightly different between AS and nr-axSpA. Recently, diagnostic guidance for nr-axSpA in Japan was proposed for epidemiological studies of a population with a low prevalence of HLA-B27 positivity and the use of molecular targeted agents suitable for the unique medical care system in Japan. A biological agent targeting interleukin-17 was approved for nr-axSpA by the Pharmaceutical and Medical Devices Agency (PMDA) in August 2020. Some other biological agents will be also available for Japanese patients with nr-axSpA in the near future.
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Espondiloartritis/diagnóstico , Antirreumáticos/administración & dosificación , Antirreumáticos/uso terapéutico , Biomarcadores/sangre , Ensayos Clínicos como Asunto , Humanos , Espondiloartritis/diagnóstico por imagen , Espondiloartritis/tratamiento farmacológico , Espondiloartritis/epidemiologíaRESUMEN
BACKGROUND: Prosthetic reconstruction for distal femoral osteosarcoma is challenging for younger children. We herein report a successful case of limb-sparing surgery for a younger patient with distal femoral osteosarcoma requiring osteo-articular resection. CASE PRESENTATION: A 5-year-old girl with high-grade conventional osteosarcoma in the left distal femur underwent a series of surgeries. After three cycles of neoadjuvant chemotherapy, limb-salvage surgery was planned because femoral rotationplasty had been refused. At 6 years and 2 months old, distal femoral resection and temporary spacer insertion using a 7-mm-diameter intramedullary nail and molded polymethylmethacrylate was performed. At 7 years and 8 months old, secondary surgery was performed because the first spacer had been dislocated and the residual femur became atrophic. The distal end of the residual femur was removed by 1 cm, but the periosteum and induced membrane around polymethylmethacrylate was preserved. In order to stabilize the spacer against the tibia, a custom-made ceramic spacer with a smooth straight 8-mm-diameter stem was utilized. The bone-spacer junction was fixed with polymethylmethacrylate and then covered with the preserved periosteum and induced membrane. After surgery, the bone atrophy improved. At 9 years and 7 months old, the second spacer was removed because it had loosened, and the knee joint was reconstructed using a custom-made growing femoral prosthesis with a curved porous 8.5-mm-diameter stem. Cancellous bone tips from the proximal tibia were grafted around the bone-prosthesis junction underneath the induced membrane. At 10 years and 5 months old, the patient was able to walk unsupported and a radiograph showed further thickening of the cortex of the residual femur without any stress shielding. Although having 5 cm of limb length discrepancy, the patient and her mother were satisfied with the function. The MSTS score was 24 out of 30 points. Repeated limb length extensions are planned. CONCLUSIONS: This case report provides an example of limb-salvage surgery after distal femoral resection in a small child. The use of a temporary spacer utilizing partial cementation and preservation of the periosteum and induced membrane appears to afford a viable limb-salvage option after distal femoral resection for younger children.
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Neoplasias Óseas , Neoplasias Femorales , Hemiartroplastia , Osteosarcoma , Neoplasias Óseas/cirugía , Niño , Preescolar , Femenino , Neoplasias Femorales/diagnóstico por imagen , Neoplasias Femorales/cirugía , Fémur/diagnóstico por imagen , Fémur/cirugía , Humanos , Lactante , Recuperación del Miembro , Osteosarcoma/cirugía , Pronóstico , Tibia/cirugía , Resultado del TratamientoRESUMEN
INTRODUCTION: Surgery for chondroblastoma in the femoral head is challenging due to its inaccessibility, with high risk of local recurrence and poor functional outcomes reported. We herein report the first case of chondroblastoma in the femoral head treated by navigation-assisted surgery. PRESENTATION OF CASE: A 12-year-old girl presented with persistent left hip pain and limited hip range of motion. Imaging studies revealed a well-defined osteolytic lesion in the left femoral head accompanied by extensive intra-osseous oedematous change. The bone lesion was radiologically diagnosed as chondroblastoma. With navigation assistance, curettage was performed via the anterior approach. The tumor was fully accessible from the femoral neck. After curettage, the bony defect was filled with bone substitute. The pathological diagnosis was chondroblastoma. The post-operative course was uneventful. Thirty months postoperatively, the patient was free of pain with full hip range of motion, and MR images showed no evidence of recurrence or osteonecrosis. DISCUSSION: This case is the first to use a navigation system for the treatment of chondroblastoma in the femoral head. The navigation system can minimize damage to intact structures and increase the efficiency of curettage by visualizing access to the tumor. CONCLUSION: Navigation assistance is an optimal surgical option for chondroblastoma in the femoral head.
RESUMEN
While the role of T cells in the regulation of bone homeostasis is well defined, little is known about the role of innate lymphoid cells (ILCs) on bone. ILCs are innate immune cells that share cytokine expression patterns with T cells but lack the T cell receptor. In this study we show that type 2 ILCs (ILC2) potently inhibit the generation of bone resorbing osteoclasts in vitro as well as favorably influence bone homeostasis under steady state conditions in vivo using loss and gain of function models. Furthermore, adoptive transfer of ILC2 completely abrogated ovariectomy-induced bone loss by significantly down-regulating osteoclast numbers in vivo. The suppressive effects of ILC2s on osteoclasts in vitro and in vivo as well as the protection from ovariectomy-induced bone loss were linked to their expression of IL-4 and IL-13 as well as STAT6 activation on the myeloid target cell, since deletion of IL-4/IL-13 in ILC2s or STAT6 in osteoclast precursors abrogated the anti-osteoclastogenic effect of ILC2s. Taken together, these findings show that ILC2 have to be considered as potent regulators of bone homeostasis.
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Inmunidad Innata , Osteoclastos , Diferenciación Celular , Citocinas , Femenino , Humanos , Linfocitos , OvariectomíaRESUMEN
X-ray Talbot-Lau interferometry is one of the x-ray phase imaging methods that has high sensitivity in depicting soft tissues. Unlike earlier x-ray phase imaging methods that required particular types of x-ray sources, such as a synchrotron or a micro-focus x-ray tube, x-ray Talbot-Lau interferometry enables to perform clinical x-ray phase imaging using a conventional x-ray source with a relatively compact configuration. We developed an apparatus to depict cartilage in the metacarpophalangeal joints of the hands. In addition, we examined the apparatus performance by applying it to healthy volunteers and patients with rheumatoid arthritis (RA). Cartilage deformation, which is thought to be a precursor of destruction of the joints, was successfully depicted by the apparatus, suggesting a potential early diagnosis of RA.
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Artritis Reumatoide/diagnóstico por imagen , Cartílago/diagnóstico por imagen , Imagenología Tridimensional , Interferometría , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/patología , Cartílago/patología , Estudios de Casos y Controles , Femenino , Humanos , Articulaciones/diagnóstico por imagen , Articulaciones/patología , Masculino , Persona de Mediana Edad , Rayos X , Adulto JovenRESUMEN
BACKGROUND: It is unclear whether antecedent primary malignancies (APMs) have any negative impact on the prognosis of soft tissue sarcoma (STS). We retrospectively reviewed STS patients with APMs (STS-APM) and compared their survival to those of STS only (STS-O). METHODS: Twenty-one cases of STS-APM from 2008 to 2017 in our institution were analyzed. One hundred and seventy cases of STS-O at the same period were compared as a control group. Overall survival was estimated using Kaplan-Meier survival curves and prognostic factors were analyzed using logistic regression analyses and contingency table analyses. RESULTS: As the final status of STS-APM patients, 12 patients were in disease-free survival, 5 were alive with disease, 3 have died of disease, and 1 has died of another disease. There was no case that died of APM. The 5-year overall survival rates were 88% in STS-APM and 78% in STS-O, showing no statistical significant ( p = 0.65). The 5-year overall survival rates in each stage of STS-APM and STS-O were 100/100% in stage I, 100/85% in stage II, 86/72% in stage III, and the 3-year overall survival rates were 67/51% in stage IV, with no statistical significance. With regard to prognostic factor, histological grade of STS was the only significant factor. Although antecedent radiotherapy tended to show a high odds ratio, the association was not statistically significant. Antecedent chemotherapy did not show any estimated prognostic risk. CONCLUSIONS: Our study suggested that APM in STS patient would not be a negative prognostic factor.