Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 322
Filtrar
1.
Bone Joint J ; 103-B(12): 1809-1814, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34847719

RESUMO

AIMS: Patients with soft-tissue sarcoma (STS) who undergo unplanned excision (UE) are reported to have worse outcomes than those who undergo planned excision (PE). However, others have reported that patients who undergo UE may have similar or improved outcomes. These discrepancies are likely to be due to differences in characteristics between the two groups of patients. The aim of the study is to compare patients who underwent UE and PE using propensity score matching, by analyzing data from the Japanese Bone and Soft Tissue Tumor (BSTT) registry. METHODS: Data from 2006 to 2016 was obtained from the BSTT registry. Only patients with STS of the limb were included in the study. Patients with distant metastasis at the initial presentation and patients with dermatofibrosarcoma protuberans and well-differentiated liposarcoma were excluded from the study. RESULTS: A total of 4,483 patients with STS of the limb were identified before propensity score matching. There were 355 patients who underwent UE and 4,128 patients who underwent PE. The five-year disease-specific survival (DSS) rate was significantly better in the patients who received additional excision after UE than in those who underwent PE. There was no significant difference in local recurrence-free survival (LRFS) between the two groups. After propensity score matching, a new cohort of 355 patients was created for both PE and UE groups, in which baseline covariates were appropriately balanced. Reconstruction after tumour excision was frequently performed in patients who underwent additional excision after UE. There were no significant differences in DSS and LRFS between the patients who underwent PE and those who had an additional excision after UE. CONCLUSION: Using propensity score matching, patients with STS of the limb who underwent additional excision after UE did not experience higher mortality and local failure than those who underwent PE. Reconstruction may be necessary when additional excision is performed. Cite this article: Bone Joint J 2021;103-B(12):1809-1814.

2.
Free Radic Biol Med ; 177: 238-246, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34737143

RESUMO

BACKGROUND: Ischemia-reperfusion (I/R) injury is a major contributor to skin flap necrosis, which is a serious complication of reconstructive surgery. The purpose of this study was to evaluate the protective effect of treatment with febuxostat, a selective xanthine oxidase inhibitor, on I/R injury in the skin flap of an animal (rat) model. METHODS: Superficial epigastric flaps were raised in Sprague-Dawley rats and subjected to ischemia for 3 h. Febuxostat at a dose of 10 mg/kg/day was administered to rats in drinking water from 1 week before the surgery (Feb group). Control animals received no drugs (Con group). The mean ratio of flap survival and contraction was evaluated and compared between animals with and without administration of febuxostat on day 5 after the surgery. In addition, infiltration by polymorphonuclear leukocytes and muscles of the panniculus carnosus in the flap were histologically evaluated using hematoxylin-eosin staining. Furthermore, xanthine oxidase activity, ATP levels, superoxide dismutase activity, and expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor-α, and interleukin-1ß were quantitatively assessed in the skin flap 24 h after the surgery. RESULTS: In the Feb group, the survival and contraction rates at the 5 d timepoint post-surgery were significantly higher and lower than those in the Con group, respectively. Histological analysis showed significant reduction in polymorphonuclear leukocyte infiltration and muscle injury scores due to I/R injury in the Feb group. The expression of 8-OHdG was also significantly inhibited in animals administered febuxostat. Biochemical analysis showed a significant reduction in xanthine oxidase activity and significant increases in ATP levels and superoxide dismutase activity in the Feb group. Furthermore, the expression of interleukin-1ß was significantly lower in the Feb group than in the Con group. CONCLUSION: Febuxostat, which is clinically used for the treatment of hyperuricemia, was effective against necrosis of the skin flap via inhibition of oxidative stress and inflammation caused by I/R injury.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34738158

RESUMO

PURPOSE: The primary aim was to evaluate the accuracy of navigation in opening wedge high tibial osteotomy (HTO). The secondary aim was to examine mid-term outcomes after HTO. METHODS: Inclusion criteria were patients with medial compartment knee osteoarthritis who underwent computer-assisted HTOs. Mechanical axis (MA), percentage MA (%MA), and change in posterior tibial slope (ΔPTS) were displayed on the navigation screen. Radiographic examinations included hip-knee-ankle (HKA) angle, medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), and PTS. Preoperative and 5 weeks postoperative standing radiographs of the whole lower extremity and knee were used. Clinical evaluations were performed using American Knee Society knee score and function score both preoperatively and at last follow-up. Radiographic evaluations were performed by orthopedic surgeons. Intraoperative navigation after osteotomy and postoperative standing radiograph were compared. MA (HKA), %MA, and ΔPTS were compared. Outliers were defined as > 3° in MA, > 10% in %MA, and > 10° in ΔPTS. Outlier and non-outlier groups were compared. The rate of conversion to arthroplasty was examined. RESULTS: This study involved 38 patients (44 knees) and last follow-up was at a mean of 5 years (range, 1-9 years). Mean American Knee Society knee score and function score improved significantly from 59 to 69 preoperatively to 95 and 85 at last follow-up, respectively. Absolute values of mean errors for MA, %MA, and ΔPTS were 2.1°, 9.3%, 1.2°, respectively. Outlier rates were 18% in MA, 39% in %MA, and 5% in ΔPTS. No significant factors were found in MA and ΔPTS. In %MA, preoperative JLCA was significantly higher in the outlier group compared to the non-outlier group. No knees underwent conversion to total knee arthroplasty. No differences in outcomes were found between outlier and non-outlier groups. CONCLUSION: Although rates of outlier values in computer-assisted opening wedge HTO were high, mid-term outcomes were excellent. LEVEL OF EVIDENCE: IV.

4.
Cancer Manag Res ; 13: 8473-8480, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34785953

RESUMO

Purpose: Here, we investigated the oncological outcomes of lung metastasectomy and/or radiofrequency ablation (RFA) of 92 patients with soft tissue sarcoma (STS) at nine institutions. Methods: The study cohort included 65 men and 27 women with a mean age of 59 years at the time of metastasis. The mean follow-up duration was 51 months. All patients underwent metastasectomy and/or RFA for lung metastasis. Results: The mean maximum size of the initial lung metastasis was 14.6 mm. At the initial evaluation, 41 patients had a single metastasis, whereas 51 patients had multiple metastases. The mean number of metastasectomies and/or RFA was 2 per patient. A total of 70 patients underwent lung metastasectomy, whereas the other 13 underwent lung RFA. The remaining nine patients underwent both RFA and metastasectomy. The 5-year post-metastatic survival rate was 52%. The patients who underwent complete treatment for the initial metastasis had better post-metastatic survival rates than those who underwent incomplete treatment. A univariate analysis of all possible prognostic factors for complete treatment confirmed the predictive value of disease-free interval, metastasis at initial presentation, distribution, tumor size, and number of lung metastases. Of the 92 patients, 74 underwent complete treatment for initial metastasis; in these patients, univariate and multivariate analyses showed that a smaller tumor size and single-lung metastasis were prognostic factors for superior post-metastatic survival. The patients with a smaller (<11.5 mm) single metastasis had better post-metastasis survival. The 5-year post-metastatic survival rates were 89.9% for patients with a smaller (<11.5 mm) single metastasis versus 22.7% for patients with larger (>11.5 mm) and multiple metastases. Discussion: We propose that complete treatment for lung metastasis in patients with STS may improve post-metastatic survival rates. Furthermore, tumor number and size are important variables for clinical decision-making.

5.
Curr Issues Mol Biol ; 43(3): 1255-1266, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34698103

RESUMO

Osteosarcoma is the most common primary malignant bone tumor. The cause of death due to osteosarcoma is typically a consequence of metastasis to the lung. Controlling metastasis leads to improved prognosis for osteosarcoma patients. The cell stiffness of several tumor types is involved in metastatic potential; however, it is unclear whether the metastatic potential of osteosarcoma depends on cell stiffness. In this study, we analyzed the cell stiffness of the low metastatic Dunn cell line and its highly metastatic LM8 subline, and compared actin organization, cell proliferation, and metastasis. Actin cytoskeleton, polymerization, stiffness, and other cellular properties were analyzed. The organization of the actin cytoskeleton was evaluated by staining F-actin with Alexa Fluor 488 phalloidin. Cell stiffness was measured using Atomic Force Microscopy (AFM). Cell proliferation, migration, invasion, and adhesion were also evaluated. All experiments were performed using mouse osteosarcoma cell lines cultured in the absence and presence of cytochalasin. In LM8 cells, actin polymerization was strongly suppressed and actin levels were significantly lower than in Dunn cells. Stiffness evaluation revealed that LM8 cells were significantly softer than Dunn. Young's modulus images showed more rigid fibrillar structures were present in Dunn cells than in LM8 cells. LM8 cells also exhibited a significantly higher proliferation. The migration and invasion potential were also higher in LM8 cells, whereas the adhesion potential was higher in Dunn cells. The administration of cytochalasin resulted in actin filament fragmentation and decreased actin staining intensity and cell stiffness in both LM8 and Dunn cells. Cells with high metastatic potential exhibited lower actin levels and cell stiffness than cells with low metastatic potential. The metastatic phenotype is highly correlated to actin status and cell stiffness in osteosarcoma cells. These results suggest that evaluation of actin dynamics and cell stiffness is an important quantitative diagnostic parameter for predicting metastatic potential. We believe that these parameters represent new reliable quantitative indicators that can facilitate the development of new drugs against metastasis.

6.
Global Spine J ; : 21925682211047473, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34672835

RESUMO

STUDY DESIGN: This study is a retrospective review. OBJECTIVE: Central sensitization (CS) is a neurological phenomenon that involves hypersensitivity of the central nervous system. The central sensitization inventory (CSI) was developed as a screening tool to assess CS-related symptoms. The purpose of this study was to evaluate the association of preoperative CSI scores with patient-reported outcome measures (PROMs) including neurological symptoms for patients who underwent spine surgeries in a multicenter study. METHODS: A consecutive 673 patients who underwent spine surgery at 8 different institutions were included in this study. Preoperative CSI scores were assessed for all subjects. The participants completed the following PROMs: the Oswestry Disability Index (ODI), the Japanese Orthopaedic Association (JOA) back pain evaluation questionnaire (JOABPEQ) for lumbar spinal diseases, and the JOA cervical myelopathy evaluation questionnaire (JOACMEQ) for cervical spinal diseases. The association of CSI scores with PROMs was statistically evaluated. RESULTS: The average CSI score for the total subjects was 23.6 ± 13.5. The subjects with CS-related symptoms (CSI ≥ 40) were 13.2% (n = 89). The CSI score showed a significant and weak-to-moderate correlation with the PROMs including neurological symptoms that included all the domains of the JOACMEQ for cervical spinal diseases, and JOABPEQ and ODI for lumbar spinal diseases. Among these, psychological factors had the most influence on the correlation with CSI score. CONCLUSION: Central sensitization evaluated by the CSI is related to neurological symptoms and health-related quality of life in patients undergoing elective spine surgery.

7.
BMC Musculoskelet Disord ; 22(1): 786, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517874

RESUMO

BACKGROUND: Hallux rigidus (HR) is a common osteoarthritis of the first metatarsophalangeal joint. However, the epidemiology and risk factors of this pathology have yet to be clarified. METHODS: We have been conducting cohort studies among individuals over 50 years old every 2 years since 1997. This study analyzed data from the 7th to 10th checkups in 2009, 2011, 2013, and 2015. We investigated the prevalence of HR and its risk factors in a total of 604 individuals (mean age, 67.1 ± 6.4 years; 208 men, 396 women). Radiographic HR was defined as Hattrup and Johnson classification grade 1 or higher. Knee osteoarthritis (KOA) was scored according to the Kellgren-Lawrence grading system. Radiographic KOA was defined as grade 2 or higher. Cases with a hallux valgus (HV) angle of 20° or higher were defined as showing HV. Statistical analyses were performed using the Kruskal-Wallis test, Fisher's exact test, logistic regression modeling, and the Cochran-Armitage trend test. All p-values presented are two-sided and values of p < .05 were considered statistically significant. RESULTS: The prevalence of HR was 26.7% (161/604). Rates of grade 0, 1, 2, and 3 HR according to the Hattrup and Johnson classification were 73.3% (443/604), 16.4% (99/604), 8.0% (48/604), and 2.3% (14/604), respectively. Overall ratio of symptomatic HR was 8.1%. Univariate analysis revealed KOA, gout attack (GA), and HV as significantly associated with HR. The same factors were confirmed as independent risk factors for HR in multivariate analysis. All parameters were significantly associated with HR. Odds ratios of KOA, HV, and GA for HR were 1.73, 3.98, and 3.86, respectively. The presence or absence of KOA was significantly associated with severity of HR. CONCLUSIONS: This study revealed that the prevalence of HR in the elderly (≥50 years) was 26.7%. KOA, HV, and GA were independent risk factors for HR. KOA was associated with severity of HR.


Assuntos
Hallux Rigidus , Idoso , Estudos Transversais , Feminino , Hallux Rigidus/diagnóstico por imagem , Hallux Rigidus/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
8.
J Pain Res ; 14: 3011-3015, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34588812

RESUMO

Purpose: Although the pain of osteoarthritis (OA) is traditionally considered to be nociceptive, some patients also have neuropathic pain. The objective of this study was to evaluate the presence of neuropathic pain in the knees of OA patients using the painDETECT questionnaire (PDQ). Methods: A total of 180 knees in 158 consecutive patients who underwent total knee arthroplasty (TKA) were enrolled prospectively. The prevalence of neuropathic pain, unclear pain, and nociceptive pain in the knee was determined before and after TKA using a numerical rating scale (NRS). All patients were evaluated preoperatively and 6 months postoperatively. Neuropathic pain and unclear pain were grouped together as possible neuropathic pain. The relationship between possible neuropathic pain and pain intensity was evaluated. Results: Before TKA, neuropathic pain and unclear pain were found in 10 and 30 knees, respectively. The remaining 140 knees were categorized as nociceptive pain. After TKA, the numbers of knees with neuropathic and unclear pain decreased to one and five, respectively. The prevalence of possible neuropathic pain decreased significantly from 22.2% to 3.3% after surgery. Among the six knees with possible neuropathic pain postoperatively, four had possible neuropathic pain preoperatively as well, while the remaining two patients had been classified as nociceptive pain preoperatively. Knees with possible neuropathic pain postoperatively had higher postoperative NRS scores than those with nociceptive pain. Conclusion: Although the prevalence of possible neuropathic pain decreased significantly after TKA, the preoperative presence of possible neuropathic pain might be associated with the development of persistent postoperative pain following TKA.

9.
Theranostics ; 11(17): 8517-8534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34373756

RESUMO

Rationale: The progression of cancer cells depends on the soil and building an inhibitory soil might be a therapeutic option. We previously created tumor-suppressive secretomes by activating Wnt signaling in MSCs. Here, we examined whether the anti-tumor secretomes can be produced from tumor cells. Methods: Wnt signaling was activated in tumor cells by overexpressing ß-catenin or administering BML284, a Wnt activator. Their conditioned medium (CM) was applied to cancer cells or tissues, and the effects of CM were evaluated. Tumor growth in the mammary fat pad and tibia in C57BL/6 female mice was also evaluated through µCT imaging and histology. Whole-genome proteomics analysis was conducted to determine and characterize novel tumor-suppressing proteins, which were enriched in CM. Results: The overexpression of ß-catenin or the administration of BML284 generated tumor-suppressive secretomes from breast, prostate and pancreatic cancer cells. In the mouse model, ß-catenin-overexpressing CM reduced tumor growth and tumor-driven bone destruction. This inhibition was also observed with BML284-treated CM. Besides p53 and Trail, proteomics analysis revealed that CM was enriched with enolase 1 (Eno1) and ubiquitin C (Ubc) that presented notable tumor-suppressing actions. Importantly, Eno1 immunoprecipitated CD44, a cell-surface adhesion receptor, and its silencing suppressed Eno1-driven tumor inhibition. A pan-cancer survival analysis revealed that the downregulation of MMP9, Runx2 and Snail by CM had a significant impact on survival outcomes (p < 0.00001). CM presented a selective inhibition of tumor cells compared to non-tumor cells, and it downregulated PD-L1, an immune escape modulator. Conclusions: The tumor-suppressive secretome can be generated from tumor cells, in which ß-catenin presented two opposing roles, as an intracellular tumor promoter in tumor cells and a generator of extracellular tumor suppressor in CM. Eno1 was enriched in CM and its interaction with CD44 was involved in Eno1's anti-tumor action. Besides presenting a potential option for treating primary cancers and metastases, the result indicates that aggressive tumors may inhibit the growth of less aggressive tumors via tumor-suppressive secretomes.

10.
Bone Res ; 9(1): 32, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230453

RESUMO

Osteocytes are the most abundant cells in bone, which is a frequent site of breast cancer metastasis. Here, we focused on Wnt signaling and evaluated tumor-osteocyte interactions. In animal experiments, mammary tumor cells were inoculated into the mammary fat pad and tibia. The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model. The results revealed that administration of osteocytes or their conditioned medium (CM) inhibited tumor progression and osteolysis. Osteocytes overexpressing Lrp5 or ß-catenin displayed strikingly elevated tumor-suppressive activity, accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53. The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound. Notably, silencing Lrp5 in tumors inhibited tumor progression, while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression. Osteocytes exhibited elevated Lrp5 expression in response to tumor cells, implying that osteocytes protect bone through canonical Wnt signaling. Thus, our results suggest that the Lrp5/ß-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes. We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.

11.
J Orthop Sci ; 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34229907

RESUMO

BACKGROUNDS: Preoperative widespread pain sensitization or pain catastrophizing could be associated with chronic pain after total knee arthroplasty (TKA). The aim of the present study was to examine the association between postoperative pain in patients undergoing TKA and preoperative factors, including patient characteristics and preoperative central sensitization as well as pain catastrophizing. METHODS: Preoperative TKA patients were evaluated using the Central Sensitization Inventory (CSI)-9 and Pain Catastrophizing Scale (PCS). Postoperative knee pain was evaluated using a numerical rating scale (NRS) 6 months after TKA. Statistical analyses were performed to assess the relationship between NRS 6 months after TKA and preoperative factors, including patient characteristics, CSI-9, and PCS. RESULTS: We enrolled 58 consecutive patients with osteoarthritis who underwent TKA. Using cutoff of 14, postoperative NRS was higher in the patients with ≥14 than the patients with <14 in CSI (p = 0.025). Postoperative NRS was higher in the patients with ≥30 than the patients with <30 in PCS (p = 0.043). Preoperative PCS was a significant risk factor of postoperative pain using a multivariate analysis. CONCLUSIONS: Surgeon should recognize preoperative PCS could affect postoperative pain 6 months after TKA.

12.
Muscle Nerve ; 64(3): 365-373, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34212392

RESUMO

INTRODUCTION/AIMS: Obesity is a factor contributing to suboptimal improvement of motor function in peripheral nerve disorders. In this study we aimed to evaluate the skeletal muscles during denervation and reinnervation after nerve crush injury in leptin-deficient (ob/ob) mice. METHODS: Experiments were performed on the skeletal muscles of the hindlimbs in 20 male ob/ob mice and controls. Characteristics of the gastrocnemius muscles were evaluated by histological analysis, immunohistological analysis, and Sircol-collagen assay after measurement of body weight and wet weight of the skeletal muscles, and by walking track analysis. The sciatic nerve was denervated by crushing with smooth forceps and reinnervation was evaluated. RESULTS: Gastrocnemius wet weight was significantly lower in the ob/ob mice than in the control mice. A smaller cross-sectional area of type II fibers and increase of type I fiber grouping of the skeletal muscles was demonstrated in the ob/ob mice. After nerve injury, motor function recovery was equal between the groups but the cross-sectional area of type II fibers was significantly smaller in the ob/ob mice than in control mice at 4 weeks. The denervated muscles showed an increase in collagen deposition in the interstitial space; predominant in the ob/ob mice after nerve injury. DISCUSSION: The results of this study suggest that fibrosis in the skeletal muscle of obese patients after nerve injury is prominent, which may impair improvement of muscle function after treatment of peripheral nerve disorders.


Assuntos
Denervação Muscular , Músculo Esquelético/patologia , Compressão Nervosa , Regeneração Nervosa/fisiologia , Obesidade/patologia , Nervo Isquiático/lesões , Animais , Camundongos , Músculo Esquelético/inervação
13.
14.
Free Radic Res ; 55(7): 810-820, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34278932

RESUMO

Cachexic condition due to malignant tumors has been a challenging problem. The aim of this study is to analyze effects of febuxostat on both in vitro and in vivo models of the wasting of skeletal muscles, due to LM8 osteosarcoma cells. C2C12 myotubes were incubated in the conditioned medium of LM8. Febuxostat was added at a concentration of 3 µM and 30 µM, and ROS, diameter of myotubes, and expression of atrogin-1 were analyzed. Furthermore, an in vivo study was performed by subcutaneous injection of LM8 on C3H mice. Febuxostat was administered in the drinking water at 5 µg/ml, and 25 µg/ml. In addition, tumor-bearing mice without febuxostat (group TB) and control mice (group C) were established. At 4 weeks, body weight, wet weights of the gastrocnemius muscles, XO activity, 8-OHdG, and expression of TNF-α and IL-6 were evaluated. ROS generation, atrophy of myotubes, and upregulation of atrogin-1 were clearly observed in C2C12 myotubes following incubation in the conditioned medium. These pathological conditions were significantly inhibited by febuxostat administration. Furthermore, mice in group TB showed significant loss of body weight and muscle weight in which XO activity, 8-OHdG, and expression of IL-6 were significantly increased compared to those in group C. Febuxostat administration not only significantly improved the body weight and muscleweight, but also reduced markers of oxidative stress and pro-inflammatory cytokines. Febuxostat did not show anti-tumor effects. Febuxostat, which is clinically used for treatment of hyperuricemia, is effective against the wasting of the skeletal muscles induced by LM8 osteosarcoma cells.

15.
In Vivo ; 35(4): 2349-2355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182517

RESUMO

BACKGROUND: This study aimed to determine whether the prognostic nutritional index (PNI) can predict the prognosis in patients with soft-tissue sarcoma (STS) before treatment and to examine whether there is an association between PNI values and clinical characteristics. PATIENTS AND METHODS: The data on 100 patients with primary STS were retrospectively reviewed. The cohort included 55 men and 45 women, with a mean age of 64 years. The mean follow-up duration was 41.7 months. RESULTS: The median PNI was 51.35. The PNI was significantly inversely associated with tumor size, tumor grade, and age. We found that the PNI was a significant prognostic marker for disease-specific and event-free survival using univariate and multivariate analyses. Patients with a low PNI had poorer disease-specific and event-free survival than those with a high PNI. CONCLUSION: These results suggest that the PNI can be used as a prognostic marker in patients with STS.


Assuntos
Avaliação Nutricional , Sarcoma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcoma/diagnóstico
16.
Drugs R D ; 21(3): 351-357, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34173221

RESUMO

BACKGROUND: Golimumab (GLM) has been reported to have lower immunogenicity than do other TNF inhibitors used for treating rheumatoid arthritis (RA). We previously found a prolonged effect of and improvement similar to that associated with infliximab (IFX) after switching to subcutaneous GLM (GLM-SC) for control of RA activity or adverse events. Thus, this study aimed to evaluate the continued maintenance of treatment efficacy and safety for > 2 years by switching to GLM-SC in RA patients with low disease activity or in remission after previous treatment with another tumor necrosis factor (TNF) inhibitor. METHODS: Thirty-two patients treated with etanercept or infliximab were switched to GLM-SC and maintained low disease activity. The patients were divided into two groups (GLMq4w and GLMq8w) through discussion with each patient, considering their general condition and convenience. The groups included patients with low disease activity or in remission who switched to 50-mg GLM therapy at 4-week and 8-week intervals, respectively. RESULTS: The mean DAS28-ESR and DAS-CRP values in the GLMq4w group (17 patients) and GLMq8w group (15 patients) were maintained from baseline throughout the 104-week treatment period. Two patients from the GLMq4w group showed disease flaring to moderate disease activity. No serious adverse events occurred, and the treatment continuation rate at 104 weeks was 100% in both groups. After > 2 years of treatment, three patients in the GLMq8w group and one patient in the GLMq4w group discontinued GLM treatment due to relapse or complications. The 5-year survival rates were 88.2% and 75.5% in the GLMq4w and GLMq8w groups, respectively. The average treatment duration was 5.0 (2.0-7.5) years. CONCLUSION: Administration of GLM-SC at 4-week and 8-week intervals after switching from TNF inhibitors showed sustained long-term efficacy and acceptable safety in RA patients with low disease activity.


Assuntos
Antirreumáticos , Artrite Reumatoide , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Humanos , Infliximab/uso terapêutico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral
17.
Clin Appl Thromb Hemost ; 27: 10760296211012094, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34027710

RESUMO

We analyzed the utility for a clot waveform analysis (CWA) of small tissue factor induced FIX activation (sTF/FIXa) assay in patients with major orthopedic surgery (including total hip arthroplasty [THA] and total knee arthroplasty [TKA]) receiving edoxaban for the prevention of venous thromboembolism (VTE). The sTF/FIXa assay using recombinant human TF in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) was performed using a CWA in the above patients to monitor the efficacy of edoxaban administration. Of 147 patients (109 THA and 38 TKA), 21 exhibited deep vein thrombosis (DVT), and 15 had massive bleeding. Increased peak heights of the CWA-sTF/FIX were observed in almost patients after surgery and prolonged peak heights of the CWA-sTF/FIX were observed in almost patients treated with edoxaban. The peak heights and times of the CWA-sTF/FIX were significantly higher and shorter, respectively, in PRP than in PPP. There were no significant differences in parameters of the CWA-sTF/FIXa between the patients with and without DVT or between those with and without massive bleeding. The peak time of CWA-sTF/FIXa were significantly longer in TKA patients than in THA patients on day 1 after surgery. The second derivative peak height of the CWA-sTF/FIXa was significantly lower in TKA patients than in THA patients on day 4. The CWA-sTF/FIX reflected hemostatic abnormalities after surgery and the administration of edoxaban, and the results were better in PRP than PPP. Further studies separately analyzing the THA and TKA subgroups should be conducted.


Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Hemostáticos/metabolismo , Procedimentos Ortopédicos/métodos , Idoso , Feminino , Humanos , Masculino
18.
J Pain Res ; 14: 1271-1280, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34040431

RESUMO

Purpose: Central sensitization (CS) is defined as the increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold afferent input. CS has been proposed as an underlying mechanism of chronic pain in musculoskeletal disorders including low back pain (LBP). A Central Sensitization Inventory (CSI) has recently been developed for screening participants with CS. However, the association of CS with chronic LBP (cLBP) in the general population remains unknown. The purpose of this study was to investigate the association of CS with cLBP using the CSI in a population-based cohort of a Japanese mountain village. Participants and Methods: Participants aged more than 50 years were recruited from the inhabitants of a mountain village in Japan. Participants completed the following patient-reported outcome measures. Severity of CS was assessed by the CSI. LBP intensity was measured on a numerical rating scale (NRS). Health-related quality of life (QOL) was measured using the EuroQol 5-dimension (EQ-5D), EuroQol-visual analogue scales (EQ-VAS), and the Oswestry Disability Index (ODI). The association of CS and each parameter was statistically evaluated. Results: A total of 272 participants (average age: 72.1 years-old) were analyzed in this study, and 28.3% had cLBP. Average NRS, ODI and CSI scores were significantly higher in the cLBP group than in the without LBP (LBP-) group. There was a significant correlation between CSI and NRS scores (r=0.34, P<0.0001), ODI (r=0.60, P<0.0001), EQ5D (r=-0.55, P<0.0001) and EQ-VAS (r=-0.52, P<0.0001). A multiple regression analysis identified that ODI, EQ-VAS and age were factors significantly associated with CSI. Conclusion: The results of this study suggest that CS is involved in the pathological condition of cLBP in the local residents of a Japanese mountain village.

19.
Arthrosc Tech ; 10(4): e995-e1000, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33981542

RESUMO

Lateral ankle sprains are very common injuries that sometimes lead to chronic lateral ankle instability. The modified Broström operation is the gold standard procedure for treatment of chronic lateral ankle instability. Currently, this operation is performed arthroscopically. Broström repair depends on the quality of the remnant ligament. In cases with an insufficient remnant ligament, Gould augmentation or reconstruction using the gracilis tendon is generally performed. Recently, tape augmentation (internal brace) also has been used to support an insufficient ligament. This article introduces arthroscopic tape augmentation with arthroscopic modified Broström operation. This technique consists of creation of a talar anchor hole and fibular anchor hole, reattachment of the remnant ligament to the fibula with tape, and tape fixation to the talus. This technique uses only one knotless anchor screwed to the fibula for both the modified Broström operation and fixation of the tape. This technique is relatively simple and produces similar results as an open procedure.

20.
Bone Res ; 9(1): 26, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031366

RESUMO

Mechanical loading to the bone is known to be beneficial for bone homeostasis and for suppressing tumor-induced osteolysis in the loaded bone. However, whether loading to a weight-bearing hind limb can inhibit distant tumor growth in the brain is unknown. We examined the possibility of bone-to-brain mechanotransduction using a mouse model of a brain tumor by focusing on the response to Lrp5-mediated Wnt signaling and dopamine in tumor cells. The results revealed that loading the tibia with elevated levels of tyrosine hydroxylase, a rate-limiting enzyme in dopamine synthesis, markedly reduced the progression of the brain tumors. The simultaneous application of fluphenazine (FP), an antipsychotic dopamine modulator, enhanced tumor suppression. Dopamine and FP exerted antitumor effects through the dopamine receptors DRD1 and DRD2, respectively. Notably, dopamine downregulated Lrp5 via DRD1 in tumor cells. A cytokine array analysis revealed that the reduction in CCN4 was critical for loading-driven, dopamine-mediated tumor suppression. The silencing of Lrp5 reduced CCN4, and the administration of CCN4 elevated oncogenic genes such as MMP9, Runx2, and Snail. In summary, this study demonstrates that mechanical loading regulates dopaminergic signaling and remotely suppresses brain tumors by inhibiting the Lrp5-CCN4 axis via DRD1, indicating the possibility of developing an adjuvant bone-mediated loading therapy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...