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1.
Anticancer Res ; 41(10): 4947-4955, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593442

RESUMO

BACKGROUND/AIM: Auranofin (AUR), a thioredoxin reductase (TXNRD) inhibitor, shows anticancer activity against several cancers. This study investigated the effects of AUR on the local progression and pulmonary metastasis of osteosarcoma (OS). MATERIALS AND METHODS: Publicly available expression cohorts were analysed to study the relationship between TXNRD-2 expression and the survival of patients with OS. The murine OS cell line LM8 was stimulated with AUR. Cell viability, apoptosis-related protein levels, caspase activity, and wound healing were analysed. Tumor progression and pulmonary metastasis were investigated in C3H mice implanted with LM8 cells. RESULTS: High-level expression of TXNRD-2 represented a negative prognostic factor for metastasis and overall survival in patients with OS. AUR induced apoptosis of OS cells via the oxidative stress-MAPK-Caspase 3 pathway, and suppressed the migration of OS cells. AUR inhibited the pulmonary metastasis of OS, but not local progression. CONCLUSION: AUR represents a potential therapeutic drug for suppressing pulmonary metastasis of OS.


Assuntos
Auranofina/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Animais , Antirreumáticos/farmacologia , Apoptose , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Movimento Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos C3H , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Hum Cell ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665443

RESUMO

Undifferentiated pleomorphic sarcoma (UPS), previously termed malignant fibrous histiocytoma, is one of the most aggressive sarcomas with no identifiable line of differentiation. Although the molecular mechanism of oncogenesis in UPS has not been clarified, radiation exposure is considered to be a risk factor in the development of UPS. In the treatment of UPS, surgical treatment remains the most important modality. While chemotherapy is considered in unresectable or metastatic cases, UPS is known to be refractory to conventional chemotherapy, leading to an unfavorable prognosis. To improve the clinical outcome of this condition, novel treatment methods are urgently needed. Patient-derived cell lines are essential tools in preclinical studies. However, owing to the rarity of UPS, only four UPS cell lines are publicly available. Thus, we established a novel UPS cell line, NCC-UPS3-C1, using a surgically resected tumor from a patient with radiation-associated UPS. NCC-UPS3-C1 cells had multiple genomic deletions including the tumor suppressor genes CDKN2A and CDKN2B. NCC-UPS3-C1 cells demonstrated constant growth, spheroid formation, and aggressive invasion ability. We also conducted a screening test using 214 drugs and identified that the histone deacetylase inhibitor, romidepsin, is highly effective on NCC-UPS3-C1 cells. Thus, we concluded that the NCC-UPS3-C1 cell line is a useful tool in preclinical studies for UPS.

3.
Glia ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559433

RESUMO

Schwann cells (SCs) are known to produce extracellular vesicles (EV) that participate in cell-cell communication by transferring cargo to target cells, including mRNAs, microRNAs, and biologically active proteins. Herein, we report a novel mechanism whereby SC EVs may regulate PNS physiology, especially in injury, by controlling the activity of TNFα. SCs actively sequester tumor necrosis factor receptor-1 (TNFR1) into EVs at high density, accounting for about 2% of the total protein in SC EVs (~1000 copies TNFR1/EV). Although TNFR2 was robustly expressed by SCs in culture, TNFR2 was excluded from SC EVs. SC EV TNFR1 bound TNFα, decreasing the concentration of free TNFα available to bind to cells and thus served as a TNFα decoy. SC EV TNFR1 significantly inhibited TNFα-induced p38 MAPK phosphorylation in cultured SCs. When TNFR1 was proteolytically removed from SC EVs using tumor necrosis factor-α converting enzyme (TACE) or neutralized with antibody, the ability of TNFα to activate p38 MAPK in the presence of these EVs was restored. As further evidence of its decoy activity, SC EV TNFR1 modified TNFα activities in vitro including: (1) regulation of expression of other cytokines; (2) effects on SC morphology; and (3) effects on SC viability. SC EVs also modified the effects of TNFα on sciatic nerve morphology and neuropathic pain-related behavior in vivo. By sequestering TNFR1 in EVs, SCs may buffer against the potentially toxic effects of TNFα. SC EVs provide a novel mechanism for the spatial and temporal regulation of neuro-inflammation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34375755

RESUMO

OBJECTIVES: This study aimed to determine antibody responses in healthcare workers who receive the BNT162b2 mRNA COVID-19 vaccine and identify factors that predict the response. METHODS: We recruited healthcare workers receiving the BNT162b2 mRNA COVID-19 vaccine at the Chiba University Hospital COVID-19 Vaccine Center. Blood samples were obtained before the 1st dose and after the 2nd dose vaccination, and serum antibody titers were determined using Elecsys® Anti-SARS-CoV-2S, an electrochemiluminescence immunoassay. We established a model to identify the baseline factors predicting post-vaccine antibody titers using univariate and multivariate linear regression analyses. RESULTS: Two thousand fifteen individuals (median age 37-year-old, 64.3% female) were enrolled in this study, of which 10 had a history of COVID-19. Before vaccination, 21 participants (1.1%) had a detectable antibody titer (≥0.4 U/mL) with a median titer of 35.9 U/mL (interquartile range [IQR] 7.8 - 65.7). After vaccination, serum anti-SARS-CoV-2S antibodies (≥0.4 U/mL) were detected in all 1774 participants who received the 2nd dose with a median titer of 2060.0 U/mL (IQR 1250.0 - 2650.0). Immunosuppressive medication (p < 0.001), age (p < 0.001), time from 2nd dose to sample collection (p < 0.001), glucocorticoids (p = 0.020), and drinking alcohol (p = 0.037) were identified as factors predicting lower antibody titers after vaccination, whereas previous COVID-19 (p < 0.001), female (p < 0.001), time between 2 doses (p < 0.001), and medication for allergy (p = 0.024) were identified as factors predicting higher serum antibody titers. CONCLUSIONS: Our data demonstrate that healthcare workers universally have good antibody responses to the BNT162b2 mRNA COVID-19 vaccine. The predictive factors identified in our study may help optimize the vaccination strategy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34366414

RESUMO

STUDY DESIGN: A retrospective, single-center, observational study. OBJECTIVE: The aim of this study was to determine the prevalence and the characteristics of AIS patients with concomitant lumbar spondylolysis. SUMMARY OF BACKGROUND DATA: The prevalence and features of lumbar spondylolysis in patients with adolescent idiopathic scoliosis (AIS) are unclear. METHODS: We included 357 patients with AIS who underwent correction and fusion surgery. Preoperative CT images were used to assess the existence of lumbar spondylolysis. Cobb angles of the curves, parameters of spinal alignment, Lenke classification, and the presence of low back pain were compared between patients with and without spondylolysis. RESULTS: Of the patients included in the study, 6.1% had lumbar spondylolysis. They had significantly greater lumbar lordosis (LL) and sacral slope (SS) than those without lumbar spondylolysis. Logistic regression analyses and receiver-operating characteristic curves showed that LL was a significant risk factor (odds ratio: 1.059; 95% confidence interval: 1.018-1.103; P = 0.005) of associating lumbar spondylolysis with a cut off value of 56.5 degrees (area under the curve [AUC]: 0.689; sensitivity = 63.6%, specificity = 71.0%). CONCLUSION: We should be vigilant for lumbar spondylolysis in AIS patients whose LL and SS are large, especially with LL larger than 56.5 degrees.Level of Evidence: 3.

6.
J Orthop Sci ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34420843

RESUMO

BACKGROUND: When treating cancer patients, the progression of symptoms is accompanied by the deterioration of systemic conditions and motor function. From a risk-benefit perspective, a certain level of physical function must be maintained to continue cancer treatment. Recently, outpatient cancer treatment has become more common. Motor function is important to determine the feasibility of continuing cancer treatment. The study aimed to evaluate the motor function of patients with visceral cancer using locomo tests established by Japanese Orthopaedic Association. METHODS: Locomo tests were performed, and the results were compared with data from non-cancer individuals. Background data were matched by propensity score matching. Data from 53 cancer patients (group C) were compared with that of 75 non-cancer patients (group N). RESULTS: The average score in the two-step test of group C was lower than that of group N (1.27: 1.37, p = 0.004). The average function in the stand-up test of group C was worse than that of group N (p = 0.001). The average score in the 25-question geriatric locomotive function scale (GLFS) of group C was significantly higher than that of group N (19.92: 5.29, SE 2.21, p < 0.001). Higher 25-question GLFS scores indicate reduced mobility. The proportion of the locomo stage 2 in group C was significantly higher than in group N (51%: 13%, p < 0.001). The results of the two field tests revealed a clinically minimal difference between the two groups, but a statistically significant difference. Locomo tests may be detect potential motor dysfunction in outpatient cancer patients with apparently maintained motor function. CONCLUSIONS: Even in cancer patients who attend outpatient clinics, their motor functions could be potentially impaired. Therapeutic interventions to maintain and enhance motor function for cancer patients could be useful for continuing cancer treatment, and furthermore, improving prognosis.

7.
Yonsei Med J ; 62(9): 829-835, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34427069

RESUMO

PURPOSE: In this multicenter retrospective observational study, we examined the early effects of romosozumab in patients with severe osteoporosis in terms of time-course changes in bone metabolism marker, improvement in bone density, and adverse effects. MATERIALS AND METHODS: Patients with severe osteoporosis were included. We investigated the progress of TRACP 5b and P1NP before and 1-2 months after the administration of romosozumab. We also investigated the bone density of lumbar spine, femoral neck, and the entire femur, measured by the DXA method, before and 5-7 months after the administration of romosozumab. RESULTS: A total of 70 patients (7 males and 63 females, age 75.0±3.6 years) participated in this study. Significant improvements in TRACP 5b and P1NP levels were observed before and 1-2 months after romosozumab administration. The average bone density of lumbar spine, femoral neck, and the entire femur were measured before and 5-7 months after romosozumab administration; and a significant increase only observed in the lumbar spine. CONCLUSION: Consistent with the findings of previous clinical studies, romosozumab has both bone formation-enhancing and bone resorption effects (dual effect). In addition, romosozumab also demonstrated improvement in bone density from the early phase after the administration, though the result was only seen in the lumbar spine.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Idoso , Anticorpos Monoclonais , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Humanos , Vértebras Lombares , Masculino , Osteoporose/tratamento farmacológico , Estudos Retrospectivos
8.
Sci Rep ; 11(1): 16673, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404826

RESUMO

This study aimed to perform a comparative analysis of postoperative results between lumbar degenerative spondylolisthesis (LDS) treated with oblique lateral interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) from the Chiba spine surgery registry database. Sixty-five patients who underwent single-level OLIF (O group) for LDS with ≥ 3 years' follow-up were retrospectively reviewed. The control group comprised 78 patients who underwent single-level TLIF (T group). The analyzed variables included global alignment, radiological parameters of fused segments, asymptomatic and symptomatic ASD incidence, clinical outcomes at 3 years postoperatively using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire data, visual analogue scale scores for low back pain, lower extremity pain, and lower extremity numbness. There was no significant change in global alignment between the two groups. The rate of improvement in anterior intervertebral disc height was not significantly different between the groups at 1-month postoperatively. However, at the final evaluation, the anterior intervertebral disc height and incidence of asymptomatic ASD were significantly higher in the O group. There was no significant difference in symptomatic ASD, reoperation cases, or clinical results between groups. Thus, single-level OLIF can maintain the corrected disc height, but as it has no effect on global alignment, its benefit is limited.

9.
Spine (Phila Pa 1976) ; 46(15): E810-E816, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34228691

RESUMO

STUDY DESIGN: An in vivo model to study the effect of an injectable hyaluronic acid (HA) hydrogel following puncture-induced lumbar disc injury in rabbits. OBJECTIVES: The aim of this study was to determine the efficacy of an injectable HA hydrogel to maintain disc height and tissue hydration, promote structural repair, and attenuate inflammation and innervation in the lumbar discs. SUMMARY OF BACKGROUND DATA: Previously, we have demonstrated that HA hydrogel alleviated inflammation, innervation, and pain to promote disc repair. Nevertheless, the effect of an injectable HA hydrogel in the lumbar disc in a weight-bearing animal model was not performed. METHODS: We have adopted a surgically puncture-induced disc injury at lumbar levels in a rabbit model. The discs were grouped into sham, puncture with water injection, and puncture with HA hydrogel injection. Postoperatively, we measured changes in disc height using x-ray. We used magnetic resonance imaging to assess disc degeneration on tissue hydration after euthanasia. Post-mortem, we determined histological changes, innervation (PGP9.5) and inflammation (interleukin [IL]-6, IL-1ß, and tumor necrosis factor [TNF]-α) in the discs. RESULTS: We have demonstrated a significant reduction of disc height and T2/T1ρ mapping with histological evidence of degenerative discs, increase of innervation and inflammation in puncture-induced disc injury over time. In the HA hydrogel group, disc height was increased at weeks four and eight. A slight increase of T2 mapping, but significantly in T1ρ mapping, was observed in the HA hydrogel group at week 8. We observed homogenous NP distribution and organised AF lamellae at week eight and a slight reduced innervation score in the treatment group. HA hydrogel significantly downregulated IL-6 expression at day 1. This, however, was only slightly reduced for IL-1ß and TNF-α. CONCLUSION: An injectable HA hydrogel had the protective effects in suppressing the loss of disc height, promoting tissue hydration for structural repair, and attenuating inflammation and innervation to prevent further disc degeneration.Level of Evidence: N/A.


Assuntos
Ácido Hialurônico , Hidrogéis , Disco Intervertebral , Substâncias Protetoras , Animais , Modelos Animais de Doenças , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/farmacologia , Hidrogéis/administração & dosagem , Hidrogéis/farmacologia , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/lesões , Imageamento por Ressonância Magnética , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Coelhos
10.
Artigo em Inglês | MEDLINE | ID: mdl-34228215

RESUMO

PURPOSE: The clinical and radiological results of adult spinal deformity (ASD) patients with a severe lumbar sagittal deformity undergoing multilevel lateral lumbar interbody fusion (LLIF) + posterior spinal fusion (PSF) were compared to patients undergoing three-column osteotomy (3CO). METHODS: We defined severe lumbar sagittal deformity as fulcrum backward bending (FBB) pelvic incidence minus lumbar lordosis (PI-LL) ≧ 20 degrees. A total of twenty-five patients with an ASD were enrolled between 2013 and 2018. Fifteen patients were in the LLIF + PSF group, and ten patients were in the 3CO group. We evaluated patient demographics, clinical outcomes, and radiographic parameters such as the Cobb angle and spinopelvic parameters from standing X-ray films in each group. RESULTS: The LLIF + PSF group had a significantly shorter follow-up time than the 3CO group. Postoperatively, the LLIF + PSF group had significantly lower PI-LL and a shorter sagittal vertical axis than the 3CO group. Postoperative PI-LL changes in the LLIF + PSF group were significantly smaller than those in the 3CO group. There were no differences in other patient demographics, radiographic parameters, or clinical outcomes between the groups. CONCLUSION: Multilevel LLIF + PSF improved the PI-LL and SVA more than did 3CO for ASD patients with severe lumbar sagittal deformity. This indicated that the multilevel LLIF with open PSF can provide good clinical outcomes even in cases with severe lumbar sagittal deformity such as large FBB PI-LL in which 3CO techniques usually are needed.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34269892

RESUMO

INTRODUCTION: Unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are established treatments for medial compartment osteoarthritis (OA) or osteonecrosis (ON) of the knee joint, and the predominance of either procedure is inconclusive. We compared the awareness of the knee after UKA and HTO using the Forgotten joint score-12 (FJS). MATERIALS AND METHODS: This was a retrospective, multicenter study. Ninety-six knees of 90 patients who received UKA or HTO and were followed-up for at least 1 year were analyzed. Postoperative FJS was compared between the two groups and evaluated for the effect of patient-related factors and clinical outcomes. Multiple linear regression analysis was performed to predict FJS. RESULTS: There was no significant difference in the FJS between the UKA and HTO groups (p = 0.24). FJS did not correlate with any of the patient-related factors. There was a correlation between the FJS and each item of the Knee Injury and Osteoarthritis Outcome Scores (KOOS) and Lysholm Knee Scoring Scale (LKS). In multiple linear regression analysis, lower BMI, the diagnosis of OA Kellgren-Lawrence (KL) grade ≥ 3, and ON were significant predictors of better FJS. In both groups, FJS was correlated with each item of the KOOS and LKS. Internal consistency in terms of Cronbach's alpha was excellent. CONCLUSIONS: There was no significant difference in FJS between patients who underwent UKA and HTO. Lower BMI, the diagnosis of OA KL grade ≥ 3, and ON were significant predictors of better FJS.

12.
Anticancer Res ; 41(8): 4027-4032, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281869

RESUMO

BACKGROUND/AIM: We aimed to investigate the effectiveness of postoperative radiotherapy (RT) on local recurrence-free survival (LRFS) in high-grade infiltrative soft tissue sarcomas (STSs) and determine its prognostic factors. PATIENTS AND METHODS: This was a retrospective cohort study and included 132 patients with high-grade STSs. Patients were divided into two groups: Group RT (n=48) who underwent postoperative RT and Group No-RT (n=84) who underwent only surgery. We analysed 5-year LRFS and its prognostic factors between these groups. Furthermore, 5-year LRFS in infiltrative and non-infiltrative STSs were evaluated. RESULTS: Five-year LRFS was not significantly different in Group RT (83.6%) and Group No-RT (79.6%) (p=0.698). Overall, significant prognostic factors influencing LRFS were age at diagnosis (p=0.02) and tumour growth pattern (p=0.04). Postoperative RT was less effective in the infiltrative than in non-infiltrative pattern of STSs. CONCLUSION: Postoperative RT does not influence local recurrence outcomes in infiltrative STSs.


Assuntos
Neoplasias de Tecidos Moles/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Estudos Retrospectivos , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Adulto Jovem
13.
Spine J ; 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34116218

RESUMO

BACKGROUND CONTEXT: Chronic low back pain (LBP) is a multifactorial disorder with complex underlying mechanisms, including associations with intervertebral disc (IVD) degeneration in some individuals. It has been demonstrated that epigenetic processes are involved in the pathology of IVD degeneration. Epigenetics refers to several mechanisms, including DNA methylation, that have the ability to change gene expression without inducing any change in the underlying DNA sequence. DNA methylation can alter the entire state of a tissue for an extended period of time and thus could potentially be harnessed for long-term pain relief. Lifestyle factors, such as physical activity, have a strong influence on epigenetic regulation. Exercise is a commonly prescribed treatment for chronic LBP, and sex-specific epigenetic adaptations in response to endurance exercise have been reported. However, whether exercise interventions that attenuate LBP are associated with epigenetic alterations in degenerating IVDs has not been evaluated. PURPOSE: We hypothesize that the therapeutic efficacy of physical activity is mediated, at least in part, at the epigenetic level. The purpose of this study was to use the SPARC-null mouse model of LBP associated with IVD degeneration to clarify (1) if IVD degeneration is associated with altered expression of epigenetic regulatory genes in the IVDs, (2) if epigenetic regulatory machinery is sensitive to therapeutic environmental intervention, and (3) if there are sex-specific differences in (1) and/or (2). STUDY DESIGN: Eight-month-old male and female SPARC-null and age-matched control (WT) mice (n=108) were assigned to exercise (n=56) or sedentary (n=52) groups. Deletion of SPARC is associated with progressive IVD degeneration and behavioral signs of LBP. The exercise group received a circular plastic home cage running wheel on which they could run freely. The sedentary group received an identical wheel secured in place to prevent rotation. After 6 months, the results obtained in each group were compared. METHODS: After 6 months of exercise, LBP-related behavioral indices were determined, and global DNA methylation (5-methylcytosine) and epigenetic regulatory gene mRNA expression in IVDs were assessed. This project was supported by the Canadian Institutes for Health Research. The authors have no conflicts of interest. RESULTS: Lumbar IVDs from WT sedentary and SPARC-null sedentary mice had similar levels of global DNA methylation (%5-mC) and comparable mRNA expression of epigenetic regulatory genes (Dnmt1,3a,b, Mecp2, Mbd2a,b, Tet1-3) in both sexes. Exercise attenuated LBP-related behaviors, decreased global DNA methylation in both WT (p<.05) and SPARC-null mice (p<.01) and reduced mRNA expression of Mecp2 in SPARC-null mice (p<.05). Sex-specific effects of exercise on expression of mRNA were also observed. CONCLUSIONS: Exercise alleviates LBP in a mouse model. This may be mediated, in part, by changes in the epigenetic regulatory machinery in degenerating IVDs. Epigenetic alterations due to a lifestyle change could have a long-lasting therapeutic impact by changing tissue homeostasis in IVDs. CLINICAL SIGNIFICANCE: This study confirmed the therapeutic benefits of exercise on LBP and suggests that exercise results in sex-specific alterations in epigenetic regulation in IVDs. Elucidating the effects of exercise on epigenetic regulation may enable the discovery of novel gene targets or new strategies to improve the treatment of chronic LBP.

14.
Cartilage ; : 19476035211021905, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34105400

RESUMO

OBJECTIVE: Cartilage lesions in the knee joint can lead to joint mechanics changes and cause knee pain. Bone marrow stimulation (BMS) promotes cartilage regeneration by perforating the subchondral bone just below the injury and inducing bone marrow cells. This study aimed to investigate whether systemic administration of granulocyte colony-stimulating factor (G-CSF) with BMS improves repair of chronic partial-thickness cartilage defects (PTCDs). DESIGN: Eighteen 6-month-old New Zealand white rabbits were divided into 3 groups: control (C, n = 6), BMS alone (n = 6), and BMS + G-CSF (n = 6). Partial cartilage defects with 5 mm diameter were created in the trochlear region of both knees; after 4 weeks, the BMS alone and BMS + G-CSF groups underwent BMS; G-CSF (50 µg/kg) or saline was administered subcutaneously for 5 days starting from 3 days before BMS. At 8 and 16 weeks after cartilage defect creation, the area of cartilage defects was macroscopically and histologically evaluated. RESULTS: International Cartilage Repair Society (ICRS) grades for macroscopic assessment were 0, 0.7, and 0.7 at 8 weeks and 0, 1.2, and 1.3 at 16 weeks in the C, BMS, and BMS + G-CSF groups, respectively. Wakitani scores for histological assessment were 9.8, 8.7, and 8.2 at 8 weeks and 9.5, 9, and 8.2 at 16 weeks in the C, BMS, and BMS + G-CSF groups, respectively. The BMS + G-CSF group showed significantly more repair than the C group, but there was no difference from the BMS group. CONCLUSIONS: The effect of BMS and G-CSF on chronic PTCDs in mature rabbit knees was limited.

15.
Hum Cell ; 34(5): 1569-1578, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34164773

RESUMO

Spindle cell/sclerosing rhabdomyosarcoma (ssRMS) is a rare subtype of rhabdomyosarcoma (RMS) that has fascicular spindle cell and/or sclerosing morphology. SsRMS has a diverse molecular background and is categorized into three groups: congenital/infantile ssRMS with a gene fusion involving the NCOA2 and VGLL2, ssRMS with the MYOD1 mutation, and ssRMS with no recurrent identifiable genetic alterations. Because ssRMS is a newly defined disease concept of RMS, the optimal treatment methods have not been determined. This results in unfavorable prognosis and consequently signals the urgent need for continuous research. Patient-derived cell lines are essential tools in basic and translational research. However, only two ssRMS cell lines with the MYOD1 mutation have been reported to date. Thus, we established a novel ssRMS cell line named NCC-ssRMS2-C1 using a surgically resected tumor tissue from an adult ssRMS patient. NCC-ssRMS2-C1 cells retained the copy number alterations corresponding to the original tumor and are categorized into the group with no recurrent identifiable genetic alterations. NCC-ssRMS2-C1 cells demonstrated constant proliferation, spheroid formation, and capability for invasion in vitro, reflecting the malignant features of the original tumor tissue. In a drug screening test, ssRMS demonstrated remarkable sensitivity to romidepsin, trabectedin, actinomycin D, and bortezomib. Hence, we conclude that the NCC-ssRMS2-C1 cell line is the first ssRMS cell line which belongs to the group with no recurrent identifiable genetic alterations, and it will be a useful resource in both basic and translational studies for ssRMS.

16.
Sci Rep ; 11(1): 12702, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135404

RESUMO

Cervical ossification of the posterior longitudinal ligament (OPLL) is a contributing factor to spinal cord injury or trauma-induced myelopathy in the elderly. To reduce the incidence of these traumas, it is essential to diagnose OPLL at an early stage and to educate patients how to prevent falls. We thus evaluated the ability of our convolutional neural network (CNN) to differentially diagnose cervical spondylosis and cervical OPLL. We enrolled 250 patients with cervical spondylosis, 250 patients with cervical OPLL, and 180 radiographically normal controls. We evaluated the ability of our CNN model to distinguish cervical spondylosis, cervical OPLL, and controls, and the diagnostic accuracy was compared to that of 5 board-certified spine surgeons. The accuracy, average recall, precision, and F1 score of the CNN for classification of lateral cervical spine radiographs were 0.86, 0.86, 0.87, and 0.87, respectively. The accuracy was higher for CNN compared to any expert spine surgeon, and was statistically equal to 4 of the 5 experts and significantly higher than that of 1 expert. We demonstrated that the performance of the CNN was equal or superior to that of spine surgeons.

17.
Breast Cancer Res Treat ; 188(3): 649-659, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33934277

RESUMO

PURPOSE: Diagnosis of breast preneoplastic and neoplastic lesions is difficult due to their similar morphology in breast biopsy specimens. To diagnose these lesions, pathologists perform immunohistochemical analysis and consult with expert breast pathologists. These additional examinations are time-consuming and expensive. Artificial intelligence (AI)-based image analysis has recently improved, and may help in ordinal pathological diagnosis. Here, we showed the significance of machine learning-based image analysis of breast preneoplastic and neoplastic lesions for facilitating high-throughput diagnosis. METHODS: Images were obtained from normal mammary glands, hyperplastic lesions, preneoplastic lesions and neoplastic lesions, such as usual ductal hyperplasia (UDH), columnar cell lesion (CCL), ductal carcinoma in situ (DCIS), and DCIS with comedo necrosis (comedo DCIS) in breast biopsy specimens. The original enhanced convoluted neural network (CNN) system was used for analyzing the pathological images. RESULTS: The AI-based image analysis provided the following area under the curve values (AUC): normal lesion versus DCIS, 0.9902; DCIS versus comedo DCIS, 0.9942; normal lesion versus CCL, 0.9786; and UDH versus DCIS, 1.000. Multiple comparison analysis showed precision and recall scores similar to those of single comparison analysis. Based on the gradient-weighted class activation mapping (Grad-CAM) used to visualize the important regions reflecting the result of CNN analysis, the ratio of stromal tissue in the whole weighted area was significantly higher in UDH and CCL than that in DCIS. CONCLUSIONS: These analyses may provide a more accurate and rapid pathological diagnosis of patients. Moreover, Grad-CAM identifies uncharted important histological characteristics for newer pathological findings and targets of research for understanding diseases.


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Inteligência Artificial , Biópsia , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Hiperplasia/patologia , Aprendizado de Máquina
18.
Foot Ankle Int ; 42(10): 1270-1276, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34018427

RESUMO

BACKGROUND: Evaluation over time is important in assessing the reduction of the syndesmosis after suture-button fixation for ankle malleolar fractures. The purposes of this study were to evaluate time-dependent change in the syndesmotic reduction immediately after suture-button fixation for ankle malleolus fractures and 1 year after surgery using computed tomography, and to investigate the reliability of the measurement values to evaluate the reduction of syndesmosis. METHODS: We assessed 28 patients who underwent suture-button fixation for ankle fractures. Syndesmotic reduction was assessed within 2 weeks of the fracture surgery and 1 year after surgery using axial computer tomographic images. Side-to-side differences in the anterior, central, and posterior tibiofibular distances, anteroposterior fibular translation, fibular rotation, and syndesmosis area were measured. RESULTS: The mean anterior tibiofibular distance and anteroposterior fibular translation were 1.8 mm and 1.5 mm, respectively, after syndesmotic fixation. They decreased to 1.2 mm and 0.6 mm, respectively, at 1 year after surgery (P = .03 and P = .01, respectively). The other measurement values did not change over time. The minimum detectable change in the distance of measurements was 1 mm or less. CONCLUSION: The anterior tibiofibular distance and anteroposterior fibular translation had decreased 1 year after fixation in ankle malleolar fractures with syndesmotic suture button. Even if the fibula is posteriorly malreduced by the time computed tomography is performed immediately after surgery, the fibula may return to a good position 1 year after surgery. LEVEL OF EVIDENCE: Level IV, case series.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34027925

RESUMO

STUDY DESIGN: A retrospective analysis of prospectively collected data. OBJECTIVE: This study aimed to create a prognostic model for surgical outcomes in patients with cervical ossification of the posterior longitudinal ligament (OPLL) using machine learning (ML). SUMMARY OF BACKGROUND DATA: Determining surgical outcomes helps surgeons provide prognostic information to patients and manage their expectations. ML is a mathematical model that finds patterns from a large sample of data and makes predictions outperforming traditional statistical methods. METHODS: Out of 478 patients, 397 and 370 patients had complete follow-up information at 1 and 2 year respectively and were included in the analysis. A minimal clinically important difference (MCID) was defined as an acquired Japanese Orthopaedic Association (JOA) score of 2.5 points or more, after which a ML model that predicts whether MCID can be achieved 1 and 2 years after surgery was created. Patient background, clinical symptoms, and imaging findings were used as variables for analysis. The ML model was created using LightGBM, XGBoost, random forest, and logistic regression, after which the accuracy and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS: The mean JOA score was 10.3 preoperatively, 13.4 at 1 year after surgery, and 13.5 at 2 years after surgery. XGBoost showed the highest AUC (0.72) and high accuracy (67.8) for predicting MCID at 1 year, while random forest had the highest AUC (0.75) and accuracy (69.6) for predicting MCID at 2 years. Among the included features, total preoperative JOA score, duration of symptoms, body weight, sensory function of the lower extremity sub-score of the JOA, and age were identified as having the most significance in most of ML models. CONCLUSION: Constructing a prognostic ML model for surgical outcomes in patients with OPLL is feasible, suggesting the potential application of ML for predictive models of spinal surgery.Level of Evidence: 4.

20.
BMC Musculoskelet Disord ; 22(1): 416, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952226

RESUMO

BACKGROUND: The appropriate position of retractors to minimize the risk of femoral nerve palsy remains uncertain. The purpose of this imaging study was to evaluate the distance between the femoral nerve (FN) and anterior acetabulum (AA) in hip osteoarthritis (OA). METHODS: Forty-one patients with unilateral hip OA underwent magnetic resonance imaging. Three measurement levels were defined and the minimum distance between the femoral nerve (FN) margin and anterior acetabulum (AA) rim was measured on axial T1-weighted images on the OA and normal sides at each level, with reference to an advanced neurography view. The cross-sectional area (CSA) of the iliopsoas muscle was also measured at each level bilaterally by three observers. Distances and CSAs were compared between the OA and normal side. Multiple regression analysis was performed to identify variables associated with the distance in OA. RESULTS: The mean minimum FN to AA distances in OA were 19.4 mm at the top of the anterior inferior iliac spine (AIIS), 24.3 mm at the bottom of the AIIS, and 21.0 mm at the tip of the greater trochanter. These distances were significantly shorter than in normal hips at the top and bottom of the AIIS, with mean differences of 1.6 and 5.8 mm, respectively (p = 0.012, p < 0.001). CSAs of the iliopsoas in OA were significantly smaller at all levels (all p < 0.001), with reductions of 10.5 to 17.9%. The CSA of the iliopsoas at the bottom of the AIIS was associated with the FN to AA distance at the same level (p = 0.026). Interobserver reliabilities for measurements were very good to perfect (intraclass correlation coefficients 0.897 to 0.966). CONCLUSIONS: To minimize the risk of femoral nerve palsy, surgeons should consider the change of the femoral nerve to anterior acetabulum distance in osteoarthritic hip surgery.


Assuntos
Artroplastia de Quadril , Osteoartrite do Quadril , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Nervo Femoral/diagnóstico por imagem , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Humanos , Osteoartrite do Quadril/diagnóstico por imagem
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