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1.
Br J Cancer ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017658

RESUMO

BACKGROUND: Dedifferentiated chondrosarcoma (DDCS) is an aggressive bone tumour with a poor prognosis and no effective treatment. Because changes in DNA methylation play critical roles in DDCS, we explored the roles that DNA methylation plays in oncogenesis to potentially identify an effective epigenetic treatment. METHODS: We identified genes downregulated in DDCS vs. conventional chondrosarcoma (CCS) due to DNA methylation using in silico analysis. The results were validated in DDCS clinical samples, and the molecular functions of the genes of interest were investigated in multiple chondrosarcoma cell lines (NDCS-1, SW1353, and OUMS-27). The therapeutic effect of decitabine, a DNA methyltransferase inhibitor, was evaluated in vitro and in vivo. RESULTS: PRKCZ was specifically downregulated by DNA methylation in DDCS. Overexpression of PRKCZ decreased the proliferation of NDCS-1 and SW1353 cells. PRKCZ directly bound to and activated ATM, which was followed by phosphorylation of CHK2 and subsequent apoptosis. Decitabine increased PRKCZ expression through de-methylating the promoter region of PRKCZ, which activated the ATM/CHK2 pathway and inhibited cell proliferation by inducing apoptosis. CONCLUSIONS: Increased DNA methylation and reduced expression of PRKCZ prevents apoptosis via inactivation of the ATM/CHK2 pathway in DDCS. Decitabine-induced expression of PRKCZ represents a promising therapy for DDCS.

2.
Calcif Tissue Int ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34989822

RESUMO

Bone material quality is important for evaluating the mechanical integrity of diseased and/or medically treated bones. However, compared to the knowledge accumulated regarding changes in bone mass, our understanding of the quality of bone material is lacking. In this study, we clarified the changes in bone material quality mainly characterized by the preferential orientation of the apatite c-axis associated with estrogen deficiency-induced osteoporosis, and their prevention using ibandronate (IBN), a nitrogen-containing bisphosphonate. IBN effectively prevented bone loss and degradation of whole bone strength in a dose-dependent manner. The estrogen-deficient condition abnormally increased the degree of apatite orientation along the craniocaudal axis in which principal stress is applied; IBN at higher doses played a role in maintaining the normal orientation of apatite but not at lower doses. The bone size-independent Young's modulus along the craniocaudal axis of the anterior cortical shell of the vertebra showed a significant and positive correlation with apatite orientation; therefore, the craniocaudal Young's modulus abnormally increased under estrogen-deficient conditions, despite a significant decrease in volumetric bone mineral density. However, the abnormal increase in craniocaudal Young's modulus did not compensate for the degradation of whole bone mechanical properties due to the bone loss. In conclusion, it was clarified that changes in the material quality, which are hidden in bone mass evaluation, occur with estrogen deficiency-induced osteoporosis and IBN treatment. Here, IBN was shown to be a beneficial drug that suppresses abnormal changes in bone mechanical integrity caused by estrogen deficiency at both the whole bone and material levels.

3.
Bone ; 157: 116309, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34998980

RESUMO

Combination therapy with bisphosphonates and vitamin D3 analogs has been frequently used for the treatment of osteoporosis. However, its effects on bone anisotropies, such as orientations of collagen and apatite at the nanometer-scale, which is a promising bone quality index, and its trabecular architecture at the micrometer scale, are not well understood despite its important mechanical properties and its role in fracture risk. In the present study, we analyzed the effects of ibandronate (IBN), eldecalcitol (ELD), and their combination on the collagen/apatite orientation and trabecular architectural anisotropy using an estrogen-deficiency-induced osteoporotic rat model. Estrogen deficiency caused by ovariectomy (OVX) excessively increased the degree of collagen/apatite orientation or trabecular architectural anisotropy along the craniocaudal axis in the lumbar vertebra compared to that of the sham-operated group. The craniocaudal axis corresponds to the direction of principal stress in the spine. The excessive material anisotropy in the craniocaudal axis contributed to the enhanced Young's modulus, which may compensate for the reduced mechanical resistance by bone loss to some extent. The solo administration of IBN and ELD prevented the reduction of bone fraction (BV/TV) determined by µ-CT, and combination therapy showed the highest efficacy in BV/TV gain. Furthermore, the solo administration and combination treatment significantly decreased the degree of collagen/apatite orientation to the sham level. Based on the results of bone mass and collagen/apatite orientation, combination treatment is an effective strategy. This is the first report to demonstrate the efficacy of IBN, ELD, and combination treatment with IBN and ELD relative to the bone micro-architectural anisotropy characterized by collagen/apatite orientation.

4.
BMC Cancer ; 22(1): 94, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35062915

RESUMO

BACKGROUND: Preoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); however, the prognostic significance of histological response to chemotherapy remains controversial. This study aimed to standardize evaluation method of histological response to chemotherapy with high agreement score among pathologists, and to establish a cut-off value closely related to prognosis. METHODS: Using data and specimens from the patients who had registered in the Japan Clinical Oncology Group study, JCOG0304, a phase II trial evaluating the efficacy of perioperative chemotherapy with doxorubicin (DOX) and ifosfamide (IFO), we evaluated histological response to preoperative chemotherapy at the central review board. RESULTS: A total of 64 patients were eligible for this study. The percentage of viable tumor area ranged from 0.1% to 97.0%, with median value of 35.7%. Regarding concordance proportion between pathologists, the weighted kappa coefficient (κ) score in all patients was 0.71, indicating that the established evaluation method achieved substantial agreement score. When the cut-off value of the percentage of the residual tumor area was set as 25%, the p-value for the difference in overall survival showed the minimum value. Hazard ratio of the non-responder with percentage of the residual tumor < 25%, to the responder was 4.029 (95% confidence interval 0.893-18.188, p = 0.070). CONCLUSION: The standardized evaluation method of pathological response to preoperative chemotherapy showed a substantial agreement in the weighted κ score. The evaluation method established here was useful for estimating of the prognosis in STS patients who were administered perioperative chemotherapy with DOX and IFO. TRIAL REGISTRATION: UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

5.
Asian J Psychiatr ; 67: 102952, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34891065

RESUMO

Several psychotropic drugs can cause cytopenia, especially after increasing dosages or initiating treatment. However, cytopenia in patients with psychiatric disorders can also be due to other conditions such as leukemia. In this report, we discuss two cases of cytopenia that occurred during the adjustment of psychotropic medications in patients with severe psychiatric illness. The initial diagnosis in each case was drug-induced cytopenia; however, later, the cause of cytopenia was found to be acute promyelocytic leukemia. When cytopenia is observed while increasing the dosage of psychotropic drugs, suspicious drugs should be discontinued, though the possibility that cytopenia could be due to other reasons should be considered. If there are no signs of recovering blood cells or if cytopenia is severe, psychiatrists should consult hematologists promptly.

6.
Nagoya J Med Sci ; 83(4): 673-681, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34916712

RESUMO

The efficacy and safety of cyclooxygenase 2 (COX2) inhibitors for the treatment of desmoid-type fibromatosis (DF) are unclear. Therefore, we systematically reviewed related literature to assess the efficacy and safety of COX2 inhibitors for DF treatment. We searched pertinent literature between January 1999 and August 2017 to identify relevant studies using the keywords "Fibromatosis, aggressive" and "Cyclooxygenase inhibitors." Thereafter, we screened and determined the quality of the studies using the Grading of Recommendations Assessment, Development, and Evaluation system and extracted the article data. The critical outcomes selected were the efficacy and adverse effects of COX2 inhibitors. Efficacy was evaluated in terms of clinical benefit when patients showed complete response, partial response, and stable disease. Thirty-one articles were identified from the database search, and one was identified through the reviewers' manual search. Finally, we retrieved six studies, including three case reports, comprising 89 patients after the first and second screenings. Fifty-three patients were excluded because three studies were reported from the same institution; hence, in total, 36 patients were included. Clinical benefit was noted in 64% of the patients. Three adverse effects were identified from the records of the six extracted studies. The strategy of watchful waiting using COX2 inhibitors with few side effects is weakly recommended for DF, especially DF patients with pain.

7.
Oncology ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34915507

RESUMO

Introduction Radiation-associated sarcoma (RAS) is one of the most life-threatening complications associated with the treatment of malignant neoplasms. Because all RAS patients have a history of radiotherapy, there have been no effective treatment options when RAS is not completely resected. Methods We retrospectively reviewed 20 RAS patients, including 4 unresectable cases treated by carbon ion radiotherapy (CIRT). Results The primary diseases targeted by radiotherapy included malignant lymphoma (n=4), cervical cancer (n=3), pharyngeal cancer (n=3), breast cancer (n=2), lung cancer (n=1), rectal cancer (n=1), maxillary cancer (n=1), synovial sarcoma (n=1), and benign neoplasms (n=4). The histological diagnoses of RAS included osteosarcoma (n=8), leiomyosarcoma (n=3), undifferentiated pleomorphic sarcoma (n=3), rhabdomyosarcoma (n=1), angiosarcoma (n=1), malignant peripheral nerve sheath tumor (n=1), spindle cell sarcoma NOS (n=1), and sarcoma not further specified (n=2). The median survival time from the diagnosis of RAS was 26 months. Eleven patients underwent surgery. Five of these patients achieved a continuous disease free status or showed no evidence disease. Four patients underwent CIRT. One of these patients with leiomyosarcoma achieved a continuous disease free status, and the other patient with osteosarcoma achieved a partial response. On the other hand, 2 patients experienced Grade 3 toxicities that required surgical treatment. Conclusion RAS originates from various types of diseases that are treated by radiotherapy and shows diverse pathological features. Complete resection achieves a good prognosis. CIRT can be an effective and feasible option for unresectable RAS.

8.
Oncology ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724663

RESUMO

INTRODUCTION: Fanconi anemia complementation group E (FANCE) is a Fanconi anemia (FA) pathway gene that regulates DNA repair. We evaluated the clinical relevance of FANCE expression in hepatocellular carcinoma (HCC). METHODS: First, the associations between the expression of FA pathway genes including FANCE and clinical outcomes in HCC patients were analyzed in two independent cohorts: The Cancer Genome Atlas (TCGA, n = 373) and our patient cohort (n = 53). Localization of FANCE expression in HCC tissues was observed by immunohistochemical staining. Gene set enrichment analysis (GSEA) and gene network analysis (SiGN_BN) were conducted using the TCGA dataset. Next, an in vitro proliferation assay was performed using FANCE-knockdown HCC cell lines (HuH7 and HepG2). The association between mRNA expression of FANCE and that of DNA damage response genes in HCC was analyzed using TCGA and Cancer Cell Line Encyclopedia datasets. Finally, the association between FANCE mRNA expression and overall survival (OS) in various digestive carcinomas was analyzed using TCGA data. RESULTS: FANCE was highly expressed in HCC cells. Multivariate analysis indicated that high FANCE mRNA expression was an independent factor predicting poor OS. GSEA revealed a positive relationship between enhanced FANCE expression and E2F and MYC target gene expression in HCC tissues. FANCE knockdown attenuated the proliferation of HCC cells, as well as reduced cdc25A expression and elevated histone H3 pSer10 expression. SiGN_BN revealed that FANCE mRNA expression was positively correlated with DNA damage response genes (H2AFX and CHEK1) in HCC tissues. Significant effects of high FANCE expression on OS were observed in hepatobiliary pancreatic carcinomas, including HCC. CONCLUSIONS: FANCE may provide a potential therapeutic target and biomarker of poor prognosis in HCC, possibly by facilitating tumor proliferation, which is mediated partly by cell cycle signaling activation.

9.
Inflamm Regen ; 41(1): 34, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34724990

RESUMO

BACKGROUND: Neuropathic pain in neuroimmunological disorders refers to pain caused by a lesion or disease of the somatosensory system such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MS and NMOSD are autoimmune disorders of the central nervous system, and ≥ 50% of patients with these disorders experience chronic neuropathic pain. The currently available medications for the management of neuropathic pain have limited effectiveness in patients with MS and NMOSD, and there is an unmet medical need to identify novel therapies for the management of chronic neuropathic pain in these patients. In this review article, we summarize the role of interleukin-6 (IL-6) in the pathogenesis of MS and NMOSD and the ameliorative effects of anti-IL-6 therapies in mouse models of experimental autoimmune encephalomyelitis (EAE). MAIN BODY: Intraperitoneal injection of MR16-1, an anti-IL-6 receptor (IL-6R) antibody, reduced mechanical allodynia and spontaneous pain in EAE mice, which was attributed to a reduction in microglial activation and inhibition of the descending pain inhibitory system. The effect of anti-IL-6 therapies in ameliorating neuropathic pain in the clinical setting is controversial; a reduction in pain intensity has been reported with an anti-IL-6 antibody in four studies, namely a case report, a pilot study, a retrospective observational study, and a case series. Pain intensity was evaluated using a numerical rating scale (NRS), with a lower score indicating lesser pain. A reduction in the NRS score was reported in all four studies. However, in two randomized controlled trials of another anti-IL-6R antibody, the change in the visual analog scale pain score was not statistically significantly different when compared with placebo. This was attributed to the low mean pain score at baseline in both the trials and the concomitant use of medications for pain in one of the trials, which may have masked the effects of the anti-IL-6R antibody on neuropathic pain. CONCLUSION: Thus, anti-IL-6 therapies might have a potential to reduce neuropathic pain, but further investigations are warranted to clarify the effect of inhibition of IL-6 signaling on neuropathic pain associated with MS and NMOSD.

10.
Bone ; 155: 116261, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34826630

RESUMO

Although increased bone fragility is a well-recognized consequence in patients with rheumatoid arthritis (RA), the essential cause of degenerate bone strength remains unknown. This study aimed to determine factors contributing to bone dysfunction in RA by focusing on the bone matrix micro-arrangement, based on the preferential orientation of collagen and the related apatite c-axis as a bone quality index. The classical understanding of RA is limited to its severe pathological conditions associated with inflammation-induced bone loss. This study examined periarticular proximal tibiae from RA patients as compared with osteoarthritis (OA) patients as controls. Bone tissue material strength was disrupted in the RA group compared with the control. Collagen/apatite micro-arrangement and vBMD were significantly lower in the RA group, and the rate of decrease in apatite c-axis orientation (-45%) was larger than that in vBMD (-22%). Multiple regression analysis showed that the degree of apatite c-axis orientation (ß = 0.52, p = 1.9 × 10-2) significantly contributed to RA-induced bone material impairment as well as vBMD (ß = 0.46, p = 3.8 × 10-2). To the best of our knowledge, this is the first report to demonstrate that RA reduces bone material strength by deteriorating the micro-arrangement of collagen/apatite bone matrix, leading to decreased fracture resistance. Our findings represent the significance of bone quality-based analysis for precise evaluation and subsequent therapy of the integrity and soundness of the bone in patients with RA.

11.
J Clin Med ; 10(21)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34768491

RESUMO

Pazopanib, trabectedin, and eribulin are administered for the treatment of soft tissue sarcomas (STSs); however, there is little consensus on which agent should be preferentially used in a clinical setting. This study assessed whether peripheral immune-related markers served as a useful reference when selecting pazopanib, trabectedin, or eribulin. This study included 63 patients who were administered pazopanib, trabectedin, or eribulin for advanced STSs between March 2015 and December 2020. Patients were divided into three groups based on the first drug administered among these three drugs. Differences in overall survival (OS) or progression-free survival (PFS) among the three groups were analyzed. OS showed no significant differences among the drugs administered first. For patients with low neutrophil-to-lymphocyte ratio (NLR), the OS of patients administered pazopanib as the first choice was shorter than the others (hazard ratio [HR] = 9.53, 95% confidence interval [CI] = 1.94-18.13, p = 0.0018). In the low platelet-to-lymphocyte ratio (PLR) subgroup, the OS of the patients administered eribulin for the first choice was longer than that of the others (HR = 0.32, 95%CI = 0.10-0.98, p = 0.046). Therefore, NLR and PLR might be used as prognostic indicators to dictate whether STS patients receive pazopanib, trabectedin, or eribulin.

12.
Pathol Res Pract ; 228: 153668, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34773915

RESUMO

Synovial sarcoma (SS) is a malignant soft tissue neoplasm harboring SS18-SSX fusion gene and is histologically characterized by spindle cells and epithelial components. Some investigations have demonstrated that desmoplastic reaction (DR) is an independent prognostic factor of cancers. However, it remains unknown whether DR is of predictive value for the prognosis of synovial sarcoma patients. Here, we reviewed the clinical and histological findings of 88 patients with SS. We defined DR as hyalinized collagenous structures and classified the degree of DR as follows: none, mild, moderate, and severe. Overall, 23 SS cases (24%) showed moderate or severe DR histologically. Statistically, the cases with moderate or severe degree of DR showed poorer prognosis than those with no or mild DR (local recurrence: P = 0.0059, distant metastasis: P = 0.0002, tumor death: P = 0.0382). The findings of the study suggest that the DR of synovial sarcoma could be an important prognostic factor.

13.
Mod Pathol ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34785767

RESUMO

In rare cases, giant cell tumor of bone (GCTB) can undergo primary or secondary malignant transformation to malignant giant cell tumor of bone (MGCTB), but the details of the molecular alterations are still unclear. The present study aimed to elucidate the clinicopathologic and molecular features of MGCTBs based on immunohistochemistry, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) of nine MGCTBs (five primary and four secondary). Seven (78%) of 9 MGCTBs were immunohistochemically positive for H3.3 G34W. In two (22%) patients, although GCTB components were focally or diffusely positive for H3.3 G34W, their malignant components were entirely negative for H3.3 G34W, which was associated with heterozygous loss of H3F3A by FISH. NGS on four MGCTBs revealed pathogenic mutations in TP53 (n = 3), EZH2 (n = 1) and several other genes. Immunohistochemical analysis of the nine MGCTBs confirmed the p53 nuclear accumulation (n = 5) and loss of H3K27me3 expression (n = 3) and showed that they were mutually exclusive. In addition, four (80%) of five cases of pleomorphic or epithelioid cell-predominant MGCTBs were positive for p53, while three (75%) of four cases of spindle cell-predominant MGCTBs were negative for trimethylation at lysine 27 of histone 3 (H3K27me3). The results suggested that p53 alteration and dysfunction of histone methylation as evidenced by H3K27me3 loss may play an important role in the malignant progression of GCTB, and might contribute to the phenotype-genotype correlation in MGCTB. The combined histologic, immunohistochemical and molecular information may be helpful in part for the diagnosis of challenging cases.

14.
Cancer Sci ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34704338

RESUMO

Colorectal cancer (CRC) is one of the most common types of cancer and a significant cause of cancer mortality worldwide. Further improvements of CRC therapeutic approaches are needed. BCL2-associated athanogene 6 (BAG6), a multifunctional scaffold protein, plays an important role in tumor progression. However, regulation of BAG6 in malignancies remains unclear. This study showed that guided entry of tail-anchored proteins factor 4 (GET4), a component of the BAG6 complex, regulates the intercellular localization of BAG6 in CRC. Furthermore, GET4 was identified as a candidate driver gene on the short arm of chromosome 7, which is often amplified in CRC, by our bioinformatics approach using the CRC dataset from The Cancer Genome Atlas. Clinicopathologic and prognostic analyses using CRC datasets showed that GET4 was overexpressed in tumor cells due to an increased DNA copy number. High GET4 expression was an independent poor prognostic factor in CRC, whereas BAG6 was mainly overexpressed in the cytoplasm of tumor cells without gene alteration. The biological significance of GET4 was examined using GET4 KO CRC cells generated with CRISPR-Cas9 technology or transfected CRC cells. In vitro and in vivo analyses showed that GET4 promoted tumor growth. It appears to facilitate cell cycle progression by cytoplasmic enrichment of BAG6-mediated p53 acetylation followed by reduced p21 expression. In conclusion, we showed that GET4 is a novel driver gene and a prognostic biomarker that promotes CRC progression by inducing the cytoplasmic transport of BAG6. GET4 could be a promising therapeutic molecular target in CRC.

15.
Int J Urol ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608669

RESUMO

OBJECTIVES: To evaluate the efficacy, safety and tolerability of vibegron for the treatment of antimuscarinic-resistant neurogenic bladder dysfunction in patients with spina bifida. METHODS: In this retrospective study, 15 patients with antimuscarinic-resistant neurogenic bladder dysfunction due to spina bifida underwent a video-urodynamic study before and during the administration of vibegron 50 mg once daily instead of antimuscarinic agents from February 2019 through April 2021. The video-urodynamic study was carried out to evaluate bladder compliance, maximum cystometric bladder capacity, detrusor overactivity, detrusor leak point pressure and vesicoureteral reflux before and >3 months after the beginning of vibegron administration. RESULTS: Treatment with vibegron significantly improved bladder compliance and maximum cystometric bladder capacity compared with antimuscarinic agents, respectively (7.4 ± 4.2 vs 30.4 ± 48.2 mL/cmH2 O, P = 0.0001; 231.4 ± 81.2 vs 325.2 ± 106.5 mL, P = 0.0005). Detrusor overactivity did not change after the administration of vibegron. Bladder deformity, which was confirmed in 12 patients, improved in half of the patients after taking vibegron. Vesicoureteral reflux, which was confirmed in two patients, was extinguished after taking vibegron. Newly occurring adverse events were not observed, and all patients continued to take vibegron during the treatment period. CONCLUSIONS: Favorable efficacy of vibegron for antimuscarinic-resistant neurogenic bladder dysfunction due to spina bifida was shown video-urodynamically without apparent adverse events. Vibegron is a favorable option for the treatment of antimuscarinic-resistant neurogenic bladder dysfunction in patients with spina bifida.

16.
Arch Osteoporos ; 16(1): 132, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515859

RESUMO

We examined osteoporosis medication use and factors affecting persistence in 497 patients with fragility hip fractures. Only 25.5% of patients received continuous medication for 3 years, and 44.1% of patients received no treatment. Low Barthel index at discharge was a risk factor for both non-treatment and non-persistence to osteoporosis medication. PURPOSE: Fragility hip fractures (FHF) caused by osteoporosis decrease the quality of life and worsen life expectancy. Use of osteoporosis medication may be an efficient method in the prevention of secondary FHF. However, previous studies have reported low rates of osteoporosis medication and persistence after FHF. This study aimed to evaluate osteoporosis medication use and factors affecting persistence in patients with FHF in the northern Kyushu area of Japan. METHODS: A total of 497 FHF patients aged ≥ 60 years with a 3-year follow-up were included. We prospectively collected data from questionnaires sent every 6 months regarding compliance with osteoporosis medication. We compared baseline characteristics among three groups: no treatment (NT), no persistence (NP), and persistence (P), and conducted multivariable regression models to determine covariates associated with non-treatment (NT vs. NP/P) and non-persistence (NP vs. P). RESULTS: There were 219 (44.1%), 151 (30.4%), and 127 (25.5%) patients in the NT, NP, and P groups, respectively. Factors associated with non-treatment were male sex, chronic kidney disease, no previous osteoporosis treatment, and low Barthel index (BI) at discharge. The only factor associated with non-persistence was a low BI at discharge. Factors associated with a low BI at discharge were male sex, older age, trochanteric fracture, and surgical delay. CONCLUSION: Low BI at discharge is a risk factor for both non-treatment and non-persistence to osteoporosis medication. Therefore, appropriate interventions to improve BI may result in persistence to osteoporosis medication.


Assuntos
Conservadores da Densidade Óssea , Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Fraturas do Quadril/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Alta do Paciente , Estudos Prospectivos , Qualidade de Vida
17.
J Hand Surg Asian Pac Vol ; 26(3): 455-459, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34380407

RESUMO

A double-barreled fibular graft was used to reconstruct both forearm bones and the humeroradial joint after tumor resection. The patient had a tumor of radius that invaded the ulna and extensor groups. After a wide tumor resection, vascularized fibular autograft and soft tissue reconstruction was performed. A fibular graft were placed as a double barrel in the proximal ulnar and radial defects including the radial head and fixed using two locking plates. Simultaneously, reconstruction of the humeroradial joint and wrist dorsiflexion was performed. Two years postoperatively, the patient is satisfied with his elbow function while performing activities of daily living. Although amputation was one of the options considered during the preoperative planning in this case, the affected limb could be preserved by grafting a double-barreled fibula and tendon transfer, which could maintain the function of his upper left limb.


Assuntos
Fíbula , Antebraço , Atividades Cotidianas , Fíbula/diagnóstico por imagem , Fíbula/cirurgia , Antebraço/cirurgia , Humanos , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/cirurgia , Ulna/diagnóstico por imagem , Ulna/cirurgia
18.
Injury ; 52(11): 3369-3376, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34373108

RESUMO

INTRODUCTION: The application of a load on the internal fixation of a trochanteric fracture exerts a moment along the lag screw, causing the proximal bone fragment to slide along the lag screw, allowing contact between the proximal and distal bone fragments, which promotes healing. However, excessive sliding is related to poor postoperative outcomes. We aimed to identify the risk factors for excessive sliding. MATERIALS AND METHODS: We conducted a multicenter retrospective study including 115 trochanteric fractures sustained through low-energy trauma in 19 male and 96 female patients aged 60 years or older (mean age: 82.9 years) between September 2013 and December 2014. We measured the postoperative sliding distance after osteosynthesis using a sliding hip screw or intramedullary nailing, and classified participants with ≥8 mm of sliding into the excessive sliding group (ESG) and with <8 mm into non-ESG. Finally, we investigated the risk factors of excessive postoperative sliding. RESULTS: Fifty participants were classified into the ESG and 65 participants into the non-ESG. Female sex (p = 0.0264), an A3 fracture type (p = 0.0003), greater tip-apex distance (p = 0.0250), and poor reduction in either the anteroposterior or lateral radiographic views (p = 0.0156) were identified as risk factors for excessive sliding by multivariate regression analysis. CONCLUSIONS: Female sex, an unstable fracture type, a greater tip-apex distance, and a poor reduction, in either the anteroposterior or lateral views, are associated with excessive postoperative sliding. Therefore, surgery should aim to achieve good reduction and stabilization from both radiographic views.


Assuntos
Pinos Ortopédicos , Fraturas do Quadril , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Humanos , Masculino , Radiografia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
19.
Clin Transl Immunology ; 10(7): e1307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249359

RESUMO

Objectives: Large vessel vasculitis (LVV) is characterised by a high relapse rate. Because accurate assessment of the LVV disease status can be difficult, an accurate prognostic marker for initial risk stratification is required. We conducted a comprehensive longitudinal investigation of next-generation RNA-sequencing data for patients with LVV to explore useful biomarkers associated with clinical characteristics. Methods: Key molecular pathways relevant to LVV pathogenesis were identified by examining the whole blood RNA from patients with LVV and healthy controls (HCs). The data were examined by pathway analysis and weighted gene correlation network analysis (WGCNA) to identify functional gene sets that were differentially expressed between LVV patients and HCs, and associated with clinical features. We then compared the expression of the selected genes during week 0, week 6, remission and relapse. Results: The whole-transcriptome gene expression data for 108 samples obtained from LVV patients (n = 27) and HCs (n = 12) were compared. The pathway analysis and WGCNA revealed that molecular pathway related to interleukin (IL)-1 was significantly upregulated in LVV patients compared with HCs, which correlated with the positron emission tomography vascular activity score, a disease-extent score based on the distribution of affected arteries. Further analysis revealed that the expression levels of genes in the IL-1 signalling pathway remained high after conventional treatment and were associated with disease relapse. Conclusion: Upregulation of the IL-1 signalling pathway was a characteristic of LVV patients and was associated with the extent of disease and a poor prognosis.

20.
Sci Rep ; 11(1): 14821, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285260

RESUMO

Giant cell tumor of bone (GCTB) is an intermediate malignant bone tumor that is locally aggressive and rarely metastasizes. Denosumab, which is a receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor, can be used to treat GCTB. We focused on potential immunotherapy for GCTB and investigated the tumor microenvironment of GCTB. Programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression and signal-regulatory protein alpha (SIRPα), forkhead box P3 (FOXP3), and cluster of differentiation 8 (CD8) infiltration were assessed by immunohistochemical studies of 137 tumor tissues from 96 patients. Of the naive primary specimens, 28% exhibited PD-L1 expression and 39% exhibited IDO1 expression. There was significantly more SIRPα+, FOXP3+, and CD8+ cell infiltration in PD-L1- and IDO1-positive tumors than in PD-L1- and IDO1-negative tumors. The frequency of PD-L1 expression and SIRPα+ cell infiltration in recurrent lesions treated with denosumab was significantly higher than in primary lesions and recurrent lesions not treated with denosumab. PD-L1 expression and higher SIRPα+ cell infiltration were significantly correlated with shorter recurrence-free survival. PD-L1 and SIRPα immune checkpoint inhibitors may provide clinical benefit in GCTB patients with recurrent lesions after denosumab therapy.


Assuntos
Antígenos de Diferenciação/metabolismo , Antígeno B7-H1/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Denosumab/administração & dosagem , Tumor de Células Gigantes do Osso/tratamento farmacológico , Receptores Imunológicos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/metabolismo , Denosumab/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Tumor de Células Gigantes do Osso/metabolismo , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Adulto Jovem
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