Bone Neoplasms Research Articles

Develop a Novel Signature to Predict the Survival and Affect the Immune Microenvironment of Osteosarcoma Patients: Anoikis-Related Genes.

Osteosarcoma (OS) represents a prevalent primary bone neoplasm predominantly affecting the pediatric and adolescent populations, presenting a considerable challenge to human health. The objective of this investigation is to develop a prognostic model centered on anoikis-related genes (ARGs), with the aim of accurately forecasting the survival outcomes of individuals diagnosed with OS and offering insights into modulating the immune microenvironment. The study's training cohort comprised 86 OS patients sourced from The Cancer Genome Atlas database, while the validation cohort consisted of 53 OS patients extracted from the Gene Expression Omnibus database. Differential analysis utilized the GSE33382 dataset, encompassing three normal samples and 84 OS samples. Subsequently, the study executed gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses. Identification of differentially expressed ARGs associated with OS prognosis was carried out through univariate COX regression analysis, followed by LASSO regression analysis to mitigate overfitting risks and construct a robust prognostic model. Model accuracy was assessed via risk curves, survival curves, receiver operating characteristic curves, independent prognostic analysis, principal component analysis, and t-distributed stochastic neighbor embedding (t-SNE) analysis. Additionally, a nomogram model was devised, exhibiting promising potential in predicting OS patient prognosis. Further investigations incorporated gene set enrichment analysis to delineate active pathways in high- and low-risk groups. Furthermore, the impact of the risk prognostic model on the immune microenvironment of OS was evaluated through tumor microenvironment analysis, single-sample gene set enrichment analysis (ssGSEA), and immune infiltration cell correlation analysis. Drug sensitivity analysis was conducted to identify potentially effective drugs for OS treatment. Ultimately, the verification of the implicated ARGs in the model construction was conducted through the utilization of real-time quantitative polymerase chain reaction (RT-qPCR). The ARGs risk prognostic model was developed, comprising seven high-risk ARGs (CBS, MYC, MMP3, CD36, SCD, COL13A1, and HSP90B1) and four low-risk ARGs (VASH1, TNFRSF1A, PIP5K1C, and CTNNBIP1). This prognostic model demonstrates a robust capability in predicting overall survival among patients. Analysis of immune correlations revealed that the high-risk group exhibited lower immune scores compared to the low-risk group within our prognostic model. Specifically, CD8+ T cells, neutrophils, and tumor-infiltrating lymphocytes were notably downregulated in the high-risk group, alongside significant downregulation of checkpoint and T cell coinhibition mechanisms. Additionally, three immune checkpoint-related genes (CD200R1, HAVCR2, and LAIR1) displayed significant differences between the high- and low-risk groups. The utilization of a nomogram model demonstrated significant efficacy in prognosticating the outcomes of OS patients. Furthermore, tumor metastasis emerged as an independent prognostic factor, suggesting a potential association between ARGs and OS metastasis. Notably, our study identified eight drugs-Bortezomib, Midostaurin, CHIR.99021, JNK.Inhibitor.VIII, Lenalidomide, Sunitinib, GDC0941, and GW.441756-as exhibiting sensitivity toward OS. The RT-qPCR findings indicate diminished expression levels of CBS, MYC, MMP3, and PIP5K1C within the context of OS. Conversely, elevated expression levels were observed for CD36, SCD, COL13A1, HSP90B1, VASH1, and CTNNBIP1 in OS. The outcomes of this investigation present an opportunity to predict the survival outcomes among individuals diagnosed with OS. Furthermore, these findings hold promise for progressing research endeavors focused on prognostic evaluation and therapeutic interventions pertaining to this particular ailment.

Prevalence and Characteristics of Pathological Fractures in Patients Referred to Specialist Palliative Care: A Retrospective Study From India.

Background: Prevalence of pathological fractures in palliative care is less studied. This study aimed to determine the annual prevalence of pathological fractures and describe the characteristics and treatments in patients with pathological fractures referred to a specialist palliative care clinic in a tertiary care cancer center in India. Methods: Data of adult cancer patients newly referred to the specialist palliative care clinic over 1year with a clinico-radiological diagnosis of pathological fracture was included. Key outcomes of interest were annual prevalence, clinical characteristics, symptoms and treatments offered. Results: 75 out of 5800 (1.29%) patients newly referred to the clinic over 1year had pathological fractures. Lung cancer was the most common primary diagnosis (n = 23).Dorsal spine (n = 25) was the most common site of fracture. Pain was the predominant symptom. Mean pain score was 7.04(SD = 1.75) and 42 patients (56%) required strong opioids for analgesia. Only 11 (16%) patients underwent surgical fixation. Median duration from diagnosis of cancer to occurrence of fracture was found to be 329days. Treatment goals changed to best supportive care in 33 patients (44%) post fracture. Patients with bone and soft tissue neoplasms and those who received only chemotherapy previously had a higher risk of occurrence of fractures. Conclusion: Annual prevalence of pathological fractures in patients referred to the specialist palliative care clinic was 1.29%. It was associated with significant symptom burden and affected oncological treatments. Close monitoring of patients with bone metastases is crucial and proactive implementation of prophylactic measures to prevent such skeletal related events is warranted.

Current approaches in tissue engineering-based nanotherapeutics for osteosarcoma treatment.

Osteosarcoma (OS) is a malignant bone neoplasm plagued by poor prognosis. Major treatment strategies include chemotherapy, radiotherapy, and surgery. Chemotherapy to treat OS has severe adverse effects due to systemic toxicity to healthy cells. A possible way to overcome the limitation is to utilize nanotechnology. Nanotherapeutics is an emerging approach in treating OS using nanoparticulate drug delivery systems. Surgical resection of OS leaves a critical bone defect requiring medical intervention. Recently, tissue engineered scaffolds have been reported to provide physical support to bone defects and aid multimodal treatment of OS. These scaffolds loaded with nanoparticulate delivery systems could also actively repress tumor growth and aid new bone formation. The rapid developments in nanotherapeutics and bone tissue engineering have paved the way for improved treatment efficacy for OS-related bone defects. This review focuses on current bifunctional nanomaterials-based tissue engineered (NTE) scaffolds that use novel approaches such as magnetic hyperthermia, photodynamic therapy, photothermal therapy, bioceramic and polymeric nanotherapeutics against OS. With further optimization and screening, NTE scaffolds could meet clinical applications for treating OS patients.

A rare clinical case of a labyrinthine lesion: an endolymphatic sac tumor

Endolymphatic sac tumors are rare neoplasms originating from the endolymphatic epithelium of the intraosseous part of the endolymphatic duct and sac, typically characterized by slow growth and local destructive changes. We present a case of an endolymphatic sac tumor in a 28-year-old man who consulted an otoneurologist with complaints of progressive hearing loss and dizziness attacks and was referred for a CT scan of the temporal bones and MRI of the inner ear with delayed contrast enhancement. The data of otoneurological and radiological examinations before and after surgical treatment and the results of surgical treatment with histological verification of the tumor are presented. The objective of this case presentation is to demonstrate the usefulness of CT and MRI methods in detecting an endolymphatic sac tumor, to compare the results of otoneurological and radiological examinations and intraoperative and histological data followed by surgery. Radiological examination revealed a neoplasm of the right temporal bone with typical imaging characteristics of endolymphatic sac tumor. Surgery was performed, the mass was removed completely, and the endolymphatic sac tumor was histologically verified. Radiologic presentation includes a typically located area of bone destruction in the petrous part of the temporal bone in the area of the vestibular aqueduct, possibly with the spread of the tumor into the cerebellopontine angle, with a heterogeneous structure, with uneven contrast enhancement. Due to the rarity of this pathology, diagnosis in the early stages is often difficult, and for the correct interpretation of radiologic findings in patients with hearing loss and dizziness, knowledge of the normal anatomy of the temporal bone and awareness of rare variants of its lesions are of key importance. Timely examination of patients with suspected temporal bone lesions and correct diagnosis are the key to successful treatment and maintaining the quality of life in this group of patients.

A rare case of an intraosseous lipoma associated with the resorption of a mandibular third molar

AbstractIntroductionIntraosseous lipomas (IL) are rare benign neoplasms of bone which very rarely occur in the facial bones such as the mandible. Of the documented cases, many are often asymptomatic and consequently, are an incidental finding discovered by the practitioner.Case ReportThe following case report recounts a 22‐year‐old patient referred for extraction of a carious molar at an Oral and Maxillofacial unit with an incidental finding of pathology involving the contralateral lower left wisdom tooth (LL8) on radiographic examination. Further investigations showed associated external root resorption of the lower left wisdom tooth and a provisional diagnosis of a radicular cyst was made. The case was managed by extracting the associated tooth and enucleating the lesion. During the procedure, fatty tissue was curetted at the apex instead of the expected cystic content. Subsequent histopathology confirmed the diagnosis of an IL.ConclusionTo the authors' knowledge, this is only the second documented case of an IL associated with tooth resorption. Findings from this case further our knowledge of the relatively uncommon pathology of intraosseous lipomas in the mandible and highlight the need for histopathological documentation and reporting of apical lesions.

Genetic effect of basal metabolic rate on the benign neoplasm of bone and articular cartilage: a Mendelian randomization study.

Previous studies have found an association between basal metabolic rate (BMR) and various malignant neoplasms, including bone tumors. BMR is also associated with bone mineral density, but the causality between BMR and benign neoplasms of bone and articular cartilage remains uncertain. Single nucleotide polymorphisms (SNPs) associated with BMR (p < 5 × 10-8) were used as instrumental variables for Mendelian randomization analysis of neoplasm risk. The inverse variance weighted (IVW) method was the primary approach, with the weighted median and MR-Egger regression serving as supplements. In this MR analysis, the IVW method supported a causal relationship between BMR and benign neoplasms of bone and articular cartilage (OR = 1.417; 95% CI, 1.039 to 1.930; p = 0.027). No evidence of heterogeneity or pleiotropy in the selected SNPs was found in our study. Thus, based on these results, we discovered a possible causal relationship between BMR and benign neoplasms of bone and articular cartilage. In this MR study, evidence suggested a genetic correlation between genetically predicted BMR and the risk of neoplasms in bone and articular cartilage.

HAS THE AGING OF BRAZILIANS IMPACTED THE OCCURRENCE OF OSTEO-CARTILAGINOUS NEOPLASMS?

In this study, we sought to evidence whether bone, joint and cartilage neoplasms are increasing with the aging of the Brazilian population, using the analysis of the DATASUS and IBGE databases, between 1979 and 2020. We compared the means and the proportion of death in Brazil, to observe the confidence interval overlaps, separated by region. Comparison between genders, age group, death and specific rate were compared via proportion tests and the trend was investigated via time series analysis. Through the analyses, we can see that there is an increasing trend of cases, about 2.5 times in the period. Separated by region, the Southeast stands out, with a number of deaths about 6 times higher than other regions. Metastatic carcinoma is the most common neoplasm treated by orthopedic surgeons, and it is essential to adapt to this future projection, with cases of pathological bone involvement resulting from metastatic carcinomas, increasingly present in the routine of orthopedic surgeons. Level of Evidence IV, Cross-Sectional Observational Study.

THE ROLE OF 3D MODELING IN INCREASING THE EFFICIENCY OF SURGICAL TREATMENT AND RESTORING THE QUALITY OF LIFE OF PATIENTS WITH MALIGNANT BONE TUMORS

Summary. Aim: to determine and study the clinical value of 3D modeling in increasing the effectiveness of treatment of patients with malignant bone neoplasms. Object and methods: endoprosthesis of hip and knee joints was performed in 69 patients after resection of a bone segment with a tumor, the boundaries of which were determined using a 3D model. Tumor models were made from optically opaque polylactide polyester, peritumoral tissues from optically transparent polylactide. Results: planning and training on 3D models significantly reduced intraoperative blood loss, duration of surgical intervention, and recovery time of limb functions. The use of training 3D models before surgical intervention with possible subsequent prosthetics with special oncological endoprostheses ensures satisfactory functional results and creates conditions for restoring the quality of life of patients. Conclusions: the proposed technique provides valuable experience in the way of implementing the principles of personalized treatment into surgical practice and creates conditions for optimizing the quality of life of patients.

Unusual sites of giant cell tumor of bone

Giant cell tumor (GCT), a benign but regionally aggressive and destructive tumor, is most frequently found at the epiphysis of long bones. The distal femur, proximal tibia, and distal radius are the three most typical locations. The pelvis, proximal femur, proximal humerus, distal tibia, and sacrum are uncommon locations. About 18– 23% of benign bone neoplasms are GCT. They often manifest in early adulthood because they happen after the growth plate has closed, with the majority of instances being documented between the ages of 20 and 50. GCT is a primarily benign bone tumor that exhibits local recurrence, has metastasis potential, and may show malignant change. Depending on the site, complications such as hemorrhage or pathological fracture, GCTs can have varied appearances. Rarely, ribs, vertebral bodies, and bones of the hand and foot may be affected. Other than the long bones, the radiographic characteristics of GCT are non-specific and resemble those of other osteolytic diseases. This review shows GCT imaging features from both typical and unusual locales.

A bibliometric and visualized analysis of nanoparticles in musculoskeletal diseases (from 2013 to 2023)

As the pace of research on nanomedicine for musculoskeletal (MSK) diseases accelerates, there remains a lack of comprehensive analysis regarding the development trajectory, primary authors, and research focal points in this domain. Additionally, there's a need of detailed elucidation of potential research hotspots. The study gathered articles and reviews focusing on the utilization of nanoparticles (NPs) for MSK diseases published between 2013 and 2023, extracted from the Web of Science database. Bibliometric and visualization analyses were conducted using various tools such as VOSviewer, CiteSpace, Pajek, Scimago Graphica, and the R package. China, the USA, and India emerged as the key drivers in this research domain. Among the numerous institutions involved, Shanghai Jiao Tong University, Chinese Academy of Sciences, and Sichuan University exhibited the highest productivity levels. Vallet-Regi Maria emerged as the most prolific author in this field. International Journal of Nanomedicine accounted for the largest number of publications in this area. The top five disorders of utmost significance in this field include osteosarcoma, cartilage diseases, bone fractures, bone neoplasms, and joint diseases. These findings are instrumental in providing researchers with a comprehensive understanding of this domain and offer valuable perspectives for future investigations.

Resection of the chest wall for bone and soft tissue neoplasms in children

Chest tumors are quite rare in children. Among them there are benign and malignant. In all cases, surgical intervention is needed; in malignant tumors, as a stage of treatment, it is aimed at removing the tumor and, if necessary, reconstructing the chest wall. Due to the different localization, local spread and involvement of underlying structures, the surgical approach may involve a large extent of chest wall resection, and a variety of plastic materials and techniques is quite wide. During the period from September 2012 to January 2022, 43 surgical interventions for neoplasms of the chest wall in children were performed in the Department of Oncology and Pediatric Surgery of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. In 11 (26.8%) cases, neoplasms were benign, 30 (73.2%) patients underwent surgical treatment for malignant tumors of various histogenesis. The surgery of the chest wall consisted of two stages. The first stage was a wide excision of the tumor within healthy tissues, performed en bloc with the involvement of underlying tissues and organs (diaphragm). If a malignant process and lung foci were detected, we simultaneously removed the foci on the affected side. The second stage was the reconstruction of the chest wall and diaphragm with local tissues or with the use of non-absorbable synthetic material (polymer meshes, dermal-derived bioprostheses, titanium meshes) shaped according to the size of the defect with a margin for fixation to the edges of the wound. Overall and relapse-free survival was evaluated. The maximum observation period was 9 years. The operative approach and the extent of surgical intervention depend on the size of the primary tumor site and its spread (multifocal lesion), the involvement of adjacent anatomical structures and are individual in each case. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.

Osteoid-osteoma of trapezium bone in a child (clinical case)

BACKGROUND: Osteoid osteoma is a benign neoplasm of bones with a diameter of up to 1.5 cm. It is most common in children in the second decade of life and at the age of 20–30 years, predominantly in men. In large neoplasms (1.5 cm) with a histological study identical to osteoid osteoma, the pathological process is regarded as osteoblastoma or giant osteoid osteoma. The tumor is most often located in long tubular bones and on the hand in 5%–15% of the patients. Differential diagnosis is carried out with rheumatoid arthritis, inflammation, and other neoplasms. Various options for the treatment of osteoid osteoma, both conservative and operative, have been proposed.&#x0D; CLINICAL CASE: A 17-year-old patient underwent surgical treatment for trapezium bone neoplasm and pronounced chronic pain syndrome.&#x0D; DISCUSSION: The identification and treatment of osteoid osteoma remain challenging, which is associated with the similarity of clinical symptoms and ineffectiveness (in the initial stages of its development) of X-ray examination. Thus, computed tomography is necessary to identify a pathological structure. If a formation on the hand is detected, surgery (tumor resection) is advised; if necessary, bone grafting of the defect is performed. After surgical treatment, relapse may occur within 7 months, which is associated with incomplete tumor removal. To confirm the diagnosis, a pathomorphological study is necessary.&#x0D; CONCLUSIONS: Chronic pain syndrome requires a thorough examination of the patient and a differential diagnosis. Surgical treatment allows the restoration of hand functions and alleviates the tumor-associated pain syndrome.

Giant Cell Tumor of Mandible : A Case Report.

Giant cell tumor is locally aggressive primary benign neoplasm of bone with tendency of frequent recurrence, metastasis and malignant transformation. Because of the rarity of the disease involving mandible, no definite treatment guideline is established. Surgical treatment is the treatment of choice for giant cell tumor. Due to its proximity to vital structures including skull base, the recurrent disease associated with less invasive procedure could be difficult to manage while more invasive procedure will result in higher morbidity and complex reconstruction. Medical management with denosumab or zoledronic acid has been advocated in surgically unresectable disease. We present a rare case of giant cell tumor of mandible. Patient was a 33 years old lady who presented with gradually progressive painful swelling in chin. After exclusion of distant metastasis by F-18 FDG PET scan, she underwent en-bloc resection of the tumor with free fibula flap reconstruction. During 6 months of follow up visit patient had no recurrence.

Cancer mortality and premature deaths among hairdressers in Brazil

Hairdresser is an occupation classified by the International Agency for Research on Cancer as probably carcinogenic (Group 2A) for lung and bladder cancer, but evidence is accumulating on its association with other cancer types. To our knowledge, this is the first study aimed to compare the cancer mortality and premature mortality between hairdressers and other workers in Brazil. Methods: In this exploratory study, information on deaths by selected cancers that occurred in Brazil, from 1996 to 2020, among workers aged 20-70y, with identified occupation was gathered from the Brazilian Mortality Information System. Sociodemographic characteristics, sex-specific mortality ratio, and Years of Potential Life Lost (YPLL) were compared between hairdressers, service workers, and general workers. We used logistic regression models to estimate crude (ORC) and adjusted (ORADJ) odds ratios. Models were adjusted by age, educational level, and ethnicity. We also used Poisson regression models to compare the YPLL rates across the occupational groups. Results: From 1996 to 2020, 23 557 deaths occurred among hairdressers, 576 428 among service workers, and 13 332 996 among general workers in Brazil. Higher mortality ORs and YPLL were observed for several types of cancer among hairdressers, compared to service and general workers, especially for women. Hairdressers' mortality was significantly higher among whites, women, younger workers, and those who completed high school. Female hairdressers had significantly higher odds of dying from cancer of the digestive, respiratory, reproductive, urinary, and hematological systems, both in crude and adjusted models. For male hairdressers, higher odds were found only for urinary tract and bladder cancer, while other significant associations indicated lower mortality than the comparison groups. YPLL analyses revealed significant premature deaths among Brazilian hairdressers. In women, this was more evident among those who died of neoplasms of salivary glands, bones and articular cartilages, and acute lymphoid leukemia; in men, tongue, pharynx, and thyroid. Conclusions: Our results suggest that Brazilian female hairdressers are more likely to die from several cancers, with potential consequences on premature deaths. Causal associations to occupational risks, such as exposure to chemicals, should be investigated by observational epidemiologic studies. Meanwhile, it is important to promote public policies, regulations, and Occupational Safety and Health (OSH) strategies to protect hairdressers’ health, mitigate occupational risks, and ensure safe workplaces.

Cementoplasty to cryoablation: review and current status.

Recent advances in percutaneous image-guided techniques have empowered interventional radiologists with diverse treatment options for the management of musculoskeletal lesions. Of note, there is growing utility for cementoplasty procedures, with indications ranging from stabilization of bone metastases to treatment of painful vertebral compression fractures. Likewise, cryoablation has emerged as a viable adjunct in the treatment of both primary and secondary bone and soft tissue neoplasms. These treatment options have been progressively incorporated into the multidisciplinary approach to holistic care of patients, alongside conventional radiotherapy, systemic therapy, surgery, and analgesia. This review article serves to outline the indications, technical considerations, latest developments, and evidence for the burgeoning role of cementoplasty and cryoablation in the musculoskeletal system, with an emphasis on pain palliation and tumour control.

Global research landscape on the crosstalk between ferroptosis and musculoskeletal diseases: A bibliometric and visualized analysis

Over the past 11 years, mounting evidence has suggested a significant association between ferroptosis and the development and progression of musculoskeletal (MSK) diseases, such as osteoporosis and osteoarthritis. However, a comprehensive bibliometric analysis summarizing the relationship between ferroptosis and MSK diseases is currently lacking. The present study collected articles and reviews on the topic of ferroptosis in MSK diseases. The data were collected from January 1st, 2012 to June 30th, 2023 by screening the Web of Science database. Various tools, including VOSviewer, CiteSpace, Pajek, the R package, and others, were used to conduct bibliometric and visualization analyses. Notably, China, the USA, and Italy emerged as primary contributors, jointly accounting for over 80 % of published documents, thereby shaping research in this domain. Among the diverse institutions, Shanghai Jiao Tong University, Soochow University, and Huazhong University of Science and Technology displayed the highest productivity levels. The most prolific authors include Sun Kai, Shang Peng, and Jing Xingzhi. Oxidative Medicine and Cellular Longevity stood out with the largest number of publications in this area. The five most significant disorders in this field are bone fractures, osteosarcoma, bone neoplasms, joint diseases, and osteoporotic fractures. This study represents an inaugural comprehensive bibliometric analysis, presenting a holistic view of the knowledge framework and developmental patterns in ferroptosis concerning MSK diseases over the previous eleven years. This information can aid researchers in acquiring a thorough grasp of this domain and offer invaluable insights for forthcoming explorations.

A case of epithelioid osteoblastoma of the thoracic vertebra in a 12-year-old male: a case report and review of literature

Introduction and importance: Osteoblastoma (OB) is a rare benign bone tumor, representing less than 1% of all bone neoplasms. In contrast to the typical OB, a smaller subset known as ‘epithelioid osteoblastoma (EO)’ exhibits a distinctive inclination for local invasion and recurrence. This rare variant can pose diagnostic challenges, particularly due to its unclear clinical and radiological presentation. Case presentation: This study details a clinical case of a 12-year-old boy experiencing pain from a lytic bone tumor located in the thoracic vertebrae (T3–T4), initially suggesting malignancy. Following extensive curettage, histopathological analysis confirmed the diagnosis of EO through immunohistochemical staining. Subsequent follow-up at 3 months revealed the absence of no pain or recurrence of the lesion. Clinical discussion: Distinguishing EO from a malignant tumor requires a multidisciplinary approach, considering clinical, radiographic, and histological features that differentiate the two entities. Conclusion: The goal of this case presentation is to increase awareness regarding this recurrent tumor variant, which poses diagnostic challenges, particularly in distinguishing it from malignant tumors, including osteosarcoma.

HLA-B27 did not protect against COVID-19 in patients with axial spondyloarthritis – data from the ReumaCov-Brasil Registry

BackgroundSome studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients.AimTo evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients.MethodsThe ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil’s subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%.ResultsFrom May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups.ConclusionsNo significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection.Trial registrationThis study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials – REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Rheumatoid arthritis increases the risk of malignant neoplasm of bone and articular cartilage: a two-sample bidirectional mendelian randomization study

ObjectivePrior research has revealed a heightened prevalence of neoplasms in individuals diagnosed with rheumatoid arthritis (RA). The primary objective of this study is to delve into the causal association between RA and two distinct types of neoplasms: benign neoplasm of bone and articular cartilage (BNBAC) and malignant neoplasm of bone and articular cartilage (MNBAC).MethodsWe employed summary data from genome-wide association analyses (GWAS) to investigate the causal relationship between RA and two neoplasms, BNBAC and MNBAC, using a two-sample bidirectional Mendelian randomization (MR) study design. The IEU OpenGWAS database provided the GWAS summary data for RA, while the Finnish consortium supplied the GWAS summary data for BNBAC and MNBAC. Our analysis involved the utilization of eight distinct MR methods, namely random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and fixed effects IVW. Subsequently, we conducted assessments to evaluate heterogeneity, horizontal pleiotropy, outliers, the impact of a single-nucleotide polymorphism (SNP), and adherence to the assumption of normal distribution in the MR analysis.ResultsThe results from the MR analysis revealed that there was no significant genetic association between RA and BNBAC (P = 0.427, odds ratio [OR] 95% confidence interval [CI] = 0.971 [0.904–1.044]). However, a positive genetic association was observed between RA and MNBAC (P = 0.001, OR 95% CI = 1.413 [1.144–1.745]). Conducting a reverse MR analysis, we found no evidence to support a genetic causality between BNBAC (P = 0.088, OR 95% CI = 1.041 [0.994–1.091]) or MNBAC (P = 0.168, OR 95% CI = 1.013 [0.995–1.031]) and RA. Our MR analysis demonstrated the absence of heterogeneity, horizontal pleiotropy, and outliers and confirmed that the effect was not driven by a single SNP. Additionally, the data exhibited a normal distribution.ConclusionThe findings of this study demonstrate that RA constitutes a significant risk factor for MNBAC. In the context of clinical application, it is advisable to conduct MNBAC screening in RA patients and remain vigilant regarding its potential manifestation. Importantly, the outcomes of this investigation introduce a fresh vantage point into the understanding of the tumorigenesis associated with RA.

Pterostilbene-Isothiocyanate Inhibits Proliferation of Human MG-63 Osteosarcoma Cells via Abrogating β-Catenin/TCF-4 Interaction-A Mechanistic Insight.

Osteosarcoma, a highly metastasizing bone neoplasm, is a leading cause of death and disability in children and adolescents worldwide. Osteosarcoma is only suboptimally responsive to surgery and radio- and chemotherapy, that too with adverse side effects. Hence, there is a necessary need for safer alternative therapeutic approaches. This study evaluated the anticancer effects of the semi-synthetic compound, pterostilbene-isothiocyanate (PTER-ITC), on human osteosarcoma MG-63 cells through cytotoxicity, wound-healing, and transwell-migration assays. Results showed that PTER-ITC specifically inhibited the survival, proliferation, and migration of osteosarcoma cells. PTER-ITC induced apoptosis in MG-63 cells by disrupting mitochondrial membrane potential, as evident from the outcomes of different cytological staining. The antimetastatic potential of PTER-ITC was evaluated through immunostaining, RT-qPCR, and immunoblotting. In silico (molecular docking and dynamic simulation) and, subsequently, biochemical [co-immunoprecipitation (Co-IP) and luciferase reporter] assays deciphered the underlying mode-of-action of this compound. PTER-ITC increased E-cadherin and reduced N-cadherin levels, thereby facilitating the reversal of epithelial-mesenchymal transition (EMT). It also modulated the expressions of proliferative cell nuclear antigen (PCNA), caspase-3, poly [ADP-ribose] polymerase (PARP-1) and matrix metalloproteinase-2/9 (MMPs-2/9) at transcriptional and translational levels. PTER-ITC interfered with the β-catenin/transcription factor-4 (TCF-4) interaction in silico by occupying the β-catenin binding site on TCF-4, confirmed by their reduced physical interactions (Co-IP assay). This inhibited transcriptional activation of TCF-4 by β-catenin (as shown by luciferase reporter assay). In conclusion, PTER-ITC exhibited potent anticancer effects in vitro against human osteosarcoma cells by abrogating the β-catenin/TCF-4 interaction. Altogether, this study suggests that PTER-ITC may be regarded as a new approach for osteosarcoma treatment.