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Aging is an inevitable biological process, and longevity may be related to bone health. Maintaining strong bone health can extend one's lifespan, but the exact mechanism is unclear. Bone and extraosseous organs, including the heart and brain, have complex and precise communication mechanisms. In addition to its load bearing capacity, the skeletal system secretes cytokines, which play a role in bone regulation of extraosseous organs. FGF23, OCN, and LCN2 are three representative bone-derived cytokines involved in energy metabolism, endocrine homeostasis and systemic chronic inflammation levels. Today, advanced research methods provide new understandings of bone as a crucial endocrine organ. For example, gene editing technology enables bone-specific conditional gene knockout models, which allows the study of bone-derived cytokines to be more precise. We systematically evaluated the various effects of bone-derived cytokines on extraosseous organs and their possible antiaging mechanism. Targeting aging with the current knowledge of the healthy skeletal system is a potential therapeutic strategy. Therefore, we present a comprehensive review that summarizes the current knowledge and provides insights for futures studies.
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Osso e Ossos , Sistema Endócrino , Humanos , Sistema Endócrino/metabolismo , Osso e Ossos/metabolismo , Envelhecimento , Longevidade , Citocinas/metabolismoRESUMO
PURPOSE: No study so far has paid attention to strabismus-related spinal imbalance. This study aimed to determine the epidemiology of thoracic scoliosis in children and adolescents with strabismus and investigate the association of two diseases. METHODS AND DESIGN: A cross-sectional study. Study group consists of 1935 consecutive candidates for strabismus surgery (4-18 years); Control group consists of the age- and sex-matched patients with respiratory diseases. All subjects underwent a screening program based on chest plain radiographs using the Cobb method. Their demographic information, clinical variables and results of Cobb angle were recorded and analyzed. RESULTS: A significantly higher prevalence of thoracic scoliosis (289/1935, 14.94% versus 58/1935, 3.00%) was found in study group compared with control group. Among strabismic patients, the coronal thoracic scoliosis curve mainly distributed in right and in main thoracic (198/289) and in the curves 10°-19° (224/289); Age range 7-9 years (103/1935), female (179/1935) and concomitant exotropia patients (159/851) were more likely to have thoracic scoliosis. According to the logistic regression, thoracic scoliosis had no significant association with age, BMI, duration of illness and onset age (p > 0.05). However, gender, BCVA, type of strabismus and degree of strabismus showed a significant relationship with the prevalence of thoracic scoliosis (p < 0.05). CONCLUSIONS: With a pooled prevalence of 14.94%, strabismus patients showed a great higher risk of developing thoracic scoliosis. Screening for scoliosis in strabismus patients can be helpful to discover a high prevalence of potential coronal scoliosis. More attention should be paid to ophthalmological problems in patients with scoliosis. These slides can be retrieved under Electronic Supplementary Material.
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Escoliose , Fusão Vertebral , Estrabismo , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Escoliose/diagnóstico por imagem , Escoliose/epidemiologia , Escoliose/cirurgia , Estrabismo/epidemiologia , Estrabismo/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Resultado do TratamentoRESUMO
Magnetic phosphorous biochar ï¼MPBCï¼ was prepared from Camellia oleifera shells using phosphoric acid activation and iron co-deposition. The materials were characterized and analyzed through scanning electron microscopy ï¼SEMï¼ï¼ X-ray diffractometry ï¼XRDï¼ï¼ specific surface area and pore size analysis ï¼BETï¼ï¼ Fourier infrared spectroscopy ï¼FT-IRï¼ï¼ and X-ray photoelectron spectroscopy ï¼XPSï¼. MPBC had a high surface area ï¼1 139.28 m2·g-1ï¼ and abundant surface functional groupsï¼ and it could achieve fast solid-liquid separation under the action of an external magnetic field. The adsorption behavior and influencing factors of sulfamethoxazole ï¼SMXï¼ in water were investigated. The adsorbent showed excellent adsorption properties for SMX under acidic and neutral conditionsï¼ and alkaline conditions and the presence of CO32- had obvious inhibition on adsorption. The adsorption process conformed to the quasi-second-order kinetics and Langmuir model. The adsorption rate was fastï¼ and the maximum adsorption capacity reached 356.49 mg·g-1. The adsorption process was a spontaneous exothermic reactionï¼ and low temperature was beneficial to the adsorption. The adsorption mechanism was mainly the chemisorption of pyrophosphate surface functional groups ï¼C-O-P bondï¼ between the SMX molecule and MPBC and also included hydrogen bondingï¼ π-π electron donor-acceptor ï¼π-πEDAï¼ interactionï¼ and a pore filling effect. The development of MPBC adsorbent provides an effective way for resource utilization of waste Camellia oleifera shells and treatment of sulfamethoxazole wastewater.
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Sulfametoxazol , Poluentes Químicos da Água , Sulfametoxazol/química , Adsorção , Espectroscopia de Infravermelho com Transformada de Fourier , Água , Poluentes Químicos da Água/análise , Carvão Vegetal/química , Fósforo , Cinética , Fenômenos MagnéticosRESUMO
BACKGROUND: Acute bone loss after fracture is associated with various effects on the complete recovery process and a risk of secondary fractures among patients. Studies have reported similarities in pathophysiological mechanisms involved in acute bone loss after fractures and osteoporosis. However, given the silence nature of bone loss and bone metabolism complexities, the actual underlying pathophysiological mechanisms have yet to be fully elucidated. AIM OF REVIEW: To elaborate the latest findings in basic research with a focus on acute bone loss after fracture. To briefly highlight potential therapeutic targets and current representative drugs. To arouse researchers' attention and discussion on acute bone loss after fracture. KEY SCIENTIFIC CONCEPTS OF REVIEW: Bone loss after fracture is associated with immobilization, mechanical unloading, blood supply damage, sympathetic nerve regulation, and crosstalk between musculoskeletals among other factors. Current treatment strategies rely on regulation of osteoblasts and osteoclasts, therefore, there is a need to elucidate on the underlying mechanisms of acute bone loss after fractures to inform the development of efficacious and safe drugs. In addition, attention should be paid towards ensuring long-term skeletal health.
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Fraturas Ósseas , Osteoporose , Humanos , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Fraturas Ósseas/complicações , Fraturas Ósseas/metabolismo , Osteoclastos/metabolismo , Osteoblastos/metabolismo , Sistema Nervoso SimpáticoRESUMO
The tremendous personal and economic burden worldwide caused by low back pain (LBP) has been surging in recent years. While intervertebral disc degeneration (IVDD) is the leading cause of LBP and vast efforts have been made to develop effective therapies, this problem is far from being resolved, as most treatments, such as painkillers and surgeries, mainly focus on relieving the symptoms rather than reversing the cause of IVDD. However, as stem/progenitor cells possess the potential to regenerate IVD, a deeper understanding of the early development and role of these cells could help to improve the effectiveness of stem/progenitor cell therapy in treating LBP. Single-cell RNA sequencing results provide fresh insights into the heterogeneity and development patterns of IVD progenitors; additionally, we compare mesenchymal stromal cells and IVD progenitors to provide a clearer view of the optimal cell source proposed for IVD regeneration.
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STUDY DESIGN: A longitudinal cohort study. OBJECTIVE: The objective of this study was to evaluate the prognostic factors and determine the difference between different surgery scopes. Nomograms were constructed and validated to predict overall survival (OS) and cancer-specific survival (CSS) of sacrum/pelvic chondrosarcoma (SC) patients. SUMMARY OF BACKGROUND DATA: Chondrosarcoma is a bone malignancy which is reported to be resistant to both chemotherapy and radiotherapy. Therefore, surgery is the most preferred treatment method. However, this remains a great challenge due to the complex anatomy of the area. MATERIALS AND METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database of patients with conventional SC between 1998 and 2016 was retrieved for analysis. Cox analysis was used to estimate the mortality hazards ratios among patients. Propensity score matching was used to compare different surgery scope. Nomograms were constructed to predict the OS and CSS of patients with SC. RESULTS: A total of 377 patients were included in this study. The cutoff value for tumor size was considered to be 118 mm. The concordance indices (C-index) value for nomogram predictions of CSS were 0.871. Following propensity score matching, 158 patients were selected for the second time and its result showed no significant difference between the scope of surgery. CONCLUSIONS: Tumor size was considered to be closely related to the outcome of SC. There is no significant difference in the scope of surgery and limb salvage can be considered. The nomograms can precisely predict OS and CSS in patients with SC. These could help clinicians to perform survival assessments and identify patients at high risk. LEVEL OF EVIDENCE: Level IV.
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Condrossarcoma , Nomogramas , Humanos , Estudos Longitudinais , Prognóstico , Pontuação de Propensão , Programa de SEER , SacroRESUMO
STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To investigate the effect and safety of acupuncture for the treatment of chronic spinal pain. METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, the WHO Clinical Trial Registry, and the US National Library of Medicine clinical trial registry were searched from January 1, 2000, to November 1, 2019. Randomized controlled trials (RCTs) involving patients with chronic spinal pain treated by acupuncture versus sham acupuncture, no treatment, or another treatment were included. RESULTS: Data was extracted from 22 RCTs including 2588 patients. Pooled analysis revealed that acupuncture can reduce chronic spinal pain compared to sham acupuncture (weighted mean difference [WMD] -12.05, 95% confidence interval [CI] -15.86 to -8.24), mediation control (WMD -18.27, 95% CI -28.18 to -8.37), usual care control (WMD -9.57, 95% CI -13.48 to -9.44), and no treatment control (WMD -17.10, 95% CI -24.83 to -9.37). In terms of functional disability, acupuncture can improve physical function at immediate-term follow-up (standardized mean difference [SMD] -1.74, 95% CI -2.04 to -1.44), short-term follow-up (SMD -0.89, 95% CI -1.15 to -0.62), and long-term follow-up (SMD -1.25, 95% CI -1.48 to -1.03). CONCLUSION: In summary, compared to no treatment, sham acupuncture, or conventional therapy such as medication, massage, and physical exercise, acupuncture has a significantly superior effect on the reduction in chronic spinal pain and function improvement. Acupuncture might be an effective treatment for patients with chronic spinal pain and it is a safe therapy.
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Aggressive inflammation is an important pathological process of secondary injury in acute spinal cord injury (SCI). However, traditional treatments of secondary injury in acute SCI have achieved little success. Novel biomaterials combined with small molecule drugs are considered as a potential treatment for SCI. Baricitinib, a highly selective JAK1/JAK2 inhibitor, can effectively inhibit the JAK2/STAT3 pathway involved in the modulation of inflammation. However, to evaluate Baricitinib's therapeutic effect on SCI remains to be confirmed. In this study, we designed an injectable PLGA-PEG-PLGA thermos-sensitive hydrogel with baricitinib (Bari-P hydrogel) and measured its efficacy, physical and biological properties in vitro. In the SCI rat, Bari-P hydrogel was injected into the injured spinal cord. Neuronal regeneration was evaluated at 3 days and 4 weeks after surgery by determining the inflammatory cytokine levels, behavioral tests, and histological analysis. The hydrogel can gel in the body, disintegrate almost within 72 h and achieve drug release. Baricitinib can effectively inhibit the JAK2/STAT3 pathway of microglia in vitro; while in vivo experiments show that Bari-P hydrogel treatment can inhibit the phosphorylation of JAK2, STAT3 and suppress the production of inflammatory cytokines, and reduces neuronal apoptosis. Histopathological analysis and behavioral tests showed that Bari-P hydrogel reduced neuronal apoptosis in the early stage of injury and later promoted functional recovery. In summary, Bari-P hydrogel reduced neuronal apoptosis and promoted functional recovery in spinal cord injured rats by inhibiting the JAK2-STAT3 pathway and controlling the expression of inflammatory cytokines in the early stages of injury.
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Hidrogéis , Traumatismos da Medula Espinal , Animais , Azetidinas , Preparações de Ação Retardada/uso terapêutico , Hidrogéis/uso terapêutico , Inflamação/tratamento farmacológico , Janus Quinase 2 , Purinas , Pirazóis , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3 , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , SulfonamidasRESUMO
OBJECTIVE: To determine whether preoperative warming can reduce the risk of surgical site infection (SSI) after surgery. BACKGROUND: Intraoperative hypothermia is a risk factor for the occurrence of SSI in patients after surgery. However, the effectiveness of preoperative warming in reducing the incidence of the condition remains unclear. MATERIALS AND METHODS: A systematic review was conducted using Medline, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs) that evaluated the risk of SSI after surgery with and without the use of a preoperative warming protocol. The primary outcome measure was the diagnosis of SSI within 10-90 days of surgery. The pooled risk ratio was estimated with a fixed-effect meta-analysis. Sensitivity analyses were performed to examine the impact of the structural design of preoperative warming on the pooled risk of SSI. RESULTS: Of the 249 studies identified, seven RCTs representing 1086 patients were included in the present meta-analysis. The use of preoperative warming was associated with a significant decrease in SSI (RR = 0.60, 95% CI 0.42-0.87, P = 0.072). Specifically, we defined patients who used forced-air warming (FAW) and integrated measures such as liquid heating and warming blankets as the MIX group and patients who used only FAW as the FAW group. Patients who used MIX methods (temperature set <43 °C and 30-min prewarming) before surgery benefited more from prewarming. CONCLUSIONS: The results of this study suggest that preoperative warming can reduce rates of SSI after surgery. We, therefore, recommend the application of MIX warming methods before surgery.
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Hipotermia/prevenção & controle , Complicações Intraoperatórias/prevenção & controle , Cuidados Pré-Operatórios , Infecção da Ferida Cirúrgica/prevenção & controle , Temperatura Alta , HumanosRESUMO
BACKGROUND: Low back pain (LBP) is a very common condition and leads to serious pain, disability, and price tag all over the world. Intervertebral disk degeneration (IDD) is one of the major reasons that contributed to LBP. The levels of interleukin 1 beta (IL-1ß) increase significantly in degenerative disks. IL-1ß also accelerates IDD. Sinapic acid (SA) has the effect of anti-inflammatory, antioxidant and antimicrobial. However, the effect of SA on IDD has never been studied. Therefore, the aim of this study was to figure out whether SA has protective effect on nucleus pulposus (NP) cells and further explore the possible underlying mechanism. METHODS: The nucleus pulposus (NP) tissues of rats were collected and cultured into NP cells. The NP cells were stimulated by IL-1ß and treated with SA. In vitro treatment effects were evaluated by ELISA, Western blot assay, immunofluorescence, TUNEL method and real-time PCR. We conducted percutaneous needle puncture in the rat tail to build intervertebral disk degeneration model and treated rats with SA. In vivo treatment effects were evaluated by hematoxylin and eosin (HE) and safranin O (SO) staining and magnetic resonance imaging (MRI) method. RESULTS: Our results showed that SA not only inhibited apoptosis but also suppressed inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in IL-1ß-stimulated NP cells. As to extracellular matrix (ECM), SA could increase collagen II and aggrecan levels and reduce the expression of MMP13 and ADAMTS5 during the stimulation of IL-1ß. Furthermore, SA could activate nuclear factor-erythroid 2-related factor-2 (Nrf2) to inhibit nuclear factor κB (NF-κB) induced by IL-1ß. Nrf2 knockdown partly reduced the protective effect of SA on NP cells. Correspondingly, SA ameliorated IDD by promoting Nrf2 expression. In vivo results also showed that SA could delay the progression of IDD. CONCLUSION: In conclusion, we demonstrated that SA could protect the degeneration of NP cells and revealed the underlying mechanism of SA on Nrf2 activation in NP cells.
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OBJECTIVE: To evaluate the conditional survival of patients with chordoma to potentially help physician planning of optimal cancer surveillance and guide better clinical decisions. METHODS: In total, 1942 patients with chordoma were identified and extracted from Surveillance, Epidemiology, and End Results (SEER) databases (1973-2015). The cumulative survival estimates were used to calculate the conditional survival rate, and the Greenwood formula was used to estimate the 95% CI. In addition, multivariable Cox regression analyses were used to calculate hazard ratios, according to the duration of survival. RESULTS: The conditional 5-year disease-specific survival in patients with regional or localized chordoma was relatively stable over time, whereas in patients with distant chordoma, there was a gradual improvement. The conditional 5-year disease-specific survival (DSS) of patients older than 60 years old and patients with a tumor size between 5 and 10 cm improved. Interestingly, for patients with a tumor larger than 10 cm, the conditional 5-year DSS decreased over time. After surviving 5 years, the hazard ratio (HR) of patients older than 60 years old decreased from 1.33 to 1.24, that of patients with a tumor size between 5 and 10 cm decreased from 1.61 to 1.52 and that of patients with distant metastasis decreased from 3.30 to 1.09. However, after surviving 5 years, the HR of patients with a tumor size larger than 10 cm increased from 2.33 to 3.77, that of patients who underwent surgical resection increased from 0.37 to 0.58 and that of patients who received radiation therapy increased from 0.81 to 1.04. CONCLUSION: Age at diagnosis, tumor size and disease stage can influence conditional survival for patients with chordoma. The HR of different factors will change over the survival time. Therefore, understanding the changing risk profile and conditional 5-year DSS of chordoma is critical for accurate clinical treatment guidance.
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Neoplasias Ósseas/mortalidade , Cordoma/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Cordoma/patologia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Programa de SEER , Análise de Sobrevida , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Meningioma incidence was reported to have risen substantially in the United States during the first decade of the 21st century. There are few reports about subsequent incidence trends. This study provides updated data to investigate trends in meningioma incidence by demographic and tumor characteristics at diagnosis in the United states from 2004 to 2015. METHODS: Trends in meningioma incidence were analyzed using data from the Surveillance, Epidemiology, and End Results-18 (SEER-18) registry database of the National Cancer Institute. The joinpoint program was used to calculate annual percent change (APC) in incidence rates. RESULTS: The overall incidence of meningioma increased by 4.6% (95% CI, 3.4-5.9) annually in 2004-2009, but remained stable from 2009 to 2015 (APC, 0; 95% CI, -0.8 to 0.8). Females (10.66 per 100 000 person-years) and blacks (9.52 per 100 000 person-years) had significant predominance in meningioma incidence. Incidence in many subgroups increased significantly up to 2009 and then remained stable until 2015. However, meningioma incidence in young and middle-aged people increased significantly throughout the entire time period from 2004 to 2015 (APC: 3.6% for <20-year-olds; 2.5% for 20-39-year-olds; 1.8% for 40-59-year-olds). The incidence of WHO II meningioma increased during 2011-2015 (APC = 5.4%), while the incidence of WHO III meningioma decreased during 2004-2015 (APC = -5.6%). CONCLUSION: In this study, the incidence of meningioma was found to be stable in recent years. Possible reasons for this finding include changes in population characteristics, the widespread use of diagnostic techniques, and changes in tumor classification and risk factors in the US population.
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Meningioma/epidemiologia , Fatores Etários , Feminino , História do Século XXI , Humanos , Incidência , Masculino , Meningioma/diagnóstico , Meningioma/história , Vigilância em Saúde Pública , Programa de SEER , Fatores Sexuais , Carga Tumoral , Estados Unidos/epidemiologiaRESUMO
Magnetically controlled growing rods have been used to treat early-onset scoliosis for the last 9 years; however, few studies have been published, with only short-term follow-up. The aim of the present study is to systematically review the outcomes of magnetically controlled growing rods in the treatment of early-onset scoliosis with a minimum of 2-year follow-up. Studies were included if patients with early-onset scoliosis (scoliosis diagnosed before 10 years of age) underwent implantation of magnetically controlled growing rods with a minimum of 2-year follow-up. The literature review and data extraction followed the established preferred reporting items for systematic review and meta-analysis guidelines. Data of distraction frequency, number of distractions, distracted length, Cobb angle, kyphosis, T1-T12 length, and T1-S1 length preoperatively, postoperatively, and at final follow-up were collected. Data regarding complications and unplanned reoperations were also extracted. The mean values of these parameters were calculated, or pooled meta-analysis was performed if available. Ten articles were included in this systematic review, with a total of 116 patients and a follow-up period between 23 and 61 months. The mean preoperative Cobb angle and kyphosis angle were 60.1° and 38.0°, respectively, and improved to 35.4° and 26.1° postoperatively. At final follow-up, the Cobb and kyphosis angles were maintained at 36.9° and 36.0°, respectively. The average preoperative T1-T12 and T1-S1 lengths were 180.6 mm and 293.6 mm, respectively, and increased to 198.3 mm and 320.3 mm postoperatively. T1-T12 and T1-S1 lengths were 212.3 mm and 339.3 mm at final follow-up, respectively. The overall rate of patients with complications was 48% (95% confidence interval [CI], 0.38-0.58) and unplanned reoperation 44% (95% CI, 0.33-0.55) after sensitivity analysis. The current evidence from different countries with a minimum of a 2-year follow-up suggests that magnetically controlled growing rods are an effective technique to treat pediatric scoliosis and promote spine growth. However, nearly half of patients still developed complications or required unplanned reoperations.
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BACKGROUND: Chordoma is a type of rare bone tumor and is a relatively slow-growing, low-grade malignancy that is locally invasive and aggressive. The nomogram is widely used in the field of cancer because it can provide a clear picture for clinicians to predict the survival rate, which can lead more accurate decisions in clinical treatment. METHODS: Overall, 875 patients with a primary spinal chordoma were identified and collected from the Surveillance, Epidemiology, and End Results registry databases (1973-2015). The nomogram was established based on 425 patients with complete data. The predictive accuracy and discriminative ability of the nomogram were determined by the concordance index (C-index) and calibration curve. RESULTS: The statistical nomogram was built on 10 independent prognostic factors: age, sex, race, disease stage, surgery, year of diagnosis, marital status, primary site, radiation, and tumor size, with C-indices of 0.76. The calibration curve to determine the probability of survival showed good agreement between the predictions by the nomogram and actual observation. Tumor diameter >10 cm (hazard ratio [HR] 2.95, 95% confidence interval [CI] 1.77-4.90, P < 0.001), regional invasive (HR 1.71, 95% CI 1.16-2.53, P < 0.01), and distant metastasis (HR 3.44, 95% CI 1.98-5.96, P< 0.001) were independent risk factors for poor survival. Undergoing subtotal resection or gross total resection (HR 0.37, 95% CI 0.25-0.56, P < 0.001; HR 0.26, 95% CI 0.17-0.41, respectively) and a primary site located in the sacrum/pelvis (HR 0.51, 95% CI 0.34-0.78, P < 0.01) were prognostic factors for better survival. CONCLUSIONS: The nomogram provided more accurate prognostic predictions for patients with spinal chordoma. Moreover, our study suggests that tumor diameter >5 cm, distant metastasis, and not performing resection are major risk factors that can dramatically decrease the survival time of patients with spinal chordoma.
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Cordoma/terapia , Nomogramas , Sacro/cirurgia , Neoplasias da Coluna Vertebral/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cordoma/mortalidade , Cordoma/patologia , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Procedimentos Neurocirúrgicos , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia , Programa de SEER , Sacro/patologia , Neoplasias da Coluna Vertebral/mortalidade , Neoplasias da Coluna Vertebral/patologia , Taxa de Sobrevida , Carga Tumoral , Adulto JovemRESUMO
BACKGROUND: Bone is one of the common metastatic sites of lung cancer, and its prognosis is not optimistic. We performed a study to evaluate the incidence, survival, and prognostic factors of lung cancer with bone metastasis (LCBM) at initial diagnosis, and to develop a nomogram to predict its outcomes. METHODS: We conducted a retrospective study choosing 13,541 patients with LCBM from the Surveillance, Epidemiology, and End Results (SEER) 18 registry database. An X-tile analysis provided the optimal age cutoff point. The incidence, overall survival, and prognosis of bone metastasis were evaluated according to the patient information, characteristics of the tumor, and therapy. We also used multivariable Cox regression to estimate mortality hazard ratios (HRs) among patients with LCBM, while a visual nomogram was established to judge the prognosis. RESULTS: The incidence of disease increased with age, but survival rates show the opposite trend. The median survival time was about 4 months. In addition, although the differences for patient race is not significant (P=0.445), White patients are prone to have bone metastases from lung cancer according to the incidence analysis. The difference for laterality is also not significant (P=0.534), while the factors of age, gender, the total number of sites, histological types, grade, tumor size, and treatment are significantly related to the outcome of patients with LCBM. Furthermore, our nomogram could predict the probability of surviving to the median survival time of the population with a c-index of 0.72. CONCLUSIONS: Age, characteristics of the tumor, and therapy should be considered for prediction of prognosis for patients with lung cancer bone metastasis. Putatively, the younger patients and the patients with chemotherapy and surgery may indicate improved survival.
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BACKGROUND: Malignant giant cell tumor of bone (MGCTB) is extremely rare. Currently, population-based prognosis studies are lacking. This study aimed to determine the impact of demographics, tumor characteristics, and treatment on prognosis among patients with MGCTB. METHODS: The Surveillance, Epidemiology, and End Results database was used to identify patients with MGCTB from 1984 to 2013. Kaplan-Meier analyses were performed to determine the overall survival (OS). Univariable and multivariable Cox analyses were conducted to identify prognostic factors. RESULTS: There were 250 patients with MGCTB included in our study. The multivariate Cox analysis revealed that age at diagnosis (hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 1.07-1.11; P < 0.001), tumor size (HR: 7.04; 95% CI: 2.38-20.77; P < 0.001), tumor extension (regional vs. localized, HR: 2.64; 95% CI: 1.10-6.34; Pâ¯=â¯0.030; distant vs. localized, HR: 6.12; 95% CI: 2.27-16.49; P < 0.001), and radiotherapy (HR: 0.41; 95% CI: 0.18-0.89; Pâ¯=â¯0.025) were independent risk factors of OS in patients with MGCTB. Notably, tumor site (HR: 1.98; 95% CI: 0.99-4.00; Pâ¯=â¯0.055) exhibited borderline significance. Additionally, we found that patients with tumors measuring >70â¯mm (Pâ¯=â¯0.015), located in the axial skeleton (P < 0.001) and presented with distant metastasis (P < 0.001) tended to receive radiotherapy. Moreover, a nomogram model integrating independent predictors was established to estimate the OS of patients with MGCTB. CONCLUSION: This study provides a population-based assessment of the largest number of patients with MGCTB. We found that older age, larger tumor size, regional or distant metastasis, and lack of radiotherapy was associated with poor OS. Surgical methods were not significantly associated with OS. Furthermore, we built a high-quality nomogram to predict 1-, 3-, and 5-year OS for patients with MGCTB. These findings may assist in the clinical diagnosis and treatment of MGCTB.
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AIM: To demonstrate the specific killing of folate receptor (FR)-positive tumor cells can be achieved by folate-targeted penicillin-G amidase (PGA) combined with its prodrug substrate N-(phenylacetyl) doxorubicin (DOXP). METHODS: Folic acid was covalently linked to PGA and folate content value was determined by quantitative UV spectrophotometry. The ability of folate conjugated PGA to hydrolyze DOXP was measured by RP-HPLC. Visual demonstration of uptake by FR (+) HeLa and SKOV3 cells was detected by using FITC labeled folate-PGA and a fluorescence microscopy. The cytotoxicity of DOXP towards the cells in the presence or absence of folate-PGA was assayed by using MTT method. RESULTS: The folate-PGA has a specific activity of 29. 8 U x mg(-1) (protein). FR selectivity was confirmed by fluorescence microscopy. The combination of DOXP prodrug with folate-PGA generated higher cytotoxicity towards the FR (+) cells than free doxorubicin. The IC50 was 0.72 micromol x L(-1) for HeLa cells and 0.75 micromol x L(-1) for SKOV3 cells, respectively. Further, the enhanced cytotoxicity reduced greatly with the addition of free folic acid. CONCLUSION: Folate conjugated PGA did not significantly compromise PGA catalytic activity and enabled binding prodrug-activating enzyme PGA to folate receptor expressing cells, and increased the sensitivity of the cells to doxorubicin followed by administration of its prodrug substrate.