ß-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture.

The autonomic nervous system plays a crucial role in regulating bone metabolism, with sympathetic activation stimulating bone resorption and inhibiting bone formation. We found that fractures lead to increased sympathetic tone, enhanced osteoclast resorption, decreased osteoblast formation, and thus hastened systemic bone loss in ovariectomized (OVX) mice. However, the combined administration of parathyroid hormone (PTH) and the ß-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice. The effect of this treatment is superior to that of treatment with PTH or propranolol alone. In vitro, the sympathetic neurotransmitter norepinephrine (NE) suppressed PTH-induced osteoblast differentiation and mineralization, which was rescued by propranolol. Moreover, NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation, whereas these effects were reversed by propranolol. Furthermore, PTH increased the expression of the circadian clock gene Bmal1, which was inhibited by NE-ßAR signaling. Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTH-stimulated osteoblast differentiation. Taken together, these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.

Targeting aging with the healthy skeletal system: The endocrine role of bone.

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.

Incidence and cost of vertebral fracture in urban China: a 5-year population-based cohort study.

BACKGROUND: Osteoporotic vertebral fractures cause pain and disability, which result in a heavy socioeconomic burden. However, the incidence and cost of vertebral fractures in China are unknown. We aimed to assess the incidence and cost of clinically recognized vertebral fractures among people aged 50 years and older in China from 2013 to 2017. MATERIALS AND METHODS: This population-based cohort study was conducted by using Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) data in China from 2013 to 2017, which covered more than 95% of the Chinese population in urban areas. Vertebral fractures were identified by the primary diagnosis (i.e. International Classification of Diseases code or text of diagnosis) in UEBMI and URBMI. The incidence and medical cost of these clinically recognized vertebral fractures in urban China were calculated. RESULTS: A total of 271 981 vertebral fractures (186 428, 68.5% females and 85 553, 31.5% males) were identified, with a mean age of 70.26 years. The incidence of vertebral fractures among patients aged 50 years and over in China increased ~1.79-fold during the 5 years, from 85.21 per 100 000 person-years in 2013 to 152.13 per 100 000 person-years in 2017. Medical costs for vertebral fractures increased from US$92.74 million in 2013 to US$505.3 million in 2017. Annual costs per vertebral fracture case increased from US$3.54 thousand in 2013 to US$5.35 thousand in 2017. CONCLUSION: The dramatic increase in the incidence and cost of clinically recognized vertebral fractures among patients aged 50 and over in urban China implies that more attention should be given to the management of osteoporosis to prevent osteoporotic fractures.

Pathophysiological mechanism of acute bone loss after fracture.

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.

Neurophysiological mechanisms of cancer-induced bone pain.

Background: Cancer-induced Bone Pain (CIBP) is an important factor affecting their quality of life of cancer survivors. In addition, current clinical practice and scientific research suggest that neuropathic pain is a representative component of CIBP. However, given the variability of cancer conditions and the complexity of neuropathic pain, related mechanisms have been continuously supplemented but have not been perfected. Aim of Review: Therefore, the current review highlights the latest progress in basic research on the field and proposes potential therapeutic targets, representative drugs and upcoming therapies. Key Scientific Concepts of Review: Notably, factors such as central sensitization, neuroinflammation, glial cell activation and an acidic environment are considered to be related to neuropathic pain in CIBP. Nonetheless, further research is needed to ascertain the mechanism of CIBP in order to develop highly effective drugs. Moreover, more attention needs to be paid to the care of patients with advanced cancer.

Controlled release of baricitinib from a thermos-responsive hydrogel system inhibits inflammation by suppressing JAK2/STAT3 pathway in acute spinal cord injury.

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.

Can Acupuncture Improve Chronic Spinal Pain? A Systematic Review and Meta-Analysis.

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.

Prognostic Nomograms to Predict Overall Survival and Cancer-specific Survival in Sacrum/Pelvic Chondrosarcoma (SC) Patients: A Population-based Propensity Score-matched Study.

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.

Association between Bone Mineral Density and Severity of Chronic Kidney Disease.

OBJECTIVE: We sought to evaluate the association between femoral neck (FN) and lumbar spine (LS) bone mineral densities (BMDs) with severity of chronic kidney disease (CKD) and prevalence of osteopenia or osteoporosis (OP) among the CKD group. METHODS: Cross-sectional data from 11050 participants aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) were analyzed. Specifically, Pearson correlation was applied to analyze the relationship between BMD and estimated glomerular filtration rate (eGFR). General linear models (GLMs) were adjusted for potential confounders and used to analyze mean BMD, based on CKD and CKD stages. RESULTS: FN BMD was positively correlated with the eGFR in the total and male CKD, but not in the female CKD population. LS BMD was not significantly associated with eGFR. After controlling for partial correlations, FN T-score was positively correlated with the eGFR in the total at-risk population. According to FN BMD, OP prevalence was positively associated with CKD stage. However, according to LS BMD, there was no significant association between OP and CKD stage. CONCLUSION: Our results may explain the higher prevalence of hip fracture, relative to that of the spine, among CKD patients and generate meaningful insights to guide care, prevention, and treatment regimens for CKD patients. However, the fact that this was a cross-sectional study may limit the possibility of drawing concrete conclusions. Nevertheless, these findings open up a new frontier for further studies to uncover the higher decrease of FN BMD compared to LS BMD among CKD cases.

The Characteristics and Mortality of Osteoporosis, Osteomyelitis, or Rheumatoid Arthritis in the Diabetes Population: A Retrospective Study.

BACKGROUND: Patients with diabetes mellitus are prone to develop osteoporosis, osteomyelitis, or rheumatoid arthritis (RA). Furthermore, the presence of these complications in those with diabetes may lead to higher mortality. The aim of our study was to assess characteristics and mortality of osteoporosis, osteomyelitis, or rheumatoid arthritis in individuals with diabetes. METHODS: We analyzed osteoporosis, osteomyelitis, and RA deaths associated with diabetes from 1999-2017 using the CDC WONDER system (CDC WONDER; https://wonder.cdc.gov). We used ICD-10 codes to categorize the underlying and contributing causes of death. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMR) per 1,000,000 person-years were calculated. RESULTS: The AAMR for osteoporosis in the population with diabetes was significantly higher in females (AAMR: 4.17, 95% CI: 4.10-4.24) than in males (AAMR: 1.12, 95% CI: 1.07-1.16). Deaths due to osteoporosis increased gradually from 1999, peaked in 2003 (AAMR: 3.78, 95% CI: 3.55-4.00), and reached a nadir in 2016 (AAMR: 2.32, 95% CI: 2.15-2.48). The AAMR for RA associated with diabetes was slightly higher in females (AAMR: 4.04, 95% CI: 3.98-4.11) than in males (AAMR: 2.45, 95% CI: 2.39-2.51). The mortality rate due to RA increased slightly from 1999 (AAMR: 3.18, 95% CI: 2.97-3.39) to 2017 (AAMR: 3.20, 95% CI: 3.02-3.38). The AAMR for osteomyelitis associated with diabetes was higher in males (AAMR: 4.36, 95% CI: 4.28-4.44) than in females (AAMR: 2.31, 95% CI: 2.26-2.36). From 1999 to 2017, the AAMR from osteomyelitis in this population was 2.63 (95% CI: 2.44-2.82) per 1,000,000 person-years in 1999 and 4.25 (95% CI: 4.05-4.46) per 1,000,000 person-years in 2017. CONCLUSIONS: We found an increase in the age-adjusted mortality rates of RA and osteomyelitis and a decrease of osteoporosis associated with diabetes from 1999 to 2017. We suggest that increased attention should therefore be given to these diseases in the population with diabetes, especially in efforts to develop preventative and treatment strategies.

Sinapic Acid Inhibits IL-1ß-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration.

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.

Real-World Evidence in Prescription Medication Use Among U.S. Adults with Neck Pain.

INTRODUCTION: Neck pain is a common condition that leads to serious pain, disability, and increased healthcare costs worldwide. Pharmacotherapy is one of the most common strategies to reduce neck pain in patients. The aim of this study was to analyze the real-world pattern of drugs prescribed for patients with neck pain in the USA. METHODS: Data on individuals who reported current neck pain in the 2009-2010 US National Health and Nutrition Examination Survey (NHANES) and with a history of persistent pain for at least 6 weeks or 3 months were extracted from the NHANES database. Those included in the study were divided into three groups based on the duration of pain: the without neck pain group (Group A); subacute group (Group B) with a history of 6 weeks of neck pain; and the chronic neck pain group (Group C) with a history of 3 months of neck pain. The use and duration of medication prescribed for Group A, B, and C patients were compared. RESULTS: The analysis revealed that opioid use was significantly more prevalent in the subacute and chronic neck pain group than in the without neck pain group (Group A) (adjusted odds ratio [aOR] 4.20, 95% confidence interval [CI] 2.07-8.52 and aOR 7.00, 95% CI 4.32-11.33, respectively). The factors strongly associated with higher opioid use included older age, low education level, and low family income. In the chronic neck group, opioids, followed in decreasing order of frequency by acetaminophen and nonsteroidal anti-infammatory drugs, were the most common analgesics used in combination with other analgesics. CONCLUSION: Our analysis of the data shows that the long-term excessive use of opioids and the underutilization of other analgesics are two major issues in the treatment of neck pain in the USA. Possible improvements include improved education of patients by healthcare professionals on the use of opioids and more consideration given to non-pharmacotherapy options. Our results reveal the potential problem in pharmacotherapy choices for neck pain treatment and may help improve the current clinical practice in the USA and other countries.

Cytotoxic aquatic pollutants and their removal by nanocomposite-based sorbents.

Water is an extremely essential compound for human life and, hence, accessing drinking water is very important all over the world. Nowadays, due to the urbanization and industrialization, several noxious pollutants are discharged into water. Water pollution by various cytotoxic contaminants, e.g. heavy metal ions, drugs, pesticides, dyes, residues a drastic public health issue for human beings; hence, this topic has been receiving much attention for the specific approaches and technologies to remove hazardous contaminants from water and wastewater. In the current review, the cytotoxicity of different sorts of aquatic pollutants for mammalian is presented. In addition, we will overview the recent advances in various nanocomposite-based adsorbents and different approaches of pollutants removal from water/wastewater with several examples to provide a backdrop for future research.

Effects of preoperative warming on the occurrence of surgical site infection: A systematic review and meta-analysis.

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.

Endocrine Therapy for the Functional Recovery of Spinal Cord Injury.

Spinal cord injury (SCI) is a major cause of physical disability and leads to patient dissatisfaction with their quality of life. Patients with SCI usually exhibit severe clinical symptoms, including sensory and motor dysfunction below the injured levels, paraplegia, quadriplegia and urinary retention, which can exacerbate the substantial medical and social burdens. The major pathological change observed in SCI is inflammatory reaction, which induces demyelination, axonal degeneration, and the apoptosis and necrosis of neurons. Traditional medical treatments are mainly focused on the recovery of motor function and prevention of complications. To date, numerous studies have been conducted to explore the cellular and molecular mechanism of SCI and have proposed lots of effective treatments, but the clinical applications are still limited due to the complex pathogenesis and poor prognosis after SCI. Endocrine hormones are kinds of molecules that are synthesized by specialized endocrine organs and can participate in the regulation of multiple physiological activities, and their protective effects on several disorders have been widely discussed. In addition, many studies have identified that endocrine hormones can promote nerve regeneration and functional recovery in individuals with central nervous system diseases. Therefore, studies investigating the clinical applications of endocrine hormones as treatments for SCI are necessary. In this review, we described the neuroprotective roles of several endocrine hormones in SCI; endocrine hormone administration reduces cell death and promotes functional repair after SCI. We also proposed novel therapies for SCI.

Incidence, prognostic factors, and a nomogram of lung cancer with bone metastasis at initial diagnosis: a population-based study.

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.

Conditional survival and changing risk profile in patients with chordoma: a population-based longitudinal cohort study.

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.

Nomogram for Individualized Prediction and Prognostic Factors for Survival in Patients with Primary Spinal Chordoma: A Population-Based Longitudinal Cohort Study.

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.

Morphometric Characteristics of Sacral-2 Alar Iliac Screw Fixation in Pediatric Population.

STUDY DESIGN: A computed tomographic assessment. OBJECTIVE: To establish morphometric data of sacral-2 alar iliac (S2AI) screw fixation in pediatric population. SUMMARY OF BACKGROUND DATA: Studies on morphometric parameters of S2AI screw fixation are mostly based on adult population. The pediatric scoliosis also needs the S2AI screw fixation, however, without the previous morphometric information of among pediatric population. METHODS: Computed tomography (CT) scans of 120 pediatric patients without spinal deformities are obtained and imported to Mimics software for 3D reconstruction. Then, a cylinder (radius of 3.25 mm) is drawn to imitate the screw trajectory of S2AI screw and adjusted to a maximum upward and downward angle to obtain the feasible region. Nine parameters of the S2AI screw are measured. Differences between age groups are compared and significant statistical correlations are carefully studied to determine the potentially important clinical relationships. RESULTS: The mean values and standard deviations (SD) for nine parameters at the maximum upward and downward angles were determined. With age increased, the S2AI screw trajectory becomes more caudal in the coronal (44.03 ±â€Š4.43°-53.15 ±â€Š4.68°) and sagittal planes (50.33 ±â€Š5.89°-57.69 ±â€Š4.21°) and more lateral in the transverse plane (49.40 ±â€Š5.90°-54.44 ±â€Š2.99°), and all of the distance parameters include max-length, sacral distance, iliac width, S2 midline, iliac wing, and skin distance increased. Age has a more significant effect on other parameters than transverse angle and skin distance (P < 0.05). CONCLUSION: The S2AI screw fixation could be used on pediatric population too, but the pediatric population had smaller size of pelvis than adults, surgeons should choose the smaller diameters and the shorter length of screws for pediatric population depends on their age. LEVEL OF EVIDENCE: N/ A.