BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objectives:To analyze the risk factors for prolonged length of stay(LOS)after lesion removal and bone graft fusion internal fixation in patients with spinal tuberculosis,and to develop and validate a predictive model.Methods:The clinical data of 152 patients with spinal tuberculosis who underwent lesion removal and bone grafting and fusion internal fixation at Honghui Hospital affiliated to Xi'an Jiaotong Univer-sity from February 2016 to December 2020 were retrospectively analyzed.The patients were divided into the prolonged LOS(PLOS)group and normal LOS(NLOS)group according to whether their postoperative LOS ex-ceeded the postoperative LOS of the 75th percentile of the overall study cohort.Univariate analyses were per-formed for gender,age,hypertension,diabetes,paraplegia,anticoagulation history,tuberculosis resistance,pre-operative anti-tuberculosis time,blood transfusion,surgical site,surgical approach,number of fused vertebrae,operative time,intraoperative blood loss(IBL),postoperative complications,blood transfusion cost,hospital cost,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),albumin(ALB),blood routine,and coagulation function in both groups.Based on Lasso regression,the risk factors significantly associated with postoperative LOS prolongation in spinal tuberculosis were selected and incorporated into a multivariate logistic regression analysis,and thereby a prediction model was established based on the results of multivariate logistic regres-sion analysis.The model was visualized by plotting a nomogram as a means of predicting the probability of risk for prolongation of LOS after spinal tuberculosis surgery.Internal validation of the model was performed using extended Bootstrap,where receiver operating characteristic(ROC)curves,calibration curves and decision curve analysis(DCA)were plotted to verify the discrimination,accuracy and clinical applicability.Results:The 152 patients enrolled in the study had a median LOS of 10d,and the 75%LOS was 14d.There were 96 patients in the PLOS group and 56 in the NLOS group.Univariate analysis showed that the differences in age,hypertension,diabetes,anticoagulation history,tuberculosis resistance,preoperative anti-tuberculosis time,surgical site,surgical approach,surgical time,IBL,postoperative complications,CRP,ESR,preoperative ALB,blood routine,and coagulation function were not statistically significant between the two groups(P＞0.05),while the differences in gender,paraplegia,blood transfusion,number of fused vertebrae,blood transfusion cost,and hospitalization cost were statistically significant(P＜0.05).The operative time,IBL,preoperative Hb,and preop-erative ALB were divided according to the Yoden index of ROC as the dividing point,and the cut-off value of operative time was 198(min),the cut-off value of IBL was 1000(mL),the cut-off value of preoperative Hb was 118(g/L),and the cut-off value of preoperative ALB was 38.8(g/L).Through Lasso regression model,the risk factors closely related to the prolongation of LOS after spinal tuberculosis were female,blood transfusion,the number of fused vertebrae≥3,operative time≥198min and IBL≥1000mL,preoperative Hb＜118g/L and preoperative ALB＜38.8g/L.Multivariate logistic regression analysis showed that female,number of fused ver-tebrae≥3,operative time≥198min and IBL≥1000mL were the risk factors for postoperative LOS prolongation in patients with spinal tuberculosis(P＜0.05).A visual nomogram model for logistic regression was constructed,and the predictors included female,number of fused vertebrae,operative time,and IBL.A Bootstrap self-sampling of 1,000 times was performed to complete the internal validation of the model,with a C-index value of 0.882 and an area under the curve(AUC)of ROC of 0.884(95%CI:0.782 to 0.985).The calibration curve showed that the apparent curve of the model fitted well with the curve after deviation correction.The DCA curve showed that the threshold range of 0.2 to 0.9 had the greatest clinical benefit.Conclusions:Female,number of fused vertebrae≥3,operative time≥198min and IBL≥1000mL are the main risk factors for pro-longed LOS after lesion removal and bone graft fusion with internal fixation in patients with spinal tuberculo-sis,and the predictive model based on the above risk factors can help physicians to make clinical decisions and optimize the perioperative management.

Objective:To investigate the current situation and organizational management policies of government procurement in public hospitals,and to improve the level of standardized management of government procurement.Methods:An electronic questionnaire survey was conducted to investigate the current status of organization and administration of government procurement in different types and levels of public hospitals across the country.The current situation of the organizational structure,management system,working mode,supervision and evaluation,budget establishment,bidding and procurement,contract signing,acceptance process,payment management,and other aspects of government procurement management in public hospitals were analyzed.Results:A total of 216 valid questionnaires were collected from 216 public hospitals in 28 provinces,municipalities and autonomous regions across the country,including 165 general hospitals,37 specialized hospitals and 13 traditional Chinese medicine hospitals,accounting for 76.39％,17.13％and 6.02％respectively;among the hospital levels,there were 202 tertiary hospitals(accounting for 93.52％).Among the surveyed government procurement management institutions of public hospitals,there were 112,103,110 and 112 organizations at the four levels of procurement management committee,procurement management office,procurement center and business and administrative logistics department,accounting for 51.85％,47.69％,50.93％and 51.85％respectively.The quota standards for public bidding for government procurement in all hospitals were in line with the requirements of national laws and regulations.The approval of funds payment must conditions of each hospital complied with relevant requirements.In terms of management effects of risk prevention and control,the hospitals with very good,good,average and inadequate were 48,125,34 and 9 respectively,accounting for 22.22％,57.87％,15.74％and 4.17％.Conclusion:The organizational framework and management system of government procurement in public hospitals are becoming increasingly standardized,and there are certain differences in the work mode and process of government procurement in different hospitals,and the supervision and evaluation are relatively weak,which is worthy of attention and strengthened administration.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective To evaluate the radiation protection of “four-in-one” dental X-ray equipment and to investigate the safety interlock of the equipment by measuring the scattered radiation at the position of the patient during operation. Methods A cone-beam CT dental phantom was used to simulate the patient’s head. The intra-oral and extra-oral components of the “four-in-one” X-ray equipment were installed in a 5 m² room. The scattered radiation at patient position was measured using a γ/X-ray survey meter, and the effects of intra-oral and extra-oral components were compared. Results For a 5 m² room, when CBCT was exposed under typical conditions, the dose at the patient's position was 10.70 uSv/h when there was an intra-oral component and 10.60 uSv/h when there was no intraoral component. The intra-oral part did not affect the radiation dose at the patient's position. When the intra-oral component was exposed, the dose rate at the patient's position was 4.05-6.85 uSv/h, and the extra-oral part did not affect the scattered dose of the patient examined with intra-oral components. Conclusion The evaluation of radiation protection of new equipment must comprehensively consider radiation safety and equipment operation safety. The results of this study provide suggestions for clinical radiation protection supervision and evaluation of “four-in-one” dental X-ray equipment.

Objective:To test and evaluate the reliability and clinical effectiveness of osteoporotic thoracolumbar fracture (OTLF) scoring and classification system.Methods:A multicenter retrospective case series study was conducted to analyze the clinical data of 530 OTLF patients admitted to 8 hospitals including Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2021 to June 2022. There were 212 males and 318 females, aged 55-90 years [(72.6±10.8)years]. There were 4 patients with grade C and 18 with grade D according to American Spinal Injury Association (ASIA) classification. According to the osteoporotic thoracolumbar injury classification and severity (OTLICS) score, all patients had an OTLICS score over 4 points and required surgical treatment. Among them, 410 patients had acute symptomatic OTLF (ASOTLF), including 24 patients with type I, 159 type IIA, 47 type IIB, 31 type IIC, 136 type IIIA, 8 type IIIB, 2 type IV (absence of neurological symptoms) and 3 type IV (presence of neurological symptoms), and 120 patients had chronic symptomatic OTLF (CSOTLF), including 62 patients with type I, 21 type II, 17 type III, 3 type IV (reducible under general anesthesia), 9 type IV (not reducible under general anesthesia), 1 type V (reducible under general anesthesia), 5 type V (presence of neurological symptoms), and 2 type V (not reducible under general anesthesia). Surgical procedures included percutaneous vertebroplasty (PVP), positional repositioning plus PVP, percutaneous kyphoplasty (PKP), posterior open reduction combined with bone graft fusion and bone cement augmented screw internal fixation, posterior open reduction combined with decompression, bone graft fusion and bone cement augmented screw internal fixation, and posterior open reduction combined with osteotomy and orthopedics, bone graft fusion and bone cement augmented screw internal fixation. A weighted Kappa was used to test the interobserver and intraobserver reliability of the OTLICS score, the ASOTLF classification, and the CSOTLF classification. The visual analog scale (VAS), Oswestry disability index (ODI), ASIA classification were compared before, at 1 month after surgery and at the last follow-up. Incidence of postoperative complications was observed.Results:The percentage of mean interobserver agreement for OTLICS staging was 93.4%, with a mean confidence Kappa value of 0.86, and the percentage of mean intraobserver agreement was 93.0%, with a mean confidence kappa value of 0.86. The percentage of mean interobserver agreement for ASOTLF staging was 94.2%, with a mean confidence Kappa value of 0.84, and the percentage of mean intraobserver agreement was 92.5%, with a mean confidence Kappa value of 0.83. The percentage of mean interobserver agreement for CSOTLF subtyping was 91.9%, with a mean confidence Kappa value of 0.80, and the percentage of mean intraobserver agreement was 91.3%, with a mean confidence Kappa value of 0.81. All the patients were followed up for 6-12 months [(9.0±2.1)months]. The VAS and ODI scores were significantly lower in patients with ASOTLF and CSOTLF classifications at 1 month after surgery and at the last follow-up than those before surgery (all P<0.05). The VAS scores in patients with ASOTLF types IIA, IIB, IIC, IIIA, and IV were significantly lower at the last follow-up than that at 1 month after surgery; the ODI scores in patients with ASOTLF types I, IIA, IIB, IIIA, IIIB and IV were significantly lower at the last follow-up than those at 1 month after surgery. The VAS scores in patients with CSOTLF types II, III, IV, and V were significantly lower at the last follow-up than those at 1 month after surgery, and the ODI scores in patients with all CSOTLF types were significantly lower at the last follow-up than those at 1 month after surgery (all P<0.05). Two patients with ASIA grade C recovered to grade D, and the rest recovered to grade E at the last follow-up ( P<0.01). No major vessel or nerve injury or internal fixation failure was found during follow-up. There were 18 patients with cement leakage, none of whom showed relevant clinical symptoms. There were 35 patients with new vertebral fractures, all of whom recovered well after symptomatic treatment. Conclusions:The OTLICS score, ASOTLF classification and CSOTLF classification have a high degree of reliability. Application of stepwise treatment for patients with different levels of injury according to the scoring and classification system can reduce pain, promote recovery of the spinal function, and reduce complications, which is of some significance in guiding the selection of clinical treatment.

Objective:To explore the efficacy of O-arm navigation system-assisted upper cervical pedicle screw internal fixation in the treatment of traumatic atlantoaxial instability.Methods:A retrospective cohort study was conducted to analyze the clinical data of 61 patients with atlantoaxial instability admitted to Affiliated Honghui Hospital of Xi′an Jiaotong University from January 2021 to June 2022, including 34 males and 27 females, aged 20-77 years [(50.2±13.1)years]. A total of 38 patients were treated with unarmed screw placement (unarmed group), and 23 with O-arm navigation system-assisted screw placement (navigation group). The unarmed group was divided into experienced group ( n=20) and unexperienced group ( n=18) based on the surgeons′ experience (whether they had 20 years or longer experience of spinal surgery and performed more than 100 atlantoaxial surgeries independently). The screw placement and surgical time of each group was recorded. The cervical CT scan was conducted at 7 days after surgery to evaluate the satisfaction rate of pedicle screw placement and cortical penetration rate according to Neo grading criteria. The cervical nerve function of the patients before, at 7 days after surgery and at the last follow-up was evaluated using the Japanese Orthopedic Association (JOA) score and the Neck Disability Index (NDI). The occurrence of complications was observed. Results:All patients were followed up for 9-25 months [(16.3±4.2)months]. There were no statistically significant differences in the screw placement and surgical time between the navigation group and the unarmed group (all P>0.05). The screw placement time of the navigation group was (41.0±7.8)minutes, longer than that of the experienced group [(23.6±6.8)minutes] ( P<0.01) and shorter than that of the unexperienced group [(50.1±10.1)minutes] ( P<0.05). The surgical time of the navigation group was (101.9±9.9)minutes, which was longer than that of the experienced group [(67.6±8.3)minutes] ( P<0.01) and shorter than that of the unexperienced group [(126.1±16.4)minutes] ( P<0.01). The satisfaction rate of pedicle screw placement and cortical penetration rate of the navigation group were 98.9% and 4.3%, respectively, which were better than those of the unarmed group (94.1% and 17.8%), the experienced group (96.2% and 13.8%), and the unexperienced group (91.7% and 22.2%) ( P<0.05 or 0.01). There was no statistically significant difference in JOA score or NDI before, at 7 days after surgery or at the last follow-up between the navigation group and the unarmed group, and no difference between the navigation group and the experienced group or the unexperienced group (all P>0.05). No complications such as spinal cord nervous or vascular injuries were observed during surgery in the navigation group or the unarmed group. Conclusions:Compared with the unarmed screw placement, O-arm navigation system-assisted upper cervical pedicle screw internal fixation shows no significant difference in screw placement time, surgical time, and postoperative neurological function status in the treatment of traumatic atlantoaxial instability, but has a higher accuracy in screw placement. Compared with the experienced surgeons′ unarmed screw placement, the technique also has higher screw placement accuracy but longer screw placement time and surgical time. Whereas in comparison with unexperienced surgeons′ unarmed screw placement, the technique can not only significantly improve its screw placement accuracy, while shortening screw placement time and surgical time so as to improve the surgical safety.

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.