Targeting KRAS mutant cancers: from druggable therapy to drug resistance.

Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is the most frequently mutated oncogene, occurring in a variety of tumor types. Targeting KRAS mutations with drugs is challenging because KRAS is considered undruggable due to the lack of classic drug binding sites. Over the past 40 years, great efforts have been made to explore routes for indirect targeting of KRAS mutant cancers, including KRAS expression, processing, upstream regulators, or downstream effectors. With the advent of KRAS (G12C) inhibitors, KRAS mutations are now druggable. Despite such inhibitors showing remarkable clinical responses, resistance to monotherapy of KRAS inhibitors is eventually developed. Significant progress has been made in understanding the mechanisms of drug resistance to KRAS-mutant inhibitors. Here we review the most recent advances in therapeutic approaches and resistance mechanisms targeting KRAS mutations and discuss opportunities for combination therapy.

The Reliability of Computer-Assisted Three-Dimensional Surgical Simulation of Posterior Osteotomies in Thoracolumbar Kyphosis Secondary to Ankylosing Spondylitis Patients.

Objectives: The study was aimed at investigating the reliability of computer-assisted three-dimensional surgical simulation (CA3DSS) of posterior osteotomies in thoracolumbar kyphosis secondary to ankylosing spondylitis (TLKAS) patients. Methods: Eligible TLKAS patients who underwent posterior correction surgery with posterior osteotomies were consecutively included. Simulated posterior osteotomies were performed in Mimics and 3-Matic Medical software. Coronal and sagittal angle and alignment parameters were measured in preoperative full-length X-ray, preoperative original 3D spine (Pre-OS), simulated 3D spine (SS), and postoperative original 3D spine (Post-OS). Reliability was tested by both intraclass correlation coefficients (ICCs) and Bland-Altman analysis. Results: A total of 30 TLKAS patients were included. Excellent consistency of radiological parameters was shown between preoperative X-ray and Pre-OS model. In SS and Post-OS models, excellent reliabilities were shown in global kyphosis (ICC 0.832, 95% CI 0.677-0.916), thoracic kyphosis (ICC 0.773, 95% CI 0.577-0.885), and lumbar lordosis (ICC 0.896, 95% CI 0.794-0.949) and good reliabilities were exhibited in the main curve (ICC 0.680, 95% CI 0.428-0.834) and sagittal vertical axis (ICC 0.619, 95% CI 0.338-0.798). ICCs of correction angle achieved by pedicle subtraction osteotomy (PSO) was 0.754 (95% CI 0.487-0.892), and that of posterior column osteotomies (PCO) was 0.703 (95% CI 0.511-0.829). Bland-Altman analysis also showed good agreement for both Cobb angle and distance measurements in Pre-OS and SS models, and good reliabilities were shown in PCO and PSO in real spine and SS models. Conclusions: CA3DSS can provide an accurate measurement, and it is a reliable and effective method to conduct proper simulation for correction surgery with posterior osteotomies in TLKAS patients. This trial is registered with Chinese Clinical Trial Registry ChiCTR2100053808.

Validity of the Roussouly classification system for assessing distal junctional problems after long instrumented spinal fusion in degenerative scoliosis.

PURPOSE: To evaluate the validity of the Roussouly classification system for assessing distal junctional problems (DJP) after long instrumented spinal fusion in degenerative scoliosis. METHODS: Sixty-four patients with degenerative scoliosis and long-segment fixation receiving treatment at our hospital between December 2012 and December 2018 were retrospectively analyzed. Patients were classified preoperatively and postoperatively (Roussouly classification) and divided into DJP and control groups. We observed whether patients restored to their preoperative Roussouly classification (based on pelvic incidence [PI]) postoperatively. RESULTS: The incidences of DJP were 11.11% and 50% in patients who did and did not match their sagittal Roussouly classification immediately postoperatively, respectively. The adjusted Chi-square test that showed whether the sagittal profile matched the Roussouly classification immediately after surgery was statistically significant (P = 0.012). PIs were 55.83 ± 4.94 and 47.21 ± 10.81 in the DJP and non-DJP groups, respectively (t' = 4.367, P < 0.001). Distal junctional kyphosis angles were 6.33 ± 4.19° and 11.56 ± 5.02° in the DJP and non-DJP groups, respectively (t = - 2.595, P = 0.015). Preoperative PI-lumbar lordosis values were 29.14 ± 13.82 and 16.67 ± 11.39 in the DJP and non-DJP groups, respectively (t = - 2.626, P = 0.013). The logistic regression model showed that patients whose Roussouly classification did not match the postoperative PI value were more likely to have DJP (odds ratio [OR] = 4.01, 95% confidence interval [CI]: 0.51-31.61) and preoperative distal junctional kyphotic changes. CONCLUSION: If the postoperative sagittal profile can be restored to match the patient's own PI value, use of the Roussouly classification can greatly reduce the possibility of postoperative DJP.

May the midline lumbar interbody fusion (MIDLIF) prevent the early radiographic adjacent segment degeneration? A minimum 3-year follow-up comparative study of MIDLIF in L4/5 with cortical bone trajectory screw versus traditional pedicle screw fixation.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare the early radiographic adjacent segment degeneration (R-ASD) and regional lumbar sagittal alignment after midline lumbar interbody fusion (MIDLIF) with cortical bone trajectory (CBT) screw fixation (CBT-MIDLIF) and posterior lumbar interbody fusion (PLIF) with the traditional pedicle screw fixation (PS-PLIF) during long-term follow-up. METHODS: All patients who underwent CBT-MIDLIF or PS-PLIF were identified by a retrospective consecutive case review. Radiographic parameters in cephalad adjacent segment (L3/4), including intervertebral space height (ISH), foraminal height (FH), foraminal width (FW), range of motion were assessed. Lumbar lordosis (LL), sacral slope (SS), L4-L5 Cobb angle, Cobb angle of the intervertebral space at L4-L5, and height of the anterior and posterior edges of the intervertebral space at L4-L5, were measured and compared on preoperative, postoperative, and 3-year follow-up radiographic evaluation. RESULTS: Seventy-four patients underwent CBT-MIDLIF (CBT-MIDLIF group) and 114 patients underwent conventional PS-PLIF (PS-PLIF group). ISH, FH and FW were significantly smaller at 6-month follow-up than before operation with PS-PLIF (p < 0.001) but showed no significant changes with CBT-MIDLIF (p > 0.05). At the last follow-up, the changes in cephalad R-ASD parameters were more remarkable after PS-PLIF than after CBT-MIDLIF (p < 0.01). LL and SS were significant larger at the last follow-up than before operation in both groups (p < 0.001). Regarding long-term outcomes, the symptoms caused by degenerative spinal disorders significantly improved in both groups (p < 0.01). CONCLUSION: CBT-MIDLIF had less radiographic degeneration in the adjacent segment than PS-PLIF at 3-year follow-up. The lumbar sagittal alignment could be improved significantly and the surgical outcomes were satisfactory after either CBT-MIDLIF or PS-PLIF.

Accuracy and safety of robot-assisted cortical bone trajectory screw placement: a comparison of robot-assisted technique with fluoroscopy-assisted approach.

OBJECTIVE: To compare the safety and accuracy of cortical bone trajectory screw placement between the robot-assisted and fluoroscopy-assisted approaches. METHODS: This retrospective study was conducted between November 2018 and June 2020, including 81 patients who underwent cortical bone trajectory (CBT) surgery for degenerative lumbar spine disease. CBT was performed by the same team of experienced surgeons. The patients were randomly divided into two groups-the fluoroscopy-assisted group (FA, 44 patients) and the robot-assisted group (RA, 37 patients). Robots for orthopedic surgery were used in the robot-assisted group, whereas conventional fluoroscopy-guided screw placement was used in the fluoroscopy-assisted group. The accuracy of screw placement and rate of superior facet joint violation were assessed using postoperative computed tomography (CT). The time of single screw placement, intraoperative blood loss, and radiation exposure to the surgical team were also recorded. The χ2 test and Student's t-test were used to analyze the significance of the variables (P < 0.05). RESULTS: A total of 376 screws were inserted in 81 patients, including 172 screws in the robot-assisted group and 204 pedicle screws in the fluoroscopy-assisted group. Screw placement accuracy was higher in the RA group (160, 93%) than in the FA group (169, 83%) (P = 0.003). The RA group had a lower violation of the superior facet joint than the FA group. The number of screws reaching grade 0 in the RA group (58, 78%) was more than that in the FA group (56, 64%) (P = 0.041). Screw placement time was longer in the FA group (7.25 ± 0.84 min) than in the RA group (5.58 ± 1.22 min, P < 0.001). The FA group had more intraoperative bleeding (273.41 ± 118.20 ml) than the RA group (248.65 ± 97.53 ml, P = 0.313). The radiation time of the FA group (0.43 ± 0.07 min) was longer than the RA group (0.37 ± 0.10 min, P = 0.001). Furthermore, the overall learning curve tended to decrease. CONCLUSIONS: Robot-assisted screw placement improves screw placement accuracy, shortens screw placement time, effectively improves surgical safety and efficiency, and reduces radiation exposure to the surgical team. In addition, the learning curve of robot-assisted screw placement is smooth and easy to operate.

Cortical screw placement with a spinous process clamp guide: a cadaver study accessing accuracy.

BACKGROUND AND OBJECTIVE: The Cortical Bone Trajectory (CBT) technique provides an alternative method for fixation in the lumbar spine in patients with osteoporosis. An accuracy CBT screw placement could improve mechanical stability and reduce complication rates. PURPOSE: The purpose of this study is to explore the accuracy of cortical screw placement with the application of implanted spinous process clip (SPC) guide. METHODS AND MATERIALS: Four lumbar specimens with T12-S1 were used to access the accuracy of the cortical screw. The SPC-guided planning screws were compared to the actual inserted screws by superimposing the vertebrae and screws preoperative and postoperative CT scans. According to preoperative planning, the SPC guide was adjusted to the appropriate posture to allow the K-wire drilling along the planned trajectory. Pre and postoperative 3D-CT reconstructions was used to evaluate the screw accuracy according to Gertzbein and Robbins classification. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to examine SPC-guided agreements for CBT screw placement. RESULTS: A total of 48 screws were documented in the study. Clinically acceptable trajectory (grades A and B) was accessed in 100% of 48 screws in the planning screws group, and 93.8% of 48 screws in the inserted screws group (p = 0.242). The incidence of proximal facet joint violation (FJV) in the planning screws group (2.1%) was comparable to the inserted screws group (6.3%) (p = 0.617). The lateral angle and cranial angle of the planned screws (9.2 ± 1.8° and 22.8 ± 5.6°) were similar to inserted screws (9.1 ± 1.7° and 23.0 ± 5.1°, p = 0.662 and p = 0.760). Reliability evaluated by intraclass correlation coefficients and Bland-Altman showed good consistency in cranial angle and excellent results in lateral angle and distance of screw tip. CONCLUSIONS: Compared with preoperative planning screws and the actually inserted screws, the SPC guide could achieve reliable execution for cortical screw placement.

Frailty as a risk factor for postoperative complications in adult patients with degenerative scoliosis administered posterior single approach, long-segment corrective surgery: a retrospective cohort study.

BACKGROUND: With the population aging worldwide, adult degenerative scoliosis (ADS) is receiving increased attention. Frailty, instead of chronological age, is used for assessing the patient's overall physical condition. In ADS patients undergoing a posterior approach, long-segment corrective surgery, the association of frailty with the postsurgical outcomes remains undefined. METHODS: ADS patients who underwent a posterior approach, long-segment fusion at the Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University (CMU), Beijing, China, in 2014-2017 were divided into the frailty and non-frailty groups according to the modified frailty index. Major postoperative complications were recorded, including cardiac complications, pneumonia, acute renal dysfunction, delirium, stroke, neurological deficit, deep wound infection, gastrointestinal adverse events, and deep vein thrombosis. Radiographic measurements and health-related quality of life (HRQOL) parameters were recorded preoperatively and at 2 postoperative years. RESULTS: A total of 161 patients were included: 47 (29.2%) and 114 (70.8%) in the frailty and non-frailty groups, respectively. Major postoperative complications were more frequent in the frailty group than the non-frailty group (29.8% vs. 10.5%, P = 0.002). Multivariable logistic regression analysis showed that frailty was independently associated with major complications (adjusted odds ratio [aOR] = 2.77, 95% confidence interval [CI] 1.12-6.89, P = 0.028). Radiographic and HRQOL parameters were improved at 2 years but with no significant between-group differences. CONCLUSIONS: Frailty is a risk factor for postoperative complications in ADS after posterior single approach, long-segment corrective surgery. Frailty screening should be applied preoperatively in all patients to optimize the surgical conditions in ADS.

Penetrating glassy carbon neural electrode arrays for brain-machine interfaces.

This paper presents a fabrication method for glassy carbon neural electrode arrays that combines 3D printing and chemical pyrolysis technology. The carbon electrodes have excellent biological compatibility and can be used in neural signal recording. A pretreated Si wafer is used as the substrate for 3D printing, and then, stereolithography 3D printing technology is employed to print photosensitive resin into a cone shape. Next, chemical pyrolysis is applied to convert the 3D prints into glassy carbon electrodes and modify the electrochemical performance of the carbon electrodes. Finally, the glassy carbon electrodes are packed with conductive wires and PDMS. The proposed fabrication method simplifies the manufacturing process of carbon materials, and electrodes can be fabricated without the need of deep reactive ion etching (DRIE). The height of the carbon electrodes is 1.5 mm, and the exposure area of the tips is 0.78 mm2, which is convenient for the implantation procedure. The specific capacitance of the glassy carbon arrays is higher than that of a platinum electrode (9.18 mF/cm2 vs 3.32 mF/cm2, respectively), and the impedance at 1 kHz is lower (7.1 kΩ vs 8.8 kΩ). The carbon electrodes were tested in vivo, and they showed excellent performance in neural signal recording. The signal-to-noise ratio of the carbon electrodes is 50.73 ± 6.11, which is higher than that of the Pt electrode (20.15 ± 5.32) under the same testing conditions. The proposed fabrication method of glassy carbon electrodes provides a novel approach to manufacture penetrating electrodes for nerve interfaces in biomedical engineering and microelectromechanical systems.

Risk factors for pulmonary complications after posterior spinal instrumentation and fusion in the treatment of congenital scoliosis: a case-control study.

BACKGROUND: Although surgery prevents the progression of deformity and maintains the overall balance of the spine in congenital scoliosis (CS) patients, it is associated with a high risk of perioperative complications. Pulmonary complication is one of the most common complications. This retrospective study aimed to investigate the risk factors for pulmonary complications in CS patients after posterior spinal instrumentation and fusion. METHODS: Analysis of consecutive patients who underwent posterior spinal instrumentation and fusion for congenital scoliosis was performed. Preoperative clinical data, intraoperative variables, and perioperative radiographic parameters were collected to analyze the risk factors for pulmonary complications. Patients were separated into groups with and without postoperative pulmonary complications. Potential risk factors were identified by univariate testing. Multivariate logistic regression was used to evaluate independent predictors of pulmonary complications. RESULTS: Three hundred and twenty-three CS patients were included. Forty-five (13.9%) patients developed postoperative pulmonary complications, which included pleural effusion in 34 (75.6%) cases, pneumonia in 24 (53.3%) cases, pneumothorax in 3 (6.7%) cases, atelectasis in 4 (8.9%) cases, pulmonary edema in 2 (4.4%) cases, respiratory failure in 2 (4.4%) cases, and prolonged mechanical ventilation in 4 (8.9%) cases. The independent risk factors for development of pulmonary complications included age (Odds ratio (OR) = 1.088, P = 0.038), reoperation (OR = 5.150, P = 0.012), preoperative pulmonary disease (OR = 10.504, P = 0.004), correction rate (OR = 1.088, P = 0.001), middle thoracic screw-setting (OR = 12.690, P = 0.043), and thoracoplasty (OR = 5.802, P = 0.001). The area under the receiver operating characteristic (ROC) curve based on predicted probability of the logistic regression was 0.903. CONCLUSIONS: Age, reoperation, preoperative pulmonary disease, correction rate, middle thoracic screw-setting, and thoracoplasty were independent risk factors for pulmonary complications after posterior spinal instrumentation and fusion in CS patients.

Risk factors for medical complications after long-level internal fixation in the treatment of adult degenerative scoliosis.

PURPOSE: This study evaluates baseline patient characteristics and surgical parameters for risk factors of medical complications in ASD patients received posterior long level internal fixation. METHODS: Analysis of consecutive patients who underwent posterior long-level instruction fixation for adult degenerative scoliosis (ADS) with a minimum of two year follow-up was performed. Pre-operative risk factors, intraoperative variables, peri-operative radiographic parameters, and surgical-related risk factors were collected to analyze the effect of risk factors on medical complications. Patients were separated into groups with and without medical complication. Then, complication group was further classified as major or minor medical complications. Potential risk factors were identified by univariate testing. Multivariate logistic regression was used to evaluate independent predictors of medical complications. RESULTS: One hundred and thirty-one ADS patients who underwent posterior long segment pedicle screws fixation were included. Total medical complication incidence was 25.2%, which included infection (12.2%), neurological (11.5%), cardiopulmonary (7.6%), gastrointestinal (6.1%), and renal (1.5%) complications. Overall, 7.6% of patients developed major medical complications, and 17.6% of patients developed minor medical complications. The radiographic parameters of pre-operative and last follow-up had no significant difference between the groups of medical complications and the major or minor medical complications subgroups. However, the incidence of cerebrospinal fluid leak (CFL) in patients who without medical complications was much lower than that with medical complications (18.4 vs. 42.4%, P = 0.005). Independent risk factors for development of medical complications included smoking (OR = 6.45, P = 0.012), heart disease (OR = 10.07, P = 0.012), fusion level (OR = 2.12, P = 0.001), and length of hospital stay (LOS) (OR = 2.11, P = 0.000). Independent risk factors for development of major medical complications were diabetes (OR 6.81, P = 0.047) and heart disease (OR = 5.99, P = 0.049). Except for the last follow-up, Oswestry Disability Index and visual analog scale of the patient experienced medical complications trend higher score; the clinical outcomes have no significant difference between the medical and major complications groups. CONCLUSION: Heart disease comorbidity is an independent risk factor for both medical and major medical complications. Smoking, fusion level, and LOS are independent risk factors for medical complication. Diabetes is the independent risk factors for major medical complications.

Percutaneous versus traditional and paraspinal posterior open approaches for treatment of thoracolumbar fractures without neurologic deficit: a meta-analysis.

PURPOSE: This study evaluated differences in outcome variables between percutaneous, traditional, and paraspinal posterior open approaches for traumatic thoracolumbar fractures without neurologic deficit. METHODS: A systematic review of PubMed, Cochrane, and Embase was performed. In this meta-analysis, we conducted online searches of PubMed, Cochrane, Embase using the search terms "thoracolumbar fractures", "lumbar fractures", ''percutaneous'', "minimally invasive", ''open", "traditional", "posterior", "conventional", "pedicle screw", "sextant", and "clinical trial". The analysis was performed on individual patient data from all the studies that met the selection criteria. Clinical outcomes were expressed as risk difference for dichotomous outcomes and mean difference for continuous outcomes with 95 % confidence interval. Heterogeneity was assessed using the χ 2 test and I 2 statistics. RESULTS: There were 4 randomized controlled trials and 14 observational articles included in this analysis. Percutaneous approach was associated with better ODI score, less Cobb angle correction, less Cobb angle correction loss, less postoperative VBA correction, and lower infection rate compared with open approach. Percutaneous approach was also associated with shorter operative duration, longer intraoperative fluoroscopy, less postoperative VAS, and postoperative VBH% in comparison with traditional open approach. No significant difference was found in Cobb angle correction, postoperative VBA, VBA correction loss, Postoperative VBH%, VBH correction loss, and pedicle screw misplacement between percutaneous approach and open approach. There was no significant difference in operative duration, intraoperative fluoroscopy, postoperative VAS, and postoperative VBH% between percutaneous approach and paraspianl approach. CONCLUSIONS: The functional and the radiological outcome of percutaneous approach would be better than open approach in the long term. Although trans-muscular spatium approach belonged to open fixation methods, it was strictly defined as less invasive approach, which provided less injury to the paraspinal muscles and better reposition effect.

Is there a risk of further displacement of the fractured fragment into the spinal canal in osteoporotic vertebral burst fractures after unilateral PKP? A prospective study.

BACKGROUND CONTEXT: The optimal treatment for osteoporotic vertebral burst fracture (OVBF) without neurological symptoms is still a matter of debate. PURPOSE: To evaluate the safety and efficacy of percutaneous kyphoplasty (PKP) for OVBF. STUDY DESIGN: The study is a prospective study and is registered in the China Clinical Trials Registry with the registration number ChiCTR-OOC-17013227. PATIENT SAMPLE: The study involved 119 patients with 137 fractured vertebrae who underwent unilateral PKP for OVBF. OUTCOME MEASURES: The measurements were carried out independently by two physicians and measured with picture archiving and communication system (PACS) and ImageJ software (National Institutes of Health, Bethesda, MD, USA). METHODS: The change in the spinal canal area and posterior wall protrusions (PWP) were measured before and after surgery via three-dimensional computed tomographic imaging (CT). Preoperative, postoperative, and final follow-up standing X-rays were used to measure the height of the anterior wall (HAW), height of the posterior wall (HPW), and local kyphotic angle (LKA). Additionally, visual analogue scale (VAS) and the Oswestry Disability Index (ODI) were also determined. RESULTS: Among the 137 vertebrae assessed, 79 exhibited an increased postoperative canal area, while 57 showed a decrease, with mean values of 8.28±6.871 mm² and -9.04±5.991 mm², respectively. Notably, no significant change in postoperative canal area was identified on the entire dataset (p>.01). There was a significant decrease between median preoperative (3.9 [IQ1-IQ3=3.3-4.8] mm) and postoperative (3.7 [IQ1-IQ3=3.0-4.4] mm) PWP (p<.01). Preoperative and postoperative HAW measurements were 19.4±6.1 mm and 23.2±5.2 mm, respectively (p<.01). However, at the final follow-up, the HAW was lower than the postoperative value. The HPW was also significantly improved after surgery (p<.01), but at the final follow-up, it was significantly decreased compared with the postoperative measurement. Following surgery, KA was significantly corrected (p<.01); however, at the final follow-up, relapse was detected (average KA: 18.4±10.3°). At the final follow-up, both VAS and ODI were significantly improved compared with the preoperative period (p<.01). As for complications, 50 patients experienced cement leakage, and 16 patients experienced vertebral refracture. All patients did not develop neurological symptoms during the follow-up. CONCLUSIONS: OVBF without neurological deficits showed significant improvement in symptoms during the postoperative period after PKP. There was no notable alteration in the spinal canal area, but a significant decrease in PWP was observed. Consequently, we posit that PKP stands as a secure and efficacious surgical intervention for treating OVBF cases devoid of neurological symptoms.

Adding sacral anchors through an S1 alar screw and multirod construct as a strategy for lumbosacral junction augmentation: an in vitro comparison to S1 pedicle screws alone with sacroiliac fixation.

OBJECTIVE: Achieving solid fusion of the lumbosacral junction continues to be a challenge in long-segment instrumentation to the sacrum. The purpose of this study was to test the condition of adding sacral anchors through an S1 alar screw (S1AS) and multirod construct relative to using S1 pedicle screws (S1PSs) alone with sacroiliac fixation in lumbosacral junction augmentation. METHODS: Seven fresh-frozen human lumbar-pelvic spine cadaveric specimens were tested under nondestructive moments (7.5 Nm). The ranges of motion (ROMs) in extension, flexion, left and right lateral bending (LB), and axial rotation (AR) of instrumented segments (L3-S1); the lumbosacral region (L5-S1); and the adjacent segment (L2-3) were measured, and the axial construct stiffness (ACS) was recorded. The testing conditions were 1) intact; 2) bilateral pedicle screw (BPS) fixation at L3-S1 (S1PS alone); 3) BPS and unilateral S2 alar iliac screw (U-S2AIS) fixation; 4) BPS and unilateral S1AS (U-S1AS) fixation; 5) BPS and bilateral S2AIS (B-S2AIS) fixation; and 6) BPS and bilateral S1AS (B-S1AS) fixation. Accessory rods were used in testing conditions 3-6. RESULTS: In all directions, the ROMs of L5-S1 and L3-S1 were significantly reduced in B-S1AS and B-S2AIS conditions, compared with intact and S1PS alone. There was no significant difference in reduction of the ROMs of L5-S1 between B-S1ASs and B-S2AISs. Greater decreased ROMs of L3-S1 in extension and AR were detected with B-S2AISs than with B-S1ASs. Both B-S1ASs and B-S2AISs significantly increased the ACS compared with S1PSs alone. The ACS of B-S2AISs was significantly greater than that of B-S1ASs, but with greater increased ROMs of L2-3 in extension. CONCLUSIONS: Adding sacral anchors through S1ASs and a multirod construct was as effective as sacropelvic fixation in lumbosacral junction augmentation. The ACS was less than the sacropelvic fixation but with lower ROMs of the adjacent segment. The biomechanical effects of using S1ASs in the control of long-instrumented segments were moderate (better than S1PSs alone but worse than sacropelvic fixation). This strategy is appropriate for patients requiring advanced lumbosacral fixation, and the risk of sacroiliac joint violation can be avoided.

The accuracy of cortical bone trajectory screw placement guided by spinous process clamp hardware in lumbar spinal surgery: a retrospective study.

This study aimed to assess the accuracy of cortical bone trajectory (CBT) screws placement guided by a spinous process clamp (SPC) guide. A total of 32 patients who received single-level midline lumbar fusion (MIDLF) surgery between June 2019 and January 2020 were retrospectively analyzed and divided into free-hand (FH) and SPC-guided groups according to the surgical approach. In the FH group, CBT screws was implanted with the assistance of fluoroscopy, while in the SPC group, CBT screws was implanted using the SPC navigator hardwire. A total of 128 screws were assessed in this study, with higher rates of clinically acceptable screw placement (grades A and B) and grade A screws in the SPC group than in the FH guide group (92.2% vs. 79.7%, P = 0.042 and 54.7% vs. 35.9%, P = 0.033, respectively). Misplacement screws (grades C, D, and E) occurred more often in the FH group than in the SPC guide group (20.3% vs. 7.8%, P = 0.042). The incidence of proximal facet joint violation (FJV) was higher in the FH group than in the SPC group (15.6% vs. 3.1%, P = 0.030). The radiation dose and time in the SPC guide group were comparable to those in the FH group (P = 0.063 and P = 0.078). The average operative time was significantly longer in the SPC guide group than in the FH group (267.8 ± 45.5 min vs. 210.9 ± 44.5 min, P = 0.001). Other clinical parameters, such as the average bone mineral density (BMD), intraoperative blood loss, and postoperative hospital stay, were not significantly different. Oswestry disability index (ODI) and back pain visual analogue scale (VAS) scores were significantly improved in both groups compared with preoperatively. SPC guided screw placement was more accurate than the fluoroscopy-assisted FH technique for single-level MIDLF at L4/5. Patients undergoing SPC-guided screw placement can achieve similar clinical outcomes as the fluoroscopy-assisted FH technique.

Expert Consensus on Clinical Application of Lateral Lumbar Interbody Fusion: Results From a Modified Delphi Study.

STUDY DESIGN: Modified Delphi study. OBJECTIVE: The objective of this study was to establish expert consensus on the application of lateral lumbar interbody fusion (LLIF) by using the modified Delphi study. METHODS: From June 2019 to March 2020, Members of the Chinese Study Group for Lateral Lumbar Spine Surgery were selected to collect expert feedback using the modified Delphi method where 65 spine surgeons from all over China agreed to participate. Four rounds were performed: 1 face-to-face meeting and 3 subsequent survey rounds. The consensus was achieved with ≥a 70.0% agreement for each question. The recommendation of grade A was defined as ≥90.0% of the agreement for each question. The recommendation of grade B was defined as 80.0-89.9% of the agreement for each question. The recommendation of grade C was defined as 70.0-79.9% of the agreement for each question. RESULTS: A total of 65 experts formed a panelist group, and the number of questionnaires collected was 63, 59, and 62 in the 3 rounds. In total, 5 sections, 71 questions, and 382 items achieved consensus after the Delphi rounds including summary; preoperative evaluation; application at the lumbar spinal stenosis, lumbar disc herniation, lumbar spondylolisthesis, adult degenerative scoliosis, postoperative adjacent segmental degeneration, and revision surgery; complications; and postoperative follow-up evaluation of LLIF. CONCLUSION: The modified Delphi method was utilized to ascertain an expert consensus from the Chinese Study Group for Lateral Lumbar Spine Surgery to inform clinical decision-making in the application of LLIF. The salient grade A recommendations of the survey are enumerated.

Accuracy of cortical bone trajectory screw fixation guided by spinous process clamp guide in lumbosacral vertebrae: A cadaver study.

BACKGROUND: The purpose of this study was to access the accuracy of cortical bone trajectory screw placement guided by spinous process clamp (SPC). METHODS: Eight formalin-treated cadaveric lumbar specimens with T12-S1 were used. A total of 96 screws were implanted in eight lumbar specimens. RESULTS: In the freehand (FH) group, clinically acceptable placement (grade A and B) was 40 screws (83.3%), meanwhile 44 screws (91.7%) in the SPC guide group (p = 0.217). The grade A screws in the SPC guide group were much more than that in the FH group (n = 40 vs. n = 31, p = 0.036). The misplacement screws (grade C, D, and E) and proximal facet joint violation (FJV) in the SPC group was comparable to the FH group. CONCLUSIONS: This cadaveric study demonstrate that implanting CBT screws guided by SPC guide was more accuracy and reduces severe deviations in important directions.

Changes in Paraspinal Muscles and Facet Joints after Minimally Invasive Posterior Lumbar Interbody Fusion Using the Cortical Bone Trajectory Technique: A Prospective Study.

In this prospective cohort study, we aimed to determine the surgical and adjacent segment changes in paraspinal muscles and facet joints in patients with lumbar spinal stenosis after minimally invasive posterior lumbar interbody fusion (PLIF) using the cortical bone trajectory (CBT) technique. We enrolled 30 consecutive patients who underwent the single-level CBT technique between October 2017 and October 2018. We evaluated preoperative and 1-month, 3-month, 6-month, and 1-year postoperative clinical data including Visual Analogue Scale (VAS) scores and Oswestry Disability Index (ODI). Magnetic resonance imaging (MRI) was performed a year after surgery. The erector spinae (ES) muscle area, volume, and fat infiltration (FI) on the surgical and adjacent segments were evaluated using the thresholding method, and the degree of adjacent facet joint degeneration was calculated using the Weishaupt scale. FI rate was graded using the Kjaer method. All patients underwent a 12-month follow-up. The VAS and ODI scores significantly improved after surgery in all patients. No patient showed degeneration of the adjacent facet joints (P > 0.05) during the 1-year follow-up postoperation. There was no significant difference in ES muscle volume, area, and FI on the surgical and adjacent segments (P > 0.05). The FI rate of the upper ES muscles increased postoperatively (P < 0.05); however, there were no significant changes in FI rate of the lower ES muscles. Patients with lumbar spinal stenosis could obtain satisfactory short-term clinical outcomes via minimally invasive PLIF using the CBT technique. Moreover, this technique may reduce the impact on the paravertebral muscles, especially the ES muscle, and the adjacent facet joints.

A nomogram for predicting screw loosening after single-level posterior lumbar interbody fusion utilizing cortical bone trajectory screw: A minimum 2-year follow-up study.

Purpose: This study aims to investigate the risk factors for screw loosening after single-level posterior lumbar interbody fusion (PLIF) utilizing cortical bone trajectory (CBT) screw and establish a nomogram for predicting screw loosening. Methods: A total of 79 patients (316 screws) who underwent single-level PLIF with CBT screw were included in the study. Preoperative, postoperative, and final follow-up demographic data, surgical data, and radiographic parameters were documented and analyzed to identify risk factors, and a predictive nomogram was established for screw loosening. The nomogram was assessed by concordance index (C-index), calibration plot, decision curve analysis (DCA), and internal validation. Results: The incidence of screw loosening was 26.6% in 79 patients and 11.4% in 316 screws. Multifactorial regression analysis confirmed that fixed to S1 (FS1, OR = 3.82, 95% CI 1.12-12.71, P = 0.029), the coronal angle of the screw (CA, OR = 1.07, 95% CI 1.01-1.14, P = 0.039), and cortical bone contacted layers (CBCLs, OR = 0.17, 95% CI 0.10-0.29, P < 0.001) were risk factors and incorporated in the nomogram for predicting screw loosening after single-level PLIF with a CBT screw. The C-index of the nomogram was 0.877 (95% CI 0.818-0.936), which demonstrated good predictive accuracy. The calibration plot indicated an acceptable calibration of the nomogram that also had a positive benefit in guiding treatment decisions. Conclusion: FS1, CA, and CBCLs are identified to be significant risk factors for screw loosening after single-level PLIF with the CBT technique. The nomogram we have established can be used to predict screw loosening and contribute to surgical decisions.

Cortical Trajectory Fixation Versus Traditional Pedicle-Screw Fixation in the Treatment of Lumbar Degenerative Patients with Osteoporosis: A Prospective Randomized Controlled Trial.

STUDY DESIGN: This was a prospective randomized controlled trial study. OBJECTIVE: To elucidate clinical and radiographic outcomes and complications of cortical bone trajectory (CBT)-screw fixation in patients with osteoporosis at 24-month follow-up and to compare the results with those after transforaminal lumbar interbody fusion (TLIF) using traditional pedicle screw (PS) fixation. METHODS: We enrolled 124 patients and randomly assigned them to two groups (each group had 62 participants). The primary outcome was fusion rate. Secondary outcomes were VAS, Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) scores, operation duration, incision length, estimated blood loss, drainage volume, radiological outcomes, and complications. RESULTS: At the 6- and 12-month follow-up points, similar fusion rates were observed based on CT scans in both groups (P=0.583 and 0.583). CBT provided significantly better short-term functional status at 3 months postoperation on ODI and JOA scores (P=0.012 and 0) and similar improvements in pain intensity and functional status at other follow-up points. In addition, CBT resulted in significantly better surgical characteristics. Notably, CBT fixation led to lower incidence of screw loosening (P=0.006). CONCLUSION: CBT-screw fixation for single-level lumbar fusion in patients with osteoporosis provided improvement in clinical symptoms comparable to that of TLIF using PS fixation. Significantly better lumbar stability was found in the CBT group. We suggest that CBT-screw fixation is a reasonable and superior alternative to PS in TLIF in osteoporosis. TRIAL REGISTRATION NUMBER: ChiCTR1900022658. DATE OF REGISTRATION: April 20, 2019.