Intraoperative Fracture during the Insertion of Advanced Locking Screws (T2 Alpha Femur Retrograde Intramedullary Nailing System): Report of Two Cases and Identifying Causes and Prevention.

Background: Recently, the T2 alpha nailing system (Stryker, Inc.), which has advanced locking screws that can attach a screw to a rod, has been used worldwide and is expected to improve fracture fixation. We analyzed two cases of supracondylar femoral fractures in older adult patients, in which intraoperative fractures occurred during the insertion of advanced locking screws of the T2 alpha femur retrograde intramedullary nail. Case presentation: A 93-year-old and an 82-year-old woman each underwent T2 alpha femur retrograde nail fixation for supracondylar femur fractures at separate hospitals, and advanced locking screws were used as the proximal transverse locking screws. In both patients, a fracture line was observed at the proximal screw postoperatively, and the fractures were refixed with distal cable wiring and/or femoral distal plates. The patients were subsequently discharged from the same facility with no remarkable pain. Conclusions: When inserting advanced locking screws, it is necessary to enlarge the screw hole in the near-bone cortex with a counterbore drill, which might add torque to the bone cortex that could result in fractures. If the sleeve is distant from the bone, the counterbore drill will not reach the bone, the screw hole will not expand, and the insertion of advanced locking screws will apply a strong torque to the bone cortex and may result in fracture. Moreover, it is important to confirm that the counterbore drill is securely inserted under fluoroscopy and to carefully enlarge the bony foramen manually to prevent fractures during screw insertion.

Constitutional varus knee due to tibial deformity is common and represents a good indication for high tibial osteotomy in Japanese population: Consideration of 1010 knees.

PURPOSE: This study aimed to elucidate the characteristics of varus knee deformities in the Japanese population, prevalence of various around knee osteotomy procedures and influence of femoral and tibial bowing. METHODS: Varus knee deformity was defined as a weight-bearing line ratio of <50%. A total of 1010 varus knees were selected from 1814 varus knees with weight-bearing full-length radiographs, obtained at two facilities, based on exclusion criteria. Various parameters were measured, and around knee osteotomy simulations based on the deformity centre were conducted using digital planning tools. Bowing of the femoral and tibial shafts was measured, with bowing defined as follows: ≤ -0.6° indicating lateral bowing and ≥ 0.6° indicating medial bowing. Statistical analysis was performed to investigate age-related correlations and their impact on surgical techniques. RESULTS: The study revealed that the proximal tibia was the centre of deformity in Japanese varus knees (42.8%), and high tibial osteotomy was frequently indicated (81.6%). Age demonstrated a mild correlation with femoral shaft bowing (r = -0.29), leading to an increase in the mechanical lateral distal femoral angle and to a decrease in the hip-knee-ankle angle and weight-bearing line ratio (r = -0.29, 0.221, 0.219). The tibial shaft bowing was unaffected by age (r = -0.022). CONCLUSION: A significant proportion of Japanese individuals with varus knees exhibit a deformity centre located in the proximal tibia, making them suitable candidates for high tibial osteotomy. No age-related alterations were discerned in tibial morphology, indicating that the occurrence of constitutional varus knees is attributable to tibial deformities in the Japanese patient cohort. LEVEL OF EVIDENCE: Level IV.

Evaluation of Conditions for the Development of Cryogenic Spinal Cord Injury Using a Canine Model: An Experimental Study on the Safety of Cryoablation for Metastatic Spinal Tumors.

BACKGROUND AND PURPOSE: Although the application of cryoablation to metastatic spinal tumors has been attempted, spinal cryoablation has the unique complication of cryogenic spinal cord injury. This study aimed to elucidate the conditions for the development of cryogenic spinal cord injury. MATERIALS AND METHODS: Fifteen canines were used in this study. A metal probe was inserted into the 13th thoracic vertebral body. Cryoablation was performed for 10 minutes by freezing the probe in liquid nitrogen. The control canine underwent probe insertion only. Spinal cord monitoring, epidural temperature measurement, motor function assessment, and pathologic examination of the spinal cord were performed. RESULTS: During the 10 minutes of cryoablation, the epidural temperature decreased and reached the lowest epidural temperature (LET) at the end of cryoablation. The LETs (degrees celsius [°C]) of each canine were -37, -30, -27, -8, -3, -2, 0, 1, 4, 8, 16, 18, 20, and 25, respectively. As the epidural temperature decreased, waveform amplitudes also decreased. At the end of cryoablation (10 minutes after the start of cryoablation), abnormal waves were observed in 92.9% (13/14) of canines. With epidural rewarming, the amplitude of the waveforms tended to recover. After epidural rewarming (2 hours after the start of cryoablation), abnormal waves were observed in 28.6% (4/14) of canines. The LETs (°C) of the canines with abnormal waves after epidural rewarming were -37, -30, -27, and -8. None of the canines with normal waves after epidural rewarming had any motor impairment. In contrast, all canines with remaining abnormal waves after epidural rewarming had motor impairment. In the pathologic assessment, cryogenic changes were found in canines with LETs (°C) of -37 -30, -27, -8, 0, and 1. CONCLUSIONS: This study showed that 10-minute spinal cryoablation with LETs (°C) of -37, -30, -27, -8, 0, and 1 caused cryogenic spinal cord injury. There was no evidence of cryogenic spinal cord injury in canines with LET of ≥4°C. The epidural temperature threshold for cryogenic spinal cord injury is between 1 and 4°C, suggesting that the epidural temperature should be maintained above at least 4°C to prevent cryogenic spinal cord injury.

Instrumentation failure following pediatric spine deformity growth-sparing surgery using traditional growing rods or vertical expandable prosthetic titanium ribs.

BACKGROUND: Instrumentation failure (IF) is a major complication associated with growth-sparing surgery for pediatric spinal deformities; however, studies focusing on IF following each surgical procedure are lacking. We aimed to evaluate the incidence, timing, and rates of unplanned return to the operating room (UPROR) associated with IF following each surgical procedure in growth-sparing surgeries using traditional growing rods (TGRs) and vertical expandable prosthetic titanium ribs (VEPTRs). METHODS: We reviewed 1,139 surgical procedures documented in a Japanese multicenter database from 2015 to 2017. Of these, 544 TGR and 455 VEPTR procedures were included for evaluation on a per-surgery basis. IF was defined as the occurrence of an implant-related complication requiring revision surgery. RESULTS: The surgery-based incidences of IF requiring revision surgery in the TGR and VEPTR groups were 4.3% and 4.0%, respectively, with no significant intergroup difference. Remarkably, there was a negative correlation between IF incidence per surgical procedure and the number of lengthening surgeries in both groups. In addition, rod breakage in the TGR group and anchor-related complications in the VEPTR group tended to occur relatively early in the treatment course. The surgery-based rates of UPROR due to IF in the TGR and VEPTR groups were 2.0% and 1.5%, respectively, showing no statistically significant difference. CONCLUSIONS: We found that IF, such as anchor related-complications and rod breakage, occurs more frequently earlier in the course of lengthening surgeries. This finding may help in patient counseling and highlights the importance of close postoperative follow-up to detect IF and improve outcomes.

Characteristics of Scoliosis in Mice Induced by Chondrocyte-specific Inactivation of L-type Amino Acid Transporter 1.

STUDY DESIGN: A mouse study of the Slc7a5 gene using conditional knockout to assess the effects of its inactivation on spinal deformity. OBJECTIVES: This study aimed to investigate whether the mice with scoliosis [induced by chondrocyte-specific inactivation of L-type amino acid transporter 1 (LAT1)] show a developmental process similar to that of pediatric scoliosis and to examine the relationship between reduced bone mineral density (BMD) and scoliosis. Furthermore, we aimed to obtain insights into elucidating the etiology and pathophysiology of scoliosis. SUMMARY OF BACKGROUND DATA: The etiology and pathogenesis of scoliosis are not fully understood despite substantial investigative efforts. LAT1 is an amino acid transporter that mediates the cellular uptake of large neutral amino acids. A recent study revealed that chondrocyte-specific inactivation of LAT1 in mice results in scoliosis (Col2a1-Cre;Slc7a5fl/fl mice: "Sko mice"). MATERIALS AND METHODS: Body length, body weight, Cobb angle, vertebral body rotation angle, and BMD at 1, 2, 4, 6, and 8 weeks of age were examined and statistically compared with those of normal control mice. Pathologic and morphologic evaluation was performed on specimens from 10-week-old euthanized mice. RESULTS: The Sko mice developed thoracic scoliosis in infancy without congenital malformations. This spinal deformity progressed rapidly during growth, with diverse curve patterns and hypoplastic vertebral bodies. Pathologic examination revealed thickening of the growth plates and decreased osteoblasts, suggesting that impaired endochondral ossification was the cause of the scoliosis. Sko mice were also observed to have decreased BMD and degraded bone microstructure. Reduced BMD and bone quality may not be the causes of the onset and progression of scoliosis in the Sko mice. CONCLUSIONS: In Sko mice, the characteristics of scoliosis and vertebral pathology showed many similarities with syndromic scoliosis in humans. Endochondral ossification defects may impair growth, leading to scoliosis and decreased BMD.

Clinical Outcomes of Total En Bloc Spondylectomy for Previously Irradiated Spinal Metastases: A Retrospective Propensity Score-Matched Comparative Study.

This study aimed to investigate the clinical outcomes of total en bloc spondylectomy (TES) for spinal metastases previously treated with radiotherapy (RT). This study enrolled 142 patients who were divided into two groups: those with and those without an RT history. Forty-two patients were selected from each group through propensity score matching, and postoperative complications, local recurrence, and overall survival rates were compared. The incidence of postoperative complications was significantly higher in the group with an RT history than in the group without an RT history (57.1% vs. 35.7%, respectively). The group with an RT history had a higher local recurrence rate than the group without an RT history (1-year rate: 17.5% vs. 0%; 2-year rate: 20.8% vs. 2.9%; 5-year rate: 24.4% vs. 6.9%). The overall postoperative survival tended to be lower in the group with an RT history; however, there was no significant difference between the two groups (2-year survival: 64.3% vs. 66.7%; 5-year survival: 47.3% vs. 57.1%). When planning a TES for irradiated spinal metastases, the risk of postoperative complications and local recurrence should be fully considered.

Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study.

Introduction: Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated. Material and methods: Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese. Results: Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI. Conclusions: Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.

The Impact of Frailty on Postoperative Complications in Total En Bloc Spondylectomy for Spinal Tumors.

Total en bloc spondylectomy (TES) is an effective treatment for spinal tumors. However, its complication rate is high, and the corresponding risk factors remain unclear. This study aimed to clarify the risk factors for postoperative complications after TES, including the patient's general condition, such as frailty and their levels of inflammatory biomarkers. We included 169 patients who underwent TES at our hospital from January 2011-December 2021. The complication group comprised patients who experienced postoperative complications that required additional intensive treatments. We analyzed the relationship between early complications and the following factors: age, sex, body mass index, type of tumor, location of tumor, American Society of Anesthesiologists score, physical status, frailty (categorized by the 5-factor Modified Frailty Index [mFI-5]), neutrophil-to-lymphocyte ratio, C-reactive protein/albumin ratio, preoperative chemotherapy, preoperative radiotherapy, surgical approach, and the number of resected vertebrae. Of the 169 patients, 86 (50.1%) were included in the complication group. Multivariate analysis showed that high mFI-5 scores (odds ratio [OR] = 2.99, p < 0.001) and an increased number of resected vertebrae (OR = 1.87, p = 0.018) were risk factors for postoperative complications. Frailty and the number of resected vertebrae were independent risk factors for postoperative complications after TES for spinal tumors.

Clinical outcomes following total en bloc spondylectomy for spinal metastases from lung cancer.

BACKGROUND: The current guidelines for the treatment of non-small cell lung cancer encourage local curative treatment for selected patients with oligometastases. This study evaluated the surgical results of total en bloc spondylectomy (TES) for isolated spinal metastases originating from lung cancer in carefully selected patients. METHODS: We retrospectively reviewed 14 patients (7 men and 7 women) who underwent TES for spinal metastases originating from lung cancer between 2000 and 2017. The primary outcome measure was the postoperative overall survival time. The histological types included adenocarcinoma (n = 12), pleomorphic carcinoma (n = 1), and small cell lung carcinoma (SCLC) (n = 1 patient). We assessed postoperative survival using Kaplan-Meier analysis and the log-rank test. RESULTS: The median postoperative survival time was 83.0 months (6-162 months) in 13 patients with non-small cell lung carcinoma (NSCLC) and 6 months in 1 patient with SCLC. The 3-, 5-, and 10-year overall survival rates in patients with NSCLC were 61.5%, 53.8%, and 15.4%, respectively. Poor postoperative performance status (PS) and Frankel grade, and preoperative irradiation to the vertebrae to be resected were significantly associated with short-term survival after TES in patients with NSCLC (p < 0.05). CONCLUSIONS: The surgical results of TES for spinal metastases of lung cancer were relatively favorable among carefully selected patients. TES may be indicated for spinal metastases of lung cancer in patients with controlled primary lung cancer, NSCLC histology, prospect of good postoperative PS, and preferably no irradiation to the target vertebrae.

Novel predictors of immune checkpoint inhibitor response and prognosis in advanced non-small-cell lung cancer with bone metastasis.

BACKGROUNDS: Immune checkpoint inhibitors (ICIs) can significantly prolong the survival of patients with advanced non-small-cell lung cancer (NSCLC); however, few studies on the therapeutic effects of ICIs on bone metastases were performed. METHODS: This retrospective study aimed to investigate the therapeutic effects of ICIs and determine predictors of favorable ICI response and prognosis in 55 advanced NSCLC patients with bone metastases who initiated ICI treatment between 2016 and 2019, with a mean follow-up period of 23.2 months. Patients were classified into responders (complete or partial response) and non-responders (stable or progressive disease) according to the MD Anderson Cancer Center (MDA) criteria, and the predictors of therapeutic response were identified using multivariate logistic regression analysis. Furthermore, overall survival from the time of ICI administration to the final follow-up or death was evaluated, and prognostic predictors were identified using Cox proportional hazards regression analysis. RESULTS: ICI response rate was 30.9% (complete in three cases, partial in 14). Median survival time was 9.3 months, with 1-year and 2-year survival rates of 40.6% and 19.3%, respectively. Responders survived significantly longer than non-responders (p = 0.03). Based on the receiver operating characteristic curve, the predictive cutoff value of the pretreatment neutrophil-to-lymphocyte ratio (NLR) was 2.1. Multivariate analysis identified female sex (p = 0.03), use of ICIs as first-line therapy (p < 0.01), and NLR <2.1 (p = 0.03) as significant predictors of therapeutic response, whereas concomitant use of a bone-modifying agent (p < 0.01), Katagiri score ≤6 points (p < 0.01), and NLR <2.1 (p = 0.02) were identified as significant predictors of good prognosis. CONCLUSIONS: This study identified some novel predictors for favorable therapeutic response and prognosis in advanced NSCLC patients with bone metastases undergoing ICI treatment. Pretreatment NLR less than 2.1 can be considered the most important predictor.

Metastasectomy of spinal lesions from thyroid carcinomas.

Patients with differentiated thyroid carcinomas (DTCs) have a favourable long-term survival. Spinal metastases (SMs) cause a decline in performance status (PS), directly affecting mortality and indirectly preventing the use of systemic therapies. Metastasectomy is indicated, if feasible, as it yields the best local tumour control. Our study aimed to examine the long-term clinical outcomes of metastasectomy for SMs of thyroid carcinomas. We collected data on 22 patients with DTC (16 follicular and six papillary carcinomas) and one patient with medullary carcinoma who underwent complete surgical resection of SMs at our institution between July 1992 and July 2017, with a minimum postoperative follow-up of five years. The cancer-specific survival (CSS) from the first spinal metastasectomy to death or the last follow-up was determined using Kaplan-Meier analysis. Potential factors associated with survival were evaluated using the log-rank test. We analyzed the clinical parameters and outcome data, including pre- and postoperative disability (Eastern Cooperative Oncology Group PS 3), lung and non-spinal bone metastases, and history of radioiodine and kinase inhibitor therapies. Lung and other bone metastases at the time of surgery were observed in ten and eight patients, respectively. Three patients experienced local tumour recurrences at the operated site. The five- and ten-year CSS rates in the 22 patients with DTC were 77% and 52%, respectively. Pre- and postoperative disability and operative site tumour recurrence were identified as risk factors for short postoperative survival. Metastasectomy for resectable SM from DTC yielded favourable results and has the potential to improve survival.

Biomechanical investigation of long spinal fusion models using three-dimensional finite element analysis.

BACKGROUND: This study represents the first finite element (FE) analysis of long-instrumented spinal fusion from the thoracic vertebrae to the pelvis in the context of adult spinal deformity (ASD) with osteoporosis. We aimed to evaluate the von Mises stress in long spinal instrumentation for models that differ in terms of spinal balance, fusion length, and implant type. METHODS: In this three-dimensional FE analysis, FE models were developed based on computed tomography images from a patient with osteoporosis. The von Mises stress was compared for three different sagittal vertical axes (SVAs) (0, 50, and 100 mm), two different fusion lengths (from the pelvis to the second [T2-S2AI] or 10th thoracic vertebra [T10-S2AI]), and two different types of implants (pedicle screw or transverse hook) in the upper instrumented vertebra (UIV). We created 12 models based on combinations of these conditions. RESULTS: The overall von Mises stress was 3.1 times higher on the vertebrae and 3.9 times higher on implants for the 50-mm SVA models than that for the 0-mm SVA models. Similarly, the values were 5.0 times higher on the vertebrae and 6.9 times higher on implants for the 100-mm SVA models than that for the 0-mm SVA models. Higher SVA was associated with greater stress below the fourth lumbar vertebrae and implants. In the T2-S2AI models, the peaks of vertebral stress were observed at the UIV, at the apex of kyphosis, and below the lower lumbar spine. In the T10-S2AI models, the peaks of stress were observed at the UIV and below the lower lumbar region. The von Mises stress in the UIV was also higher for the screw models than for the hook models. CONCLUSION: Higher SVA is associated with greater von Mises stress on the vertebrae and implants. The stress on the UIV is greater for the T10-S2AI models than for the T2-S2AI models. Using transverse hooks instead of screws at the UIV may reduce stress in patients with osteoporosis.

Development of a novel regenerative therapy for malignant bone tumors using an autograft containing tumor inactivated by high hydrostatic pressurization (HHP).

Surgical resection of malignant bone tumors leads to significant defects in the normal surrounding tissues that should be reconstructed to avoid amputation. Our research aimed to inactivate osteosarcoma (OS)-affected bone to obtain autologous bone grafts for bone defect reconstruction using a novel therapy called high hydrostatic pressurization (HHP) therapy. The key points are complete tumor death and preservation of the non-denatured native extracellular matrix (ECM) and bone tissue by HHP. Previously, we found that HHP at 200 MPa for 10 min can completely inactivate cells in normal skin and skin tumors, including malignant melanoma and squamous cell carcinoma while maintaining their original biochemical properties and biological components. Based on our previous research, this study used HHP at 200 MPa for 10 min to eradicate OS. We prepared an OS cell line (LM8), pressurized it at 200 MPa for 10 min, and confirmed its inactivation through morphological observation, WST-8 assay, and live/dead assay. We then injected OS cells with or without HHP into the bone marrow of the murine tibia, after which we implanted tumor tissues with or without HHP into the anterior surface of the tibia. After HHP, OS cells did not proliferate and were assessed using a live/dead assay. The pressurized cells and tumors did not grow after implantation. The pressurized bone was well prepared as tumor-free autologous bone tissues, resulting in the complete eradication of OS. This straightforward and short-pressing treatment was proven to process the tumor-affected bone to make a transplantable and tumor-free autologous bone substitute.

A Modified Spinal Reconstruction Method Reduces Instrumentation Failure in Total En Bloc Spondylectomy for Spinal Tumors.

Introduction: Long-term spinal stability after total en bloc spondylectomy (TES) is challenging. The aim of this study was to examine whether the new method could reduce the incidence of instrumentation failure (IF). Methods: We retrospectively compared 116 patients with spinal tumors who underwent TES between 2010 and 2019 and were followed up for >1 year. IF, cage subsidence, and complications were evaluated. Propensity score matching between conventional and new method groups was performed for age, sex, body mass index, preoperative radiotherapy, number of resected vertebrae, number of instrumented vertebrae, tumor level, and follow-up period. There were 25 cases each in the conventional and new method groups. The conventional method used a titanium mesh cage for anterior reconstruction and 5.5-mm-diameter titanium alloy rods for posterior fixation. The new method used a more robust cage for anterior reconstruction, bone grafting was performed around the cage, and 6.0-mm-diameter cobalt chromium rods were used for posterior fixation. We compared the incidence of IF and cage subsidence after TES between the conventional and new method groups. Results: While 5 out of 25 patients (20.0%) in the conventional method group experienced IF, none from the new method group experienced IF. Three-year implant survival rates were 87.3% in the conventional and 100% in the new method groups. The new method group had a significantly higher implant survival rate (p<0.01). Cage subsidence was observed in 11 of 25 (44/0%) patients in the conventional method and 1 of 25 (4.0%; significantly lower, p<0.05) in the new method group. Conclusions: The new reconstruction method significantly reduced IF incidence in patients with TES.

Characteristics and risk factors of instrumentation failure following total en bloc spondylectomy.

AIMS: The aim of this study was to investigate the incidence and characteristics of instrumentation failure (IF) after total en bloc spondylectomy (TES), and to analyze risk factors for IF. METHODS: The medical records from 136 patients (65 male, 71 female) with a mean age of 52.7 years (14 to 80) who underwent TES were retrospectively reviewed. The mean follow-up period was 101 months (36 to 232). Analyzed factors included incidence of IF, age, sex, BMI, history of chemotherapy or radiotherapy, tumour histology (primary or metastasis; benign or malignant), surgical approach (posterior or combined), tumour location (thoracic or lumbar; junctional or non-junctional), number of resected vertebrae (single or multilevel), anterior resection line (disc-to-disc or intravertebra), type of bone graft (autograft or frozen autograft), cage subsidence (CS), and local alignment (LA). A survival analysis of the instrumentation was performed, and relationships between IF and other factors were investigated using the Cox regression model. RESULTS: A total of 44 patients (32.4%) developed IF at a median of 31 months (interquartile range 23 to 74) following TES. Most IFs were rod fractures preceded by a mean CS of 6.1 mm (2 to 18) and LA kyphotic enhancement of 10.8° (-1 to 36). IF-free survival rates were 75.8% at five years and 56.9% at ten years. The interval from TES to IF peaked at two to three years postoperatively and continued to occur over a period of time thereafter; the early IF-developing group had greater CS at one month postoperatively (CS1M) and more lumbar TES. CS1M ≥ 3 mm and sole use of frozen autografts were identified as independent risk factors for IF. CONCLUSION: IF is a common complication following TES. We have demonstrated that robust spinal reconstruction preventing CS, and high-quality bone grafting are necessary for successful reconstruction.Cite this article: Bone Joint J 2023;105-B(2):172-179.

Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression.

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR).

Incidence and causes of instrument-related complications after primary definitive fusion for pediatric spine deformity.

OBJECTIVE: Various complications have been reported in the treatment of pediatric spinal deformities. Among these, instrument-related complications could be critical concerns and risks of reoperation. This study aimed to identify the incidence and causes of complications after primary definitive fusion for pediatric spine deformities. METHODS: The authors retrospectively collected data from 14 institutions about patients who underwent primary definitive fusion between 2015 and 2017. There were 1490 eligible patients (1184 female and 306 male), with a mean age of 13.9 years. The incidence, causes, and reoperation rates were analyzed according to 4 etiologies of pediatric spine deformity (congenital, neuromuscular, syndromic, idiopathic). The complications were also categorized as screw-, hook-, or rod-related complications, implant loosening or backout, and junctional problems. RESULTS: The incidence of overall instrument-related complications was 5.6% (84 cases). Regarding etiology, the incidence rates were 4.3% (idiopathic), 6.8% (syndromic), 7.9% (congenital), and 10.4% (neuromuscular) (p < 0.05). The most common causes were pedicle screw malposition (60.7%), followed by implant backout or loosening (15.4%), junctional problems (13.1%), rod breakage (4.8%), and other complications (6.0%). Univariate analysis showed that etiology, type of deformity (kyphosis), surgical procedure, operation time, and estimated blood loss were significant factors. Multivariate analysis revealed that etiology (neuromuscular), surgical procedure (combined approach), and operation time (> 5 hours) remained as significant risk factors. Among all patients with instrument-related complications, 45% (38/84) required revision surgery. Of these cases, > 50% were related to pedicle screw malposition. Medial breach was the most common complication regardless of location, from upper thoracic to lumbar spine. CONCLUSIONS: Pedicle screw malposition was the primary cause of overall complications and subsequent reoperation. In addition to more precise screw insertion techniques, meticulous confirmation of pedicle screw placement, especially of medial breach, may reduce the overall instrument-related complications and revision rates.

The influence of costal resection on pulmonary function after total en bloc spondylectomy for spine tumor.

BACKGROUND: Total en bloc spondylectomy (TES) is one of the surgical procedures which has been recognized as a complete resection for spine tumors. Although the surgery achieves favorable local control for solitary spinal lesion, performing the procedure in the thoracic spine requires circumferential dissection around the vertebral body and bilateral rib resections which might result in decline of pulmonary function postoperatively. This study aimed to clarify whether the number of rib resections negatively impacts pulmonary function after the procedure. METHODS: This study included 31 patients who underwent vertebrectomy (17 males and 14 females) with a mean age of 54.2 years. Pulmonary function testing (PFT) was performed before surgery and at 1 month, 6 months, and 1 year postoperative visits. Patients with restrictive disorders such as space occupying lesions in the lung, obstructive problems such as a history of asthma, and smoking history were excluded from this study. Associations between the number of rib resections and PFT data were analyzed based on the resected level of the thoracic spine. RESULTS: There was a significant decrease in forced vital capacity (FVC) at 1 month (72% of preoperative value), followed by gradual recovery at 6 months (89%) and 1 year (90%). The percentage of predicted forced expiratory volume in 1 s remained stable. Patients who underwent three pairs of rib resections showed a significant decrease in the FVC (83.5% of the preoperative value) and FEV1 (82.1% of the preoperative value) compared with one or two pairs of rib resections. CONCLUSION: FVC decreased 1 month after vertebrectomy and returned to 90% of preoperative value at 1 year postoperatively. Three pairs of rib resections showed a significant decrease in FVC, suggesting the influence of a greater numbers of rib resections on pulmonary function.

Risk factors that hinder locomotive syndrome improvement following surgery for musculoskeletal diseases in older patients: A multicentre prospective study.

OBJECTIVES: This study aimed to evaluate preoperative and post-operative locomotive syndrome (LS) in older adults undergoing surgical treatment for musculoskeletal diseases of the lumbar spine and lower extremities and identify risk factors that impede LS improvement after surgery. METHODS: The baseline evaluation included 471 patients 65 years or older [276 in the pre-old-age (65-74 years) group; 195 in the old-age (75 years or older) group] and examined the preoperative and post-operative LS data. The second evaluation performed to identify risk factors, including anthropometric measurements, comorbidity, and frailty, that hinder LS improvement after surgery included 378 patients with preoperative LS Stage 3. RESULTS: Preoperatively, 80% of the patients had LS Stage 3; this rate decreased to 40% post-operatively. Half of the patients exhibited post-operative LS improvement. The LS improvement rate was higher in the pre-old-age group than in the old-age group. According to the multiple logistic regression analysis, old age, high body mass index, weak hand grip strength, and high 5-factor modified frailty index score were significant risk factors that hinder LS improvement after surgery. CONCLUSIONS: Ageing, obesity, weak muscle strength, and frailty can hinder LS improvement in older patients who undergo surgery.