Delayed paraparesis after posterior spinal fusion for congenital scoliosis: a case report.

INTRODUCTION: Although multimodal intraoperative neuromonitoring (IONM), which has high sensitivity and specificity, is typically performed during spinal deformity surgery, neurological status may deteriorate with delay after surgical maneuvers. Here, we report a rare case of delayed postoperative neurological deficit (DPND) that was not detected by IONM during posterior spinal fusion (PSF) for congenital scoliosis. CASE PRESENTATION: A 14-year-old male presented with congenital scoliosis associated with T3 and T10 hemivertebrae. Preoperative Cobb angle of proximal thoracic (PT) and main thoracic (MT) curves were 50° and 41°, respectively. PSF (T1-L1) without hemivertebrectomy was performed, and the curves were corrected to 31° and 21° in the PT and MT curves, respectively, without any abnormal findings in IONM, blood pressure, or hemoglobin level. However, postoperative neurological examination revealed complete loss of motor function. A revision surgery, release of the curve correction by removing the rods, was immediately performed and muscle strength completely recovered on the first postoperative day. Five days postoperatively, PSF was achieved with less curve correction (36° in the PT curve and 26° in the MT curve), without postoperative neurological deficits. DISCUSSION: Possible mechanisms of DPND in our patient are spinal cord ischemia due to spinal cord traction caused by scoliosis correction and spinal cord kinking by the pedicle at the concave side. Understanding the possible mechanisms of intra- and postoperative neural injury is essential for appropriate intervention in each situation. Additionally, IONM should be continued to at least skin closure to detect DPND observed in our patient.

Self-Reported Sleep Duration and Bedtime Are Associated with Dementia Risk in Community-Dwelling People Aged 40-74 Years: The Murakami Cohort Study.

Background: Sleep is a potentially modifiable factor associated with dementia, including Alzheimer's disease, but current evidence supporting this is insufficient. Objective: This study aimed to determine whether sleep duration and bedtime patterns are associated with the risk of dementia among middle-aged and older people. Methods: This cohort study had an eight-year follow-up period. Participants were 13,601 community-dwelling people aged 40-74 years living in Murakami (Niigata, Japan). Data were collected using a self-administered questionnaire. Predictors were self-reported sleep duration and bedtime, and the outcome was newly-diagnosed dementia determined using the long-term care insurance database. Covariates were demographic characteristics, body mass index, smoking, alcohol consumption, total physical activity, insomnia symptoms, disease history, and either bedtime or sleep duration. Cox proportional hazard models were used to calculate hazard ratios (HRs). Results: The mean age of participants at baseline was 59.2 years. Over a mean follow-up period of 8.0 years, 319 cases of dementia were observed. A long self-reported sleep duration relative to the reference sleep duration (7 hours) was associated with increased dementia risk, with the "8 hours" group (adjusted HR = 1.30, 95% CI:0.99-1.73) and "≥9 hours" group (adjusted HR = 1.46, 95% CI:1.00-2.15) having an increased risk (marginally significant) relative to the reference group. Early bedtime was associated with increased dementia risk (adjusted p for trend = 0.0010), with the "21 : 00 or earlier" group (adjusted HR = 1.61, 95% CI:1.14-2.28) having an increased risk relative to the reference ("23 : 00"). Conclusions: A long self-reported sleep duration and early bedtime are both associated with increased dementia risk in middle-aged and older people.

Low plasma 25-hydroxyvitamin D levels are not associated with a high risk of recurrent falls in community-dwelling Japanese adults: the Murakami cohort study.

Reports on the association between vitamin D levels and fall risk have been mixed, and long-term follow-up studies are lacking. This 5-year cohort study of 5,343 community-dwelling Japanese people aged 40-74 years found that low vitamin D levels are not associated with a high risk of recurrent falls. PURPOSE: Findings of cohort studies on the association between plasma 25-hydoxyvitamin D (25[OH]D) levels and fall risk have been mixed, and long-term follow-up studies are lacking. The present study investigated whether low plasma 25(OH)D levels are longitudinally associated with a high risk of recurrent falls in adults. METHODS: This 5-year cohort study included 5,343 community-dwelling Japanese people aged 40-74 years. Baseline blood collection and a questionnaire survey were conducted in 2011-2013. Plasma 25(OH)D levels were determined and divided into quintiles after stratification by season, sex, and age group. Information on recurrent falls occurring in the year before the survey 5 years later was obtained, and participants with two or more falls were considered to have experienced recurrent falls. Covariates were sex, age, marital status, education, occupation, BMI, total physical activity levels, calcium intake, vitamin K intake, smoking, drinking, and disease history. RESULTS: Mean age and 25(OH)D levels were 60.9 years and 50.9 nmol/L, respectively. In the follow-up survey, 209 recurrent falls were reported. Plasma 25(OH)D levels were not significantly associated with the occurrence of recurrent falls in men, women, or men/women-combined (adjusted P for trend = 0.1198, 0.8383, and 0.2355, respectively). In men and men/women-combined, adjusted ORs for recurrent falls in the lowest quintile were significantly lower (adjusted OR = 0.42 and 0.59, respectively) than the middle quintile (reference). CONCLUSION: Low plasma 25(OH)D levels are not associated with a high risk of recurrent falls in middle-aged and older people. Further longitudinal studies will be needed to confirm our findings in other populations.

Quantitative assessment of muscle activity of back and lower extremities, whole body sagittal alignment, body sway, and health-related quality of life in adult spinal deformity patients before and after spinopelvic correction surgery: From the standpoint of the "cone of economy".

BACKGROUND AND AIMS: Pain and muscle fatigue in the low back and lower extremity associated with adult spinal deformity (ASD) markedly limit daily activities and affect quality of life. This study aimed to clarify if spinal correction surgery decreases the muscle activity requirements in relation to alignment and balance parameters. METHODS: Integrated electromyogram (I-EMG) studies of the low back and lower extremity in addition to whole body alignment, body sway, and health-related quality of life (HRQOL) were evaluated in 16 patients with ASD before and after surgery. Sixteen healthy volunteers were included as control subjects. Muscle activities of the bilateral lumbar paravertebral, biceps femoris, rectus femoris, gastrocnemius, and tibialis anterior were measured using surface electromyogram in both resting and working standing positions. Surgical outcomes were based on improvements in muscle fatigue using the sum of the whole muscle I-EMGs and body sway. HRQOL was evaluated by SRS-22r, which measures 4 domains (function, pain, self-image, mental health) and subtotal scores. RESULTS: In controls, the sum of the 10 whole I-EMGs (mVms; mean ± SD) was 3316 ± 1247 in the resting standing position and 5625 ± 2065 in the working standing position. The I-EMG values were higher in ASD patients than in healthy subjects; in the resting standing position, the sum of the whole 10 I-EMGs significantly decreased from baseline (9125 ± 3529) to 3 (6088 ± 1793) and 6 (6381 ± 1776) months postoperatively (p < 0.01). In the working standing position, the sum in ASD patients also significantly decreased from baseline (14,160 ± 5474) to 3 (8085 ± 2540) and 6 (8557 ± 3025) months postoperatively (p < 0.01). I-EMG values did not differ significantly between the 3- and 6-month time points in either condition. Body sway was also improved postoperatively at 3 months and maintained at 6 months along with the amelioration of whole-body sagittal alignment, and 4 domains and subtotal SRS-22r scores significantly increased postoperatively. CONCLUSION: Following spinopelvic correction surgery, whole body sagittal alignment was improved, and muscle activity based on I-EMG and body sway were significantly decreased. The SRS-22r scores after surgery also indicated significant improvement, suggesting that muscle fatigue in the standing position was ameliorated, i.e., the "cone of economy" was normalized.

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.

Anatomical Pelvic Parameters Using the Anterior Pelvic Plane: Normative Values and Estimation of the Standing Sagittal Alignment in Healthy Volunteers.

Introduction: In this study, we aim to estimate the natural standing sagittal alignment in patients with adult spinal deformity (ASD), firstly by investigating the normative values of anatomical pelvic parameters based on the anterior pelvic plane (APP) in a healthy population, and to clarify the relationships between the anatomical and positional pelvic parameters in standing position. Methods: The images of biplanar slot-scanning full-body stereoradiography in 140 healthy Japanese volunteers (mean age, 39.5 years; 59.3% female) were examined. In addition to three-dimensional measurements including pelvic incidence (PI), sacral slope (SS), and pelvic tilt (PT), the APP angle (APPA; anterior tilting=positive) was measured as the angle between the APP and the vertical line using the two-dimensional lateral image. Anatomical SS and PT (aSS and aPT) were calculated as the angles of SS and PT in reference to APP. Results: The mean (range) values of APPA, aSS, and aPT were determined to be 0.7° (-16.8°/15.5°), 36.8° (18.3°/64.9°), and 13.2° (-0.6°/28.7°), respectively. Moreover, SS was found to be significantly correlated with PI and aSS, while PT was significantly correlated with PI, aSS, aPT, and body weight. Also, PT was significantly larger in females than in males. Multiple linear regression analysis deduced the following equations: SS=0.404×aSS+0.203×PI+12.463, PT=-0.391×aSS+0.774×PI+1.950×sex (male=0, female=1)-12.971, wherein aSS had the greatest effect for predicting SS among the included factors and PI had the greatest effect for predicting PT. In addition, no significant differences were noted between PT/PI and aPT/PI. Conclusions: As per the results of this study, significant correlations were noted among parameters and predicting models for positional parameters (SS and PT) using anatomical parameters (aSS and aPT) in a healthy population. This novel measurement concept based on the APP has been considered to be useful in estimating natural SS and PT in standing position using the anatomical pelvic parameters in patients with ASD.

Usefulness of the spectral shaping dual-source computed tomography imaging technique in posterior corrective fusion for adolescent idiopathic scoliosis.

PURPOSE: Since childhood exposure to radiation has been demonstrated to increase cancer risk with increase in radiation dose, reduced radiation exposure during computed tomography (CT) evaluation is desired for adolescent idiopathic scoliosis (AIS). Therefore, this retrospective study aimed to investigate the radiation dose of dual-source CT using a spectral shaping technique and the accuracy of the thoracic pedicle screw (TPS) placement for posterior spinal fusion (PSF) in patients with AIS. METHODS: Fifty-nine female patients with thoracic AIS who underwent PSF using CT-guided TPSs were included and divided into two groups comprised of 23 patients who underwent dual-source CT (DSCT) with a tin filter (DSCT group) and 36 who underwent conventional multislice CT (MSCT group). We assessed the CT radiation dose using the CT dose index (CTDIvol), effective dose (ED), and accuracy of TPS insertion according to the established Neo's classification. RESULTS: The DSCT and MSCT groups differed significantly (p < 0.001) in the mean CTDIvol (0.76 vs. 3.31 mGy, respectively) and ED (0.77 vs. 3.47 mSv, respectively). Although the correction rate of the main thoracic curve in the DSCT group was lower (65.7% vs. 71.2%) (p = 0.0126), the TPS accuracy (Grades 0-1) was similar in both groups (381 screws [88.8%] vs. 600 screws [88.4%], respectively) (p = 0.8133). No patient required replacement of malpositioned screws. CONCLUSION: Spectral shaping DSCT with a tube-based tin filter allowed a 75% radiation dose reduction while achieving TPS insertion accuracy similar to procedures based on conventional CT without spectral shaping.

Characteristics of back pain in patients with adolescent idiopathic scoliosis: Considerations in candidates for corrective surgery.

BACKGROUND: Previous studies have demonstrated that the point prevalence of back pain ranges from 12 % to 33 % and that the lifetime prevalence of back pain ranges from 28 % to 51 % in adolescents. However, few studies on back pain in patients with Adolescent idiopathic scoliosis (AIS) have been conducted, and these studies had significant limitations, including a lack of comparative controls and detailed information about scoliotic deformity or pain location. This study aimed to determine whether adolescents with AIS experience back pain in specific regions. METHODS: This retrospective case-control study included 189 female adolescents with AIS who underwent corrective fusion from 2008 to 2020. Questionnaires on back pain and health-related quality of life (HRQOL) using the Scoliosis Research Society Outcomes Instrument-22 (SRS-22) were conducted preoperatively. The control group included 2909 general female adolescents. RESULTS: The mean Cobb angles in the main thoracic and thoracolumbar/lumbar curves were 51.4 ± 15.3° and 40.4 ± 12.9°. Back pain characteristics included higher point prevalence (25.9 %) and lifetime prevalence (64.6 %) compared to healthy controls. Adolescents with back pain showed lower scores in the pain and mental health domains of the SRS-22. Adolescents with major thoracic AIS showed more back pain in the upper and middle right back compared to adolescents with major thoracolumbar/lumbar AIS. CONCLUSION: The point and lifetime prevalence of back pain were definitely higher in patients with AIS, which affected their HRQOL. There was a relationship between pain around the right scapula and the right major thoracic curve with a rib hump deformity.

Gait Analysis by the Severity of Gait Disturbance in Patients with Compressive Cervical Myelopathy.

Introduction: Gait disturbance due to compressive cervical myelopathy has been previously described. However, data on how gait disturbance varies with the degree of lower extremity motor impairment are limited. Therefore, we investigated the characteristics of gait analysis based on severity and determined how gait disturbance progresses in compressive cervical myelopathy. Methods: We enrolled 44 patients (32 men and 12 women; mean age, 65.0 years) out of 108 consecutive patients with compressive cervical myelopathy who underwent spinal cord decompression surgery in our hospital. The exclusion criteria were inability to gait and complications affecting gait. Twenty-two patients with Japanese Orthopaedic Association scores 1 or 2 for lower extremity motor functions were assigned to the severe group, and 22 patients who scored 3 or 4 were assigned to the moderate group. Gait analysis was performed preoperatively using a long thin-type sensor sheet, and 25 healthy volunteers were assigned to the control group. Results: Stride length, swing phase, and gait speed decreased whereas step angle, stance phase, and double support duration increased as myelopathy progressed. Step width was significantly larger in the severe group than in the moderate and control groups. The cutoff values based on severe myelopathy with the inability to ascend or descend stairs without support were 60% for the stride length percentage of body height and 100 cm/s for gait speed. Conclusions: Decreases in stride length, swing phase, and gait speed and increases in step angle, stance phase, and double support duration are compensatory changes as cervical myelopathy progresses. Step width is a compensatory change that is not significantly altered in moderate myelopathy but increases when gait becomes affected, such that the patient cannot ascend or descend stairs without support.

[Case of hereditary Y69H (p.Y89H) transthyretin variant leptomeningeal amyloidosis presenting with drop attacks and recurrent transient language disorder].

We report a 73-year-old woman who started developing recurrent transient aphasia at the age of 66 years. During the attacks, she was aware she could not understand what was being said and both her spoken and written speech were meaningless. The attacks usually lasted for a few days, following which she could explain what had happened. Anti-epileptics did not improve her symptoms. She also noticed tremor of her right hand and gait disturbance at the age of 71 years. The recurrent transient aphasia was followed by drop attacks. At the time of her admission to our hospital, she showed paraplegia, phonological paraphasia, and difficulty in understanding complex sentences. Her language disturbance resembled a logopenic variant of primary progressive aphasia. However, the symptoms fluctuated for a few days and subsequently improved. Electroencephalography showed no abnormalities. Gadolinium-enhanced brain and spinal MRI showed diffuse leptomeningeal enhancement over the surface of the spinal cord, brain stem, and cerebrum on T1-weighed imaging. Surgical biopsy of a varicose vein in the subarachnoid space at the level of the Th11 spinal cord was performed. Pathological evaluation of the biopsied specimens revealed TTR-immunolabeled amyloid deposits in the subarachnoid vessel walls and on the arachnoid membrane. Gene analysis revealed c.265T>C, p.Y89H (Y69H) TTR mutation, which is known as one of the causative mutations of familial leptomeningeal amyloidosis. Leptomeningeal forms of transthyretin amyloidosis might present transient focal neurological episodes.

Usefulness and limitations of intraoperative pathological diagnosis using frozen sections for spinal cord tumors.

BACKGROUND: Intraoperative pathological diagnosis has a major influence on the intra- and postoperative management of spinal cord tumors. Thus, the aim of this study was to assess the reliability of intraoperative pathological diagnosis for spinal cord lesions by comparing it with the final pathological diagnosis and to determine its usefulness and limitations. METHOD: Three-hundred and three consecutive patients (mean age, 53.9 years) with neoplastic spinal cord lesions who underwent initial surgery between 2000 and 2021 were included. The anatomical locations of the spinal cord tumors and the implementation rate of intraoperative pathological diagnosis in each tumor type were evaluated. As the primary outcome, we determined the concordance rates between the intraoperative pathological diagnosis and the final diagnosis. When the intraoperative pathological diagnosis and final diagnosis were the same, the diagnosis was defined as a "match." Otherwise, the diagnosis was defined as a "mismatch." RESULTS: The overall implementation rate of intraoperative pathological diagnosis was 53%, with implementation rates of 71%, 45%, 47%, and 50% for intramedullary, intradural extramedullary, extradural, and dumbbell tumors, respectively. The overall concordance rate was 87.6%, with concordance rates of 80%, 95%, 75%, and 90% for intramedullary, intradural extramedullary, extradural, and dumbbell tumors, respectively (p < 0.05). The diagnoses of ependymomas, low-grade astrocytomas, and high-grade astrocytomas was occasionally difficult among intramedullary tumors. Among intradural extramedullary tumors, differentiation between grade 1 meningioma and high-grade meningioma was difficult using intraoperative pathological diagnosis. CONCLUSIONS: Surgeons must recognize the lower accuracy of intraoperative pathological diagnosis for intramedullary and extradural lesions and make a final decision by considering the intraoperative gross findings, preoperative clinical course, and imaging.

Genetic insights into ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development.

Y-site Injection Physical Compatibility of Remdesivir with Select Intravenous Drugs Used in Palliative Care and for Treating Coronavirus Disease 2019.

BACKGROUND: No compatibility tests are available for remdesivir other than 0.9% sodium chloride. In this study, we aimed to evaluate the physical compatibility of remdesivir with drugs used in palliative care and COVID-19 treatment. METHODS: Remdesivir was tested for compatibility with 10 different drugs (fentanyl, morphine, hydromorphone, oxycodone, heparin, furosemide, octreotide, acetated Ringer's injection, 2-in-1 peripheral parenteral nutrition, and 2-in-1 total parenteral nutrition). Remdesivir was formulated to a final concentration of 1 mg/mL, and the other drugs were prepared at clinical concentrations. Three test solutions were used for compatibility testing, with remdesivir and the target drugs compounded in a 1:1 ratio. Appearance measurements, including Tyndall effect, turbidity, and pH, were performed immediately after mixing and at 1 h and 4 h after mixing. Changes in appearance, including the Tyndall effect, turbidity (turbidity change of ≥ 0.5 nephelometric turbidity unit [NTU] based on control solution for each test drug), and pH (a change of ≥ 10% based on the pH immediately after mixing) were used to determine physical compatibility. RESULTS: All the drugs tested were compatible with remdesivir. The combination of remdesivir and furosemide produced the highest turbidity (0.23 ± 0.03 NTU) 1 h after mixing. The lowest and highest pH values were observed at 4 h after mixing for the combinations of remdesivir and morphine (3.23 ± 0.02) and remdesivir and furosemide (8.81 ± 0.06). CONCLUSIONS: The drugs tested in this study show Y-site physical compatibility with remdesivir.

Alcohol consumption, smoking, and risk of dementia in community-dwelling Japanese people aged 40-74 years: The Murakami cohort study.

OBJECTIVE: Alcohol drinking and tobacco smoking have impacts on lifestyle-related diseases, but their association with dementia remains a debated topic. This study aimed to examine longitudinal associations between alcohol consumption, smoking, and dementia risk in middle-aged and older Japanese people. METHODS: This study used a cohort design with an 8-year follow-up. Participants were community-dwelling Japanese people (N = 13,802) aged 40-74 years. The baseline survey, including a self-administered questionnaire, was conducted in 2011-2013. Predictors were alcohol consumption and tobacco smoking. The outcome was incident dementia obtained from a long-term care insurance database. Covariates were demographics, lifestyle factors, body mass index, general health status, and history of stroke, diabetes, and depression. RESULTS: Participant mean age was 59.0 years. The 1-149, 150-299, and 300-449 g ethanol/week groups had significantly lower adjusted hazard ratios (HRs) (0.62, 0.59, and 0.47, respectively) compared with the reference group, with no significant linear association. HRs increased toward 1 when past-drinkers and those with poor health status and a disease history were excluded (0.80, 0.66, and 0.82, respectively). Higher smoking levels were dose-dependently associated with a higher HR (adjusted P for trend = 0.0105), with the ≥20 cigarettes/day group having a significantly higher adjusted HR (1.80). Heavy drinkers (≥449 g ethanol/week) with smoking habits, but not those without smoking habits, had higher dementia risk (P for interaction = 0.0046). CONCLUSION: Light-to-moderate alcohol consumption is associated with decreased dementia risk, and smoking is dose-dependently associated with increased dementia risk, with an interaction between high alcohol consumption and smoking on dementia risk.

Whole exome and transcriptome analysis revealed the activation of ERK and Akt signaling pathway in canine histiocytic sarcoma.

Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients.

Marriage and childbirth of patients who were surgically and non-surgically treated for adolescent idiopathic scoliosis: a survey at the age of 30 years or older.

PURPOSE: We aimed to investigate the marital status and childbirth in adolescent idiopathic scoliosis (AIS) patients. METHODS: This study included women who were treated surgically or non-surgically for AIS with a scoliosis magnitude ≥ 30° before surgery or at skeletal maturity and were followed up until age 30 years or older. Patients were divided into surgically treated (S-AIS, n = 55) and non-surgically treated AIS groups (N-AIS, n = 86). Data from the national fertility survey were used as control values. RESULTS: There were no significant differences in age at the final follow-up between the S- (40.7 years) and N-AIS (42.1 years) groups. The unmarried rate among all women and the nulliparous rate among married women in the S-AIS group (29.1% and 18.4%, respectively) were similar to those in the N-AIS group (26.7% and 16.1%, respectively). The mean number of children per married woman also did not differ between the S- and N-AIS groups (1.5 vs 1.4). Compared to the control group, after adjusting for age, the common odds ratio in the AIS group was 1.56 (p = 0.031) for unmarried status and 1.88 (p = 0.026) for nulliparity among married women. Moreover, the mean number of children per married woman was significantly lower in the AIS group than in the control group (1.3 vs 1.7, p < 0.001). CONCLUSION: Surgically and non-surgically treated women with AIS had a similar status with regard to marriage and childbirth, while women with AIS were more likely to be unmarried and nulliparous and to have fewer children compared to the nationwide population.

Preparation of NanoMEDIC Extracellular Vesicles to Deliver CRISPR-Cas9 Ribonucleoproteins for Genomic Exon Skipping.

The CRISPR-Cas9 system has quickly become the standard tool for genome editing. To deliver this system to target cells, adeno-associated virus (AAV) vectors are commonly used. In fact, AAV vectors have been utilized to deliver the CRISPR-Cas9 system to induce genomic exon skipping and restore the dystrophin protein in various Duchenne muscular dystrophy model animals. Despite the high transduction efficiency, AAV vector-mediated delivery has several limitations, such as the packaging size, prolonged overexpression of Cas9, immunogenicity against the AAV capsid, and the risk of integrating a part of the AAV genomic sequence into the host cell. To overcome these issues, we have recently engineered a transient delivery system utilizing VSV-G pseudotyped extracellular vesicles (EVs) termed NanoMEDIC (nanomembrane-derived extracellular vesicles for the delivery of macromolecular cargo). NanoMEDIC utilizes an HIV-derived Gag protein to package Cas9 protein and gRNA into EVs. The Cas9 and Gag proteins are fused to a heterodimerizer and conditionally dimerized by the addition of an inducible chemical ligand to recruit Cas9 protein into EVs. sgRNA is packaged into EVs through an HIV-derived RNA packaging signal and is subsequently released by two self-cleaving ribozymes. Utilizing these features, NanoMEDIC can achieve highly efficient packaging of the Cas9 protein and gRNA for genome editing into a variety of target cells and in vivo. Here, we describe a step-by-step protocol, including the gRNA-expressing vector construction and large-scale NanoMEDIC production, for in vivo genome editing.

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.

Axial Neck-Shoulder Pain After Posterior Correction and Fusion for Adolescent Idiopathic Scoliosis With Structural Thoracic Curve: Does Cranial Fusion Level Affect Neck Symptoms?

STUDY DESIGN: A retrospective cohort study using prospectively collected data. OBJECTIVES: To investigate the incidence and impact of fusion to the upper thoracic spine on neck-shoulder symptoms after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Axial neck-shoulder pain is established as a sequela of posterior cervical spine surgery and is mainly caused by the dissection of extensor muscles in the cervical and upper thoracic spine. MATERIALS AND METHODS: Sixty-three female patients with AIS who underwent PSF using segmental pedicle screw constructs for structural main thoracic curve with a minimum 2-year follow-up were included. Axial neck-shoulder pain was assessed using the visual analog scale and cervical spine function domain score of the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire. The patients were divided into 2 groups, a higher group (underwent fusion up to T3 or above, n=27) and a lower group (underwent fusion up to T4 or below, n=36), and radiologic and clinical outcomes were compared. RESULTS: The incidence of axial neck-shoulder pain (visual analog scale ≥30) preoperatively and at the 2-year follow-up was 29 and 40%, respectively. The pain and mental health domains of the Scoliosis Research Society-22 and cervical spine function domain of the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire were correlated with the severity of axial neck pain. In the comparison of clinical outcomes between the 2 groups, the pain domain score of the Scoliosis Research Society-22 in the lower group was significantly better than that in the higher group at the 2-year follow-up ( P <0.05). Other parameters showed no significant differences preoperatively or at the 2-year follow-up. CONCLUSION: Female patients with AIS had a relatively high incidence of axial neck-shoulder pain after PSF, which affected their health-related quality of life. Both groups showed similar clinical outcomes, and the cranial fusion level did not affect axial neck-shoulder pain and cervical spine function. LEVEL OF EVIDENCE: Level 3.

Dynamics of surgical smoke in the operating room during spinal surgery: Comparison of particulate matter 2.5-air concentration between the electric scalpel with and without a smoke evacuation pencil: A cross-sectional study.

BACKGROUND: Surgical smoke is a vaporous by-product generated during tissue incision and cauterization with an electric scalpel. This smoke contains tissue- and blood/vascular-derived substances, bacteria, viruses, and chemical substances. Among them, it contains many fine particles called particulate matter (PM) 2.5, which are harmful and hazardous to the human body. We aimed to investigate the occurrence of PM2.5 in surgical smoke produced during spinal surgery and to evaluate the efficacy of an electric scalpel with a smoke evacuation pencil. METHODS: In this retrospective observational study, 89 patients who underwent spinal surgery between June 2019 and May 2021 were included. A dust monitor was installed in the operating room to measure the PM2.5 air concentration during the surgery. During each surgery, the total amount of PM2.5, the maximum PM2.5 air concentration, the exposure time to PM2.5, and the average value of PM2.5 air concentration from the start to the end of the surgery were calculated. RESULTS: We found that in 29 of the 89 cases (32.6%), the air concentration of PM2.5 increased to a level that could cause health damage during the surgery. Twelve cases (13.4%) reached the level that could cause serious health damage, and 8 cases (9%) reached an emergency warning level. The total amount and the maximum and average levels of PM2.5 were significantly suppressed in the surgery with a smoke evacuation pencil group than in the surgery without a smoke evacuation pencil group. CONCLUSION: We detected hazardous levels of PM2.5 in the air during spinal surgery, highlighting the importance of considering smoke control or reduction during spinal surgery. We recommend using an electric scalpel with a smoke evacuation pencil for regulating PM2.5 levels in the operating room.