Association between High HbA1c Levels and Mast Cell Phenotype in the Infrapatellar Fat Pad of Patients with Knee Osteoarthritis.

Diabetes mellitus (DM) has been suggested as a potential risk factor for knee osteoarthritis (KOA), and its underlying mechanisms remain unclear. The infrapatellar fat pad (IPFP) contributes to OA through inflammatory mediator secretion. Mast cells' (MCs) role in diabetic IPFP pathology is unclear. In 156 KOA patients, hemoglobin A1c (HbA1c) was stratified (HbA1c ≥ 6.5, n = 28; HbA1c < 6.5, n = 128). MC markers (TPSB2, CPA3) in IPFP were studied. Propensity-matched cohorts (n = 27 each) addressed demographic differences. MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF) were isolated, comparing MC markers and genes elevated in diabetic skin-derived MC (PAXIP1, ARG1, HAS1, IL3RA). TPSB2 and CPA3 expression were significantly higher in HbA1c ≥ 6.5 vs. <6.5, both before and after matching. MC-RF showed higher TPSB2 and CPA3 expression than MC-PF in both groups. In the HbA1c ≥ 6.5 group, PAXIP1 and ARG1 expression were significantly higher in the MC-RF than MC-PF. However, no statistical difference in the evaluated genes was detected between the High and Normal groups in the MC-RF. Elevated TPSB2 and CPA3 levels in the IPFP of high HbA1c patients likely reflect higher numbers of MCs in the IPFP, though no difference was found in MC-specific markers on a cell-to-cell basis, as shown in the MC-RF comparison. These findings deepen our understanding of the intricate interplay between diabetes and KOA, guiding targeted therapeutic interventions.

A nationwide multicenter study of the cost effectiveness of five leading drugs for pharmacological management of cervicobrachial symptoms.

BACKGROUND: Cervicobrachial pain frequently affects the quality of life (QOL) of the general public and has a significant economic impact on the health care systems of various countries. There are a number of treatment options for this disease, including widely-used drug therapy, but the effectiveness of each option is indeterminate, and there have been no published cost-effectiveness analysis studies so far. This prospective observational study aimed to examine the cost-effectiveness of drug treatment for cervicobrachial symptoms. METHODS: A 6-month medication regimen for each of five frequently-prescribed drugs for cervicobrachial symptoms was administered to 322 patients at 24 centers in Japan. Outcome measures, including of the EuroQol Group 5D, Short Form-8, and Visual Analog Scale (VAS), were investigated at baseline and every month thereafter. Incremental cost-effectiveness ratios (ICERs) of the drug cost to quality-adjusted life years (QALYs) were calculated. A stratified analysis of patient characteristics was also performed to identify baseline factors potentially affecting cost-effectiveness. RESULTS: The ICER of entire drug treatment for cervicobrachial symptoms was 7,491,640 yen. Compared with the reference willingness-to-pay, the ICER was assumed to not be cost-effective. A certain number of QALYs were gained during the first 3 months after the treatment intervention, but almost no QALYs were gained during the following 3 months. Stratified analysis showed that cost-effectiveness was extremely low for patients with high baseline VAS and high QOL. CONCLUSIONS: The available medications for cervicobrachial symptoms did not have excellent cost-effectiveness. Although a certain number of QALYs were gained during the first 3 months after medication, no QALYs were gained in the latter half of the study period, suggesting that it is not advisable to continue the medication needlessly. LEVEL OF EVIDENCE: II, prospective cohort study.

Medermycin Inhibits TNFα-Promoted Inflammatory Reaction in Human Synovial Fibroblasts.

Synovial inflammation plays a crucial role in the destruction of joints and the experience of pain in osteoarthritis (OA). Emerging evidence suggests that certain antibiotic agents and their derivatives possess anti-inflammatory properties. Medermycin (MED) has been identified as a potent antibiotic, specifically active against Gram-positive bacteria. In this study, we aimed to investigate the impact of MED on TNFα-induced inflammatory reactions in a synovial cell line, SW-982, as well as primary human synovial fibroblasts (HSF) using RNA sequencing, rtRT-PCR, ELISA, and western blotting. Through the analysis of differentially expressed genes (DEGs), we identified a total of 1478 significantly upregulated genes in SW-982 cells stimulated with TNFα compared to the vehicle control. Among these upregulated genes, MED treatment led to a reduction in 1167 genes, including those encoding proinflammatory cytokines such as IL1B, IL6, and IL8. Pathway analysis revealed the enrichment of DEGs in the TNF and NFκB signaling pathway, further supporting the involvement of MED in modulating inflammatory responses. Subsequent experiments demonstrated that MED inhibited the expression of IL6 and IL8 at both the mRNA and protein levels in both SW982 cells and HSF. Additionally, MED treatment resulted in a reduction in p65 phosphorylation in both cell types, indicating its inhibitory effect on NFκB activation. Interestingly, MED also inhibited Akt phosphorylation in SW982 cells, but not in HSF. Overall, our findings suggest that MED suppresses TNFα-mediated inflammatory cytokine production and p65 phosphorylation. These results highlight the potential therapeutic value of MED in managing inflammatory conditions in OA. Further investigations utilizing articular chondrocytes and animal models of OA may provide valuable insights into the therapeutic potential of MED for this disease.

Muscle strength rather than appendicular skeletal muscle mass might affect spinal sagittal alignment, low back pain, and health-related quality of life.

Sarcopenia is defined as decreasing in muscle strength and mass, and dynapenia is defined as decreasing in muscle strength and maintained muscle mass. This study elucidated the prevalence and characteristics of sarcopenia and dynapenia and evaluate in elderly spinal disorders patients. 1039 spinal disorders patients aged ≥ 65 years were included. We measured age, grip strength, muscle mass, spinal sagittal alignment parameters, low back pain (LBP) scores and health-related quality of life (HR-QoL) scores. Based on the previous reports, patients were categorised into normal group: NG, pre-sarcopenia group: PG, dynapenia group: DG, and sarcopenia group: SG. Pre-sarcopenia, dynapenia, and sarcopenia were found in 101 (9.7%), 249 (19.2%), and 91 (8.8%) patients, respectively. The spinal sagittal alignment parameters, trunk muscle mass, LBP, and HR-QoL scores were significantly worse in DG and SG compared with those in PG and NG. Spinal alignment, trunk muscle mass, and clinical outcomes, including LBP and HR-QoL scores, were maintained in the PG and poor in the DG and SG. Thus, intervention for muscle strength may be a treatment option for changes of spinal sagittal alignment and low back pain.

In situ-formed hyaluronan gel/BMP-2/hydroxyapatite composite promotes bone union in refractory fracture model mice.

BACKGROUND: A combination of synthetic porous materials and BMP-2 has been used to promote fracture healing. For bone healing to be successful, it is important to use growth factor delivery systems that enable continuous release of BMP-2 at the fracture site. We previously reported that in situ-formed gels (IFGs) consisting of hyaluronan (HyA)-tyramine (TA), horseradish peroxidase and hydrogen peroxide enhance the bone formation ability of hydroxyapatite (Hap)/BMP-2 composites in a posterior lumbar fusion model. OBJECTIVE: We examined the effectiveness of IFGs-HyA/Hap/BMP-2 composites for facilitating osteogenesis in refractory fracture model mice. METHODS: After establishing the refractory fracture model, animals were either treated at the site of fracture with Hap harboring BMP-2 (Hap/BMP-2) or IFGs-HyA with Hap harboring BMP-2 (IFGs-HyA/Hap/BMP-2) (n = 10 each). Animals that underwent the fracture surgery but did not receive any treatment were considered the control group (n = 10). We determined the extent of bone formation at the fracture site according to findings on micro-computed tomography and histological studies four weeks following treatment. RESULTS: Animals treated with IFGs-HyA/Hap/BMP-2 demonstrated significantly greater bone volume, bone mineral content and bone union than those treated with vehicle or IFG-HyA/Hap alone. CONCLUSIONS: IFGs-HyA/Hap/BMP-2 could be an effective treatment option for refractory fractures.

Posterior Spinal Fusion Surgery for Neuromuscular Disease Patients with Severe Scoliosis Whose Cobb Angle Was over 100 Degrees.

Background and objectives: Patients with neuromuscular diseases usually have progressive neuromuscular scoliosis (NMS), requiring invasive surgery. Some patients present with severe scoliosis at the time of consultation and are difficult to treat. Posterior spinal fusion (PSF) surgery combined with anterior release and pre- or intraoperative traction would be effective for severe spinal deformities but would be invasive. This study aimed to evaluate the outcomes of PSF-only surgery for patients with severe NMS with a Cobb angle > 100°. Materials and Methods: Thirty NMS patients (13 boys and 17 girls; mean age 13.8 years) who underwent PSF-only surgery for scoliosis with a Cobb angle > 100° were included. We reviewed the lower instrumented vertebra (LIV), duration of surgery, blood loss, perioperative complications, preoperative clinical findings, and radiographic findings, including Cobb angle and pelvic obliquity (PO) in the sitting position pre- and postoperatively. The correction rate and correction loss of the Cobb angle and PO were also calculated. Results: The mean duration of surgery was 338 min, intraoperative blood loss was 1440 mL, preoperative %VC was 34.1%, FEV1.0 (%) was 91.5%, and EF was 66.1%. There were eight cases of perioperative complications. The Cobb angle and PO correction rates were 48.5% and 42.0%, respectively. We divided the patients into two groups: the L5 group, in which the LIV was L5, and the pelvis group, in which the LIV was the pelvis. The duration of surgery and PO correction rate in the pelvis group were significantly higher than those in the L5 group. Conclusions: Patients with severe NMS demonstrated severe preoperative restrictive ventilatory impairments. PSF surgery without anterior release or any intra-/preoperative traction showed satisfactory outcomes, including acceptable scoliosis correction and improved clinical findings, even in patients with extremely severe NMS. Instrumentation and fusion to the pelvis for severe scoliosis in patients with NMS showed good PO correction and low correction loss of Cobb angle and PO, but a longer duration of surgery.

Preoperative Symptom Duration Influences Neurological Recovery and Patient-Reported Outcome Measures After Surgical Treatment of Cervical Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: A prospective multicenter study. OBJECTIVE: To investigate the effect of preoperative symptom duration on neurological recovery for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: The optimal timing to perform surgery in the setting of cervical OPLL remains unknown. It is important to know the influence of symptom duration on postoperative outcomes to facilitate discussions regarding the timing of surgery. PATIENTS AND METHODS: The study included 395 patients (291 men and 104 women; mean age, 63.7 ± 11.4 yr): 204 were treated with laminoplasty, 90 with posterior decompression and fusion, 85 with anterior decompression and fusion, and 16 with other procedures. The Japanese Orthopedic Association (JOA) score and patient-reported outcomes of the JOA Cervical Myelopathy Evaluation Questionnaire were used to assess clinical outcomes preoperatively and 2 years after surgery. Logistic regression analysis was used to identify factors associated with the achievement of minimum clinically important difference (MCID) after surgery. RESULTS: The recovery rate was significantly lower in the group with symptom duration of ≥5 years compared with the groups with durations of <0.5 years, 0.5 to 1 year, and 1 to 2 years. Improvement of JOA Cervical Myelopathy Evaluation Questionnaire in the upper extremity function score ( P < 0.001), lower extremity function ( P = 0.039), quality of life ( P = 0.053), and bladder function ( P = 0.034) were all decreased when the symptom duration exceeded 2 years. Duration of symptoms ( P = 0.001), age ( P < 0.001), and body mass index ( P < 0.001) were significantly associated with the achievement of MCID. The cutoff value we established for symptom duration was 23 months (area under the curve, 0.616; sensitivity, 67.4%; specificity, 53.5%). CONCLUSIONS: Symptom duration had a significant impact on neurological recovery and patient-reported outcome measures in this series of patients undergoing surgery for cervical OPLL. Patients with symptom duration exceeding 23 months may be at greater risk of failing to achieve MCID after surgery. LEVEL OF EVIDENCE: 3.

Factors Associated With Loss of Cervical Lordosis After Laminoplasty for Patients With Cervical Ossification of the Posterior Longitudinal Ligament: Data From a Prospective Multicenter Study.

STUDY DESIGN: A prospective multicenter study. OBJECTIVE: The objective of this study was to investigate the incidence of loss of cervical lordosis after laminoplasty for cervical ossification of the posterior longitudinal ligament (OPLL). We also sought to determine associated risk factors and the relationship with patient-reported outcomes. SUMMARY OF BACKGROUND DATA: Loss of cervical lordosis is a sequelae often observed after laminoplasty, which may adversely impact surgical outcomes. Cervical kyphosis, especially in OPLL, is associated with reoperation, but risk factors and relationship to postoperative outcomes remain understudied at this time. MATERIALS AND METHODS: This study was conducted by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. We included 165 patients who underwent laminoplasty and completed Japanese Orthopaedic Association (JOA) score or Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaires (JOACMEQ), as well as Visual Analog Scales (VAS) for pain, with imaging. The participants were divided into two groups: those with loss of cervical lordosis of >10° or 20° after surgery and those without loss of cervical lordosis. A paired t test was applied to evaluate the association between changes in cervical spinal angles, range of motion, and cervical JOA and VAS scores before and at 2 years postoperatively. Mann-Whitney U test was used for JOACMEQ. RESULTS: Postoperative loss of cervical lordosis >10° and >20° was observed in 32 (19.4%) and 7 (4.2%), respectively. JOA, JOACMEQ, and VAS scores were not significantly different between those with, and without, loss of cervical lordosis. Preoperative small extension range of motion (eROM) was significantly associated with postoperative loss of cervical lordosis, and the cutoff values of eROM were 7.4° [area under the curve (AUC): 0.76] and 8.2° (AUC: 0.92) for loss of cervical lordosis >10° and >20°, respectively. A large occupation ratio of OPLL was also associated with loss of cervical lordosis, with a cutoff value of 39.9% (AUC: 0.94). Laminoplasty resulted in functional improvement in most patient-reported outcomes; however, neck pain and bladder function tended to become worse postoperatively in cases with postoperative loss of cervical lordosis >20°. CONCLUSIONS: JOA, JOACMEQ, and VAS scores were not significantly different between those with, and without, loss of cervical lordosis. Preoperative small eROM and large OPLL may represent factors associated with loss of cervical lordosis after laminoplasty in patients with OPLL.

Protective Attitudes toward Occupational Radiation Exposure among Spine Surgeons in Japan: An Epidemiological Description from the Survey by the Society for Minimally Invasive Spinal Treatment.

Background and Objectives: The global trend toward increased protection of medical personnel from occupational radiation exposure requires efforts to promote protection from radiation on a societal scale. To develop effective educational programs to promote radiation protection, we clarify the actual status and stage of behavioral changes of spine surgeons regarding radiation protection. Materials and Methods: We used a web-based questionnaire to collect information on the actual status of radiation protection and stages of behavioral change according to the transtheoretical model. The survey was administered to all members of the Society for Minimally Invasive Spinal Treatment from 5 October to 5 November 2020. Results: Of 324 members of the Society for Minimally Invasive Spinal Treatment, 229 (70.7%) responded. A total of 217 participants were analyzed, excluding 12 respondents who were not exposed to radiation in daily practice. A trunk lead protector was used by 215 (99%) participants, while 113 (53%) preferred an apron-type protector. Dosimeters, thyroid protector, lead glasses, and lead gloves were used by 108 (50%), 116 (53%), 82 (38%), and 64 (29%) participants, respectively. While 202 (93%) participants avoided continuous irradiation, only 120 (55%) were aware of the source of the radiation when determining their position in the room. Regarding the behavioral change stage of radiation protection, 134 (62%) participants were in the action stage, while 37 (17%) had not even reached the contemplation stage. Conclusions: We found that even among the members of the Society for Minimally Invasive Spinal Treatment, protection of all vulnerable body parts was not fully implemented. Thus, development of educational programs that cover the familiar risks of occupational radiation exposure, basic protection methods in the operating room, and the effects of such protection methods on reducing radiation exposure in actual clinical practice is warranted.

Comparison of Surgical Outcomes of Anterior and Posterior Fusion Surgeries for K-line (-) Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Multicenter Study.

STUDY DESIGN: A prospective multicenter study. OBJECTIVE: The objective of this study is to compare the surgical outcomes of anterior and posterior fusion surgeries in patients with K-line (-) cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: Although laminoplasty is effective for patients with K-line (+) OPLL, fusion surgery is recommended for those with K-line (-) OPLL. However, whether the anterior or posterior approach is preferable for this pathology has not been effectively determined. MATERIALS AND METHODS: A total of 478 patients with myelopathy due to cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for two years. Of the 478 patients, 45 and 46 with K-line (-) underwent anterior and posterior fusion surgeries, respectively. After adjusting for confounders in baseline characteristics using a propensity score-matched analysis, 54 patients in both the anterior and posterior groups (27 patients each) were evaluated. Clinical outcomes were assessed using the cervical Japanese Orthopaedic Association and the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire. RESULTS: Both approaches showed comparable neurological and functional recovery. The cervical range of motion was significantly restricted in the posterior group because of the large number of fused vertebrae compared with the anterior group. The incidence of surgical complications was comparable between the cohorts, but the posterior group demonstrated a higher frequency of segmental motor paralysis, whereas the anterior group more frequently reported postoperative dysphagia. CONCLUSIONS: Clinical improvement was comparable between anterior and posterior fusion surgeries for patients with K-line (-) OPLL. The ideal surgical approach should be informed based on the balance between the surgeon's technical preference and the risk of complications.

Intraoperative Blood Loss at Different Surgical-Procedure Stages during Posterior Spinal Fusion for Idiopathic Scoliosis.

Background and Objectives: Several predictive factors have been reportedly associated with intraoperative total blood loss (TBL) during posterior spinal fusion (PSF) for idiopathic scoliosis (IS). To reduce TBL, preoperative factors and interoperative factors are considered important. However, there are few reports that have evaluated bleeding patterns according to surgical stages. This study aimed to elucidate bleeding patterns at different surgical stages and determine the predictive factors for TBL during PSF surgery in patients with IS. Materials and Methods: Preoperative data, radiographic parameters, and intraoperative data of patients undergoing PSF for IS were retrospectively collected. We divided the patients into six stages: stage 1, exposure; stage 2, implant placement; stage 3, release; stage 4, correction; stage 5, bone grafting; and stage 6, closure; then we reviewed the blood loss and bleeding speed. Multiple-regression analysis was performed to generate a predictive formula for blood loss using preoperative and intraoperative factors, including blood loss at stage 1, as explanatory variables. Results: Forty-five patients (mean age: 17.6 years) were included. The mean operative time and TBL were 287.9 min and 756.5 mL, respectively. Blood loss was the highest at stage 3, followed by stage 4. Bleeding speed was the highest at stage 4, followed by stage 3. Bleeding speeds at stages 3 and 4 were significantly higher than those at stages 1 and 2. Preoperative Cobb angle, activated partial thromboplastin time (aPTT), number of fused vertebrae, and blood loss at stage 1 were significant contributing factors. Conclusions: Blood loss and bleeding speed during the release and correction stages were high. Specifically, bleeding speed significantly increased during and after the release procedure. The preoperative Cobb angle, aPTT, number of fixed vertebrae, and blood-loss volume during PSF were significantly associated with TBL. Our findings would be helpful for reducing TBL in patients undergoing PSF for IS.

Residual Neuropathic Pain in Postoperative Patients With Cervical Ossification of Posterior Longitudinal Ligament.

STUDY DESIGN: A prospective multi-institutional observational study. OBJECTIVE: To investigate and identify risk factors for residual neuropathic pain after surgery in patients with cervical ossification of posterior longitudinal ligament (c-OPLL). SUMMARY OF BACKGROUND DATA: Patients with c-OPLL often require surgery for numbness and paralysis of the extremities; however, postoperative neuropathic pain can considerably deteriorate their quality of life. METHODS: Out of 479 patients identified from multicenter c-OPLL registries between 2014 and 2017, 292 patients who could be followed up for 2 years postoperatively were reviewed, after excluding patients with nervous system comorbidities. Demographic details; medical history; radiographic factors including the K-line, spinal canal occupancy rate of OPLL, cervical kyphosis angle, and presence of spinal cord myelomalacia; preoperative Japanese Orthopaedic Association (JOA) score; surgical procedure (fusion or decompression surgery); postoperative neurological deterioration; and the visual analogue scale for pain and numbness in the upper extremities (U/E) or trunk/lower extremities (L/E) at baseline and at 2 years postoperatively were assessed. Patients were grouped into residual and non-residual groups based on a postoperative visual analogue scale ≥40 mm. Risk factors for residual neuropathic pain were evaluated by multiple logistic regression analysis. RESULTS: The prevalence of U/E and L/E residual pain in postoperative c-OPLL patients was 51.7% and 40.4%, respectively. The U/E residual group had a poor preoperative JOA score and longer illness duration, and fusion surgery was more common in the residual group than in non-residual group. The L/E residual group was older with a poorer preoperative JOA score. On multivariate analysis, risk factors for U/E residual pain were long illness duration and poor preoperative JOA score, whereas those for L/E residual pain were age and poor preoperative JOA score. CONCLUSIONS: The risk factors for residual spinal neuropathic pain after c-OPLL surgery were age, long duration of illness, and poor preoperative JOA score. LEVEL OF EVIDENCE: IV.

Deep learning-based prediction model for postoperative complications of cervical posterior longitudinal ligament ossification.

PURPOSE: Postoperative complication prediction helps surgeons to inform and manage patient expectations. Deep learning, a model that finds patterns in large samples of data, outperform traditional statistical methods in making predictions. This study aimed to create a deep learning-based model (DLM) to predict postoperative complications in patients with cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: This prospective multicenter study was conducted by the 28 institutions, and 478 patients were included in the analysis. Deep learning was used to create two predictive models of the overall postoperative complications and neurological complications, one of the major complications. These models were constructed by learning the patient's preoperative background, clinical symptoms, surgical procedures, and imaging findings. These logistic regression models were also created, and these accuracies were compared with those of the DLM. RESULTS: Overall complications were observed in 127 cases (26.6%). The accuracy of the DLM was 74.6 ± 3.7% for predicting the overall occurrence of complications, which was comparable to that of the logistic regression (74.1%). Neurological complications were observed in 48 cases (10.0%), and the accuracy of the DLM was 91.7 ± 3.5%, which was higher than that of the logistic regression (90.1%). CONCLUSION: A new algorithm using deep learning was able to predict complications after cervical OPLL surgery. This model was well calibrated, with prediction accuracy comparable to that of regression models. The accuracy remained high even for predicting only neurological complications, for which the case number is limited compared to conventional statistical methods.

Trunk flexibility using a sit-and-reach test after surgery for adolescent idiopathic scoliosis.

PURPOSE: Spinal fusion reduces flexibility, but we do not have detailed knowledge that accounts for growth or sex differences. We sought to determine trunk flexibility pre- and postoperatively in patients with adolescent idiopathic scoliosis (AIS). METHODS: We included data from 109 patients with AIS in this retrospective, single-center observational study. Patients had performed a sit-and-reach (SR) test preoperatively, and 1 and 2 years postoperatively, and measurements were standardized to Z scores according to age and sex. The patient data were divided into three groups according to the level of lower instrumented vertebra (LIV): (1) Group A (fusion above L2); (2) Group B (fusion to L2), and (3) Group C (fusion to L3 or L4). The change in the Z score for various levels was determined and compared. RESULTS: The preoperative Z score for all patients was -0.622. At 2 years postoperatively, the Z score in Groups A and B was not significantly different from the preoperative score; in Group C, the Z score decreased by 1 year postoperatively, improved during the second year, but remained significantly lower than the preoperative score. Our study was the first to assess trunk flexibility using the SR test in patients with scoliosis. CONCLUSIONS: Preoperatively, patients with AIS had lower SR test Z-scores than the general population, indicating a lower trunk flexibility in these patients. At 2 years after surgery in these patients, trunk flexibility had returned to preoperative levels when LIV was at L2 or above, but when LIV was at L3 or L4, trunk flexibility was less than it was preoperatively. LEVEL OF EVIDENCE: Prognostic Level II: retrospective study.

Somnolence and Dizziness During Mirogabalin Treatment in Patients With Neuropathic Pain Related to Lumbar Disease Who Switched From Pregabalin: A Retrospective Study.

STUDY DESIGN: Multicenter retrospective study. OBJECTIVES: To investigate adverse events (AEs) in patients with neuropathic pain related to lumbar disease who switched to mirogabalin from pregabalin. METHODS: This study surveyed the records of 82 patients with peripheral neuropathic leg pain related to lumbar disease who switched to mirogabalin from pregabalin. We evaluated AEs associated with pregabalin and mirogabalin, the continuation rate of mirogabalin, and the pain-relieving effect at 4 weeks after switching from pregabalin to mirogabalin. We compared patients who switched due to lack of efficacy (LoE group) and patients who switched due to AEs (AE group). RESULTS: The incidence rates of somnolence and dizziness with pregabalin were 12.2% and 14.6%, respectively, while the incidence rates with mirogabalin were reduced to 7.3% for somnolence and 4.9% for dizziness. The incidence of AEs with pregabalin was significantly higher in the AE group (LoE group: 11.1%, AE group 100%), especially for somnolence (LoE group: 3.2%, AE group: 47.1%) and dizziness (LoE group: 4.8%, AE: 52.9%). After switching, the incidences of AEs with mirogabalin were not significantly different between the 2 groups (LoE group: 15.9%, AE group: 23.5%), including for somnolence (LoE group: 7.9%, AE group: 5.9%) and dizziness (LoE group: 4.8%, AE group: 5.9%). There were no significant differences in continuation rate of mirogabalin or the pain-relieving effect between groups. CONCLUSIONS: The patients who experience somnolence and dizziness with pregabalin might be able to continue safely receiving treatment for their pain by switching to mirogabalin.

Prospective Investigation of Surgical Outcomes after Anterior Decompression with Fusion and Laminoplasty for the Cervical Ossification of the Posterior Longitudinal Ligament: A Propensity Score Matching Analysis.

The ideal surgical strategy for cervical ossification of the posterior longitudinal ligament (OPLL) remains controversial due to the lack of high-quality evidence. Herein, we prospectively investigated the surgical outcomes of anterior cervical decompression with fusion (ADF) and laminoplasty (LAMP) with cervical OPLL. Three hundred patients were included in this study (ADF: n = 89; LAMP: n = 211 patients), and propensity score matching yielded 67 pairs of patients with ADF and LAMP, in which clinical outcomes were compared. Crude analysis revealed that the ADF group showed greater neurological recovery in cervical Japanese Orthopedic Association scores at two years, compared with that in the LAMP group (53.1% vs. 44.3%, p = 0.037). The ratio of minimum clinically important difference (MCID) success was significantly greater in the ADF group (59.6% vs. 43.6%, p = 0.016). Multivariate analysis showed that the factors affecting MCID success were age, body mass index, duration of symptoms, and choice of ADF. In the 1:1 matched analysis, neurological improvement was more favorable in the ADF group (57.2%) compared to the LAMP group (46.8%) at two years (p = 0.049). However, perioperative complications, such as dysphagia and graft-related complications, were more common in the ADF group.

Multicenter Retrospective Analysis of Intradiscal Condoliase Injection Therapy for Lumbar Disc Herniation.

Background and Objectives: Intradiscal injection of Condoliase (chondroitin sulfate ABC endolyase), a glycosaminoglycan-degrading enzyme, is employed as a minimally invasive treatment for lumbar disc herniation (LDH) and represents a promising option between conservative treatment and surgical intervention. Since its 2018 approval in Japan, multiple single-site trails have highlighted its effectiveness, however, the effect of LDH types, and influences of patient age, sex, etc., on treatment success remains unclear. Moreover, data on teenagers and elderly patients has not been reported. In this retrospective multi-center study, we sought to classify prognostic factors for successful condoliase treatment for LDH and assess its effect on patients < 20 and ≥70 years old. Materials and Methods: We reviewed the records of 137 LDH patients treated through condoliase at four Japanese institutions and assessed its effectiveness among different age categories on alleviation of visual analog scale (VAS) of leg pain, low back pain and numbness, as well as ODI and JOA scores. Moreover, we divided them into either a "group-A" category if a ≥50% improvement in baseline leg pain VAS was observed or "group-N" if VAS leg pain improved <50%. Next, we assessed the differences in clinical and demographic distribution between group-A and group-N. Results: Fifty-five patients were classified as group-A (77.5%) and 16 patients were allocated to group-N (22.5%). A significant difference in Pfirrmann classification was found between both cohorts, with grade IV suggested to be most receptive. A posterior disc angle > 5° was also found to approach statical significance. In all age groups, average VAS scores showed improvement. However, 75% of adolescent patients showed deterioration in Pfirrmann classification following treatment. Conclusions: Intradiscal condoliase injection is an effective treatment for LDH, even in patients with large vertebral translation and posterior disc angles, regardless of age. However, since condoliase imposes a risk of progressing disc degeneration, its indication for younger patients remains controversial.

TNF-α Suppresses Apelin Receptor Expression in Mouse Quadriceps Femoris-Derived Cells.

Expression of the apelin receptor, APJ, in skeletal muscle (SM) is known to decrease with age, but the underlying mechanism remains unclear. Increased tumor necrosis factor (TNF)-α levels are observed in SM with age and are associated with muscle atrophy. To investigate the possible interconnection between TNF-α elevation and APJ reduction with aging, we investigated the effect of TNF-α on APJ expression in cells derived from the quadriceps femoris of C57BL/6J mice. Expression of Tnfa and Apj in the quadriceps femoris was compared between 4- (young) and 24-month-old (old) C57BL/6J mice (n = 10 each) using qPCR. Additionally, APJ-positive cells and TNF-α protein were analyzed by flow cytometry and Western blotting, respectively. Further, quadricep-derived cells were exposed to 0 (control) or 25 ng/mL TNF-α, and the effect on Apj expression was examined by qRT-PCR. Apj expression and the ratio of APJ-positive cells among quadricep cells were significantly lower in old compared to young mice. In contrast, levels of Tnfa mRNA and TNF-α protein were significantly elevated in old compared to young mice. Exposing young and old derived quadricep cells to TNF-α for 8 and 24 h caused Apj levels to significantly decrease. TNF-α suppresses APJ expression in muscle cells in vitro. The increase in TNF-α observed in SM with age may induce a decrease in APJ expression.

Clinical Indicators of Surgical Outcomes After Laminoplasty for Patients With Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Multicenter Study.

STUDY DESIGN: A prospective multicenter study. OBJECTIVE: This study aims to evaluate patient-reported outcomes using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) and clarify clinical factors that affect the therapeutic effects for patients with cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: Although previous studies identified factors that affected the surgical outcomes, their assessment was mainly based on the Japanese Orthopedic Association score, which only includes neurological function. Investigating this pathology through multiple functions and quality of life (QOL) is pivotal to understanding the comprehensive clinical pictures of the cervical OPLL and its therapeutic outcomes. MATERIALS AND METHODS: This study was performed by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. A total of 478 patients with myelopathy caused by cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for 2 years. Of the patients, 168 received laminoplasties and fully completed questionnaires. Demographic information, imaging findings, and clinical outcomes were collected. Patients were grouped according to effective or ineffective surgical outcomes as defined by the JOACMEQ using logistic regression analyses. RESULTS: Laminoplasty resulted in functional improvement in the cervical spine and upper extremity around 40% of the patients, while QOL showed only 21.4% ( P <0.01). Multivariable analyses revealed that younger age and a postoperative decrease in arm or hand pain were correlated with significantly improved function of the upper extremities. A reduction in lower limb pain favorably affected the postoperative lower extremity function. A postoperative reduction in upper extremity pain enhanced the QOL recovery. CONCLUSIONS: Surgeons should recognize the diversity of surgical outcomes after laminoplasty and understand the necessity of pain management even after the surgery to enhance bodily functions and QOL in patients with cervical OPLL.

The Relationship Between Falling Distance and Trauma Severity Among Fall Injury Survivors Who Were Transported to a Trauma Center.

Introduction Falls from >6 meters have been shown to cause multiple traumas and serious injuries. However, especially among fall survivors who were transported to trauma centers, the relationship between falling distance and trauma severity remains unclear. This study aimed to investigate the relationship between falling distance and trauma severity among fall injury survivors who were transported to a trauma center and clarify the characteristics of trauma among survivors of falls from high places from an orthopedic surgeon's perspective. Methods We retrospectively reviewed the medical records of 65 fall injury survivors who were transported to a trauma center for falling distance; whether the fall was a suicide attempt; abdominal, chest, and head trauma; the numbers of upper-limb, lower-limb, and spinal vertebral fractures; McCormack load-sharing classification score; unstable pelvic fracture; Frankel classification; injury severity score (ISS); and duration of intensive care unit (ICU) and hospital stay. We evaluated the correlations between falling distance and the other factors and compared all factors between those falling <6 meters and those falling >6 meters. Results Falling distance was weakly positively correlated with durations of ICU and hospital stay. The percentage of cases that were suicide attempts, the number of lower-limb fractures, the McCormack load-sharing classification score, and the durations of ICU and hospital stay were significantly higher among those falling from >6 meters than among those falling from <6 meters. Conversely, there were no significant differences in abdominal trauma, chest trauma, head trauma, number of upper-limb fractures, number of vertebral fractures, unstable pelvic fracture, or Frankel classification between the two groups. Conclusion The findings indicate that falling from a higher distance may increase lower-limb and vertebral fracture severity and may lead to longer ICU and hospital stays among fall injury survivors who are transported to trauma centers.