Disease-Modifying Effects of Lenvatinib, a Multiple Receptor Tyrosine Kinase Inhibitor, on Posttraumatic Osteoarthritis of the Knee.

Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral-tibial (FT), femoral-patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn's grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA.

Impact of Osteoporosis on Short-Term Surgical Outcomes in Lumbar Degenerative Disease Patients Undergoing Lateral Lumbar Interbody Fusion: A Retrospective Analysis.

OBJECTIVE: This retrospective study assesses the influence of osteoporosis on the short-term clinical outcomes of lateral lumbar interbody fusion (LLIF) surgery in patients with lumbar degenerative diseases (LDDs), focusing on complications, pain intensity, and quality of life (QOL) improvements. The primary aim of this study is to investigate the impact of osteoporosis on the short-term clinical outcomes following LLIF surgery in LDD patients, with a particular focus on the incidence of cage subsidence (CS) and overall patient well-being postoperatively. METHODS: A retrospective review was conducted on 73 patients who underwent LLIF for LDD. Patients were categorized into 2 groups based on osteoporosis status determined by dual-energy X-ray absorptiometry scans: those with osteoporosis (n = 20) and those without osteoporosis (n = 53). Data collection included demographics, surgical details, complications, magnetic resonance imaging analysis, pain intensity, and QOL (Japanese Orthopaedic Association Back Pain Evaluation Questionnaire). RESULTS: The groups had no significant differences regarding operative time, estimated blood loss, and hospital stay duration. However, the incidence of CS was 40% in patients with osteoporosis, compared to 17% in nonosteoporotic patients. Despite this, significant improvements in spinal canal dimensions were observed in both groups. Both groups experienced significant reductions in pain intensity, with notable improvements in functional outcomes assessed by the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, indicating the overall effectiveness of LLIF in enhancing patient well-being and functionality, irrespective of osteoporosis status. CONCLUSIONS: Osteoporosis increases the risk of CS in LLIF surgery for LDD patients but does not affect short-term pain relief and QOL improvements.

Quantifying Satisfaction of Degenerative Lumbar Spinal Stenosis Patients in Post-lateral Lumbar Interbody Fusion Surgery: Establishing Critical JOABPEQ Cutoff Scores.

OBJECTIVE: This retrospective study aimed to determine the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) cutoff scores for assessing patient satisfaction postlateral lumbar interbody fusion (LLIF) in degenerative lumbar spinal stenosis (DLSS) patients. METHODS: Analyzing 136 DLSS patients (83 males, 53 females), the study evaluated demographics, pain (Numeric Rating Scale), and JOABPEQ outcomes (low back pain, lumbar function, walking ability, social life, mental health). Patient satisfaction was surveyed, and based on their responses, patients were categorized into "Beneficial" and "Nonbeneficial" groups. Statistical analysis encompassed the Kolmogorov-Smirnov test, t-tests, Mann-Whitney U test, and Receiver Operating Characteristic (ROC) curve analysis for JOABPEQ cutoff determination. RESULTS: Postoperative improvements in JOABPEQ scores, especially in walking ability, social life function, and mental health, were significant. Pain intensity, assessed using the Numeric Rating Scale, also showed notable reductions. The Δ walking ability cutoff was set at 25.00, indicating substantial mobility improvement. This domain's area under the curve (AUC) was 0.815 (95% CI: 0.726-0.903), demonstrating high effectiveness in assessing patient satisfaction postsurgery. The study also found no significant differences in complication rates between groups for conditions like transient motor weakness, thigh pain/numbness, and revision surgery. CONCLUSIONS: This study underscores the value of patient-centered outcomes in evaluating LLIF surgery success for DLSS. The identified JOABPEQ cutoff values provide a quantitative tool for assessing patient satisfaction, emphasizing the necessity of comprehensive postoperative evaluations beyond traditional clinical metrics for improved patient care and life quality.

Gustatory Responsiveness of Honey Bees Colonized with a Defined or Conventional Gut Microbiota.

Gut microbes have many beneficial functions for host animals, such as food digestion and development of the immune system. An increasing number of studies report that gut bacteria also affect host neural function and behavior. The sucrose responsiveness of the western honey bee Apis mellifera, which harbors a characteristic gut microbiota, was recently reported to be increased by the presence of gut microbes. However, this responsiveness may vary depending on the experimental design, as animal behavior may be modulated by physiological states and environmental conditions. To evaluate the robustness of the effects of the gut microbiota on host gustatory responsiveness, we herein examined the sucrose responsiveness of honey bees colonized with a defined bacterial community or a conventional gut microbiota extracted from a field-collected bee. Although colonization was experimentally verified, sucrose responsiveness did not significantly differ among treatments after the 2- or 5-h starvation period. We concluded that the sucrose responsiveness of A. mellifera is not always affected by its gut microbiota. Therefore, host physiological conditions and environmental factors need to be considered when evaluating the impact of the gut microbiota on host neural function and behavior.

Evaluating the Efficacy of IL-6 as Predictors of Lateral Lumbar Interbody Fusion Success: Insights From Pain Scores and JOABPEQ Assessments.

STUDY DESIGN: A prospective study. OBJECTIVES: This study aims to explore the correlation between interleukin (IL)- 6 levels in intervertebral disc (IVD) tissue and clinical outcomes in patients undergoing lumbar surgery for lumbar degenerative disease (LDD). METHODS: This prospective study analyzed 32 patients (22 men and 10 women, average age 69.6 years) who underwent lateral lumbar interbody fusion (LLIF). IL-6 gene expression in IVD tissues collected during surgery was measured and correlated with pre- and postoperative clinical outcomes, including pain intensity assessed via Numeric Rating Scales (NRS) and quality of life (QOL) evaluated through the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). RESULTS: IL-6 levels showed statistical correlations with postoperative intensity of low back pain (LBP) and several JOABPEQ domains. Patients with higher expression of IL-6 levels experienced more severe postoperative LBP and lower scores in lumbar function, walking ability, social life function, and mental health. The effectiveness rate of JOABPEQ scores was exceptionally high for low back pain (.548), walking ability (.677), and social functioning (.563), demonstrating the effectiveness of LLIF. The average operation time was 105.6 minutes, and the estimated blood loss was 85.6 mL. CONCLUSIONS: The study underscores IL-6 as a potential biomarker for predicting surgical outcomes in LDD. High IL-6 levels correlate with worse postoperative LBP and lower QOL scores. Integrating molecular markers like IL-6 with patient-reported outcomes could provide a more comprehensive approach to postoperative care in spinal disorders, aiming to improve the overall QOL for LDD patients undergoing LLIF surgery.

ISSLS PRIZE in Basic Science 2024: superiority of nucleus pulposus cell- versus mesenchymal stromal cell-derived extracellular vesicles in attenuating disc degeneration and alleviating pain.

PURPOSE: To investigate the therapeutic potential of extracellular vesicles (EVs) derived from human nucleus pulposus cells (NPCs), with a specific emphasis on Tie2-enhanced NPCs, compared to EVs derived from human bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a coccygeal intervertebral disc degeneration (IDD) rat model. METHODS: EVs were isolated from healthy human NPCs cultured under standard (NPCSTD-EVs) and Tie2-enhancing (NPCTie2+-EVs) conditions. EVs were characterized, and their potential was assessed in vitro on degenerative NPCs in terms of cell proliferation and senescence, with or without 10 ng/mL interleukin (IL)-1ß. Thereafter, 16 Sprague-Dawley rats underwent annular puncture of three contiguous coccygeal discs to develop IDD. Phosphate-buffered saline, NPCSTD-EVs, NPCTie2+-EVs, or BM-MSC-derived EVs were injected into injured discs, and animals were followed for 12 weeks until sacrifice. Behavioral tests, radiographic disc height index (DHI) measurements, evaluation of pain biomarkers, and histological analyses were performed to assess the outcomes of injected EVs. RESULTS: NPC-derived EVs exhibited the typical exosomal morphology and were efficiently internalized by degenerative NPCs, enhancing cell proliferation, and reducing senescence. In vivo, a single injection of NPC-derived EVs preserved DHI, attenuated degenerative changes, and notably reduced mechanical hypersensitivity. MSC-derived EVs showed marginal improvements over sham controls across all measured outcomes. CONCLUSION: Our results underscore the regenerative potential of young NPC-derived EVs, particularly NPCTie2+-EVs, surpassing MSC-derived counterparts. These findings raise questions about the validity of MSCs as both EV sources and cellular therapeutics against IDD. The study emphasizes the critical influence of cell type, source, and culture conditions in EV-based therapeutics.

SOD2 orchestrates redox homeostasis in intervertebral discs: A novel insight into oxidative stress-mediated degeneration and therapeutic potential.

Low back pain (LBP) is a pervasive global health concern, primarily associated with intervertebral disc (IVD) degeneration. Although oxidative stress has been shown to contribute to IVD degeneration, the underlying mechanisms remain undetermined. This study aimed to unravel the role of superoxide dismutase 2 (SOD2) in IVD pathogenesis and target oxidative stress to limit IVD degeneration. SOD2 demonstrated a dynamic regulation in surgically excised human IVD tissues, with initial upregulation in moderate degeneration and downregulation in severely degenerated IVDs. Through a comprehensive set of in vitro and in vivo experiments, we found a suggestive association between excessive mitochondrial superoxide, cellular senescence, and matrix degradation in human and mouse IVD cells. We confirmed that aging and mechanical stress, established triggers for IVD degeneration, escalated mitochondrial superoxide levels in mouse models. Critically, chondrocyte-specific Sod2 deficiency accelerated age-related and mechanical stress-induced disc degeneration in mice, and could be attenuated by ß-nicotinamide mononucleotide treatment. These revelations underscore the central role of SOD2 in IVD redox balance and unveil potential therapeutic avenues, making SOD2 and mitochondrial superoxide promising targets for effective LBP interventions.

Hounsfield Unit Values as an Adjunct Diagnostic Tool: Investigating Its Relationship with Bone Mineral Density and Vertebral Bone Quality in Lumbar Degenerative Disease Patients.

OBJECTIVE: With an increasing prevalence of osteoporosis due to demographic shifts, accurate diagnostic methods are vital, particularly before spinal surgeries. This research investigated the correlation between bone mineral density T-scores of the lumbar spine and femoral neck, Hounsfield Unit (HU) values from computed tomography (CT), and vertebral bone quality (VBQ) scores from Magnetic Resonance Imaging (MRI) in patients with lumbar degenerative disease. METHODS: We analyzed data from 100 patients with lumbar degenerative disease who underwent CT, dual-energy X-ray absorptiometry (DXA), and MRI between 2019 and 2023. HU values were measured individually from L1 to L4, while T-scores were obtained from DXA scans of the lumbar spine and the femoral neck. The VBQ scores were derived from T1-weighted MRIs. RESULTS: A notable association between the lumbar and femoral neck T-scores and HU values was found. The VBQ score had a faint correlation with HU values and lacked any with the T-score. Notably, the HU values derived via the Youden index and regression closely matched. Lumbar spine HU values related to T-scores of 85.6 and 84.4 and femoral neck T-scores of 98.9 and 103.6, with a low T-score at 98.9 and 104.6. CONCLUSIONS: This study underscores a strong correlation between bone mineral density and HU values from CT scans in lumbar degenerative disease patients, suggesting the utility of HU measurements as an adjunct diagnostic tool for osteoporosis. However, the correlation with the VBQ score remains weak. Further multicenter studies are essential for more robust validation.

MPFL Reconstruction Combined with a Modified Elmslie-Trillat Procedure for Recurrent Patellofemoral Instability.

Several combined procedures have been reported for treating recurrent patellofemoral instability (RPI) with various types and severity of morphological abnormalities, but none have identified absolute threshold values as indications for surgery. We performed medial patellofemoral ligament (MPFL) reconstruction combined with a modified Elmslie-Trillat (ET) procedure on 24 knees (10 male and 11 female patients) to treat RPI with morphological abnormalities corresponding to elevated tibial tubercle-trochlear groove (TT-TG) distance, significant patella alta, and trochlear dysplasia. The inclusion criteria were RPI with morphological abnormalities corresponding to one or more of the following: sulcus angle > 160 degrees, trochlear dysplasia of Dejour classification C or D, Caton-Deschamps index > 1.5, lateral shift ratio > 50%, congruence angle > 15 degrees, or TT-TG distance > 20 mm, including habitual dislocation of the patella. Skeletally immature patients and those with congenital dislocation of the patella were excluded. The Kujala score, International Knee Documentation Committee subjective score, Knee Injury and Osteoarthritis Outcome score (KOOS), and each item of the KOOS improved significantly after surgery. Patellar apprehension sign was present preoperatively in all cases, but all disappeared postoperatively. No instance of postoperative redislocation was observed. On radiographic examination, the mean Q angle, tilting angle, lateral shift ratio, congruence angle, Caton-Deschamps index, Insall-Salvati index, and TT-TG distance improved significantly after surgery. There were no significant differences in sulcus angle after surgery. These results suggest MPFL reconstruction combined with a modified ET procedure provides satisfactory outcomes based on radiological and clinical evaluations for RPI with morphological abnormalities corresponding to elevated TT-TG distance, significant patella alta, and trochlear dysplasia.

Recombinant Laminin-511 Fragment (iMatrix-511) Coating Supports Maintenance of Human Nucleus Pulposus Progenitor Cells In Vitro.

The angiopoietin-1 receptor (Tie2) marks specific nucleus pulposus (NP) progenitor cells, shows a rapid decline during aging and intervertebral disc degeneration, and has thus sparked interest in its utilization as a regenerative agent against disc degeneration. However, the challenge of maintaining and expanding these progenitor cells in vitro has been a significant hurdle. In this study, we investigated the potential of laminin-511 to sustain Tie2+ NP progenitor cells in vitro. We isolated cells from human NP tissue (n = 5) and cultured them for 6 days on either standard (Non-coat) or iMatrix-511 (laminin-511 product)-coated (Lami-coat) dishes. We assessed these cells for their proliferative capacity, activation of Erk1/2 and Akt pathways, as well as the expression of cell surface markers such as Tie2, GD2, and CD24. To gauge their regenerative potential, we examined their extracellular matrix (ECM) production capacity (intracellular type II collagen (Col2) and proteoglycans (PG)) and their ability to form spherical colonies within methylcellulose hydrogels. Lami-coat significantly enhanced cell proliferation rates and increased Tie2 expression, resulting in a 7.9-fold increase in Tie2-expressing cell yields. Moreover, the overall proportion of cells positive for Tie2 also increased 2.7-fold. Notably, the Col2 positivity rate was significantly higher on laminin-coated plates (Non-coat: 10.24% (±1.7%) versus Lami-coat: 26.2% (±7.5%), p = 0.010), and the ability to form spherical colonies also showed a significant improvement (Non-coat: 40.7 (±8.8)/1000 cells versus Lami-coat: 70.53 (±18.0)/1000 cells, p = 0.016). These findings demonstrate that Lami-coat enhances the potential of NP cells, as indicated by improved colony formation and proliferative characteristics. This highlights the potential of laminin-coating in maintaining the NP progenitor cell phenotype in culture, thereby supporting their translation into prospective clinical cell-transplantation products.

Minimally Invasive Approach for Degenerative Spondylolisthesis: Lateral Single-Position Surgery with Intraoperative Computed Tomography Navigation and Fluoroscopy: A Technical Note.

OBJECTIVE: Degenerative spondylolisthesis (DS) is a prevalent condition that leads to low back pain and neurological symptoms. This technical note presents a novel surgical strategy for treating DS using lateral single-position surgery (SPS) in combination with intraoperative computed tomography navigation and fluoroscopy. METHODS: Fifteen patients (5 males and 10 females, mean age 70.2 years) diagnosed with DS with a slip of 5 mm or more underwent lateral lumbar interbody fusion (LLIF) with percutaneous pedicle screw (PPS) fixation using this technique. The procedure involved slip reduction using an upside PPS and rod fixation, followed by LLIF performed in the same lateral position. The term "upside PPS" refers to a PPS that is inserted on the ceiling side of the patient's surgical field. Preoperative and postoperative radiographic assessments were conducted to evaluate the effectiveness of the lateral SPS. RESULTS: The results demonstrated significant improvements in various parameters, including spondylolisthesis reduction, segmental lordosis, disc height, and spinal canal dimensions. The lateral-SPS procedure exhibited several advantages over traditional flip LLIF approaches for slip reduction. Additionally, the technique provided accurate intraoperative navigation guidance through computed tomography imaging, ensuring precise implant placement and slip reduction. CONCLUSIONS: Combining LLIF and PPS fixation in a single procedure presents a precise, efficient approach for DS treatment, minimizing repositioning needs. This technique enables effective lumbar reconstruction, restoration of spinal stability, and improved patient outcomes. Although further investigation is warranted, lateral SPS surgery may hold promise as an innovative solution for managing DS by reducing surgical invasiveness and optimizing surgical efficiency.

Comprehensive Assessment of Indirect Decompression Through Lateral Lumbar Interbody Fusion for Degenerative Lumbar Spinal Stenosis: A Japanese Orthopedic Association Back Pain Evaluation Questionnaire-Based Analysis.

STUDY DESIGN: A retrospective study. OBJECTIVE: This study aimed to comprehensively evaluate the clinical outcomes of lateral lumbar interbody fusion (LLIF) as an indirect decompression technique for degenerative spondylolisthesis (DS) and concomitant degenerative lumbar spinal stenosis (DLSS) patients. We utilized the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) to assess treatment success and its impact on patient's quality of life (QOL). METHODS: We included 124 patients who underwent LLIF. Pre- and postoperative JOABPEQ evaluations indicated treatment success. Subgroup analysis categorized patients' perceptions of surgery as beneficial or non-beneficial. RESULTS: 89% of patients (110/124) reported satisfaction with LLIF. Lateral lumbar interbody fusion achieved successful indirect decompression, increasing canal diameter and central canal area. Significant improvements occurred across all JOABPEQ domains, notably for low back pain, lumbar function, walking ability, social life function, and mental health. Patients who perceived the surgery as beneficial experienced fewer postoperative complications, lower numeric rating scale scores for pain relief, and greater functional outcome improvements compared to non-beneficial patients. CONCLUSIONS: Our findings highlight the utility of JOABPEQ as a valuable and sensitive tool for assessing treatment effectiveness and patient-reported outcomes in DS and concomitant DLSS patients. Patients undergoing LLIF. The results affirm the favorable outcomes of LLIF as a surgical option for DLSS patients and emphasize the importance of considering patient perspectives when evaluating overall treatment success. The study provides valuable insights into the impact of indirect decompression on patients' QOL, supporting the effectiveness of LLIF as a minimally invasive technique for DLSS and DS management.

Investigation of the Mitigation of DMSO-Induced Cytotoxicity by Hyaluronic Acid following Cryopreservation of Human Nucleus Pulposus Cells.

To develop an off-the-shelf therapeutic product for intervertebral disc (IVD) repair using nucleus pulposus cells (NPCs), it is beneficial to mitigate dimethyl sulfoxide (DMSO)-induced cytotoxicity caused by intracellular reactive oxygen species (ROS). Hyaluronic acid (HA) has been shown to protect chondrocytes against ROS. Therefore, we examined the potential of HA on mitigating DMSO-induced cytotoxicity for the enhancement of NPC therapy. Human NPC cryopreserved in DMSO solutions were thawed, mixed with equal amounts of EDTA-PBS (Group E) or HA (Group H), and incubated for 3-5 h. After incubation, DMSO was removed, and the cells were cultured for 5 days. Thereafter, we examined cell viability, cell proliferation rates, Tie2 positivity (a marker of NP progenitor cells), and the estimated numbers of Tie2 positive cells. Fluorescence intensity of DHE and MitoSOX staining, as indicators for oxidative stress, were evaluated by flow cytometry. Group H showed higher rates of cell proliferation and Tie2 expressing cells with a trend toward suppression of oxidative stress compared to Group E. Thus, HA treatment appears to suppress ROS induced by DMSO. These results highlight the ability of HA to maintain NPC functionalities, suggesting that mixing HA at the time of transplantation may be useful in the development of off-the-shelf NPC products.

Comparative Analysis of Hounsfield Units and Vertebral Bone Quality Scores for Predicting Proximal Junctional Failure in Female Adult Spinal Deformity Patients Undergoing Planned 2-Stage Corrective Surgery with Lateral Lumbar Interbody Fusion.

OBJECTIVE: This study aimed to evaluate the utility of computed tomography (CT)-based Hounsfield units (HUs) and magnetic resonance imaging-based Vertebral Bone Quality (VBQ) scores as alternatives to dual-energy x-ray absorptiometry for predicting the risk of proximal junctional failure (PJF) in female patients with adult spinal deformity (ASD) undergoing 2-stage corrective surgery with lateral lumbar interbody fusion (LLIF). METHODS: The study included 53 female patients with ASD who underwent 2-stage corrective surgery with LLIF from January 2016 to April 2022 with a minimum follow-up of 1 year. CT and magnetic resonance imaging scans were evaluated for their correlation with PJF. RESULTS: Of the 53 patients (mean age 70.2 years), 14 had PJF. Patients with PJF had significantly lower HU values at the upper instrumented vertebra (UIV) (113.0 ± 29.4 vs. 141.1 ± 41.5, P = 0.036) and L4 (113.4 ± 59.5 vs. 160.0 ± 64.9, P = 0.026) than those without PJF. However, there was no difference in VBQ scores between the 2 groups. PJF correlated with HU values at UIV and L4 but not with VBQ scores. Patients with PJF also had significantly different pre- and postoperative thoracic kyphosis, postoperative pelvic tilt, pelvic incidence minus lumbar lordosis, and proximal junctional angle compared to those without PJF. CONCLUSIONS: The findings suggest that measuring HU values at UIV or L4 by CT may be useful for predicting the risk of PJF in female ASD patients undergoing 2-stage corrective surgery with LLIF. Therefore, CT-based HUs should be considered in ASD surgery planning to reduce the risk of PJF.

Adolescent Idiopathic Scoliotic Deformity Correction Surgery Assisted by Smart Glasses Can Enhance Correction Outcomes and Accuracy and Also Improve Surgeon Fatigue.

OBJECTIVE: Augmented reality (AR) is becoming more common and slowly being integrated into the surgical field. With the continuous progression of navigation and visualization techniques, AR has great potential to improve surgical quality and safety. Nevertheless, the effects of AR on surgical outcomes and surgeons' well-being remains poorly studied. The present prospective controlled study aims to assess the effect of surgery assisted with AR smart glasses on adolescent idiopathic scoliosis (AIS) deformity correction outcomes and surgeon fatigue. METHODS: AIS patients scheduled for surgical deformity correction were prospectively recruited and assigned to standard or AR-supported surgery, using lightweight AR smart glasses. The demographic and clinical features were recorded. The pre- and postoperative spinal features, operative time, and blood loss were recorded and compared. Finally, the participating surgeons were asked to complete a questionnaire (e.g., visual analog scale for fatigue) to compare the effects of AR on their well-being. RESULTS: Our results have shown enhanced spinal deformity corrections with Cobb angle (-35.7° vs. -46.9°), thoracic kyphosis (8.1° vs. 11.6°), and vertebral rotation (-9.3° vs. -13.8°) changes favoring AR-supported surgery. Moreover, AR resulted in significantly lower violation rates per patient (7.5% vs. 6.6%; P = 0.023). Finally, the visual analog scale for fatigue scores consistently showed a significant reduction in fatigue (5.7 ± 1.7 vs. 3.3 ± 1.2; P < 0.001) and other fatigue classifiers for the surgeons after AR-supported surgery. CONCLUSIONS: Our controlled study has highlighted the enhanced spinal correction rates in AR-supported surgery and also improved surgeons' well-being and fatigue. These results endorse the adaptation of AR techniques to support AIS surgical correction.

Early Radiological Assessment of Static and Expandable Cages in Lateral Single Position for Indirect Decompression- Lateral Lumbar Interbody Fusion.

OBJECTIVE: This study aimed to compare the postoperative alignment of static and expandable cages in lateral single-position (LSP) for indirect decompression in lateral lumbar interbody fusion (LLIF). METHODS: We included sixty-seven patients who underwent LSP-LLIF for lumbar degenerative disease. We performed radiological assessments preoperatively and two weeks postoperatively using computed tomography and magnetic resonance imaging. We divided the patients into the expandable cage group (23 patients) and the static cage group (44 patients). We measured disc height (DH), segmental lordosis (SL), and foraminal area (FA) from computed tomography images and the area of the dural sac from magnetic resonance imaging. We recorded surgical outcomes and complications. RESULTS: Both static and expandable cages demonstrated improvements in DH, SL, FA, and dural sac expansion. However, we found no statistically significant differences in the average change in DH (4.4 ± 2.1 mm vs. 4.2 ± 1.8 mm, P = 0.685), the average change in SL (1.0 ± 4.4° vs. 1.9 ± 3.6°, P = 0.310), or FA change (32.5 ± 31.7 mm2 vs. 34.9 ± 29.5 mm2, P = 0.966) between the expandable and static cage groups. We also found no statistically significant difference in dural sac enlargement between the two groups. We observed no significant differences in operation time, estimated blood loss, or length of hospital stay between the two groups. No severe adverse events or additional surgeries were reported. CONCLUSIONS: In LSP-LLIF without facet joint resection or other posterior techniques, static and expandable cages showed comparable effectiveness in achieving increased DH, SL, FA, and indirect decompression.

Analysis of intervertebral disc CCR6 and IL-6 gene levels with short-term postoperative low back pain after spinal fusion in lumbar degenerative disease.

Background: Previous studies have reported that specific pro-inflammatory cytokines or chemokines are more highly expressed in painful than in nonpainful intervertebral discs (IVDs). However, few studies have investigated their correlation with postsurgical outcomes or the relationship between postoperative pain and inflammatory cytokines in IVDs. Thus, the present study examined the correlation among the gene expression levels of pro-inflammatory cytokines and chemokines in IVD tissues removed during surgery and low back pain (LBP), leg pain (LP), and leg numbness (LN) at one year after spinal fusion surgery in patients with a lumbar degenerative disease (LDD). Methods: Chemokine and cytokine gene expression levels were measured in IVD samples from 48 patients with LDD. The associations between chemokine and cytokine gene expression levels and pain intensity (numeric rating scale [NRS]) were also analyzed. A correlation analysis was performed between gene expression in each IVD and preoperative and postoperative pain intensity. Results: In the preoperative analysis, CCR6 was associated with NRSLBP (r = -0.291, P = 0.045). Postoperative pain analysis revealed correlations between postoperative NRSLBP and CCR6 (r = -0.328, P = 0.023) and between postoperative NRSLBP and IL-6 (r = -0.382, P = 0.007). Furthermore, patients with high postoperative LBP intensity (NRSLBP ≥ 7) also had high LBP intensity (NRSLBP ≥ 6) before surgery, and a correlation was observed (r = 0.418, P = 0.003). None of the gene mRNAs correlated with NRSLP or NRSLN, respectively. Conclusions: CCR6 and IL-6 gene expression in the IVD was associated with postoperative LBP intensity and may indicate a need for postoperative pain management.

The Analysis of Preoperative Roussouly Classification on Pain Scores and Radiological Data in Lateral Lumbar Interbody Fusion for Patients with Lumbar Degenerative Disease.

STUDY DESIGN: A retrospective observational study. OBJECTIVE: The type of sagittal profile defined by Roussouly has affected spinal degeneration and surgical outcome. This study aimed to investigate the effect of preoperative Roussouly classification on pain intensity and radiological data of patients with lumbar degenerative disease who underwent indirect decompression with lateral lumbar interbody fusion (LLIF). METHODS: We retrospectively investigated 102 patients who underwent LLIF without direct decompression. Patients were subdivided into 4 groups according to the Roussouly classification determined from preoperative full-length and lateral spine X-rays, and classified according to Roussouly types I, II, and IV in the nonstandard group and Roussouly type III in the standard group. RESULTS: The nonstandard group showed improved sagittal vertical axis and lumbar lordosis after LLIF surgery, but the midsagittal canal diameter and axial central canal area of the thecal sac using T2-weighted sagittal and axial magnetic resonance imaging were smaller than those in the standard group. On the other hand, each numeric rating scale score 1 year after surgery improved in all patients. Changes in numeric rating scale scores in low back pain, leg pain, and numbness were not statistically significant between Roussouly classification types. CONCLUSIONS: These results suggest that the nonstandard group may have less indirect decompression effect from LLIF than the standard group. In the short term, we show for the first time after LLIF surgery that preoperative sagittal spinal alignment and the pelvic position may not significantly impact pain improvement.

Postoperative Radiological Improvement after Staged Surgery Using Lateral Lumbar Interbody Fusion for Preoperative Coronal Malalignment in Patients with Adult Spinal Deformity.

This retrospective observational study evaluated improvement in coronal malalignment (CM) after anteroposterior staged surgery using lateral lumbar interbody fusion (LLIF) in patients with coronal lumbar curve adult spinal deformity (ASD). Sixty patients with ASD underwent surgery; 34 had SRS-Schwab type L lumbar curve. Patients with a coronal balance distance (CBD) ≥20 mm were diagnosed with CM. Using the Obeid CM classification, we classified the preoperative coronal pattern as concave CM (type 1) or convex CM (type 2). Demographic, surgical, and radiological parameters were compared. Whole-spine standing radiographs were assessed preoperatively and postoperatively. Twenty-three patients had type 1A, six had type 2A, five had no CM, and none had type 1B or 2B according to the Obeid CM classification. Compared with patients with Obeid type 1A, those with Obeid type 2A had significantly higher preoperative and postoperative coronal L4 tilts and a smaller change in corrected CBD (Δ|CBD|) (76.6 mm vs. 24.1 mm, p < 0.001). At the final follow-up, 58.6% (17/29 patients) of patients with SRS-Schwab type L CM showed improvement after corrective fusion using LLIF. Although the difference was not statistically significant, CM improved in 69.6% (16/23 patients) of patients with Obeid type 1A type but only 16.7% (1/6 patients) of those with Obeid type 2A type (p = 0.056). CM was more likely to remain after anteroposterior staged surgery using LLIF in patients with preoperative Obeid type 2A ASD.

A novel chondrocyte sheet fabrication using human-induced pluripotent stem cell-derived expandable limb-bud mesenchymal cells.

BACKGROUND: Cell sheet fabrication for articular cartilage regenerative medicine necessitates a large number of chondrocytes of consistent quality as a cell source. Previously, we have developed human-induced pluripotent stem cell (iPSC)-derived expandable PRRX1+ limb-bud mesenchymal cells (ExpLBM) with stable expansion and high chondrogenic capacity, while in this study; our ExpLBM technology was combined with cell sheet engineering to assess its potential as a stable cell source for articular cartilage regeneration. METHODS: ExpLBM cells derived from human-induced pluripotent stem cells (hiPSCs), including 414C2 and Ff-KVs09 (HLA homozygous), were seeded onto a culture plate and two-dimensional chondrogenic induction (2-DCI) was initiated. After 2-DCI, ExpLBM-derived chondrocytes were stripped and transferred to temperature-responsive culture inserts and the chondrocyte sheets were histologically examined or transplanted into osteochondral knee defects of immunodeficient rats. RESULTS: Immunohistochemistry revealed that ExpLBM-derived cell sheets were positive for Safranin O, COL2, and ACAN but that they were negative for COL1 and RUNX2. Furthermore, the engrafted tissues in osteochondral knee defects in immunodeficient rats were stained with SafO, human VIMENTIN, ACAN, and COL2. CONCLUSIONS: The present study is the first to report the chondrocyte sheet fabrication with hiPSC-derived cell source. hiPSC-derived ExpLBM would be a promising cell source for cell sheet technology in articular cartilage regenerative medicine.