Predicting the Occurrence of New Vertebral Fractures Using the Vertebral Bone Quality Score: A Prospective Cohort Study Using 11-Year MRI Follow-up Data from the Minami-Aizu Study.

Background: Previous studies have recognized the potential of the Vertebral Bone Quality (VBQ) score for predicting fractures. However, these studies often have lacked longitudinal perspectives and have not focused on community populations. Our study aimed to enhance the predictive capacity of the VBQ score by investigating its correlation with new vertebral fractures (NVFs) that were detected 11 years later in a community-based cohort and by developing a comprehensive prediction model. Methods: This study was a population-based study conducted in the Minami-Aizu area in Fukushima Prefecture, Japan. One hundred and thirty participants voluntarily underwent T1-weighted magnetic resonance imaging (MRI) of the lumbar spine in 2004 and 2015. VBQ scores were ascertained from the 2004 scans. NVFs that occurred between 2004 and 2015 were detected based on a ≥20% reduction in vertebral height on the midsagittal sections of the MRI. Other predictors that were considered included age, sex, body mass index, smoking history, heart disease, cerebrovascular disease, respiratory disease, and existing vertebral fractures (EVFs). A logistic regression analysis was conducted. Results: The logistic regression analysis indicated that the VBQ score, age, sex, and EVFs were significant predictors of NVFs. The prediction model showed an area under the curve of 0.84, suggesting excellent discriminatory power. The calibration capacity was confirmed using the Hosmer-Lemeshow test. Conclusions: The VBQ score was significantly correlated with the long-term incidence of NVFs in a community population. The prediction model exhibited satisfactory discrimination and calibration capacities, highlighting the use of the VBQ score as a potential tool for long-term prediction of NVFs. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Foot Tapping Test as a Simple Quantitative Index of Motor Function for Lumbosacral Radiculopathy.

STUDY DESIGN: We conducted a retrospective review of data from patients who underwent surgical treatment for lumbosacral radiculopathy. OBJECTIVE: To assess the effectiveness of the foot tapping test (FTT) in evaluating lower limb motor function in patients with lumbosacral radiculopathy pre- and post-surgery. SUMMARY OF BACKGROUND DATA: Lumbosacral radiculopathy is becoming increasingly common in aging populations. Despite standard treatments, paralysis often leads to incomplete postoperative recovery, necessitating early detection and interventions. METHODS: We enrolled individuals who underwent surgery for lumbosacral radiculopathy at our facility between 2009 and 2020. Patients with a history of lumbar surgeries, dialysis, rheumatoid arthritis, and transitional vertebrae were excluded. The FTT score was measured by having the sole of the foot tap as many times as possible for 10 s while keeping the heel in contact with the floor. The L4, L5, and S1 groups were assigned using the scores on the side of the radiculopathy, and the control group was assigned using the scores on the intact side. Data were analyzed using Dunnett's test for group comparisons and paired t-tests for pre-post-surgery comparisons. RESULTS: Of the 522 eligible patients, 80 (159 nerve roots, one patient with hemi-prosthetic leg) were analyzed. The preoperative FTT scores in the L4 and L5 groups were significantly lower than those in the control group, indicating functional impairment. One year post-surgery, all groups showed improvements in FTT scores, with the L5 group exhibiting significant improvements compared to the control; this was supported by the results of sensitivity analyses considering the effects of paralysis and pain. CONCLUSION: The FTT is a valuable tool for the early detection of lower limb motor dysfunction in lumbosacral radiculopathy, particularly for L5 nerve root impairment, where it aids in timely surgical intervention and may improve postoperative outcomes and quality of life.

Walking ability after resection of soft tissue sarcoma of the thigh and the sciatic nerve.

Walking ability may be fairly well maintained after sciatic nerve resection combined with wide resection of soft tissue sarcoma, therefore, surgeons should not hesitate to perform sciatic nerve resection to achieve an adequate surgical margin.

Differences in macrophage expression in induced membranes by fixation method - Masquelet technique using a mouse's femur critical-sized bone defect model.

INTRODUCTION: Masquelet's induced membrane technique (MIMT) is an emerging method for reconstructing critical-sized bone defects. However, an incomplete understanding of the underlying biological and physical processes hinders further optimization. This study investigated the effect of different bone-defect fixation methods on macrophage expression in an induced membrane using a novel mouse plate-fixed Masquelet model. METHODS: Mice were divided into Plate-fixed Masquelet (P-M), Intramedullary-fixed Masquelet (IM-M), Plate-fixed Control (P-C), and Back subfascial (B) groups. In the P-M and IM-M groups, a polymethylmethacrylate (PMMA) spacer was implanted into a 3 mm bone defect, while the defect in the P-C group remained unfilled. In group B, a spacer was inserted under the back fascia to examine membrane formation caused by a simple foreign body reaction. Tissues were collected at 1, 2, and 4 weeks postoperatively. Hematoxylin and eosin (H&E) staining and immunohistochemistry (CD68 and CD163: macrophage markers) were performed to assess macrophage expression within the membrane. qPCR was performed to measure the expression of CD68, CD163, and fibroblast growth factor 2 (FGF2). RESULTS: Four weeks post-operation, the P-M group presented with minimal callus growth, whereas the IM-M group exhibited vigorous growth. The P-M and IM-M groups displayed a tri-layered membrane structure, which is consistent with the results of previous studies. The IM-M group had significantly thicker membranes, whereas the P-M group exhibited higher expression levels of CD68, CD163, and FGF2. Group P-C showed no osteogenesis, whereas group B maintained a thin, cell-dense membrane structure. The P-M group consistently showed higher gene expression levels than the P-C and P-B groups. CONCLUSION: This study introduced a mouse plate fixation model for MIMT. The induced membranes could be adequately evaluated in this model. Induced membranes are formed by foreign body reactions to PMMA spacers; however, their properties are clearly different from those of simple foreign body reaction capsules and granulation tissues that infiltrate bone defects, suggesting that they are more complex tissues. The characteristics and expression of macrophages within these induced membranes varied according to the bone defect fixation method.

Forearm compartment syndrome due to acquired hemophilia that required massive blood transfusions after fasciotomy: A case report.

BACKGROUND: Acquired hemophilia is rare. In some cases, the bleeding in muscle causes compartment syndrome. However, it is not clear whether fasciotomy should be performed for the compartment syndrome caused by acquired hemophilia because of the risk of bleeding and the unknown functional results. CASE SUMMARY: A 75-year-old woman was admitted with severe pain of the right forearm with no preceding traumatic event. The right forearm was obviously swollen, and stretch pain was observed. Subcutaneous hematomas were suspected in various parts of the body. Compartment pressure was 110 mmHg on the volar side. Activated partial thromboplastin time (aPTT) was prolonged to 54.9 s. Fasciotomy was performed, and hematoma was observed in the volar compartment. Postoperative laboratory examinations revealed a low level of factor VIII (FVIII) activity (12.5%) and a high level of FVIII inhibitor (15.2 bethesda units/mL). Acquired hemophilia A was diagnosed. Though recombinant clotting factors were administered, transfusion of red blood cells reached 46 units (140 mL/unit). Hemostasis was achieved 9 d after fasciotomy. The total cost of the clotting factor concentrates administered reached 28834600 yen. With prednisolone, FVIII activity and aPTT recovered gradually. Final function of the hand was good in the index finger and excellent in the others. CONCLUSION: Fasciotomy resulted in good function of the hand in a case of non-traumatic compartment syndrome caused by acquired hemophilia, but life-threatening bleeding occurred, and the cost of clotting factor treatment was high. Preparation of sufficient blood transfusion, preoperative administration of recombinant activated clotting factor VII, and prompt fasciotomy could be ideal for such cases.

Restoration of Elbow Flexion with a Pedicled Latissimus Dorsi Myocutaneous Flap to a Brachial Plexus Injury at the Terminal Nerve Level.

A pedicled latissimus dorsi (LD) myocutaneous flap is a reliable reconstructive method for elbow flexion, though there are no reports regarding its application to a terminal nerve level injury of the brachial plexus. A 29-year-old man presented with dysfunction of elbow flexion, wrist extension, and finger extension. Physical examination and electromyography showed that the palsy was caused by an injury at the terminal nerve level of the brachial plexus without dysfunction of the axillary nerve. Bipolar transfer of LD for reconstruction of elbow flexion and subsequent tendon transfer for wrist and finger extension were performed. The final British Medical Research Council grade was 4 for elbow flexion, and active range of motion was 0/135. An injury at the terminal nerve level of the brachial plexus should be listed in the differential diagnosis of elbow flexion dysfunction even if shoulder function is intact, and a suitable reconstructive method for this atypical type of palsy could be bipolar transfer of a LD flap.

Expression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc: Association with Inflammation and Matrix Remodeling.

Transient receptor potential (TRP) channels have emerged as potential sensors and transducers of inflammatory pain. The aims of this study were to investigate (1) the expression of TRP channels in intervertebral disc (IVD) cells in normal and inflammatory conditions and (2) the function of Transient receptor potential ankyrin 1 (TRPA1) and Transient receptor potential vanilloid 1 (TRPV1) in IVD inflammation and matrix homeostasis. RT-qPCR was used to analyze human fetal, healthy, and degenerated IVD tissues for the gene expression of TRPA1 and TRPV1. The primary IVD cell cultures were stimulated with either interleukin-1 beta (IL-1ß) or tumor necrosis factor alpha (TNF-α) alone or in combination with TRPA1/V1 agonist allyl isothiocyanate (AITC, 3 and 10 µM), followed by analysis of calcium flux and the expression of inflammation mediators (RT-qPCR/ELISA) and matrix constituents (RT-qPCR). The matrix structure and composition in caudal motion segments from TRPA1 and TRPV1 wild-type (WT) and knock-out (KO) mice was visualized by FAST staining. Gene expression of other TRP channels (A1, C1, C3, C6, V1, V2, V4, V6, M2, M7, M8) was also tested in cytokine-treated cells. TRPA1 was expressed in fetal IVD cells, 20% of degenerated IVDs, but not in healthy mature IVDs. TRPA1 expression was not detectable in untreated cells and it increased upon cytokine treatment, while TRPV1 was expressed and concomitantly reduced. In inflamed IVD cells, 10 µM AITC activated calcium flux, induced gene expression of IL-8, and reduced disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and collagen 1A1, possibly via upregulated TRPA1. TRPA1 KO in mice was associated with signs of degeneration in the nucleus pulposus and the vertebral growth plate, whereas TRPV1 KO did not show profound changes. Cytokine treatment also affected the gene expression of TRPV2 (increase), TRPV4 (increase), and TRPC6 (decrease). TRPA1 might be expressed in developing IVD, downregulated during its maturation, and upregulated again in degenerative disc disease, participating in matrix homeostasis. However, follow-up studies with larger sample sizes are needed to fully elucidate the role of TRPA1 and other TRP channels in degenerative disc disease.

Temporal and Spatial Changes of µ-Opioid Receptors in the Brain, Spinal Cord and Dorsal Root Ganglion in a Rat Lumbar Disc Herniation Model.

STUDY DESIGN: Controlled, interventional, animal study. OBJECTIVE: To investigate the spatial and temporal changes of µ-opioid receptor (MOR) expression in a rat lumbar disc herniation (LDH) model. SUMMARY OF BACKGROUND DATA: MORs widely express in the peripheral and central nervous systems, and opioid drugs produce an analgesic effect through their activation. However, the efficacy of opioid drugs is sometimes inadequate in several pathological conditions of pain. MORs in the brain as well as the spinal cord (SC) and dorsal root ganglion (DRG) are thought to be associated with pain-related behavior, but the underlying mechanisms are not completely understood. METHODS: In all, 91 adult female Sprague-Dawley rats were used. Autologous nucleus pulposus (NP) was applied onto the left L5 DRG in the NP group rats. Rats were divided into two surgical groups, the NP and the sham group. The von Frey test of left hind paw was performed before surgery, and 2, 7, 14, 21 and 28 days after surgery. Immunohistochemistry and immunoblotting in the DRG, SC, Caudate putamen, nucleus accumbens (NAc) and periaqueductal grey matter were performed before surgery, and 2, 7, 14, 21 and 28 days after surgery. RESULTS: The thresholds in the NP group were significantly lower than those in the sham group from day 2 onwards. At days 7 and 14, MOR expression in the injured-side SC and DRG were significantly lower than those in the sham group. At day 21, MOR in the NAc was significantly decreased compared to that in the sham group. CONCLUSION: Changes of MOR expression in the NAc, SC and DRG were associated with pain-related behavior. This result might show the underling pathogenesis of the resistance to MOR agonists in the patient with LDH. LEVEL OF EVIDENCE: N/A.

Antibacterial effects of nano-imprinted moth-eye film in practical settings.

BACKGROUND: Recent studies report that surfaces displaying micrometer- or nanometer-sized undulating structures exhibit antibacterial effects. In previous work, we described the use of an advanced nanofabrication technique to generate an artificial biomimetic Moth-eye film by coating a polyethylene terephthalate (PET) film with nanoscale moth-eye protrusions made from a hydrophilic resin. This moth-eye film exhibited enhanced antibacterial effects in in vitro experiments. The aim of the present study was to verify the antibacterial efficacy of the Moth-eye film in practical environments. MATERIALS AND METHODS: The antibacterial effects of three types of film (Moth-eye film, Flat film, and PET film) were compared. Sample films were pasted onto hand washing basins at the testing locations. After several hours, bacteria were collected from the surface of the sample films with one of three kinds of culture media stamper (to permit identification of bacterial species). The stampers were incubated for 48 hours at 35°C, and the numbers of colonies were counted. RESULTS AND DISCUSSION: The number of common bacteria including E. coli and S. aureus obtained from the Moth-eye film was significantly lower than those from the PET film (p<0.05) and Flat film at 1 hour (p<0.05). This study found that the Moth-eye film showed a long-term (6h) antibacterial effect and the Moth-eye structure (PET coated with nanoscale cone-shaped pillars) demonstrated a physical antibacterial effect from earlier time points. Therefore, the Moth-eye film appears to have potential general-purpose applications in practical environments.

p38 MAPK Facilitates Crosstalk Between Endoplasmic Reticulum Stress and IL-6 Release in the Intervertebral Disc.

Degenerative disc disease is associated with increased expression of pro-inflammatory cytokines in the intervertebral disc (IVD). However, it is not completely clear how inflammation arises in the IVD and which cellular compartments are involved in this process. Recently, the endoplasmic reticulum (ER) has emerged as a possible modulator of inflammation in age-related disorders. In addition, ER stress has been associated with the microenvironment of degenerated IVDs. Therefore, the aim of this study was to analyze the effects of ER stress on inflammatory responses in degenerated human IVDs and associated molecular mechanisms. Gene expression of ER stress marker GRP78 and pro-inflammatory cytokines IL-6, IL-8, IL-1ß, and TNF-α was analyzed in human surgical IVD samples (n = 51, Pfirrmann grade 2-5). The expression of GRP78 positively correlated with the degeneration grade in lumbar IVDs and IL-6, but not with IL-1ß and TNF-α. Another set of human surgical IVD samples (n = 25) was used to prepare primary cell cultures. ER stress inducer thapsigargin (Tg, 100 and 500 nM) activated gene and protein expression of IL-6 and induced phosphorylation of p38 MAPK. Both inhibition of p38 MAPK by SB203580 (10 µM) and knockdown of ER stress effector CCAAT-enhancer-binding protein homologous protein (CHOP) reduced gene and protein expression of IL-6 in Tg-treated cells. Furthermore, the effects of an inflammatory microenvironment on ER stress were tested. TNF-α (5 and 10 ng/mL) did not activate ER stress, while IL-1ß (5 and 10 ng/mL) activated gene and protein expression of GRP78, but did not influence [Ca2+]i flux and expression of CHOP, indicating that pro-inflammatory cytokines alone may not induce ER stress in vivo. This study showed that IL-6 release in the IVD can be initiated following ER stress and that ER stress mediates IL-6 release through p38 MAPK and CHOP. Therapeutic targeting of ER stress response may reduce the consequences of the harsh microenvironment in degenerated IVD.

Beauty parlor stroke syndrome due to a bone fragment from an osteophyte of the atlas: case report.

Beauty parlor stroke syndrome (BPSS) is a rare condition characterized by mechanical impingement of a vertebral artery (VA) during neck rotation and/or hyperextension followed by vertebrobasilar insufficiency. However, there have been no reports of BPSS in which the cause of mechanical impingement was identified and no cases for which surgical treatment was reported. The authors report the case of a 56-year-old Japanese man who presented with presyncope that occurred during cervical extension. Given the possibility of vertebrobasilar insufficiency, digital subtraction angiography and CT angiography were performed. These studies revealed that the right VA was hypoplastic and the left VA was dominant. Moreover, in the position of cervical extension, the dominant left VA showed constriction caused by a bone fragment of an osteophyte of the atlas. Removal of the bone fragment was performed. Postoperative left vertebral angiography showed improvement of blood flow in the extended position, and the presyncope completely disappeared. The pathomechanism of this case was a bone fragment compressing the left VA in the C-1 groove during neck extension. In BPSS patients with recurrent transient symptoms, the possibility of this mechanism of VA constriction by a free bone fragment should be considered.

Brain Metabolite Changes in the Anterior Cingulate Cortex of Chronic Low Back Pain Patients and Correlations Between Metabolites and Psychological State.

OBJECTIVES: In chronic low back pain (CLBP) patients, study of altered brain metabolites in the anterior cingulate cortex (ACC) using magnetic resonance spectroscopy (MRS) could reveal the detailed pathology of CLBP and depression. The aim was to detect the central difference between CLBP and controls by means of measuring the metabolites in the ACC, and to analyze the correlations between depression and metabolites in ACC. MATERIALS AND METHODS: MRS was performed in CLBP (n=60) and control participants (n=56) to evaluate the effects of CLBP on metabolites in the ACC and to analyze the correlations between metabolites and questionnaire scores in a cross-sectional study. RESULTS: Adjusting for age and sex, a negative effect of CLBP on the N-acetylaspartate (NAA) level (estimated regression slope coefficient [B]=-0.685, P<0.001) and positive effects on the glutamate +glutamine (Glx)/creatine (B=0.136, P=0.016) and Glx/myoinositol (B=0.140, P<0.048) ratios in the ACC were found. The correlation analysis demonstrated that there was a significant moderate correlation between some questionnaire scores of emotional disorders and metabolites in the ACC of CLBP participants (absolute r>0.4, P<0.05). DISCUSSION: Lower NAA levels and higher Glx/creatine and Glx/myoinositol ratios in the ACC of CLBP participants compared with controls were revealed. The result suggests the hypothesis that excessive Glx leads to neuronal dysfunction and/or death, which was reflected as a low NAA level in the ACC of individuals with CLBP. Measurement of these metabolites using MRS potentially helps evaluate CLBP patients' condition and psychological status objectively.

Measurement of mechanical withdrawal thresholds and gait analysis using the CatWalk method in a nucleus pulposus-applied rodent model.

BACKGROUND: There are some previous reports of gait analysis using a rodent pain model. Applying the CatWalk method, objective measurements of pain-related behavior could be evaluated, but this method has not been investigated using the nucleus pulposus (NP) applied model, which was developed as a model of lumber disc herniation. We aimed to measure mechanical withdrawal thresholds and analyze gait patterns using the CatWalk method for the evaluation of the pain-related behavior caused by NP application. METHODS: Twenty-four nine-week-old female Sprague-Dawley rats were randomly divided into two experimental groups, the NP group (n = 12), in which autologous NP from the tail was applied to the left L5 dorsal root ganglion, and the sham-operated group (n = 12). Measurements of mechanical withdrawal thresholds were performed using von Frey filaments touching the left footpads, and gait analysis was performed using the CatWalk method. These experiments were conducted 1 day before surgery and 7, 14, 21, and 28 days after surgery. Data were statistically analyzed using the Wilcoxon rank-sum test. RESULTS: The NP group showed significantly lower withdrawal thresholds than the sham group at days 14 and 21. Stand (duration of contact of a paw with the glass plate) was significantly higher in the NP group at days 7 and 14, whereas step cycle (duration between two consecutive initial contacts of the same paw) and duty cycle (stand as a percentage of step cycle) were the same at day 7. Long initial dual stance (duration of ground contact for both hind paws simultaneously, but the first one in a step cycle of a target hind paw) of the right hind paw was measured at days 7 and 14. The left hind paw per right hind paw ratio of the stand index (speed at which the paw loses contact with the glass plate) and mean intensity (mean intensity of the complete paw) changed at day 7 or 14. Phase dispersion (parameter describing the temporal relationship between placement of two paws) of the hind paws decreased at day 7. CONCLUSIONS: Rats with applied NP showed a decreased withdrawal threshold and abnormal gait. The differences in gait parameters between the NP and sham groups were observed at an earlier time point than the withdrawal thresholds. Gait analysis could be an effective method for understanding pain caused by applied NP.

Investigation of the Effect of Diabetes on Radiculopathy Induced by Nucleus Pulposus Application to the DRG in a Spontaneously Diabetic Rat Model.

STUDY DESIGN: A controlled, interventional animal study. OBJECTIVE: The aim of this study was to evaluate the effect of diabetes mellitus (DM) on radiculopathy due to lumbar disc herniation (LDH), by investigating pain-related behavior and the expression of tumor necrosis factor-alpha (TNF-α) and growth-associated protein 43 (GAP43) in type 2 diabetic rats following application of nucleus pulposus (NP) to the dorsal root ganglion (DRG). SUMMARY OF BACKGROUND DATA: Previous clinical studies suggested negative effects of DM on radiculopathy due to LDH, and that inflammation and nerve regeneration could interact with DM and radiculopathy. METHODS: We applied autologous NP to the left L5 DRG of adult male Wistar rats and Goto-Kakizaki rats. Behavioral testing measured the mechanical withdrawal threshold of rats. We immunohistochemically evaluated the localization of ionized calcium-binding adapter molecule-1 (Iba-1), receptor of advanced glycation end products (RAGE), and TNF-α in DRGs. TNF-α and GAP43 expression levels in DRG were determined by quantitative real-time PCR and western blotting. RESULTS: The mechanical withdrawal threshold significantly declined in the non-DM NP group compared with the non-DM sham group for 28 days, whereas the decline in threshold extended to 35 days in the DM NP group compared with the DM sham group. RAGE and TNF-α expression in DRGs was colocalized in Iba-1 positive cells. The non-DM NP rats had higher TNF-α protein expression levels versus the non-DM sham rats on day 7, and the DM NP group had higher levels versus the DM sham group on days 7 and 14. The non-DM NP group had higher GAP43 mRNA expression than the non-DM sham group for 28 days, while the DM NP group had a higher level than the DM sham group for 35 days. CONCLUSION: DM prolongs the pain-related behavior caused by NP. The prolonged inflammation and nerve regeneration could elucidate the pathogenesis of continuous pain of radiculopathy initiated by LDH. LEVEL OF EVIDENCE: N /A.