Spine Tissue Research Articles

Coxiella burnetii caused lumbar infection: A case report and literature review

Coxiella burnetii (C. burnetii)is a significant microbe linked to the zoonotic disease Q fever, known for its atypical clinical manifestations and sporadic cases. It can cause lumbar infections. In this report, we present a 66-year-old male sheep farmer who experienced low back pain for five months, with worsening numbness in both lower limbs over two months. Several standard diagnostic tests were negative. Metagenomic next-generation sequencing (mNGS) was performed on lumbar spine tissue obtained via biopsy, identifying C. burnetii infection. After surgical excision of the lesion, the patient received a combination of levofloxacin, doxycycline, rifampicin, and supportive medications. Postoperatively, the patient's condition stabilized, showing a significant reduction in low back pain. This case highlights mNGS as a valuable tool for diagnosing rare infections, especially in patients with a history of animal exposure. It underscores the importance of considering zoonotic infections and the need for combined antibiotic and surgical management in suspected cases.

Lumbar spine marker placement errors and soft tissue artifact during dynamic flexion/extension and lateral bending in individuals with chronic low back pain

Quantitative in vivo biomechanical assessments are typically performed with optoelectronic motion capture (MoCap) using retroreflective markers attached to skin. This technique inherently contains measurement errors from both marker placement on palpated bony landmarks and skin motion relative to the underlying bone (i.e., soft tissue artifact (STA)). Research on lumbar spine STA is scarce and limited to young, healthy participants in static positions. This study aimed to evaluate static placement errors, lumbar spine STA from MoCap marker clusters (MMC), and linear relationships between STA and patient characteristics. Thirty-nine participants with cLBP performed three trials each of flexion/extension and lateral bending while imaged simultaneously by MoCap (120 Hz) and dynamic biplane radiography DBR (20 Hz). MMCs were placed 29.5 ± 18.0 mm and 27.1 ± 13.4 mm superior to the most prominent aspect of the L1 and L5 spinous process, respectively. L1 relative to L5 STA was larger during flexion/extension (8.6 ± 5.7°) than lateral bending (4.5 ± 2.1°) (p < 0.001). After correcting for marker placement errors, components of the L1 and L5 STA averaged as much as 16.3 mm and 11.4° during flexion/extension, but only 4.0 mm and 4.8° or less during lateral bending. On average, STA for individual L1 and L5 vertebrae increased as participants moved away from the upright neutral position. STA was participant-dependent, however, age and BMI did not model STA well. Given the inaccuracy in marker placement and wide range of patterns of STA, caution is urged when making clinical decisions or when using computational models to estimate spine tissue loading based upon lumbar spine kinematics obtained from skin-mounted markers.

The utility of disc space and vertebral body specimens cell count differential for the diagnosis of native vertebral osteomyelitis: a prospective cohort study.

Diagnostic methods for native vertebral osteomyelitis (NVO) often yield inconclusive results. Image-guided spine biopsies for culture are specific but diagnose NVO in only 50% of cases. Pre-exposure to antimicrobials further reduces diagnostic yield. Our study assesses the value of neutrophil percentage in disc space fluid and vertebral body (DS/VB) samples for diagnosing NVO. Adults referred for spine biopsy at Mayo Clinic from August 2022 to September 2023 were consented and enrolled at the time of biopsy. Following routine specimen collection, the biopsy needle was rinsed in saline into an EDTA tube for cell analysis. NVO diagnosis required organism identification in spine tissue or blood and/or positive histopathology, and consistent symptoms and imaging. Sixty-eight patients were prospectively enrolled, comprising 14 with NVO and 54 with alternative diagnoses. The median biopsy sample polymorphonuclear (PMN) percentage for NVO patients was 80.5% (IQR 72.5-85.2), compared to 64.5% (IQR 54.0-69.0) for those without NVO (p < 0.001). Nine (64.3%) NVO patients received antibiotics within 10 days prior to spine biopsy. As a continuous measure, PMN differential showed a moderately strong ability in classifying NVO status with an area under ROC curve of 0.795; an optimal point on the curve of 71.5% corresponded to a sensitivity of 78.6%, specificity of 79.6%, negative predictive value of 93.5% and positive predictive value of 50.0%. PMN differential in DS/VB biopsies may serve as an effective diagnostic tool in the evaluation of patients with NVO particularly in ambiguous cases with an initially negative spine biopsy. Future efforts will aim to implement these findings within routine clinical practice.

Flexible support material maintains disc height and supports the formation of hydrated tissue engineered intervertebral discs in vivo.

Mechanical augmentation upon implantation is essential for the long-term success of tissue-engineered intervertebral discs (TE-IVDs). Previous studies utilized stiffer materials to fabricate TE-IVD support structures. However, these materials undergo various failure modes in the mechanically challenging IVD microenvironment. FlexiFil (FPLA) is an elastomeric 3D printing filament that is amenable to the fabrication of support structures. However, no present study has evaluated the efficacy of a flexible support material to preserve disc height and support the formation of hydrated tissues in a large animal model. We leveraged results from our previously developed FE model of the minipig spine to design and test TE-IVD support cages comprised of FPLA and PLA. Specifically, we performed indentation to assess implant mechanical response and scanning electron microscopy to visualize microscale damage. We then implanted FPLA and PLA support cages for 6 weeks in the minipig cervical spine and monitored disc height via weekly x-rays. TE-IVDs cultured in FPLA were also implanted for 6 weeks with weekly x-rays and terminal T2 MRIs to quantify tissue hydration at study endpoint. Results demonstrated that FPLA cages withstood nearly twice the deformation of PLA without detrimental changes in mechanical performance and minimal damage. In vivo, FPLA cages and stably implanted TE-IVDs restored native disc height and supported the formation of hydrated tissues in the minipig spine. Displaced TE-IVDs yielded disc heights that were superior to PLA or discectomy-treated levels. FPLA holds great promise as a flexible and bioresorbable material for enhancing the long-term success of TE-IVD implants.

Prevalence of cervical dysfunction in those referred for treatment of vertigo or dizziness

BACKGROUND: Cervical spine dysfunction has been shown to cause symptoms of dizziness and vertigo in patients, due to its connection to the vestibular system. There is a sparsity of prospective studies describing the prevalence of cervical involvement in these patients. OBJECTIVE: To identify the prevalence of cervical mobility restrictions in patients with symptoms of dizziness and vertigo prospectively. METHODS: Eighty-two subjects referred to physical therapy were assessed for mobility restrictions from the Atlanto-occipital joint to the level of C5 using evidenced-based manual techniques. These techniques included the seated and supine cervical flexion rotation tests and posterior to anterior joint mobility assessments. RESULTS: The prevalence of cervical mobility restrictions was 72% overall. Restrictions were found in 70% of those referred for dizziness/vertigo, 64% with benign paroxysmal positional vertigo (BPPV) and 90% of those referred for concussion. None of the referring providers had considered cervical involvement prior to making the referral. CONCLUSIONS: Afferent input from the muscles, joint and connective tissues in the cervical spine can cause the symptoms associated with dizziness, vertigo and concussion. This prospective study demonstrates the high prevalence of cervical mobility restrictions in these patients. This study provides much needed evidence for the need for early manual assessment of the cervical spine and surrounding structures if an appropriate rehabilitation program is to be designed. Physical therapists, athletic trainers and those who care for patients with complaints of dizziness, vertigo, BPPV or concussion should assess their patient for mobility restrictions early on in the evaluation process and treat accordingly.

A Multidisciplinary Approach to Swallowing Rehabilitation in Patients with Forward Head Posture.

(1) Background and Objectives: The forward head posture (FHP) is characterized by increased extensions of upper cervical vertebrae and flexion of the lower cervical vertebrae and upper thoracic regions, associated with muscle shortening. The compressive loading on the tissues in the cervical spine negatively impacts suprahyoid and infrahyoid muscles and generates increased tension of the masticatory muscles. The tongue has relations with the suprahyoid and the infrahyoid muscles. The pattern of swallowing evolves gradually from birth to the age of four. If this developmental transition does not occur, the result is persistent infantile or atypical swallowing-an orofacial myofunctional disorder with the tongue in improper position during swallowing, causing strain and stress on the jaw, face, head and neck. In FHP, muscles crucial to swallowing are biomechanically misaligned. The lengthening of the suprahyoid muscles necessitates stronger contractions to achieve proper hyolaryngeal movement during swallowing. This study assesses the added benefits of physiotherapy to the traditional myofunctional swallowing rehabilitation for patients with FHP. The underlying hypothesis is that without addressing FHP, swallowing rehabilitation remains challenged and potentially incomplete. (2) Materials and Methods: A total of 61 participants (12-26 years) meeting the inclusion criteria (FHP and atypical swallowing) were divided into two similar groups. Group A attended one orofacial myofunctional therapy (OMT) and one physiotherapy session per week, group B only one OMT session per week, for 20 weeks. Exclusion criteria were as follows: ankyloglossia, neurological impairment affecting tongue and swallowing, cervical osteoarticular pathology, other previous or ongoing treatments for FHP and atypical swallowing. (3) Results: There is a significant improvement in terms of movement and use of the orofacial structures (tongue, lips, cheeks), as well as in breathing and swallowing in both groups. Group A achieved better outcomes as the CVA angle was directly addressed by manual therapy and GPR techniques. (4) Conclusions: The combined therapy proved to be more effective than single OMT therapy.

Crown-of-thorns starfish spines secrete defence proteins.

The crown-of-thorns starfish (COTS; Acanthaster species) is a slow-moving corallivore protected by an extensive array of long, sharp toxic spines. Envenomation can result in nausea, numbness, vomiting, joint aches and sometimes paralysis. Small molecule saponins and the plancitoxin proteins have been implicated in COTS toxicity. Brine shrimp lethality assays were used to confirm the secretion of spine toxin biomolecules. Histological analysis, followed by spine-derived proteomics helped to explain the source and identity of proteins, while quantitative RNA-sequencing and phylogeny confirmed target gene expression and relative conservation, respectively. We demonstrate the lethality of COTS spine secreted biomolecules on brine shrimp, including significant toxicity using aboral spine semi-purifications of >10 kDa (p>0.05, 9.82 µg/ml), supporting the presence of secreted proteins as toxins. Ultrastructure observations of the COTS aboral spine showed the presence of pores that could facilitate the distribution of secreted proteins. Subsequent purification and mass spectrometry analysis of spine-derived proteins identified numerous secretory proteins, including plancitoxins, as well as those with relatively high gene expression in spines, including phospholipase A2, protease inhibitor 16-like protein, ependymin-related proteins and those uncharacterized. Some secretory proteins (e.g., vitellogenin and deleted in malignant brain tumor protein 1) were not highly expressed in spine tissue, yet the spine may serve as a storage or release site. This study contributes to our understanding of the COTS through functional, ultrastructural and proteomic analysis of aboral spines.

Cutibacterium acnes in spine tissue: characteristics and outcomes of non-hardware-associated vertebral osteomyelitis.

Cutibacterium acnes isolation from spine tissue can be challenging because the organism can represent a contaminant. There is a paucity of data regarding the role of C.acnes in non-hardware-associated vertebral osteomyelitis (VO). Herein we evaluate the clinical and microbiological characteristics, treatment, and outcome of patients with C.acnes VO. Data were retrospectively collected from adults with a positive spine culture for C.acnes at Mayo Clinic, Rochester (MN), from 2011 to 2021. Patients with spinal hardware and polymicrobial infections were excluded. Of the subjects, 16 showed radiological and clinical findings of VO: 87.5 % were male, the average age was 58years ( SD), and back pain was the predominant symptom. Of the lesions, 89.5 % involved the thoracic spine. Of the subjects, 69 % had experienced an antecedent event at the site of VO. In five subjects, C.acnes was isolated after 7 d of anaerobic culture incubation. Thirteen subjects were treated with parenteral -lactams, and three with oral antimicrobials, without any evidence of recurrence. Twenty-one subjects were not treated for VO, as C.acnes was considered a contaminant; at follow-up, none had evidence of progressive disease. C.acnes should be part of microbiological differential diagnosis in patients with suspected VO, especially in the context of a prior spinal procedure. Anaerobic spine cultures should undergo prolonged incubation to enable recovery of C.acnes. C.acnes VO may be managed with oral or parenteral antimicrobial therapy. Without clinical and radiological evidence of VO, a single positive culture of C.acnes from spine tissue frequently represents contaminants.

Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain

Spine degeneration is an aging-related disease, but its molecular mechanisms remain unknown, although elevated β-catenin signaling has been reported to be involved in intervertebral disc degeneration. Here, we determined the role of β-catenin signaling in spinal degeneration and in the homeostasis of the functional spinal unit (FSU), which includes the intervertebral disc, vertebra and facet joint and is the smallest physiological motion unit of the spine. We showed that pain sensitivity in patients with spinal degeneration is highly correlated with β-catenin protein levels. We then generated a mouse model of spinal degeneration by transgenic expression of constitutively active β-catenin in Col2+ cells. We found that β-catenin-TCF7 activated the transcription of CCL2, a known critical factor in osteoarthritic pain. Using a lumbar spine instability model, we showed that a β-catenin inhibitor relieved low back pain. Our study indicates that β-catenin plays a critical role in maintaining spine tissue homeostasis, its abnormal upregulation leads to severe spinal degeneration, and its targeting could be an avenue to treat this condition.

Toward the Identification of Distinct Phenotypes: Research Protocol for the Low Back Pain Biological, Biomechanical, and Behavioral (LB3P) Cohort Study and the BACPAC Mechanistic Research Center at the University of Pittsburgh.

As a member of the Back Pain Consortium (BACPAC), the University of Pittsburgh Mechanistic Research Center's research goal is to phenotype chronic low back pain using biological, biomechanical, and behavioral domains using a prospective, observational cohort study. Data will be collected from 1,000 participants with chronic low back pain according to BACPAC-wide harmonized and study-specific protocols. Participation lasts 12 months with one required in person baseline visit, an optional second in person visit for advanced biomechanical assessment, and electronic follow ups at months 1, 2, 3, 4, 5, 6, 9, and 12 to assess low back pain status and response to prescribed treatments. Behavioral data analysis includes a battery of patient-reported outcomes, social determinants of health, quantitative sensory testing, and physical activity. Biological data analysis includes omics generated from blood, saliva, and spine tissue. Biomechanical data analysis includes a physical examination, lumbopelvic kinematics, and intervertebral kinematics. The statistical analysis includes traditional unsupervised machine learning approaches to categorize participants into groups and determine the variables that differentiate patients. Additional analysis includes the creation of a series of decision rules based on baseline measures and treatment pathways as inputs to predict clinical outcomes. The characteristics identified will contribute to future studies to assist clinicians in designing a personalized, optimal treatment approach for each patient.

Protocol for Biospecimen Collection and Analysis Within the BACPAC Research Program.

The Biospecimen Collection and Processing Working Group of the National Institutes of Health (NIH) HEAL Initiative BACPAC Research Program was charged with identifying molecular biomarkers of interest to chronic low back pain (cLBP). Having identified biomarkers of interest, the Working Group worked with the New York University Grossman School of Medicine, Center for Biospecimen Research and Development-funded by the Early Phase Pain Investigation Clinical Network Data Coordinating Center-to harmonize consortium-wide and site-specific efforts for biospecimen collection and analysis. Biospecimen collected are saliva, blood (whole, plasma, serum), urine, stool, and spine tissue (paraspinal muscle, ligamentum flavum, vertebral bone, facet cartilage, disc endplate, annulus fibrosus, or nucleus pulposus). The omics data acquisition and analyses derived from the biospecimen include genomics and epigenetics from DNA, proteomics from protein, transcriptomics from RNA, and microbiomics from 16S rRNA. These analyses contribute to the overarching goal of BACPAC to phenotype cLBP and will guide future efforts for precision medicine treatment.

Ethnicity and Fracture Risk Stratification from Trabecular Bone Score in Canadian Women: The Manitoba BMD Registry

Lumbar spine Trabecular Bone Score (TBS), a grey-level texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. An unresolved and controversial question is whether there are ethnic differences that affect the utility of TBS for fracture risk assessment. The current analysis examined whether self-identified ethnicity (White, Asian, Black) in women age 40 years and older referred for DXA testing affected fracture risk stratification from TBS using a large clinical registry. The study population comprised 63,078 White women, 1,915 Asian women and 329 Black women (n=329) with mean follow up 9.0±5.2 years. There were between group differences in BMI (Black>White>Asian), lumbar spine fat percentage (Asian>White>Black) and lumbar spine tissue thickness (Black>White>Asian). Despite this, lumbar spine TBS was not significantly different between the subgroups, though there was a significant difference in lumbar spine and total hip BMD (Black >White>Asian). TBS provided significant stratification for MOF and any fracture for all ethnicity subgroups, and for hip fracture in White and Asian subgroups (insufficient numbers for analysis in Black women). No significant difference in White vs. Asian or White vs. Black women were identified using a Bonferroni adjusted p-value. In summary, we found that lumbar spine TBS measurements were similar among White, Asian and Black women referred for DXA assessment in Manitoba, Canada. TBS and BMD measurements significantly stratified fracture risk in all three populations without a meaningful difference between groups. This suggests that TBS does not need to be used differently in White vs. non-White populations.

Intermittent Short-Term Infusion vs. Continuous Infusion of Piperacillin: Steady State Concentrations in Porcine Cervical Spine Tissue Evaluated by Microdialysis.

Background: Piperacillin is a central drug in the treatment of Pseudomonas aeruginosa spondylodiscitis. Intermittent short-term infusion (STI) remains standard treatment in most centres, although the application of continuous infusion (CI) has shown promising results in other clinical settings. We aimed to evaluate time above the minimal inhibitory concentration (fT > MIC) of the free fraction of piperacillin in steady state conditions in porcine cervical spine tissue following CI and STI using microdialysis with MIC targets of 4, 8, and 16 g/mL. Methods: 16 female pigs were randomized to receive piperacillin/tazobactam as STI (4/0.5 g every 6 h) or CI (4/0.5 g as a bolus followed by 12/1.5 g) for 18 h. Microdialysis catheters were placed for sampling of piperacillin concentrations from the intervertebral disc, vertebral cancellous bone, paravertebral muscle, and adjacent subcutaneous tissue during the third dosing interval (12–18 h). Blood samples were collected as reference. Results: CI resulted in fT > MIC > 82% across all compartments and targets, except for intervertebral disc (37%) and vertebral cancellous bone (28%) at MIC = 16 g/mL. In Group STI, >72% fT > MIC was reached for MIC = 4 g/mL in all investigated compartments, while for MIC = 16 g/mL only subcutaneous tissue exhibited fT > MIC > 50%. Conclusion: CI of piperacillin resulted in higher fT > MIC compared to STI infusion across the investigated tissues and targets. CI should therefore be considered in spondylodiscitis cases requiring piperacillin treatment.

Mechanically induced histochemical and structural damage in the annulus fibrosus and cartilaginous endplate: a multi-colour immunofluorescence analysis.

The annulus fibrosus (AF) and endplate (EP) are collagenous spine tissues that are frequently injured due to gradual mechanical overload. Macroscopic injuries to these tissues are typically a by-product of microdamage accumulation. Many existing histochemistry and biochemistry techniques are used to examine microdamage in the AF and EP; however, there are several limitations when used in isolation. Immunofluorescence may be sensitive to histochemical and structural damage and permits the simultaneous evaluation of multiple proteins-collagen I (COL I) and collagen II (COL II). This investigation characterized the histochemical and structural damage in initially healthy porcine spinal joints that were either unloaded (control) or loaded via biofidelic compression loading. The mean fluorescence area and mean fluorescence intensity of COL II significantly decreased (- 54.9 and - 44.8%, respectively) in the loaded AF (p ≤ 0.002), with no changes in COL I (p ≥ 0.471). In contrast, the EP displayed similar decreases in COL I and COL II fluorescence area (- 35.6 and - 37.7%, respectively) under loading conditions (p ≤ 0.027). A significant reduction (-31.1%) in mean fluorescence intensity was only observed for COL II (p = 0.043). The normalized area of pores was not altered on the endplate surface (p = 0.338), but a significant increase (+ 7.0%) in the void area was observed on the EP-subchondral bone interface (p = 0.002). Colocalization of COL I and COL II was minimal in all tissues (R < 0.34). In conclusion, the immunofluorescence analysis captured histochemical and structural damage in collagenous spine tissues, namely, the AF and EP.

Anatomical prior based vertebra modelling for reappearance of human spines

Scoliosis is a disease caused by deformation of the spine, and precise imaging of human spine tissues is crucial and instructive for the subsequent treatment. Currently, radiographs are clinically used to monitor disease progress. However, radiation exposure is a safety concern and is undesirable for regular monitoring during rehabilitation intervention. In this study, we developed a novel technique to generate the 3D structure of human spine from a tracked freehand ultrasound scanning. First of all, we designed an approach for detection and location of every vertebra in the spine by firstly detecting the vertebral landmarks from the ultrasound B-scan sequence, then computing the size, location and posture of every vertebra and finally using a method of interpolation to form the whole spine according to the prior knowledge of vertebral anatomical structure. Deep learning based object detection methods were used to find the landmarks of the vertebrae, and those landmarks were then clustered to model every vertebra (i.e. computing its location, posture and real size). Due to the situations where the vertebra is not clearly seen, we therefore used the technique of interpolation to estimate the location of those missing vertebrae with respect to the anatomical prior. In addition, we reconnected all vertebral models and reappeared the whole spine in 3D space. With that, the Cobb angle could be easily measured. The phantom and in vivo experiments were also conducted to further verify the precision of the proposed approaches. The results have demonstrated its feasibility in the clinical practice of adolescent idiopathic scoliosis patients (R2 = 0.9780,p < 0.001), which is beneficial for the regular quantitative monitoring of disease progression.

Impact of the mouse estrus cycle on cannabinoid receptor agonist-induced molecular and behavioral outcomes.

Sexual dimorphisms are observed in cannabinoid pharmacology. It is widely reported that female animals are more sensitive to the cataleptic, hypothermic, antinociceptive, and anti‐locomotive effects of cannabinoid receptor agonists such as CP55,940. Despite awareness of these sex differences, there is little consideration for the pharmacodynamic differences within females. The mouse estrus cycle spans 4–5 days and consists of four sex hormone‐mediated phases: proestrus, estrus, metestrus, and diestrus. The endocannabinoid system interacts with female sex hormones including β‐estradiol, which may influence receptor expression throughout the estrus cycle. In the current study, sexually mature female C57BL/6 mice in either proestrus or metestrus were administered either 1 mg/kg i.p. of the cannabinoid receptor agonist CP55,940 or vehicle. Mice then underwent the tetrad battery of behavioral assays measuring catalepsy, internal body temperature, thermal nociception, and locomotion. Compared with female mice in metestrus, those in proestrus were more sensitive to the anti‐nociceptive effects of CP55,940. A similar trend was observed in CP55,940‐induced catalepsy; however, this difference was not significant. As for cannabinoid receptor expression in brain regions underlying antinociception, the spine tissue of proestrus mice that received CP55,940 exhibited increased expression of cannabinoid receptor type 1 relative to treatment‐matched mice in metestrus. These results affirm the importance of testing cannabinoid effects in the context of the female estrus cycle.

Optimization of a lumbar interspinous fixation device for the lumbar spine with degenerative disc disease.

Interspinous spacer devices used in interspinous fixation surgery remove soft tissues in the lumbar spine, such as ligaments and muscles and may cause degenerative diseases in adjacent segments its stiffness is higher than that of the lumbar spine. Therefore, this study aimed to structurally and kinematically optimize a lumbar interspinous fixation device (LIFD) using a full lumbar finite element model that allows for minimally invasive surgery, after which the normal behavior of the lumbar spine is not affected. The proposed healthy and degenerative lumbar spine models reflect the physiological characteristics of the lumbar spine in the human body. The optimum number of spring turns and spring wire diameter in the LIFD were selected as 3 mm and 2 turns, respectively—from a dynamic range of motion (ROM) perspective rather than a structural maximum stress perspective—by applying a 7.5 N∙m extension moment and 500 N follower load to the LIFD-inserted lumbar spine model. As the spring wire diameter in the LIFD increased, the maximum stress generated in the LIFD increased, and the ROM decreased. Further, as the number of spring turns decreased, both the maximum stress and ROM of the LIFD increased. When the optimized LIFD was inserted into a degenerative lumbar spine model with a degenerative disc, the facet joint force of the L3-L4 lumbar segment was reduced by 56%–98% in extension, lateral bending, and axial rotation. These results suggest that the optimized device can strengthen the stability of the lumbar spine that has undergone interspinous fixation surgery and reduce the risk of degenerative diseases at the adjacent lumbar segments.

Investigating the Feasibility of In Vivo Perfusion Imaging Methods for Spinal Cord Using Hyperpolarized [13C]t-Butanol and [13C,15N2]Urea

This study examined the feasibility of using two novel agents, hyperpolarized [13C]t-butanol and [13C,15N2]urea, for assessing in vivo perfusion of the intact spinal cord in rodents. Due to their distinct permeabilities to blood brain barrier (BBB), we hypothesized that [13C]t-butanol and [13C,15N2]urea exhibit unique 13C signal characteristics in the spinal cord. Dynamic 13C t-butanol MRI data were acquired from healthy Long-Evans rats using a symmetric, ramp-sampled, partial-Fourier 13C echo-planar imaging sequence after the injection of hyperpolarized [13C]t-butanol solution. In subsequent scans, dynamic 13C urea MRI data were acquired after the injection of hyperpolarized [13C,15N2]urea. The SNRs of t-butanol and urea were calculated for regions corresponding to spine, supratentorial brain, and blood vessels and plotted over time. Mean peak SNR and AUC were calculated from the dynamic plots for each region and compared between t-butanol and urea. In spine and supratentorial brain, the mean peak SNR and AUC of t-butanol were significantly higher than those of urea (p < 0.05). In contrast, urea was predominantly contained within vasculature and exhibited significantly higher levels of mean peak SNR and AUC compared to t-butanol in blood vessels (p < 0.05). This study has demonstrated the feasibility of using hyperpolarized [13C]t-butanol and [13C,15N2]urea for assessing in vivo perfusion in cervical spinal cord. Due to differences in blood-brain barrier permeability, t-butanol rapidly crossed the blood-brain barrier and diffused into spine and brain tissue, while urea predominantly remained in vasculature. The results from this study suggest that this technique may provide unique non-invasive imaging tracers that are able to directly monitor hemodynamic processes in the normal and injured spinal cord.

Changes in the related indicators of bone formation and bone resorption in severely burned rats

Objective: To observe the changes in the related indicators of bone formation and bone resorption in severely burned rats. Methods: The experimental research method was adopted. Thirty female Sprague-Dawley rats aged 6 to 8 weeks were divided into sham injury group, 12% total body surface area (TBSA) full-thickness burn group, and 24%TBSA full-thickness burn group according to the random number table, with 10 rats in each group. The rats were treated on the back correspondingly, after which, the burned rats were rehydrated by intraperitoneal injection according to the Parkland formula, and the wound was coated with 20 g/L iodophor until wound healing. On post injury day (PID) 28, the tibia tissue of rats in each group was collected. The new bone tissue and the number of osteoclasts were observed after staining with Masson and tartrate-resistant acid phosphatase, respectively. The abdominal aortic blood of rats in each group was harvested for serum preparation. The bone metabolism indexes of serum calcium ion and phosphorus ion concentration were determined by the methyl thymol blue colorimetric method and phosphomolybdic acid method, respectively. The serum levels of bone formation marker of aminoterminal propeptide of type 1 procollagen (P1NP) and bone resorption marker of beta-carboxy-terminated peptide of type Ⅰ collagen (β-CTX) were determined by enzyme-linked immunosorbent assay. The first lumbar spine tissue of rats in each group was collected, and the mRNA expression levels of osteoprotegerin, receptor activator of nuclear factor-κB ligand (RANKL), tumor necrosis factor receptor-associated factor 6 (TRAF-6), nuclear factor of activated T cell 1 (NFATC1), c-Fos, and c-Src were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction. Data were statistically analyzed with one-way analysis of variance, Bonferroni method, Welch test, Games-Howell test, Kruskal-Wallis test, Mann-Whitney U test, and Bonferroni correction. Results: On PID 28, compared with that in sham injury group, the formation of new bone tissue in the tibia tissue of rats in the two burn groups was decreased, and the larger the burn area, the more obvious the decrease. The numbers of osteoclasts in the tibia tissue of rats in the two burn groups were similar, both significantly more than the number in sham injury group. On PID 28, the serum calcium ion concentration and serum level of β-CTX of rats in the three groups were similar (P>0.05). The serum phosphorus ion concentration of rats in 24%TBSA full-thickness burn group was significantly higher than that in 12%TBSA full-thickness burn group (P<0.05), and the serum phosphorus ion concentrations in the two burn groups were significantly higher than the concentration in sham injury group (P<0.01). The serum level of P1NP of rats in 24%TBSA full-thickness burn group was significantly lower than that in sham injury group (P<0.01). On PID 28, the mRNA expression levels of osteoprotegerin in the first lumbar spine tissue of rats in sham injury group, 12%TBSA full-thickness burn group, and 24%TBSA full-thickness burn group were 1.01±0.20, 1.71±0.83, and 2.24±0.51, respectively, and that in 24%TBSA full-thickness burn group was significantly higher than that in sham injury group (P<0.01). The mRNA expression level of RANKL in the first lumbar spine tissue of rats in 24%TBSA full-thickness burn group was 1.31±0.17, which was significantly higher than 1.00±0.14 in sham injury group and 0.97±0.10 in 12%TBSA full-thickness burn group (P<0.01). The mRNA expression levels of TRAF-6, NFATC1 (Z=3.141, 3.782), and c-Src in the first lumbar tissue of rats in 12%TBSA full-thickness burn group and 24%TBSA full-thickness burn group and the mRNA expression level of c-Fos in the first lumbar tissue of rats in 12%TBSA full-thickness burn group were significantly higher than those in sham injury group (P<0.05 or P<0.01). The mRNA expression levels of c-Fos and c-Src in the first lumbar spine tissue of rats in 12%TBSA full-thickness burn group were significantly higher than those in 24%TBSA full-thickness burn group (P<0.01). Conclusions: Severe burns can cause a decrease in the generation of new bone tissue, an increase in the number of osteoclasts and the serum phosphorus ion concentration, and a decrease in the serum level of P1NP in rats. The level of osteoprotegerin, RANKL, TRAF-6, NFATC1, c-Fos, and c-Src in bone tissue showed an increasing trend while the level of NFATC1, c-Fos, and c-Src showed a decreasing trend with the increase of burn area.

A randomized trial on the application of a nurse-led early rehabilitation program after minimally invasive lumbar internal fixation

Lumbar degenerative disease (LDD) is a narrowing of the spinal canal and intervertebral foramina caused by aging and degeneration of lumbar spine tissue. Minimally invasive internal lumbar spine fixation is emerging in the treatment of LDD. However, no standard early rehabilitation protocol for orthopedic robot-assisted minimally invasive internal lumbar spine fixation exits. To investigate the effect of a nurse-led early rehabilitation program in the postoperative recovery of patients with lumbar degenerative lesions undergoing orthopedic robot-assisted minimally invasive lumbar internal fixation. Eighty patients with minimally invasive orthopedic robot-assisted lumbar degenerative lesions admitted to our hospital between January 2019 and January 2021 were recruited to this study. The patients were randomly allocated to a control group (n=40), involving conventional care, and an observation group (n=38; 40 initially and 2 later excluded) including a nurse-led early rehabilitation program added on the basis of the control group. The primary outcomes were the general postoperative conditions, scores of daily living ability, the degree of low back pain and functional recovery. Participants were also compared in terms of their compliance with the care regimen and the incidence of complications. Participants in the observation group had a significantly shorter first time on the floor after surgery (P<0.001) and shorter hospital stay (P=0.003). Meanwhile, participants in the observation group had higher Barthel index (BI) scores (P=0.039), lower visual analogue scale (VAS) scores (P=0.028), and Oswestry disability index (ODI) scores (P=0.002) at 3 days postoperatively, and there was no difference in the three scores between the two groups at 1 month postoperatively (all P>0.05). The compliance of participants in the observation group was significantly higher than that of the control group (P<0.001). Participants in the observation group were less likely to experience constipation (P=0.043) and bloating (P=0.012) within 1 month after surgery. Implementation of a nurse-led early rehabilitation program in patients undergoing orthopedic robotic-assisted minimally invasive treatment of lumbar degenerative lesions can significantly improve patient compliance, significantly shorten postoperative flooring and hospitalization time, reduce the incidence of gastrointestinal adverse events, and accelerate postoperative recovery. Chinese Clinical Trial Registry ChiCTR2100048698.