Mobile health supported multi-domain recovery trajectories after major arthroplasty or spine surgery: a pilot feasibility and usability study.

BACKGROUND: Recovery after surgery intersects physical, psychological, and social domains. In this study we aim to assess the feasibility and usability of a mobile health application called PositiveTrends to track recovery in these domains amongst participants undergoing hip, knee arthroplasty or spine surgery. Our secondary aim was to generate procedure-specific, recovery trajectories within the pain and medication, psycho-social and patient-reported outcomes domain. METHODS: Prospective, observational study in participants greater than eighteen years of age. Data was collected prior to and up to one hundred and eighty days after completion of surgery within the three domains using PositiveTrends. Feasibility was assessed using participant response rates from the PositiveTrends app. Usability was assessed quantitatively using the System Usability Scale. Heat maps and effect plots were used to visualize multi-domain recovery trajectories. Generalized linear mixed effects models were used to estimate the change in the outcomes over time. RESULTS: Forty-two participants were enrolled over a four-month recruitment period. Proportion of app responses was highest for participants who underwent spine surgery (median = 78, range = 36-100), followed by those who underwent knee arthroplasty (median = 72, range = 12-100), and hip arthroplasty (median = 62, range = 12-98). System Usability Scale mean score was 82 ± 16 at 180 days postoperatively. Function improved by 8 and 6.4 points per month after hip and knee arthroplasty, respectively. In spine participants, the Oswestry Disability Index decreased by 1.4 points per month. Mood improved in all three cohorts, however stress levels remained elevated in spine participants. Pain decreased by 0.16 (95% Confidence Interval: 0.13-0.20, p < 0.001), 0.25 (95% CI: 0.21-0.28, p < 0.001) and 0.14 (95% CI: 0.12-0.15, p < 0.001) points per month in hip, knee, and spine cohorts respectively. There was a 10.9-to-40.3-fold increase in the probability of using no medication for each month postoperatively. CONCLUSIONS: In this study, we demonstrate the feasibility and usability of PositiveTrends, which can map and track multi-domain recovery trajectories after major arthroplasty or spine surgery.

Reduction and Stabilization of an Extension-Distraction Injury in a Patient with Ankylosing Spondylitis: A Case Report.

CASE: The authors reported a case of an 83-year-old man with ankylosing spondylitis throughout the cervical, thoracic, and lumbar spine who sustained a three-column T10 osteoligamentous extension-distraction injury after low-energy trauma. A closed reduction was performed using incremental flexion on a variable flexion-extension table and subsequent stabilization with robotic-assisted percutaneous pedicle screw placement. Postoperative radiographs at 7-month follow-up showed intact implants with adequate alignment with the patient remaining at neurological baseline. CONCLUSION: A closed reduction method using a variable flexion-extension table with stabilization through percutaneous pedicle screw placement is a safe and appropriate method to achieve spinal realignment in select patients.

Heterogeneous macrophages contribute to the pathology of disc herniation induced radiculopathy.

BACKGROUND CONTEXT: Macrophages play important roles in the progression of intervertebral disc herniation and radiculopathy. PURPOSE: To better understand the roles of macrophages in this process, we developed a new mouse model that mimics human radiculopathy. STUDY DESIGN/SETTING: A preclinical randomized animal study. METHODS: Three types of surgeries were performed in randomly assigned Balb/c mice. These were spinal nerve exposure, traditional anterior disc puncture, and lateral disc puncture with nerve exposure (n=16/group). For the nerve exposure group, the left L5 spinal nerve was exposed without disc injury. For the traditional anterior puncture, L5/6 disc was punctured by an anterior approach as previously established. For lateral puncture with nerve exposure, the left L5 spinal nerve was exposed by removing the psoas major muscle fibers, and the L5/6 disc was punctured laterally on the left side with a 30G needle, allowing the nucleus to protrude toward the L5 spinal nerve. Mechanical hyperalgesia (pain sensitivity) of hind paws was assessed with electronic von Frey assay on alternative day for up to 2 weeks. MRI, histology, and immunostaining were performed to confirm disc herniation and inflammation. RESULTS: Ipsilateral pain in the lateral puncture with nerve exposure group was significantly greater than the other groups. Pro-inflammatory cytokines IL-1ß and IL-6 were markedly elevated at the hernia sites of both puncture groups and the spinal nerve of lateral puncture with never exposure group on postoperative day 7. Heterogeneous populations of macrophages were detected in the infiltration tissue of this mouse model and in tissue from patients undergone discectomy. CONCLUSIONS: We have established a new mouse model that mimics human radiculopathy and demonstrated that a mixed phenotype of macrophages contribute to the pathogenesis of acute discogenic radiculopathy. CLINICAL SIGNIFICANCE: This study provides a clinically relevant in vivo animal model to elucidate complex interactions of disc herniation and radicular pain, which may present opportunities for the development of macrophage-anchored therapeutics to manage radiculopathy.

Quantifying Biofield Therapy through Biophoton Emission in a Cellular Model.

Biofield therapy has shown positive results over a broad range of pathology from preclinical research to human studies. However, biofield therapy investigation is limited by an inability to quantify the therapeutic effect. This study aimed to measure the effects Reiki had on mice intervertebral disc (IVD) cells compared with sham and to quantify Reiki by measuring photon emission. We treated mice IVD cells with ten-minute sessions of either Reiki or sham on three successive days. During treatment, we placed the cells in a specifically constructed box with an installed photomultiplier tube (PMT). Reiki significantly increased the photon emission of the cells post-treatment compared with Reiki pre-treatment and sham (p < 0.05). Real time PCR (RT PCR) showed an increase in collagen II and aggrecan (p < 0.05). We present a means to quantify biofield therapy by measuring the post-treatment photon emission. We concurrently demonstrate Reiki's effect on the anabolic healing response.

Animal models for disc degeneration-an update.

Intervertebral disc degeneration is considered a major cause of back pain that places a heavy burden on society, both because of its effect on the physiology of individuals and its consequences on the world economy. During the past few decades, research findings in the pre-clinical setting have led to a significant increase in the understanding of intervertebral disc degeneration, although many aspects of the disease remain unclear. The goal of this review is to summarize existing animal models for disc degeneration studies and the difficulties that are associated with the use of such models. A firm understanding of the cellular and molecular events that ensue as a result of injuries, as well as environmental factors, could be instrumental in the development of targeted therapies for the treatment of intervertebral disc degeneration.

miR-221 attenuates the osteogenic differentiation of human annulus fibrosus cells.

BACKGROUND: In the moderate and end stages of intervertebral disc (IVD) degeneration, endochondral ossifications are found in the IVD. PURPOSE: The aim of this study was to investigate whether endochondral ossification in the late stages of disc degeneration is due to the differentiation of resident progenitor cell in the annulus fibrosus (AF) and the potential signaling pathways in vitro. STUDY DESIGN: This is an in vitro study of AF cell osteogenic differentiation and possible mechanisms METHODS: Normal annulus fibrosus (NAF) and degenerated annulus fibrosus (DAF) cells were isolated from tissue removed surgically from juvenile patients with idiopathic scoliosis and adult patients with degenerative scoliosis. Osteogenic differentiation was investigated using quantitative reverse transcription polymerase chain reaction (RT-PCR) and histology. The effects of miR-221 on osteogenesis were measured by overexpression of miR-221 with lentivirus. BMP2 and phospho-Smad proteins were detected by Western blotting. RESULTS: Both NAF and DAF cells underwent osteogenic differentiation, which was confirmed by detecting mineralization of the cell cultures and by an increase in the expression mRNAs for BMP2, runx2, alkaline phosphatase (ALP), and osteocalcin. DAF cells exhibited increased osteogenic differentiation potential over the NAF cells. By contrast to the elevated phospho-Smads, the basal level of miR-221 significantly decreased in DAF cells compared with that in NAF cells. Cultures of both cell types in osteogenic medium showed a decrease in miR-221 expression, and overexpression of miR-221 markedly decreased the level of BMP2, phospho-Smads, and the expression of osteogenic genes in DAF cells. The osteogenic potential of DAF cells diminished by the overexpression of miR-221. CONCLUSION: Compared with NAF cells, AF cells from degenerated discs have a greater tendency for osteogenic differentiation, which involves the BMP-Smad pathways and can be regulated by miR-221. These observations may be developed into a therapeutic to prevent the endochondral ossification.

The applications of buckminsterfullerene C60 and derivatives in orthopaedic research.

Abstract Buckminsterfullerene C60 and derivatives have been extensively explored in biomedical research due to their unique structure and unparalleled physicochemical properties. C60 is characterized as a "free radical sponge" with an anti-oxidant efficacy several hundred-fold higher than conventional anti-oxidants. Also, the C60 core has a strong electron-attracting ability and numerous functional compounds with widely different properties can be added to this fullerene cage. This review focused on the applications of C60 and derivatives in orthopaedic research, such as the treatment of cartilage degeneration, bone destruction, intervertebral disc degeneration (IVDD), vertebral bone marrow disorder, radiculopathy, etc., as well as their toxicity in vitro and in vivo. We suggest that C60 and derivatives, especially the C60 cores coupled with functional groups presenting new biological and pharmacological activities, are advantageous in orthopaedic research and will be promising in clinical performance for musculoskeletal disorders treatment; however, the pharmacokinetics and toxicology of these agents as local/systemic administration need to be carefully determined.

Fullerol nanoparticles suppress inflammatory response and adipogenesis of vertebral bone marrow stromal cells--a potential novel treatment for intervertebral disc degeneration.

BACKGROUND CONTEXT: Intervertebral disc degeneration, leading to chronic back pain, is a major health problem in western societies. Vertebral bone marrow has been considered to play an important role in nutrition supply and metabolic exchange for discs. Vertebral bone marrow lesions, including fatty marrow replacement and inflammatory edema, noted on magnetic resonance imaging were first described in 1988. PURPOSE: To investigate the potential of a free radical scavenger, fullerol nanoparticles, to prevent vertebral bone marrow lesion and prevent disc degeneration by inhibiting inflammation and adipogenic differentiation of vertebral bone marrow stromal cells (vBMSCs). STUDY DESIGN/SETTING: Fullerol nanoparticle solutions were prepared to test their in vitro suppression effects on mouse vBMSC inflammation and adipogenic differentiation compared with non-fullerol-treated groups. METHODS: With or without fullerol treatment, vBMSCs from Swiss Webster mice were incubated with 10 ng/mL interleukin-1 ß (IL-1 ß). The intracellular reactive oxygen species (ROS) were measured with fluorescence staining and flow cytometry. In addition, vBMSCs were cultured with adipogenic medium (AM) with or without fullerol. Gene and protein expressions were evaluated by real-time polymerase chain reaction and histologic methods. RESULTS: Fluorescence staining and flow cytometry results showed that IL-1 ß markedly increased intracellular ROS level, which could be prevented by fullerol administration. Fullerol also decreased the basal ROS level to 77%. Cellular production of matrix metalloproteinase (MMP)-1, 3, and 13 and tumor necrosis factor alpha (TNF-α) induced by IL-1 ß was suppressed by fullerol treatment. Furthermore, adipogenic differentiation of the vBMSCs was retarded markedly by fullerol as revealed by less lipid droplets in the fullerol treatment group compared with the adipogenic group. The expression of adipogenic genes PPARγ and aP2 was highly elevated with AM but decreased on fullerol administration. CONCLUSIONS: These results suggest that fullerol prevents the catabolic activity of vBMSCs under inflammatory stimulus by decreasing the level of ROS, MMPs, and TNF-α. Also, fat formation in vBMSCs is prevented by fullerol nanoparticles, and, therefore, fullerol may warrant further in vivo investigation as an effective biological therapy for disc degeneration.

Enhancement of matrix production and cell proliferation in human annulus cells under bioreactor culture.

Tissue engineering is a promising approach for treatment of disc degeneration. Herein, we evaluated effects of rotating bioreactor culture on the extracellular matrix production and proliferation of human annulus fibrosus (AF) cells. AF cells were embedded into alginate beads, and then cultured up to 3 weeks in a rotating wall vessel bioreactor or a static vessel. By real-time reverse transcription-polymerase chain reaction, expression of aggrecan, collagen type I and type II, and collagen prolyl 4-hydroxylase II was remarkably elevated, whereas expression of matrix metalloproteinase 3 and a disintegrin and metalloproteinase with thrombospondin motifs 5 was significantly decreased under bioreactor. Biochemical analysis revealed that the levels of the whole cell-associated proteoglycan and collagen were approximately five- and twofolds in rotating bioreactor, respectively, compared to those in static culture. Moreover, AF cell proliferation was augmented in rotating bioreactor. DNA contents were threefolds higher in rotating bioreactor than that in static culture. Expression of the proliferating cell nuclear antigen was robustly enhanced in rotating bioreactor as early as 1 week. Our findings suggested that rotating bioreactor culture would be an effective technique for expansion of human annulus cells for tissue engineering driven treatment of disc degeneration.