Enriched Peripheral Blood-Derived Mononuclear Cells for Treating Knee Osteoarthritis.

Osteoarthritis (OA) is a common chronic skeletal disease in the elderly. There is no effective therapy to reverse disease severity and knee OA (KOA) progression, particularly at the late stage. This study aims to examine the effect of peripheral blood-derived mononuclear cells (PBMNCs) on pain and motor function rescue in patients with Kellgren-Lawrence (KL) grade II to IV KOA. Participants received one intra-articular (IA) injection of autologous PBMNCs. The mononuclear cells were isolated from peripheral blood, enriched by a specialized medium (MoFi medium), and separated by Ficoll-Paque solution. The isolated and enriched PBMNCs could differentiate into M1 and M2 macrophages in vitro. The in vivo anti-inflammatory effect of the PBMNCs was similar to that of bone marrow mesenchymal stem cells, evaluated by complete Freund's adjuvant-induced arthritis in rodents. A single-arm and open-label pilot study showed that patients' knee pain and motor dysfunction were significantly attenuated after the cell transplantation, assessed by visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 and 12 months post-treatment. Notably, the therapeutic effect of the PBMNCs treatment can be stably maintained for 24 months, as revealed by the KOOS scores. These preclinical and pilot clinical data suggest that IA injection of MoFi-PBMNCs might serve as a novel medical technology to control the pain and the progress of KOA.

Deviating from the Recommended Torque on Set Screws Can Reduce the Stability and Fatigue Life of Pedicle Screw Fixation Devices.

Background and Objectives: Using an appropriate torque to tighten set screws ensures the long-term stability of spinal posterior fixation devices. However, the recommended torque often varies between different devices and some devices do not state a recommended torque level. The purpose of this study is to evaluate the effect of set screw torque on the overall construct stability and fatigue life. Materials and Methods: Two commercial pedicle screw systems with different designs for the contact interface between the set screw and rod (Group A: plane contact, Group B: line contact) were assembled using torque wrenches provided with the devices to insert the set screws and tighten to the device specifications. The axial gipping capacity and dynamic mechanical stability of each bilateral construct were assessed in accordance with ASTM F1798 and ASTM F1717. Results: Increasing or decreasing the torque on the set screw by 1 Nm from the recommended level did not have a significant effect on the axial gripping capacity or fatigue strength of Group A (p > 0.05). For Group B, over-tightening the set screw by 1 Nm did cause a significant reduction in the fatigue strength. Conclusions: Excessive torque can damage the rod surface and cause premature failure. When insertion using a manual driver is preferred, a plane contact interface between the set screw and rod can reduce damage to the rod surface when the set screw is over-torqued.

Radiofrequency neurotomy in chronic lumbar and sacroiliac joint pain: A meta-analysis.

BACKGROUND: Effective treatment of low back pain (LBP) originating in the lumbar and sacroiliac joints is difficult to achieve. The objective of the current study was to compare the clinical effectiveness of radiofrequency (RF) neurotomy versus conservative nonsurgical approaches for the management of chronic lumbar and sacroiliac joint pain. METHODS: The PICOS framework was adhered to (P [population]: patients with a history of chronic function-limiting lumbar and sacroiliac joint pain lasting at least 6 months; I [intervention]: RF neurotomy; C [comparator]: other nonsurgical treatments; O [outcomes]: the Oswestry Disability Index (ODI), measurement for pain, and a quality of life (QoL) questionnaire; S [study design]: meta-analysis). Two trained investigators systematically searched Medline, Cochrane, EMBASE, and ISI Web of Knowledge databases for relevant studies published in English through March 2019. RESULTS: Patients treated with RF neurotomy (n = 528) had significantly greater improvement in ODI scores, pain scores and QoL measured by EQ-5D compared with controls (n = 457); however, significant heterogeneity was observed when data were pooled from eligible studies. In subgroup analyses, patients who received RF neurotomy had a significantly greater improvement in ODI scores compared with those with sham treatment. Patients treated with RF achieved significantly greater improvement in pain scores compared with controls who received sham treatment or medical treatment. In a subgroup analysis of pain in the sacroiliac joint and in lumbar facet joints, the RF neurotomy group achieved a significantly greater improvement in ODI score and pain scores compared with the control group. The ODI score and pain score were improved after 2 months of follow up in the analyses stratified by follow-up duration. CONCLUSIONS: Use of RF neurotomy as an intervention for chronic lumbar and sacroiliac joint pain led to improved function; however, larger, more directly comparable studies are needed to confirm this study's findings.

Magnesium-responsive genes are downregulated in diabetic patients after a three-month exercise program on a bicycle ergometer.

BACKGROUND: Exercise is an effective therapy for the management of diabetes because it helps regulate glucose and magnesium homeostasis. Nevertheless, the mechanisms by which exercise exerts effects on magnesium transport remain unclear. This study investigated the expression of genes encoding magnesium transporters (GMTs) after a three-month exercise program in diabetic patients. METHODS: This study was conducted with a within-subject pre-post design. A total of 15 adult patients with type 2 diabetes mellitus (T2DM) were recruited and underwent a three-month indoor bicycle exercise program. The expression of five GMTs (CNNM2, TRPM6, TRPM7, SLC41A1, and SLC41A3) was determined in blood samples. Relevant anthropometric values and biochemical parameters were also determined. RESULTS: Although the body weight and body mass index decreased after three months exercise, there were no significant differences. Fasting blood glucose, glycated hemoglobin (HbA1c), waist circumference, and magnesium levels decreased after the exercise program (p < 0.05). The expression of SLC41A1 and SLC41A3 were downregulated after exercise, but only CNNM2, TRPM6, and TRPM7 showed significantly decreased expression levels compared with those before the exercise program (p < 0.05). CONCLUSION: The three-month exercise program ameliorated blood glucose levels and downregulated the expression of magnesium-responsive genes in patients with T2DM.

The effect of annular repair on the failure strength of the porcine lumbar disc after needle puncture and punch injury.

PURPOSE: The purpose was to quantify the structural integrity of annulus fibrosis (AF) after injuries with repair. METHODS: Punctures in the AF of 6-month-old porcine spine specimens were made with 18-, 20-, 22-, 24-, and 26-gauge needles. Leakage testing was performed immediately after needle puncture (Group 1), after the puncture was repaired with a modified purse-string suture (MPSS) (Group 2), and after needle puncture with immediate repair (Group 3). Punch injuries repaired with the MPSS alone, or with an AF graft and MPSS were also examined. RESULTS: There was no leakage from 26-gauge needle punctures. Pressures at which the nucleus pulposus leaked from the 24-, 22-, 20- and 18-gauge needle punctures (Group 1) were 4.28, 2.03, 1.27, and 1.06 MPa, respectively. Failure pressure after repair (Group 2, 3) was significantly greater than without (Group 1). Failure pressure in Group 3 was much greater than in Group 2 with 18- and 20-gauge punctures. Punch injury repaired with a graft and MPSS had significantly greater failure pressure than repair with MPSS alone (1.88 vs. 1.02 MPa, p = 0.0001). CONCLUSIONS: The MPSS can restore the mechanical integrity of the AF after needle puncture. An annular graft along with a MPSS may increase the structural integrity of the AF after a punch injury. As this was an acute animal study, the measurements and results may not directly translate to the human intervertebral disc.

The effects of different articulate curvature of artificial disc on loading distribution.

PURPOSE: Deeper insights into the mechanical behavior of lumbar disc prostheses are required. Prior studies on the biomechanical performance of artificial discs were mostly performed with finite element analyses, but this has never been analyzed with altering articulate curvature. This study aimed to ascertain the influence of the geometry of a ball-and-socket disc prosthesis for the lumbar spine. MATERIALS AND METHODS: Three-dimensional finite element model of human L4-L5 was reconstructed. Convex, concave, and elliptic artificial disc models were also established with Computer-Aided-Design software. Simulations included: (1) three articulate types of polyethylene (PE) insert were implanted inferiorly and (2) concave and convex PE inserts were implanted on the superior or inferior sides in flexion/extension, lateral bending, and axial rotation in the lumbar spine. Shear stresses and von Mises stresses on PE insert were assessed for their loading distributions. RESULTS: High shear stresses of all articulate types occurred in flexion, and convex PE insert performed the maximum stress of 23.81 MPa. Under all conditions, stresses on concave PE inserts were distributed more evenly and lower than those on the convex type. Elliptic geometry enabled confining the rotation of the motion unit. The shear force on the convex PE insert on the inferior side could induce transverse crack because the shear stress exceeded yielding shear stress. CONCLUSIONS: The concave PE insert on the inferior side not only decreased loading concentration but had relatively low stress. Such a design may be applicable for artificial discs.

Retaining intradiscal pressure after annulotomy by different annular suture techniques, and their biomechanical evaluations.

BACKGROUND: The adverse effects of annulotomy during lumbar discectomy have been increasingly recognized, and methods are developing to repair the annular defect. Biomechanically, the repair should retain the intra-nuclear pressure, which is doubtful using the current suture techniques. Therefore, a new suture technique was designed and tested to close a simpler type of annular incision. METHODS: A new suture technique, the modified purse-string suture, was introduced into a re-validated nonlinear finite element human disk model after creating a standard transverse slit incision, as well as two other suture techniques: either two simple sutures, or a horizontal crossed suture, and compared their contact pressure on the cleft contact surface. Then, porcine lumbar endplate-disk-endplate complexes with transverse slit incisions were repaired using the three techniques. Quantitative discomanometry was then applied to compare their leakage pressure, as a parameter of disk integrity. FINDINGS: In finite element model, the new technique created the greatest contact pressure along the suture range (the outer annulus), and generated a minimum contact pressure at the critical point, which was 68% and 55% higher than the other two suture techniques. In quantitative discomanometry, the new suture technique also had an average leakage pressure of 85% and 49% higher than the other two suture techniques. INTERPRETATION: The modified purse-string suture can generate higher contact pressure than the other two techniques at finite element analysis and in realistic animal models, which aids in retaining intra-discal pressure, and should be encouraged in clinical practice.

Monostotic Vertebral Paget's Disease of the Lumbar Spine.

Paget's disease in the Far East is quite rare. Age at diagnosis is usually greater than 50 years, and the disease typically affects the spine. Most patients are usually diagnosed with Paget's disease following radiographic examination for other purposes. It usually occurs at multiple vertebral levels, with only 10-25% of vertebral Paget's disease being monostotic. The disease rarely causes neurologic complications resulting from compression of intraspinal nerve tissue. Here, we present 2 cases of monostotic vertebral Paget's disease of the third lumbar vertebra. The first patient, who may be the first documented case of Paget's disease in the lumbar spine with progressive neurologic deficiency in an Asian population, received decompressive laminectomy due to marked spinal stenosis with neurologic deficits. The symptoms were greatly relieved following surgery, and ambulatory ability was restored. The second patient was diagnosed with Paget's disease following surgical biopsy. He remained asymptomatic at the most recent follow-up.

Comparison of cage application modality in posterior lumbar interbody fusion with posterior instrumentation--a finite element study.

BACKGROUND: Posterior lumbar interbody fusion (PLIF) cages have achieved satisfactory fusion results, but cases of cage migration or mechanical failure were repeatedly reported. Therefore, we conducted a finite element study to determine the impact of cage applications including number, positioning, and adding posterior instrumentation (PI). METHODS: A finite element model of the lumbar spine was generated from Computer Tomography scans and was validated. Partial laminectomy, diskectomy with partial facetectomy, and single or double-cage insertion were simulated onto the model, with or without posterior pedicle screws instrumentation. The maximal von Mises stresses between different loading conditions were compared between modalities to evaluate the risks of migration or mechanical failure. RESULTS: Posterior instrumentation decreases at least half the distortion stress of cage-endplate interface and facet joints, and diminishes the differences between the stresses of inserting one or two cages. Based on one cage insertion, adding posterior instrumentation provides more efficient stability than an additional cage. Furthermore, an obliquely inserted cage with posterior instrumentation produced lower stress than a cage inserted on one side due to better structural symmetry. Conclusively, one oblique anterior cage and bilateral posterior pedicle screws reconstructed the tripod system as the intact disc and facet joints, and provided similar stability as two cages did.

Anterior cervical fusion using a polyetheretherketone cage containing a bovine xenograftp: three to five-year follow-up.

STUDY DESIGN: Retrospective review of an anterior polyetheretherketone (PEEK) cage incorporated with a bovine xenograft to treat disorders of the cervical disc. OBJECTIVE: To assess the achievement of fusion by PEEK cage with xenograft radiographically and clinically when used to perform ACDF. SUMMARY OF BACKGROUND DATA: Anterior cervical discectomy and fusion is the therapy of choice for degenerative disc disorders of the cervical spine. Although cage device increases initial stability of the levels treated, fusion is the key factor for satisfactory results. Filling the cage devices with autologous iliac bone grafts enable achievement of the best fusion result. Although the volume of harvested bone graft is minimal, donor-site morbidity is still a complication of concern. To avoid this adverse issue, we used a new bovine xenograft in place of autologous bone graft. METHODS: Fifty-six patients (33 men and 23 women aged 31-78 years) underwent anterior cervical discectomy and fusion using PEEK cage with a bovine xenograft bone substitute to treat symptomatic cervical disorders. Radiographic and clinical results were assessed over 3 to 5 years of follow up. RESULTS: Almost all patients had symptomatic improvement, and 84% reported good-to-excellent satisfaction. All cases achieved solid fusion, confirmed by radiographs and computed tomography, but cage subsidence occurred at 8 levels. CONCLUSION: As applied in anterior cervical fusion, the cage incorporated with the xenograft prevented donor-site morbidity and provided successful fusion.

Isoflavones prevent bone loss following ovariectomy in young adult rats.

Soy protein, a rich source of phytoestrogens, exhibit estrogen-type bioactivity. The purpose of this study was to determine if ingestion of isoflavones before ovariectomy can prevent bone loss following ovariectomy. Twenty-four nulliparous Wistar rats were randomly divided into four groups. In the normal diet groups, a sham operation was performed on Group A, while ovariectomy was performed on Group B. For Groups C and D, all rats were fed with an isoflavone-rich (25 mg/day) diet for one month, then bilateral ovariectomy were performed. In the rats in Group C, a normal diet was begun following the ovariectomy. The rats in Groups D continued to receive the isoflavone-rich diet for two additional months postoperatively. All rats were sacrificed 60 days after surgery. The weight of bone ash of the long bones and whole lumbar spine were determined. A histological study of cancellous bone was done and biochemical indices of skeletal metabolism were performed and analyzed. The markers of bone metabolism exhibited no significant changes. When compared with the sham-operated rats fed a normal diet, the bone mass of ovariectomized rats decreased significantly; pre-ovariectomy ingestion of an isoflavone-rich diet did not prevent bone loss. The bone mass of rats treated with an isoflavone-rich diet for three months was higher than controls two months after ovariectomy. Dietary isoflavones did not prevent the development of post-ovariectomy bone loss, but long-term ingestion of an isoflavone-rich diet increased the bone mineral contents after ovariectomy in young rats.

Effects of shock waves on tenocyte proliferation and extracellular matrix metabolism.

The shock wave is an effective noninvasive modality for resolving various tendon pathologies. However, scientific rationale and mechanism of shock wave therapy remains limited. This study aims to investigate the effects of shock waves and their biochemical mechanisms on tenocyte proliferation and collagen synthesis. Tenocytes harvested from Achilles tendons of Sprague-Dawley rats were used in this study. Cell viability was assayed by trypan blue exclusion methods. The colorimetric assay was determined to evaluate the mitochondria activity of the tenocytes after shock wave exposure. Synthesis of collagen, nitric oxide (NO) and transforming growth factor-beta1 (TGF-beta1) were determined and their gene expression was also studied. The results showed that there was a dose-dependent impairment of cell viability observed in 0.36 mJ/mm2 and 0.68 mJ/mm2 stimulation. In the proliferation assay, low energy level with low impulses (0.36 mJ/mm2 with 50 and 100 impulses) showed positive stimulatory effects, whereas the high energy level with high impulses (0.68 mJ/mm2 with 250 and 500 impulses) had significant inhibitory effects. At 0.36 mJ/mm2, 100 impulse shock waves treatment, up-regulation of proliferating cell nuclear antigen (PCNA) (at 6 and 24 h) and collagen type I, collagen type III and TGF-beta1 gene expression (at 24 h) were observed; these were followed by the increases in NO production (at 24 h), TGF-beta1 release (at 48 and 96 h) and collagen synthesis (at the 7th day). This study revealed that shock waves can stimulate tenocyte proliferation and collagen synthesis. The associated tenocyte proliferation is mediated by early up-regulation of PCNA and TGF-beta1 gene expression, endogenous NO release and synthesis and TGF-beta1 protein and then collagen synthesis.