Comparison of minimally invasive transforaminal lumbar interbody fusion and midline lumbar interbody fusion in patients with spondylolisthesis.

BACKGROUND: This study aimed to compare surgical outcomes, clinical outcomes, and complications between minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) and midline lumbar interbody fusion (MIDLIF) in patients with spondylolisthesis. METHODS: This study retrospectively compared the patients who underwent MIS TLIF (n = 37) or MIDLIF (n = 50) for spinal spondylolisthesis. Data of surgical outcomes (postoperative one-year fusion rate and time to bony fusion), clinical outcomes (visual analog scale [VAS] for pain and Oswestry Disability Index [ODI] for spine function), and complications were collected and analyzed. RESULTS: There was more 2-level fusion in MIDLIF (46% vs. 24.3%, p = 0.038). The MIS TLIF and MIDLIF groups had similar one-year fusion rate and time to fusion. The MIDLIF group had significantly lower VAS at postoperative 3-months (2.2 vs. 3.1, p = 0.002) and postoperative 1-year (1.1 vs. 2.1, p = < 0.001). ODI was not significantly different. The operation time was shorter in MIDLIF (166.1 min vs. 196.2 min, p = 0.014). The facet joint violation is higher in MIS TLIF (21.6% vs. 2%, p = 0.009). The other complications were not significantly different including rate of implant removal, revision, and adjacent segment disease. CONCLUSION: In this study, postoperative VAS, operation time, and the rate of facet joint violation were significantly higher in the MIS TLIF group. Comparable outcomes were observed between MIDLIF and MIS TLIF in terms of fusion rate, time to fusion, and postoperative ODI score.

Preclinical Animal Study and Pilot Clinical Trial of Using Enriched Peripheral Blood-Derived Mononuclear Cells for Intervertebral Disc Degeneration.

Low back pain (LBP) is a leading cause of long-term disability globally. Intervertebral disk degeneration (IVDD) is mainly responsible for discogenic pain in LBP-affected young patients. There is no effective therapy to reverse disease severity and IVDD progression. This study investigates the effect of human peripheral blood-derived mononuclear cells (PBMCs) on pain relief and life quality improvement in IVDD patients. The enriched monocytes of the PBMCs could differentiate into CD14 and CD206 double-positive M2 macrophages in vitro. Preclinical evidence in rats showed that the transplanted PBMCs exhibited anti-inflammatory and moderate tissue-repair effects on controlling IVDD progress in the rat model. The PBMCs significantly steered the aggrecan and type II collagen expressions and attenuated the pro-inflammatory cytokines in the affected disk. Based on the animal results, 36 patients with chronic low back pain (CLBP) were included in clinical trials. The control group was conservative care only, and the experimental group was platelet-rich plasma (PRP) and PBMCs intradiscal injections. We first confirmed the single lumbar disk causing the discogenic pain by provocative discography or magnetic resonance imaging (MRI). Discogenic LBP participants received one intradiscal injection of autologous PBMCs and followed for 6 months. Our clinical trial showed that patients' LBP and disability were significantly ameliorated after the PBMCs transplantation rather than PRP. These preclinical and pilot clinical studies indicate that intradiscal injection of the enriched PBMCs might be a feasible and potential cell therapy to control pain and disability in IVDD patients.

Minimal amount of exercise prevents incident dementia in cognitively normal older adults with osteoarthritis: a retrospective longitudinal follow-up study.

Robust evidence suggests that regular exercise, including walking more than 6000 steps, is effective for preventing dementia; however, such activity is less feasible in older people with osteoarthritis (OA) or other motor disabilities. Therefore, we aimed to test whether the minimal amount of exercise (MAE) could help prevent dementia in older adults with OA. A retrospective longitudinal study was performed and a non-demented cohort (≥ 50-years-old) of 242 people (155 [64.0%] non-converters and 87 [36.0%] converters) from three centers in Taiwan was analyzed with a mean follow-up of 3.1 (range 0.3-5.9) and 2.9 (range 0.5-6.0) years, respectively. MAE was defined as walking for approximately 15-30 min or 1500-3000 steps. Rate of MAE (0, 1-2, or ≥ 3) within one week were defined as MAE-no, MAE-weekly, or MAE-daily, respectively. The incidence rates of dementia were compared between groups. Multivariate logistic regression and Cox proportional hazards analyses were used to study the influence of MAE on dementia occurrence. Age, education, sex, activities of daily living, neuropsychiatric symptoms, cognition, multiple vascular risk factors, and related medications were adjusted. Compared to the MAE-no group, the odds ratios for the incidents of dementia were 0.48 and 0.19 in the MAE-weekly and MAE-daily groups, respectively. In addition, older age, poorer cognition, poorer ADL performance, and congestive heart failure increased the incidence of dementia. Daily and weekly MAE prevented dementia in older adults with OA. As such, an informative public health policy may help promote adequate exercise in at-risk groups.

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.

Induction of type II collagen expression in M2 macrophages derived from peripheral blood mononuclear cells.

The human type II collagen (Col II), specifically expressed in chondrocytes, is a crucial component of the adult hyaline cartilage. We examine the potential of artificial induction of Col II in human peripheral blood mononuclear cells (PBMNCs) as a novel Col II provider. Human PBMNCs were purified and were treated with high doses of macrophage-colony stimulating factor (M-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), or granulocyte-colony stimulating factor (G-CSF) and examined the Col II expression at indicated days. Quantitative Col II expression was validated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and flow cytometry. We demonstrate that monocytes in PBMNCs can be artificially induced to express both Col II proteins and M2 macrophage markers by the high concentration of colony-stimulating factors, especially M-CSF and GM-CSF. The Col II proteins were detected on the cell membrane and in the cytoplasm by flow cytometry and immunocytostaining. Combination with IL-4 provided a synergistic effect with M-CSF/GM-CSF to trigger Col II expression in M2 macrophages. These CD206 and Col II double-expressing cells, named modified macrophages, share M2 macrophages' anti-inflammatory potency. We demonstrated that the modified macrophages could significantly attenuate the inflammatory progress of Complete Freund's adjuvant (CFA)-induced arthritis and collagen-induced arthritis in rodents. Here, we provide the first evidence that a modified macrophage population could ectopically express Col II and control the progress of arthritis in animals.

The efficacy of oral vitamin D supplements on fusion outcome in patients receiving elective lumbar spinal fusion-a randomized control trial.

BACKGROUND: Previous studies have reported that vitamin D supplement could improve fracture healing, but evidence regarding the role of vitamin D supplements in spinal fusion was limited. Thus, this study aimed to evaluate the effectiveness of oral vitamin D supplements on fusion outcomes in patients undergoing lumbar spinal fusion. METHODS: This randomized, double-blind, parallel-designed, active-control trial included the patients who planned for elective lumbar spinal fusion. Eligible patients were randomly assigned to receive either daily vitamin D3 (cholecalciferol) 800 IU and daily calcium citrate 600 mg (experimental group) or only daily calcium citrate 600 mg (control group). All supplements were given from postoperative day 1 and lasted for 3 months. Primary outcome was postoperative 1-year fusion rate, and secondary outcomes included time to fusion, Oswestry Disability Index (ODI), and visual analogue scale (VAS) for pain. RESULTS: Among the included 34 patients (21 in the experimental group and 13 in the control group), baseline 25-hydroxyvitamin D (25[OHVitD) level was 26.7 (10.4) ng/ml. Preoperative prevalence of vitamin D deficiency and insufficiency were 23.5% and 47.1%, respectively. Postoperative 1-year fusion rate was not significantly different between the two groups (95.2% vs. 84.6%, P = 0.544). The experimental group had significantly shorter time to fusion (Kaplan-Meier estimated: 169 days vs. 185 days [interquartile range: 88-182 days vs. 176-324 days], log-rank test: P = 0.028), lower postoperative 6-month ODI (P < 0.001), and lower postoperative 6-month VAS (P < 0.001) than the control group. Time to fusion was significantly and negatively correlated with preoperative, postoperative 3-month, and 6-month 25(OH)VitD levels (all P < 0.01). CONCLUSION: The patient with vitamin D supplements had shorter time to fusion, better spinal function and less pain after elective spinal fusion. Further research is warranted to identify the patients who can benefit the most from vitamin D supplements and the appropriate dose of vitamin D supplements. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05023122. Registered 20 August 2021. Retrospectively registered, http://clinicaltrials.gov/ct2/show/NCT03793530 .

Numerical Comparison of Restored Vertebral Body Height after Incomplete Burst Fracture of the Lumbar Spine.

BACKGROUND AND OBJECTIVES: Vertebral compression fracture is a major health care problem worldwide due to its direct and indirect negative influence on health-related quality of life and increased health care costs. Although a percutaneous surgical intervention with balloon kyphoplasty or metal expansion, the SpineJack, along with bone cement augmentation has been shown to efficiently restore and fix the lost vertebral height, 21-30% vertebral body height loss has been reported in the literature. Furthermore, the effect of the augmentation approaches and the loss of body height on the biomechanical responses in physiological activities remains unclear. Hence, this study aimed to compare the mechanical behavior of the fractured lumbar spine with different restored body heights, augmentation approaches, and posterior fixation after kyphoplasty using the finite element method. Furthermore, different augmentation approaches with bone cement and bone cement along with the SpineJack were also considered in the simulation. MATERIALS AND METHODS: A numerical lumbar model with an incomplete burst fracture at L3 was used in this study. Two different degrees of restored body height, namely complete and incomplete restorations, after kyphoplasty were investigated. Furthermore, two different augmentation approaches of the fractured vertebral body with bone cement and SpineJack along with bone cement were considered. A posterior instrument (PI) was also used in this study. Physiological loadings with 400 N + 10 Nm in four directions, namely flexion, extension, lateral bending, and axial rotation, were applied to the lumbar spine with different augmentation approaches for comparison. RESULTS: The results indicated that both the bone cement and bone cement along with the SpineJack could support the fractured vertebral body to react similarly with an intact lumbar spine under identical loadings. When the fractured body height was incompletely restored, the peak stress in the L2-L3 disk above the fractured vertebral body increased by 154% (from 0.93 to 2.37 MPa) and 116% (from 0.18 to 0.39 MPa), respectively, in the annular ground substance and nucleus when compared with the intact one. The use of the PI could reduce the range of motion and facet joint force at the implanted levels but increase the facet joint force at the upper level of the PI. CONCLUSIONS: In the present study, complete restoration of the body height, as possible in kyphoplasty, is suggested for the management of lumbar vertebral fractures.

Musculoskeletal injuries and management of victims from collapsed buildings in the 2016 Taiwan earthquake: Experiences in a tertiary medical center.

BACKGROUND: Previous studies have seldom focused on injury patterns, especially musculoskeletal injuries, caused by building collapse during earthquakes. The aim of this study was to investigate the musculoskeletal injury profiles and management of patients rescued from collapsed buildings in the 2016 Taiwan earthquake. METHODS: We conducted a retrospective study using the electronic medical record (EMR) system. We enrolled 31 patients rescued from specific collapsed buildings (the WJ group) and 56 patients injured in the same earthquake as a control group. We investigated the admission history, injury profile, treatment, and outcomes for these patients. RESULTS: The WJ group (51%) had significantly higher admission rates compared to the control group (25%) (p = 0.012). Although the odds ratio (OR) of fracture incidence was lower in the WJ group (OR: 0.79), there was a higher OR of multiple fractures (OR: 2.617) and axial skeletal fractures (OR: 2.893 for vertebral fracture, and OR: 1.893 ribs for rib fractures) in the WJ group. Among the 28 fracture patients, 9 (32.1%) underwent surgical interventions. A higher incidence of rhabdomyolysis was noted in the WJ group (OR: 34.73). Also, all 5 rhabdomyolysis cases combined with acute kidney injury were in the WJ group, and 1 of them required emergent hemodialysis for severe hyperkalemia. CONCLUSION: Patients extricated from collapsed buildings have a higher incidence of multiple fractures and axial skeletal fractures. More severe soft tissue injuries, including rhabdomyolysis and compartment syndrome, were also identified. The medical system should develop rescue and treatment strategies for this rare situation.

Design and synthesis of 4-anilinoquinazolines as Raf kinase inhibitors. Part 1. Selective B-Raf/B-RafV600E and potent EGFR/VEGFR2 inhibitory 4-(3-hydroxyanilino)-6-(1H-1,2,3-triazol-4-yl)quinazolines.

This paper presents the design and synthesis of 4-(3-hydroxyanilino)-6-(1H-1,2,3-triazol-4-yl)quinazolines of scaffold 9 as selective B-Raf/B-RafV600E and potent EGFR/VEGFR2 kinase inhibitors. Total 14 compounds of scaffold 9 having different side chains at the triazolyl group with/without fluoro substituents at the anilino group were synthesized and investigated. Among them, 9m with a 2-carbamoylethyl side chain and C-4'/C-6' difluoro substituents was the most potent, which selectively inhibited B-Raf (IC50: 57 nM) and B-RafV600E (IC50: 51 nM) over C-Raf (IC50: 1.0 µM). Compound 9m also actively inhibited EGFR (IC50: 73 nM) and VEGFR2 (IC50: 7.0 nM) but not EGFRT790M and PDGFR-ß (IC50: >10 µM). Despite having good potency for B-Raf and B-RafV600E in the enzymatic assays, 9m was less active to inhibit melanoma A375 cells which proliferate due to constitutively activated B-Raf600E. The inferior activity of 9m for A375 was similar to that of sorafenib (6), suggesting that 9m might bind to the inactive conformations of B-Raf and B-RafV600E. Docking simulations could thus be performed to reveal the binding poses of 9m in B-Raf, B-RafV600E, and VEGFR2 kinases.

Computational comparison of bone cement and poly aryl-ether-ether-ketone spacer in single-segment posterior lumbar interbody fusion: a pilot study.

Posterior lumbar interbody fusion (PLIF) with a spacer and posterior instrument (PI) via minimally invasive surgery (MIS) restores intervertebral height in degenerated disks. To align with MIS, the spacer has to be shaped with a slim geometry. However, the thin spacer increases the subsidence and migration after PLIF. This study aimed to propose a new lumbar fusion approach using bone cement to achieve a larger supporting area than that achieved by the currently used poly aryl-ether-ether-ketone (PEEK) spacer and assess the feasibility of this approach using a sawbone model. Furthermore, the mechanical responses, including the range of motion (ROM) and bone stress with the bone cement spacer were compared to those noted with the PEEK spacer by finite element (FE) simulation. An FE lumbar L3-L4 model with PEEK and bone cement spacers and PI was developed. Four fixing conditions were considered: intact lumbar L3-L4 segment, lumbar L3-L4 segment with PI, PEEK spacer plus PI, and bone cement spacer plus PI. Four kinds of 10-NM moments (flexion, extension, lateral bending, and rotation) and two different bone qualities (normal and osteoporotic) were considered. The bone cement spacer yielded smaller ROMs in extension and rotation than the PEEK spacer, while the ROMs of the bone cement spacer in flexion and lateral bending were slightly greater than with the PEEK spacer. Compared with the PEEK spacer, peak contact pressure on the superior surface of L4 with the bone cement spacer in rotation decreased by 74% (from 8.68 to 2.25 MPa) and 69.1% (from 9.1 to 2.82 MPa), respectively, in the normal and osteoporotic bone. Use of bone cement as a spacer with PI is a potential approach to decrease the bone stress in lumbar fusion and warrants further research.

Role of screw proximity in the fixation of transverse patellar fractures with screws and a wire.

PURPOSE: Clinical and biomechanical studies have reported that using supportive screws and a wire instead of the common Kirschner wires for modified tension band wiring improves the stability of fractured patellae. However, the effect of screw proximity on the fixation of a fractured patella remains unclear. Therefore a numerical study was conducted to examine the effects of screw proximity on biomechanical responses in a simulated patellar fracture fixed using two parallel cannulated screws and anterior tension band wiring. METHODS: A patellar model with a transverse fracture and loads simulating patellar tendon forces applied on the patella were used in the present simulation. The surgical fixation consisted of two 4.0-mm parallel partially threaded cannulated screws with a figure-of-eight tension band made using a 1.25-mm stainless steel wire. Biomechanical responses at two screw proximities, 5 and 10 mm from the leading edge of the patella, were investigated. RESULTS: Superficial screw placement (5 mm) yielded higher stability, lower wire loads, and lower bone contact pressures than the deep placement (10 mm). The deep placement of screws exerted a higher load on the wire but a lower force on the screw than superficial placement did. CONCLUSION: This is the first numerical study to examine the effects of screw location on the fixation of a fractured patella using cannulated screws and tension band wiring. Considering the favorable biomechanical responses, superficial placement (5 mm below the leading edge of the patella) is recommended for screw insertion when treating a transverse fractured patella.