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.

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.

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.