Ruey-Mo Lin

Plaster casting has been effective in fracture rehabilitation due to its immobility capability. Thermoplastic casting gains some efficiency and convenience from clinical processing but fitting and immobility are two major tradeoffs. Three-dimensional (3D)-printed braces have demonstrated improvements in innovation, customization, and appearance, but one may question their effectiveness in rehabilitation. Via a science-based data-centric approach, we evaluated the feasibility of customizing 3D-printed braces for wrist fractures after surgery. First, we established a framework for determining a proper timeframe for reliable pressure measurement for plaster casts, devised a method to evaluate the immobilization capability of the plaster casts and customized braces, and assessed changes in immobilization capability due to the clearance adjustment of customized braces. Second, we compared the customized wrist braces and plaster casts in immobilization capability and functional effectiveness in clinical trials. Thirty-three patients were recruited (9, control; 24, experimental). Both the Disability of Arm, Shoulder, and Head, and the Manual Ability Measure surveys showed significant differences between the control and experimental groups after brace wearing time frames of 2, 4, 8, and 12 weeks, and 6 and 12 months. We found that customized braces can match plaster casts in immobilization ability and can promote effective functional recovery.

Background: Vertebral compression fractures, resulting in significant pain and disability, commonly occur in elderly osteoporotic patients. However, the current literature lacks long-term follow-up information related to image parameters and bone formation following vertebroplasty. Purpose: To evaluate new bone formation after vertebroplasty and the long-term effect of vertebroplasty. Methods: A total of 157 patients with new osteoporotic compression fractures who underwent vertebroplasty were retrospectively analyzed. The image parameters, including wedge angles, compression ratios, global alignment, and new bone formation, were recorded before and after vertebroplasty up to three years postoperatively. Results: The wedge angle improved and was maintained for 12 months. The compression ratios also improved but gradually deteriorated during the follow-up period. New bone formation was found in 40% of the patients at 36 months, and the multivariate analysis showed that this might have been related to the correction of the anterior compression ratio. Conclusions: Vertebroplasty significantly restored the wedge angles and compression ratios up to one year postoperatively, and new bone formation was noted on plain radiographs, which increased over time. Last, the restoration of vertebral parameters may contribute to new bone formation.

Despite improvements in cancer treatments resulting in higher survival rates, the proliferation and metastasis of tumors still raise new questions in cancer therapy. Therefore, new drugs and strategies are still needed. Midazolam (MDZ) is a common sedative drug acting through the γ-aminobutyric acid receptor in the central nervous system and also binds to the peripheral benzodiazepine receptor (PBR) in peripheral tissues. Previous studies have shown that MDZ inhibits cancer cell proliferation but increases cancer cell apoptosis through different mechanisms. In this study, we investigated the possible anticancer mechanisms of MDZ on different cancer cell types. MDZ inhibited transforming growth factor β (TGF-β)-induced cancer cell proliferation of both A549 and MCF-7 cells. MDZ also inhibited TGF-β-induced cell migration, invasion, epithelial-mesenchymal-transition, and Smad phosphorylation in both cancer cell lines. Inhibition of PBR by PK11195 rescued the MDZ-inhibited cell proliferation, suggesting that MDZ worked through PBR to inhibit TGF-β pathway. Furthermore, MDZ inhibited proliferation, migration, invasion and levels of mesenchymal proteins in MDA-MD-231 triple-negative breast cancer cells. Together, MDZ inhibits cancer cell proliferation both in epithelial and mesenchymal types and EMT, indicating an important role for MDZ as a candidate to treat lung and breast cancers.

Intervertebral disc (IVD) is an avascular tissue under hypoxic condition after adulthood. Our previous data showed that inflammatory cytokines (interleukin (IL)-1β), IL-20, and bone morphogenetic protein-2 (BMP-2) play important roles in the healing process after disc injury. In the current study, we investigated whether IL-1β, IL-20, or BMP-2 modulate the expression of pro-inflammatory cytokines, chemotaxis factor, and angiogenesis factor on IVD cells under hypoxia. IVD cells were isolated from patients with intervertebral disc herniation (HIVD) at the levels of L4–5 and L5–S1. We found that the expression of IL-1β, IL-20, BMP-2, hypoxia-inducible factor (HIF)-1α, IL-6, IL-8, angiogenetic factor (vascular endothelial growth factor (VEGF)), chemotactic factor (monocyte chemoattractant protein 1 (MCP-1)), and matrix metalloproteinase-3 (MMP-3) was upregulated in IVD cells under hypoxia conditions. In addition, IL-1β upregulated the expression of pro-inflammatory cytokines (IL-6 and IL-8), VEGF, MCP-1, and disc degradation factor (MMP-3) in IVD cells under hypoxia conditions. IL-20 upregulated MCP-1 and VEGF expression. BMP-2 also upregulated the expression of MCP-1, VEGF, and IL-8 in IVD cells under hypoxia conditions. Treatment with antibody against IL-1β decreased VEGF and MMP-3 expression, while treatment with IL-20 or BMP-2 antibodies decreased MCP-1, VEGF, and MMP-3 expression. Moreover, IL-1β modulated both the expression of IL-20 and BMP-2, but IL-20 only modulated BMP-2 either under a hypoxic or normoxic condition. Therefore, we concluded that the inflammation, chemotaxis, matrix degradation, and angiogenesis after disc herniation are influenced by the hypoxic condition and controlled by IL-1β, IL-20, and BMP-2.

Degenerative lumbar spondylolisthesis (DLS) is a major cause of spinal canal stenosis and is often related to lower back pain. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory bone disorders likes intervertebral disc herniation, rheumatoid arthritis (RA), osteoporosis, and bone fracture. IL-19 also acts as a proinflammatory cytokine in RA. The aim of the present study was to investigate whether IL-19 and IL-20 are involved in DLS and compare three different tissues including disc, facet joint, and ligamentum flavum of patients with DLS to verify which tissue is affected more by inflammation. Disc, facet joint and ligamentum flavum from 13 patients with DLS was retrieved, and the expression pattern of IL-19, IL-20, IL-20R1, IL-20R2, TNF-α, IL-1β, and MCP-1 was evaluated using immunohistochemical staining with specific antibodies. The disc cells were isolated and incubated with IL-19 and IL-20 under CoCl2-mimicked hypoxic conditions to analyze the proinflammatory cytokine expression pattern using real-time quantitative PCR with specific primers. IL-19 and IL-20 were positively stained and accompanied by abundant expression of TNF-α, IL-1β, and MCP-1 in facet joints of DLS patients. IL-19 and IL-20’s receptors (IL-20R1 and IL-20R2) were expressed on chondrocytes and fibrocytes/fibroblasts in facet joint and ligamentum flavum tissues from patients with DLS. There was a significant correlation between the expression of IL-20 and IL-1β in facet joint. In vitro assay, IL-19 and IL-20 upregulated the expression of IL-1β, IL-6, TNF-α, IL-8, VEGF, and MCP-1 in primary cultured DLS disc cells under CoCl2-mimicked hypoxic conditions. IL-19, IL-20, and their receptors as well as proinflammatory cytokines (TNF-α, IL-1β, and MCP-1) were expressed more in facet joints than the other tissues in patients with DLS; therefore, the etiology of inflammation might be more facet-centric. IL-19 and IL-20 induced proinflammatory cytokine expression in disc cells and might play a role in the pathogenesis of DLS.

Objective: We assessed our results of short-segment decompression and fixation for osteoporotic thoracolumbar fractures with neurological deficits. Methods: We evaluated 20 elderly patients (age, 60–89 years; mean, 73.2 years) with osteoporotic thoracolumbar fractures and neurological deficits. They underwent short-segment decompression and fixation and followed up for 40.6 (range, 24–68) months. A visual analog scale (VAS) and the Oswestry Disability Index (ODI) were used to measure back pain and disability. We also analyzed patients’ radiologic findings and neurological status. Perioperative and postoperative complications were recorded. Results: At the latest follow-up, the average VAS score for back pain and ODI scores had significantly improved. The radiologic assessment showed significant improvements in local kyphosis, anterior vertebral height, and the vertebral wedge angle compared with the original measures. Neurological function also improved in 18 of 20 patients. No major complications occurred perioperatively. Our techniques included preservation of the posterior ligament complex, decortication of facet joints for fusion, no tapping to increase the screw insertional torque, pre-contouring of the rods according to the “adaptive” curve obtained from postural reduction, and postoperative spinal bracing. Conclusions: Posterior short-segment decompression and fixation could be an effective surgical option for osteoporotic thoracolumbar burst fractures with neurological deficits.

Giant invasive sacral schwannomas are rare tumors. Surgical excision is the standard treatment and total resection is performed if feasible. Advances in three-dimensional (3D) imaging technology have facilitated treatment designs of complex surgical procedures. Our aim was to evaluate virtual surgical planning, computer-aided design (CAD), and manufacturing with 3D printing technology of the customized osteotomy guiding device in giant invasive sacral schwannoma resection. A digital 3D model of the sacrum, including the giant invasive sacral schwannoma, was rendered from patient computer tomography (CT) images. The surgeon chose excision margins of the tumor. Based on the virtual surgical planning, the customized guiding tool for osteotomy was designed and manufactured using the CAD and 3D printing. We used the guiding block to successfully excise a giant sacral schwannoma using only a posterior approach to achieve gross total resection. No augmented spinal instrumentation was used to prevent iatrogenic spinal instability. Clinical symptoms resolved dramatically after operation. No spinal instability occurred during follow-up. With the assistance of an image-based customized osteotomy guiding device, we achieved both goals of tumor resection and bone preservation in giant sacral schwannoma resection. With thorough surgical planning, this technology can be applied to the complex surgical procedures easily and reliably.

The thoracolumbar junction is the transition from a stiff (thoracic spine) to a mobile zone (lumbar spine) and is relatively unstable compared with the thoracic and lumbar portions of the spine. The need for anterior reconstruction after a corpectomy has been emphasized by several authors. However, for patients with a relatively short life expectancy, anterior reconstruction may be unnecessary. Posterior instrumentation alone may be sufficient to provide pain relief and stability for such patients. The goal of this study was to assess the postoperative outcomes and survival rates of patients with tumor metastases of the lower thoracic spine and thoracolumbar junction (T10–L1) who underwent transpedicular partial corpectomy without anterior vertebral reconstruction. From November 2001 to February 2015, 29 patients diagnosed with symptomatic spinal cord compression caused by tumor metastasis involving T10 to L1 underwent palliative surgery that involved a posterolateral transpedicular partial corpectomy without anterior reconstruction. The surgical indication was neurologic progression. A follow-up was conducted for all of the patients, including reviewing medical records and performing an examination in the outpatient department. The patients ranged in age from 33 to 83 years (mean, 61.6 years). Neurologic improvement by at least one Frankel grade was noted in 75.9 % of the patients (N = 22). Neither intraoperative mortality nor implant failure was reported. The median survival rate was 7.43 months (range, 0.47–28 months). The results of this study suggest that the stability of implants can be maintained up to 28 months with satisfying functional outcome after a palliative posterolateral transpedicular partial corpectomy without anterior reconstruction.