Po-Ting Wu

Role of Macrophage CCAAT/Enhancer Binding Protein Delta in the Pathogenesis of Rheumatoid Arthritis in Collagen-Induced Arthritic Mice

Background The up-regulation of CCAAT/enhancer binding protein delta (CEBPD) has frequently been observed in macrophages in age-associated disorders, including rheumatoid arthritis (RA). However, the role of macrophage CEBPD in the pathogenesis of RA is unclear. Methodology and Principal Findings We found that the collagen-induced arthritis (CIA) score and the number of affected paws in Cebpd−/− mice were significantly decreased compared with the wild-type (WT) mice. The histological analysis revealed an attenuated CIA in Cebpd−/− mice, as shown by reduced pannus formation and greater integrity of joint architecture in affected paws of Cebpd−/− mice compared with WT mice. In addition, immunohistochemistry analysis revealed decreased pannus proliferation and angiogenesis in Cebpd−/− mice compared with WT mice. CEBPD activated in macrophages played a functional role in promoting the tube formation of endothelial cells and the migration and proliferation of synoviocytes. In vivo DNA binding assays and reporter assays showed that CEBPD up-regulated CCL20, CXCL1, IL23A and TNFAIP6 transcripts through direct binding to their promoter regions. CCL20, IL23A, CXCL1 and TNFAIP6 contributed to the migration and proliferation of synoviocytes, and the latter two proteins were involved in tube formation of endothelial cells. Finally, two anti-inflammatory chemicals, inotilone and rosmanol, reduced the expression of CEBPD and its downstream targets and mitigated the above phenomena. Conclusions and Significance Collectively, our findings suggest that CEBPD and its downstream effectors could be biomarkers for the diagnosis of RA and potentially serve as therapeutic targets for RA therapy.

Intraoperative use of somatosensory-evoked potential in monitoring nerve roots.

Different intraoperative neuromonitoring modalities (mixed-nerve somatosensory-evoked potential [M-SSEP], dermatomal somatosensory-evoked potential [D-SSEP], compound motor-evoked potential [CMEP], electromyography [EMG], and the Hoffmann reflex [H-reflex]) have been developed for early detection of nerve root injury, for timely revision, and for damage reduction. In this study, we discuss the advantages and disadvantages of M-SSEP and D-SSEP by reviewing experimental evidence from animal models and clinical practice.

Blood Loss After Minimally Invasive Total Knee Arthroplasty: Effects of Imageless Navigation

A prospective cohort study of 100 patients undergoing primary minimally invasive total knee arthroplasty was carried out to determine blood loss after this procedure and to examine the efficacy of navigation on blood saving. The patients were divided into two groups according to the surgical technique, and underwent either computer‐assisted navigation or manual procedures. All operations were performed by a single surgeon using an identical approach. To minimize blood loss, an intraoperative tourniquet was used, but no postoperative drainage was applied. Although the mean surgical time was longer in the navigated group than in the manual group (119.2 vs. 90.9 min; p < 0.001), the reductions in hemoglobin level (1.40 vs. 1.38 g/dL; p = 0.642) and calculated blood loss (470.77 vs. 482.73 mL; p = 0.796) were similar in both groups. Four patients in both groups required blood transfusion. With minimally invasive techniques and drainage avoidance, our study suggests that the blood loss after minimally invasive total knee arthroplasty was not significantly affected by the use of imageless navigation.

Is progressive early digit mobilization intervention beneficial for patients with external fixation of distal radius fracture? A pilot randomized controlled trial:

Objective: To investigate whether progressive early digit mobilization resulted in better outcomes for hand stiffness and related functional results, as well as the effects on the bone healing process. Design: Prospective, pilot randomized controlled trial. Setting: A university hospital in southern Taiwan. Participants: Twenty-two patients with distal radius fracture randomized into two groups: early digit mobilization or control. Interventions: The intervention group received 45 minutes per treatment session and three sessions per week until the external fixator was removed 6 weeks after fracture. The control group received usual home programmes. After removing fixators, both groups received regular rehabilitation programmes until 12 weeks after surgery. Main measures: Hand strength, dexterity and functional outcomes were obtained using a dynamometer, Purdue pegboard and self-report assessment, respectively, and X-rays of the distal radius were taken to reveal bone healing 1, 3, 6 and 12 weeks after surgery. A motion tracking system measured various kinematic parameters. Results: The recovery rates between the groups showed statistically significant differences in both thumb workspace (81.55% vs. 69.54%, P = 0.04) and finger workspace (89.22% vs. 59.97%, P = 0.03) 12 weeks after injury. However, no statistical differences were found in finger dexterity, strength and self-reported outcomes. The radiographic assessment showed no significant differences between the groups for radial inclination, radial height and volar tilt throughout the examinations. Conclusions: The findings suggest that early rehabilitative intervention for digits is applicable for distal radius fracture treatment, and does not produce additional bone deformities.

High-molecular-weight hyaluronic acid attenuated matrix metalloproteinase-1 and -3 expression via CD44 in tendinopathy

Evidence indicates that hyaluronic acid (HA) mitigates tendinopathy, but the effect of molecular weight is unclear. We investigated the effects of different concentrations and different molecular weights of HA (350 kDa, 1500 kDa, and 3000 kDa) on matrix metalloproteinase (MMP)-1 and -3 expression in IL-1β-stimulated rat tenocytes, and on their dynamic expression in peritendinous effusion from patients with long head of biceps (LHB) tendinopathy after high-molecular-weight (HMW)-HA treatments. Reverse transcription PCR, real-time PCR, and ELISA were used to determine MMP-1 and -3expression. Because CD44 was clearly expressed in the plasma membranes of cultured tenocytes, OX-50, a CD44 antagonist, was used to inhibit CD44 to evaluate the HA mechanism. HA (3000 kDa) significantly (p < 0.001) downregulated the mRNA and protein expression of MMP-1 and -3 in IL-1β-stimulated tenocytes. Its attenuating effects were dose-dependent (p < 0.01). In OX-50-pretreated cells, the mRNA expression of CD44 was not significantly altered, but the mRNA expression of MMP-1 and -3 was significantly upregulated. Visual analogue scale scores were significantly lower, and MMP-1 and -3 expression was significantly (p < 0.05) lower one month posttreatment. HMW-HA attenuated tendinopathy by downregulating MMP-1 and -3 expression. Inhibiting CD44 blocked the effects of HMW-HA.

Inflammation is present in de Quervain Disease--correlation study between biochemical and histopathological evaluation

BackgroundDe Quervain disease is a stenosing condition of the sheath of the abductor pollicis longus and extensor pollicis brevis tendons at the radial styloid process. Previous studies consistently reported that the pathological change of this condition is thought to be primarily an extensor retinaculum thickened by fibrosis and angiogenesis instead of inflammation. Contradictorily, the conservative treatment for de Quervain disease is anti-inflammatory medication. The inflammatory response may be involved in this disease; however, there is no present study directly evidencing whether the inflammatory responses exist in de Quervain disease or not. The histopathology of de Quervain disease is yet to be elucidated clearly. PurposeTo grade all specimens in the different stages and characterize specific inflammatory cell and factors to examine whether inflammatory response is involved in de Quervain disease. MethodsRetinaculum samples were collected from 13 patients with de Quervain disease after surgery. The specimens were evaluated histologically by collagen structure grading and immunohistochemically by quantifying the presence of neutrophil elastase, macrophages, cyclooxygenase, and vascular endothelium. ResultsNeutrophil elastase and cyclooxygenase occur in the de Quervain disease retinaculum and increased with the grade of collagen structure. After angiogenesis, macrophage infiltration occurs in the grade II matrix worse than grade III matrix. ConclusionsInflammation is present in de Quervain disease. This study provides direct evidence for inflammatory cell and infiltration factors and offer valuable clues for specific pharmacological therapies for de Quervain disease.

Feasibility of a Novel Functional Sensibility Test as an Assisted Examination for Determining Precision Pinch Performance in Patients with Carpal Tunnel Syndrome

To understand the feasibility of a novel functional sensibility test for determining precision pinch performance in patients with carpal tunnel syndrome, this study investigates the validity, sensitivity and specificity of functional sensibility derived from a pinch-holding-up activity (PHUA) test. Participants include 70 clinically defined carpal tunnel syndrome (CTS) patients with 119 involved hands and 70 age- and gender-matched controls. To examine the discriminating ability of the functional sensibility test, the differences in the ability of pinch force adjustments to the inertial load of handling object between CTS and control subjects are analyzed. The results of functional sensibility are correlated with the severity of CTS to establish concurrent validity. The receiver operating characteristic (ROC) curve is constructed to demonstrate the accuracy of the proposed test. The functional sensibility score significantly discriminates the patients and control groups (respectively, 12.94±1.72 vs. 11.51±1.15N in peak pinch force (FPPeak), p<0.001; 2.92±0.41 vs. 2.52±0.24 in force ratio, p<0.001) and is moderately correlated (r = 0.42–0.54, p<0.001) with the results of traditional sensibility tests (touch-pressure threshold and two-point discrimination test). In addition, there is a statistical difference in the results of functional sensibility (p<0.001) among the subgroups of CTS severity based on electrophysiological study. The sensitivity and specificity are 0.79 and 0.76, respectively, for the functional sensibility test. The areas under the ROC curve are 0.85 and 0.80 for the force ratio and FPPeak, respectively. In conclusion, the functional sensibility test could be feasibly used as a clinical tool for determining both the sensibility and precision pinch performance of hands for the patients with CTS.

Efficacy of topical cross‐linked hyaluronic acid hydrogel in preventing post laminectomy/laminotomy fibrosis in a rat model

Post‐laminectomy/laminotomy epidural fibrosis (EF) has been implicated as an important cause of failed back syndrome (FBS). The various clinical approaches used to control EF yield mixed outcomes. Cross‐linked hyaluronic acid hydrogel (cHA) was synthesized to increase mechanical stability and residence time. We evaluated the therapeutic attenuation of proliferative EF in laminectomy/laminotomy groups treated and not treated with cHA. A bilateral T11‐L1 total laminectomy or unilateral T12 laminotomy was done on four groups (n = 10 each) of Sprague‐Dawley rats and then histologically examined 2 months post‐surgery: (I) laminectomy group treated with and (II) not treated with cHA, (III) laminotomy group treated with and (IV) not treated with cHA. The grade of EF, the diameters within the spinal canal, dura mater thickness, and the area of the epidural space, subarachnoid space, and conus medullaris space were assessed. The cHA‐treated subgroups (I, III) had a significantly lower grade of EF, thinner dura mater, and larger epidural and subarachnoid spaces than did the control subgroups (II, IV) (p < 0.05). The cHA formed a solid interpositional membrane barrier that prevented invasive fibrosis, and also helped reduce pathological changes to the adjacent structures. In conclusion, topically applied cHA is effective for reducing EF.

Investigation into the safety of perineural application of 1,4-butanediol diglycidyl ether-crosslinked hyaluronan in a rat model.

Hyaluronan (HA) is well known for its biocompatibility and has widespread clinical use. To change its mechanical and physiologic properties to adapt to specific clinical scenarios, HA is crosslinked with chemically reactive linker molecules, most of which are toxic chemical reagents. Adverse events related to clinical use of crosslinked HA have been documented. Although approved by the FDA as dermal filler, the safety of perineural application of 1,4-butanediol diglycidyl ether (BDDE)-crosslinked HA has not been assessed critically. Concern exists owing to the vulnerability of neural tissues, because of their elongated morphology, high ratio of membrane surface area to cell volume, and complicated electrophysiologic properties. In this study, we systematically investigated the toxicity profile of BDDE-crosslinked HA, using in vitro and in vivo experiments in a rat model. The in vivo experiments included the evaluation of aspects of histopathology, electrophysiology, and neurobehavior. There were no significant changes in the treatment group compared with the control group in all aspects of the experiments, except for the increased epineurial vascular formation in the 0.5% crosslinked HA-treated group during 2 weeks of observation. Further studies involving perineural application of BDDE-crosslinked HA can be done based on our findings, which ruled out the safety concern of cytotoxicity and adverse changes in electrophysiology and neurobehavior.

Impact of Distal Median Neuropathy on Handwriting Performance for Patients with Carpal Tunnel Syndrome in Office and Administrative Support Occupations

Purpose This study investigates the handwriting performance of patients with carpal tunnel syndrome (CTS) and healthy controls in office and administrative support occupations, adopting both biomechanical and functional perspectives. This work also explores how surgical intervention altered the performance of the CTS patients. Methods Fourteen CTS patients and 14 control subjects were recruited to complete a self-reported survey and participate in sensory tests, hand strength, dexterity and handwriting tasks using a custom force acquisition pen along with motion capture technology. Based on the results of these, the sensory measurements, along with functional and biomechanical parameters, were used to determine the differences between the groups and also reveal any improvements that occurred in the CTS group after surgical intervention. Results The CTS patients showed significantly poorer hand sensibility and dexterity than the controls, as well as excessive force exertion of the digits and pen tip, and less efficient force adjustment ability during handwriting. After surgery and sensory recovery, the hand dexterity and pen tip force of the CTS patients improved significantly. The force adjustment abilities of the digits also increased, but these changes were not statistically significant. Conclusions This study provides the objective measurements and novel apparatus that can be used to determine impairments in the handwriting abilities of office or administrative workers with CTS. The results can also help clinicians or patients to better understand the sensory-related deficits in sensorimotor control of the hand related to CTS, and thus develop and implement more suitable training or adaptive protocols.