Aligned nanofiber nerve conduits inhibit alpha smooth muscle actin expression and collagen proliferation by suppressing TGF-ß1/SMAD signaling in traumatic neuromas.

Transforming growth factor-beta 1 (TGF-ß1) is a powerful activator of connective tissue synthesis that is strongly associated with the pathophysiology of traumatic neuroma. Previous studies have demonstrated that aligned nanofiber conduits made from silk fibroin and poly (L-lactic acid-co-ε-caprolactone; PLCL) could prevent traumatic neuromas. In the present study, the possible mechanisms of conduits in treating traumatic neuromas were investigated to provide theoretical basis for procedures. Aligned nanofiber conduits were used for nerve capping. Sciatic nerves of Sprague-Dawley rats were used to create an animal model. The present study contains two parts, each including four experimental groups. SB-431542/SRI-011381 hydrochloride was used to suppress/enhance TGF-ß1/SMAD signaling. Part I discussed the connections between traumatic neuroma and the proliferation of alpha smooth muscle actin (α-SMA) and collagen; it also investigated the therapeutic effect of conduits. Part II hypothesized that conduits suppressed TGF-ß1/SMAD signaling. Histological characteristics, quantitative analysis of α-SMA, collagens and signaling-related parameters were assessed and compared among groups one month postoperatively. Results from Part I demonstrated that aligned nanofiber conduits suppressed the expression of α-SMA and collagens; and results from Part II revealed the downregulation of pathway-related proteins, suggesting that the suppression was mediated by TGF-ß1/SMAD signaling. Aligned nanofiber conduits may be effective nerve capping biomaterials. One of the mechanisms involves suppressing TGF-ß1/SMAD signaling. Novel treatments using aligned nanofiber conduits could be developed to manage traumatic neuromas.

The efficacies and limitations of fasciectomy and collagenase clostridium histolyticum in Dupuytren's contracture management: A meta-analysis.

BACKGROUND: We intend to assess the efficacies and limitations of collagenase clostridium histolyticum (CCH) and fasciectomy in treating Dupuytren's contracture, and the associated complications and rate of recurrences aiming to present a treatment algorithm. METHODS: A literature search within the PubMed, Web of Sciences, Cochrane Library, and EMBASE databases was performed using the combined key words 'Dupuytren, palmar aponeurosis contracture, collagenase clostridium histolyticum and fasciectomy', including all possible studies with a set of predefined inclusion and exclusion criteria. RESULTS: Thirty studies were assessed for eligibility from 215 identified records. Seventeen publications satisfied the inclusion criteria including 2142 joints in 1784 patients. The mean follow-up time was 18.0 months (3-60). CONCLUSION: Acceptable contractures release was obtained in both techniques. Severe complications associated with fasciectomy outrank those of CCH, whereas the low rate of recurrence favors the fasciectomy technique.

An aligned nanofiber nerve conduit that inhibits painful traumatic neuroma formation through regulation of the RhoA/ROCK signaling pathway.

OBJECTIVE: Traumatic neuromas represent a prevalent source of neuropathic pain. As of yet, there has been no single treatment method that can guarantee permanent relief of symptoms. Although nerve-capping techniques have shown promise, their exact mechanisms remain elusive. The authors' aim was to examine the role of the RhoA/ROCK signaling pathway in the prevention of neuroma formation after neurectomy utilizing a nerve-capping technique. METHODS: An aligned nanofiber tube was fabricated to cap the sciatic nerve in Sprague Dawley rats. The rats (n = 60) were randomly divided into the aligned SF/P (LLA-CL) capping group (capping group, n = 20), the capping and Y-27632 (ROCK pathway inhibitor) intervention group (intervention group, n = 20), and the no-capping group (control group, n = 20). The authors undertook a comprehensive assessment of the capping group, examining the animals' behavior, the extent of neuroma development, histology, gene and protein expression, and ultrastructural changes associated with the RhoA/ROCK signaling pathway. These findings were compared with those in the intervention and control groups. RESULTS: The inciting injury resulted in the expression of the RhoA/ROCK signaling pathway, as well as its further upregulation in peripheral neurons. Axon outgrowth was significantly increased when RhoA/ROCK signaling pathway was suppressed. The average autotomy score in the capping group was observed to be much lower than that of the intervention and control groups. At 30 days postneurectomy, the capping group displayed no obvious neuroma formation, while a bulbous neuroma was found in the nerve stumps of both the control and intervention groups. Quantitative real-time polymerase chain reaction and the Western blot analysis demonstrated that the expression of myelin-associated glycoprotein was substantially upregulated in the capping group; in contrast, the expression of NF-200 was significantly downregulated. The expression of myosin light chain was notably lower in the intervention group, but there was no significant difference when compared with the control group (p > 0.05). CONCLUSIONS: The RhoA/ROCK signaling pathway has emerged as a critical player in the process of traumatic neuroma formation after neurectomy. It is possible that the nerve-capping technique could generate a "regenerative brake" based on the regulation of the RhoA/ROCK signaling pathway in this event. These findings may provide concrete evidence that could help develop new strategies for the management of painful neuromas.

The effect of chemical hemodynamic regulation on the survival of arterialized venous flaps.

The role of nitric oxide (NO) on the microcirculation of arterialized venous flaps (AVFs) remains controversial. We aimed to investigate the effect of hemodynamic regulation using nitric oxide synthase (NOS) inhibitor and its agonist as a chemical intervention on the survival of AVF. A 10 × 8 cm arterialized venous flap was designed symmetrically on the rabbit abdomen. Thirty-six rabbits were used and randomly divided into three groups: control group, L-arg group and L-NAME group, respectively. The L-arg group and the L-NAME group received intraperitoneal injections of L-arginine (a NOS agonist, 1 g/kg/d) and L-NAME (nitro-L-arginine-methyl ester, a NOS inhibitor, 50 mg/kg/d) respectively, whereas the control group received intraperitoneal injections of the same amount of saline. Flap viability, water content, status of vascular perfusion and gene expression of eNOS and HIF-1α in each group were observed and analyzed. The average value of water content (venous congestion) in the L-arg group was the highest in comparison with the control group and the L-NAME group with a statistically significant difference (all p < .001). Similar results regarding blood perfusion state, gene expression of eNOS and HIF-1α and flap survival status were found among the three groups. The early application of L- NAME as a chemical hemodynamic intervention could stop the cascade of flap swelling, congestion and necrosis due to overexpression of NO and be beneficial to the AVF survival. Our findings may develop a new strategy as a solution for the inconsistent survival of AVFs.

Allogenic endothelial progenitor cell transplantation increases flap survival through an upregulation of eNOs and VEGF on venous flap survival in rabbits.

BACKGROUND: Endothelial progenitor cells (EPCs) are one type of bone marrow hematopoietic stromal cells which play a vital role in neovascularization and tissue repair. In this study, we investigated whether EPCs promote flap survival in a rabbit venous model. MATERIALS AND METHODS: EPCs were customized from CHI Scientific, Inc, China. Thirty-six rabbits were randomly assigned to either the sham group (n = 12), the control group (n = 12) or the EPC transplantation group (n = 12). A 10 × 6 cm venous flap was created on the rabbit abdomen. Both the EPC transplantation and control groups had the same volume of EPCs-PBS (phosphate buffered saline) and PBS on postoperative day 1. Flap survival, blood flow, histopathology, expression of endothelial nitric oxide synthase (eNOs) and Vascular Endothelial Growth Factor (VEGF) were detected on postoperative day 10. RESULTS: Cellular immunofluorescence assay positively confirmed that the EPCs were undergoing differentiation. The survival rate of the flap in the EPC transplantation group was 58.4 ± 7.1%, which was significantly higher than that of the control group (4.8 ± 3.4%) (p<0.01). Histological examination revealed that the EPC transplantation group had higher microvessel density, fewer inflammatory cells, and a higher expression of eNOs and VEGF. Significantly increased blood flow perfusion was seen in the EPC transplantation group using laser Doppler imaging. The Western Blot technique revealed that the expression of eNOs and VEGF in the EPC transplantation group were both significantly higher than those in the control group. CONCLUSION: This study demonstrated that EPC transplantation improved venous flap survival in rabbits. The present findings may provide insight into the promotion of venous flap survival in clinical practice in the future.

Individual Treatment of Delayed Distal Biceps Tendon Rupture: Case Report and Literature Review.

INTRODUCTION: Complicated elbow injuries (elbow injuries with bone and soft tissue injury) with distal biceps tendon ruptures (DBTRs) are not uncommon. There are several treatment modalities in different situations of injuries. In this article, we reported 3 successful individual treatments of delayed DBTR with complicated elbow injuries. MATERIALS AND METHODS: Three cases of complicated elbow injuries treated between 2010 and 2016 were reviewed. The delayed DBTR cases were summarized and treated. Mayo Elbow Performance Score value, range of motion, and visual analog scale score were used to assess outcomes after a minimum follow-up of 12 months. RESULTS: All 3 patients were male, aged 47 to 54 years (mean, 49.6 years). Patients received surgical treatments. After a mean follow-up of 13.7 months, in cases 1 and 2, Mayo Elbow Performance Score values improved by 50% and 100%, elbow flexion-extension arc were 115 degrees and 110 degrees, pronation-supination arc were 130 degrees and 120 degrees. Arthrodesis case reported pain relief; visual analog scale score for pain was 0 to 1. No postoperative complications were observed, and all patients were satisfied with the results. CONCLUSIONS: Individual treatment is advised in DBTR with complicated elbow injuries. Secondary treatment of DBTR can achieve satisfactory results using individual strategies depending on patients' overall condition.

Metformin relieves neuropathic pain after spinal nerve ligation via autophagy flux stimulation.

Neuropathic pain is a well-known type of chronic pain caused by damage to the nervous system. Autophagy is involved in the development and/or progression of many diseases, including neuropathic pain. Emerging evidence suggests that metformin relieves neuropathic pain in several neuropathic pain models; however, metformin's cellular and molecular mechanism for pain relief remains unknown. In this study, we investigated the therapeutic effects of metformin on pain relief after spinal nerve ligation (SNL) and its underlying mechanism of autophagy regulation. Behavioural analysis, histological assessment, expression of c-Fos and molecular biological changes, as well as ultrastructural features, were investigated. Our findings showed that the number of autophagosomes and expression of autophagy markers, such as LC3 and beclin1, were increased, while the autophagy substrate protein p62, as well as the ubiquitinated proteins, were accumulated in the ipsilateral spinal cord. However, metformin enhanced the expression of autophagy markers, while it abrogated the abundance of p62 and ubiquitinated proteins. Blockage of autophagy flux by chloroquine partially abolished the apoptosis inhibition and analgesic effects of metformin on SNL. Taken together, these results illustrated that metformin relieved neuropathic pain through autophagy flux stimulation and provided a new direction for metformin drug development to treat neuropathic pain.

Treatment of osteoarthritis of the elbow with open or arthroscopic debridement: a narrative review.

BACKGROUND: Elbow osteoarthritis (OA) is a common disabling condition because of pain and loss of motion. Open and arthroscopic debridement are the preferred treatment, however there is no consensus on which treatment modality is suited to which category of patient or stage of disease. The objective of this study was to narratively review the literature for a more comprehensive understanding of its treatment options and associated outcomes, trying to provide a better treatment plan. METHODS: The PubMed database, EMBASE, Cochrane Library, and Google Scholar were searched, using the keywords (elbow [title/abstract] and osteoarthritis [title/abstract] and (surgery or open or arthroscop* or debridement or ulnohumeral arthroplasty) including all possible studies with a set of inclusion and exclusion criteria. RESULTS: A total of 229 studies were identified. Twenty-one articles published between 1994 and 2016 satisfied the inclusion and exclusion criteria including 651 elbows in 639 patients. After comparison, mean postoperative improvement in (ROM) was 28.6° and 23.3°,Mayo elbow performance score/index(MEPS/MEPI) 31 and 26.8 and the total complication rate was 37(11.5%), and 18(5.5%) for open and arthroscopic procedure. CONCLUSIONS: This narrative review could not provide an insight on which surgical procedure is superior to the other due to the poor orthopedics literature. However, from the data we obtained the open and arthroscopic debridement procedures seem to be safe and effective in the treatment of elbow OA. The optimal surgical intervention for the treatment of symptomatic elbow OA should be determined depending on patients' conditions.

Debridement arthroplasty of a rare case of elbow stiffness. A case report and literature review.

INTRODUCTION: Elbow stiffness is a common condition that affects the quality of life of patients. Melorheostosis of the elbow associated with elbow stiffness is extremely rare. PRESENTATION OF CASE: We report the case of a 28 yr old male who presented with elbow stiffness which occurred within one year without prior history of trauma or infection. The patient had decrease in range of motion together with progressive worsening pain that forced him to seek medical attention. DISCUSSION: There is no standard treatment for melorheostosis, and management plans must be made on an individual patient basis. The aims of treatment are pain relief and maintaining function. CONCLUSION: Debridement arthroplasty is safe and effective in treating elbow stiffness associated with Melorheostosis.

Bilateral Locking of the Metacarpophalangeal Joint: A Case Report and Systematic Literature Review.

BACKGROUND: The purposes of this article were to present an exemplary case of bilateral locked metacarpophalangeal (MCP) joint of the second metacarpal and to review the literature for a more comprehensive understanding of this condition. METHODS: For the literature review, PubMed and Google Scholar research were performed using the term "metacarpophalangeal joint (MCP joint) locking or locked metacarpophalangeal joint (MCP Joint)" with a set of inclusion and exclusion criteria. RESULTS: We recently treated a patient with bilateral locked MCP, which presented to our office on 2 separate occasions in the space of 3 years. The left hand was affected in 2015 and the right hand in 2018. After clinical and imaging investigations, the patient was operated on. The patient had a locking of the accessory collateral ligament behind a radial sided prominence of the second metacarpal head. After surgery, the patient regained full function of her index finger. On the basis of our literature review, we found 47 cases described in the literature, plus our case, the index finger (22), and the long finger (11) were most commonly involved. CONCLUSION: Left untreated, the locked MCP joint may lead to a flexion contracture and disabilities in performing daily life activities. The diagnosis is mainly clinical. The radiographs can show degenerative changes or a particular shape of the metacarpal head/neck as a first clue to the possible cause. Gentle closed reduction can be attempted, but surgery is most often required. The surgical approach depends on the presumed localization of the pathology.

The timing of open surgical release of post-traumatic elbow stiffness: A systematic review.

BACKGROUND: Open release of post-traumatic elbow stiffness is effective in restoring elbow function, but there is no guideline on the optimal time point of surgical release so far. The purpose of this article was to summarize the current available literature reporting on the timing of open release of post-traumatic elbow stiffness. METHODS: The PubMed, Cochrane Library, and EMBASE were searched with a set of predefined inclusion and exclusion criteria. Manual searches for references were performed to find potential relevant studies. Two authors separately extracted data from all the articles selected. RESULTS: 27 articles published between 1989 and 2017 were included with an overall enrollment of 836 patients. We divided all included studies into 3 groups according to the timing of surgical release: group 1 (6-10 months after injury), group 2 (11-20 months after injury), and group 3(>20 months after injury). The mean postoperative Mayo Elbow Performance Score (MEPS) and recurrence rate were similar among the 3 groups; however, the mean gain in arc of motion in group 1 was the highest with the lowest complication rate among the 3 groups. CONCLUSION: There was a trend toward a shorter waiting time from injury to open arthrolysis from 12 months to 6 months. The shorter waiting period of 6 to 10 months yielded better results. Therefore, early surgical release of stiff elbows is recommended for a shorter rehabilitation time and earlier return to work. LEVEL OF EVIDENCE: Level IV, Systematic Review.

Treatments of traumatic neuropathic pain: a systematic review.

Traumatic neuropathic pain caused by traumatic neuroma has long been bothering both doctors and patients, the mechanisms of traumatic neuropathic pain are widely discussed by researchers and the treatment is challenging. Clinical treatment of painful neuroma is unclear. Numerous treatment modalities have been introduced by experts in this field. However, there is still no single standard recognized treatment. Different forms of treatments have been tested in animals and humans, but pharmacotherapies (antidepressants, antiepileptics) remain the basis of traumatic neuropathic pain management. For intractable cases, nerve stump transpositions into a muscle, vein or bone are seen as traditional surgical procedures which provide a certain degree of efficacy. Novel surgical techniques have emerged in recent years, such as tube guided nerve capping, electrical stimulation and adipose autograft have substantially enriched the abundance of the treatment for traumatic neuropathic pain. Several treatments show advantages over the others in terms of pain relief and prevention of neuroma formation, making it difficult to pick out a single modality as the reference. An effective and standardized treatment for traumatic neuropathic pain would provide better choice for researchers and clinical workers. In this review, we summarized current knowledge on the treatment of traumatic neuropathic pain, and found a therapeutic strategy for this intractable pain. We tried to provide a useful guideline for choosing the right modality in management of traumatic neuropathic pain.