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This study aimed to compare the clinically established autologous extrasynovial tendon graft to a newly developed tissue-engineered allograft (Eng-allograft) in terms of functional outcomes following flexor tendon reconstruction in a canine model. The second and fifth flexor digitorum profundus (FDP) tendons from 16 dogs were transected and repaired in Zone II. After 6 weeks of cage activity, the repaired tendons were intentionally ruptured, creating a clinically relevant model for reconstruction. The re-ruptured FDP tendons were then reconstructed using either the clinically standard autologous extrasynovial tendon graft or the Eng-allograft, which had been revitalized with autologous bone marrow-derived mesenchymal stem cells (BMSCs) and synovialized using carbodiimide derivatized synovial fluid (cd-SYN). Following 12 weeks of postoperative rehabilitation, the functional outcomes of the surgical digits were evaluated. The Eng-allograft group exhibited improved digital function, including lower digit work of flexion and reduced adhesion status, while maintaining similar tendon gliding resistance compared to the autograft group. However, the failure load of both the distal and proximal host/graft conjunctions in the Eng-allograft group was significantly lower than that of the autograft group with higher graft rupture at the host-graft junction. In conclusion, the decellularized allogenic intrasynovial tendon, when revitalized BMSCs and synovialized with cd-SYN, demonstrates positive effects on digital function improvement and adhesion reduction. However, the healing at both proximal and distal graft/host junctions is far lower than the autograft. Further research is needed to enhance the healing capacity of allograft conjunctions, aiming to achieve a comparable level of healing seen with autografts.
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Aloenxertos , Tendões , Engenharia Tecidual , Animais , Cães , Engenharia Tecidual/métodos , Tendões/transplante , Traumatismos dos Tendões/cirurgia , Transplante de Células-Tronco Mesenquimais/métodos , Feminino , MasculinoRESUMO
Background: Prevention of adhesion formation following flexor tendon repair is essential for restoration of normal finger function. Although many medications have been studied in the experimental setting to prevent adhesions, clinical application is limited due to the complexity of application and delivery in clinical translation. Methods: In this study, optimal dosages of gelatin and pentamidine were validated by gelatin concentration test. Following cell viability, cell migration, live and dead cell, and cell adhesion assay of the Turkey tenocytes, a model of Turkey tendon repair was established to evaluate the effectiveness of the Pentamidine-Gelatin sheet. Results: Pentamidine carried with gelatin, a Food and drug administration (FDA) approved material for drug delivery, showed good dynamic release, biocompatibility, and degradation. The optimal dose of pentamidine (25ug) was determined in the in vivo study using tenocyte viability, migration, and cell adhesion assays. Further biochemical analyses demonstrated that this positive effect may be due to pentamidine downregulating the Wnt signaling pathway without affecting collagen expression. Conclusions: We tested a FDA-approved antibiotic, pentamidine, for reducing adhesion formation after flexor tendon repair in both in vitro and in vivo using a novel turkey animal model. Compared with the non-pentamidine treatment group, pentamidine treated turkeys had significantly reduced adhesions and improved digit function after six weeks of tendon healing. The translational potential of this article: This study for the first time showed that a common clinical drug, pentamidine, has a potential for clinical application to reduce tendon adhesions and improve tendon gliding function without interfering with tendon healing.
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Several tendon and ligament animal models were presented at the 2022 Orthopaedic Research Society Tendon Section Conference held at the University of Pennsylvania, May 5 to 7, 2022. A key objective of the breakout sessions at this meeting was to develop guidelines for the field, including for preclinical tendon and ligament animal models. This review summarizes the perspectives of experts for eight surgical small and large animal models of rotator cuff tear, flexor tendon transection, anterior cruciate ligament tear, and Achilles tendon injury using the framework: "Why, Who, What, Where, When, and How" (5W1H). A notable conclusion is that the perfect tendon model does not exist; there is no single gold standard animal model that represents the totality of tendon and ligament disease. Each model has advantages and disadvantages and should be carefully considered in light of the specific research question. There are also circumstances when an animal model is not the best approach. The wide variety of tendon and ligament pathologies necessitates choices between small and large animal models, different anatomic sites, and a range of factors associated with each model during the planning phase. Attendees agreed on some guiding principles including: providing clear justification for the model selected, providing animal model details at publication, encouraging sharing of protocols and expertise, improving training of research personnel, and considering greater collaboration with veterinarians. A clear path for translating from animal models to clinical practice was also considered as a critical next step for accelerating progress in the tendon and ligament field.
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Lesões do Ligamento Cruzado Anterior , Lesões do Manguito Rotador , Traumatismos dos Tendões , Animais , Tendões , Ligamento Cruzado Anterior/cirurgiaRESUMO
The Questionnaire for Patient-Surgeon Relationship (Q-PASREL) is a French "Patient-Reported Experience Measure" for hand surgery patients. It is the only one which considers the impact of the patient-surgeon relationship on time to return to work and cooperation by the surgeon for administrative issues. It has been shown that a good Q-PASREL score is associated with shorter sick leave and faster return to work. To make this instrument available to more countries, we translated the Q-PASREL into six languages (English, Spanish, German, Italian, Arabic and Persian), following a validated "translation and cultural adaptation" process guideline. This process includes multiple forward and backward translations, discussions and reconciliations with final harmonization and cognitive debriefing. For each language, a team was set up, comprising a key in-country hand surgery consultant, native target-language speaker and fluent in French, and several forward and back translators. The final translated versions were reviewed and approved by the project manager. The six versions of Q-PASREL are now available in the appendices of this publication.
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Idioma , Cirurgiões , Humanos , Traduções , Inquéritos e Questionários , Licença MédicaRESUMO
Over the years, various physical and chemical/biological methods of inhibiting adhesion formation have been developed, focusing on how to suppress healing around the tendon and not inhibit healing within the tendon. Unfortunately, however, these methods are accompanied by drawbacks, both large and small, and no absolute antiadhesion method capable of maintaining tendon repair strength has yet been developed. Recent innovations in biomaterials science and tissue engineering have produced new antiadhesion technologies, such as barriers combined with cytokines and cells, which have improved outcomes in animal models, and which may find clinical relevance in the future.
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Traumatismos dos Tendões , Animais , Humanos , Traumatismos dos Tendões/cirurgia , Tendões/cirurgia , Cicatrização , Aderências Teciduais/prevenção & controle , CitocinasRESUMO
BACKGROUND: Flexor digitorum profundus (FDP) tendon injury is common in hand trauma, and flexor tendon reconstruction is one of the most challenging procedures in hand surgery because of severe adhesion that exceeds 25% and hinders hand function. The surface properties of a graft from extrasynovial tendons are inferior to those of the native intrasynovial FDP tendons, which has been reported as one of the major causations. Improved surface gliding ability of the extrasynovial graft is needed. Thus, this study used carbodiimide-derivatized synovial fluid and gelatin (cd-SF-gel) to modify the surface of the graft, thus improving functional outcomes using a dog in vivo model. METHODS: Forty FDP tendons from the second and fifth digits of 20 adult women underwent reconstruction with a peroneus longus (PL) autograft after creation of a tendon repair failure model for 6 weeks. Graft tendons were either coated with cd-SF-gel ( n = 20) or not. Animals were euthanized 24 weeks after reconstruction, and digits were collected after the animals were euthanized for biomechanical and histologic analyses. RESULTS: Adhesion score (cd-SF-gel, 3.15 ± 1.53; control, 5 ± 1.26; P < 0.00017), normalized work of flexion (cd-SF-gel, 0.47 ± 0.28 N-mm/degree; control, 1.4 ± 1.45 N-mm/degree; P < 0.014), and distal interphalangeal joint motion (cd-SF-gel, 17.63 ± 6.77 degrees; control, 7.07 ± 12.99 degrees; P < 0.0015) in treated grafts all showed significant differences compared with nontreated grafts. However, there was no significant difference in repair conjunction strength between the two groups. CONCLUSION: Autograft tendon surface modification with cd-SF-gel improves tendon gliding ability, reduces adhesion formation, and enhances digit function without interfering with graft-host healing. CLINICAL RELEVANCE STATEMENT: The authors demonstrate a clinically relevant and translational technology by using the patient's own synovial fluid to "synovialize" an autologous extrasynovial tendon graft to improve functional outcomes following flexor tendon reconstruction.
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PURPOSE: The flexor digitorum superficialis (FDS) tendon transfer can be used to restore opposition of the thumb. Several pulley designs have been proposed for this transfer. Gliding resistance is considered to be an important factor influencing the efficiency of the pulley design. Our purpose was to compare the gliding resistance among 4 commonly used pulleys for the FDS oppositional transfer. METHODS: Ten fresh-frozen cadaver specimens were studied. The ring FDS was used as the donor tendon. An oppositional transfer was created using 4 pulley configurations: FDS passed around the flexor carpi ulnaris (a-FCU), FDS passed through a 2.5-cm circumference distally based FCU loop (2.5-FCU), FDS passed through a 3.5-cm circumference distally based FCU loop (3.5-FCU), and FDS passed through a longitudinal split in the FCU tendon (s-FCU). The gliding resistance was measured with the thumb in radial abduction and maximum opposition. RESULTS: In abduction, the average FDS gliding resistance of a-FCU, 2.5-FCU, 3.5-FCU, and s-FCU was 0.66 N (SD, 0.14 N), 0.70 N (SD, 0.14 N), 0.68 N (SD, 0.16 N), and 0.79 N (SD, 0.15 N), respectively. The peak gliding resistance of a-FCU, 2.5-FCU, 3.5-FCU, and s-FCU was 0.75 N (SD, 0.16 N), 0.74 N (SD, 0.15 N), 0.74 N (SD, 0.15 N), and 0.86 N (SD, 0.15 N), respectively. CONCLUSIONS: The average gliding resistance of the s-FCU was found to be significantly higher than that of the a-FCU and 3.5-FCU pulleys. In opposition, there were no differences in average or peak gliding resistance among the different pulley designs. CLINICAL RELEVANCE: In this in vitro cadaveric study, the FDS split pulley produced higher gliding resistance. Consideration of the pulley configuration may improve the overall thumb function by decreasing forces needed to overcome gliding resistance.
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Transferência Tendinosa , Tendões , Humanos , Tendões/cirurgia , Dedos , Músculo Esquelético , Polegar/cirurgia , Fenômenos BiomecânicosRESUMO
The intrinsic healing following tendon injury is ideal, in which tendon progenitor cells proliferate and migrate to the injury site to directly bridge or regenerate tendon tissue. However, the mechanism determining why and how those cells are attracted to the injury site for tendon healing is not understood. Since the tenocytes near the injury site go through apoptosis or necrosis following injury, we hypothesized that secretions from injured tenocytes might have biological effects on cell proliferation and migration to enhance tendon healing. Tenocyte apoptosis was induced by 24 h cell starvation. Apoptotic body-rich media (T-ABRM) and apoptotic body-depleted media (T-ABDM) were collected from culture media after centrifuging. Tenocytes and bone marrow-derived stem cells (BMDSCs) were isolated and cultured with the following four media: (1) T-ABRM, (2) T-ABDM, (3) GDF-5, or (4) basal medium with 2% fetal calf serum (FCS). The cell activities and functions were evaluated. Both T-ABRM and T-ABDM treatments significantly stimulated the cell proliferation, migration, and extracellular matrix synthesis for both tenocytes and BMDSCs compared to the control groups (GDF-5 and basal medium). However, cell proliferation, migration, and extracellular matrix production of T-ABRM-treated cells were significantly higher than the T-ABDM, which indicates the apoptotic bodies are critical for cell activities. Our study revealed the possible mechanism of the intrinsic healing of the tendon in which apoptotic bodies, in the process of apoptosis, following tendon injury promote tenocyte and stromal cell proliferation, migration, and production. Future studies should analyze the components of the apoptotic bodies that play this role, and, thus, the targeting of therapeutics can be developed.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , Traumatismos dos Tendões , Proliferação de Células , Células Cultivadas , Meios de Cultura/farmacologia , Fator 5 de Diferenciação de Crescimento/farmacologia , Humanos , Células-Tronco Mesenquimais/fisiologia , Soroalbumina Bovina/farmacologia , Traumatismos dos Tendões/terapia , TenócitosRESUMO
Rotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age-related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age-related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased nonmineralized zone. Proliferation, migration, and colony-forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and highlights the importance of using age-appropriate models, as well as provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.
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Lesões do Manguito Rotador , Manguito Rotador , Adipogenia , Animais , Condrogênese , Osteogênese , RatosAssuntos
Desenvolvimento Muscular , Músculos , Animais , Expressão Gênica , Desenvolvimento Muscular/genética , RatosRESUMO
BACKGROUND: Carpal tunnel syndrome patients demonstrate diminished motion of the median nerve and fibrotic changes in the subsynovial connective tissue within the carpal tunnel. Currently, there are few prognostic factors to help predict the outcome of commonly performed treatments including surgical carpal tunnel release and corticosteroid injections. This study aimed to non-invasively assess the changes in the dynamic response of the subsynovial tissue relative to tendon motion after the intervention and to correlate this with disease severity. METHODS: A total of 145 patients with carpal tunnel syndrome were recruited into this study. Clinical and demographic data, electrophysiological severity and dynamic ultrasound images were collected before and after treatment, either by injection or surgery. The relative motion of the subsynovial tissue with the underlying middle finger flexor digitorum superficialis tendon was measured using a speckle tracking algorithm and was expressed as a shear index (SI). Baseline and follow-up data, the association between change in SI and severity, and the role of treatment modality were analyzed and statistically compared. FINDINGS: Overall, there was a significant increase (more relative motion) after treatment in the mean shear index from 79.9% (±15.4% SD) to 82.9% (±14.8% SD) (p = 0.03). Secondary analyses showed that this change was mostly present in those with mild disease severity undergoing surgery (p = 0.01). INTERPRETATION: This study shows that the relative subsynovial tissue movement increases in patients after intervention. The present study lays a foundation for future studies to non-invasively assess the role of carpal tunnel dynamics in response to treatment.
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Síndrome do Túnel Carpal , Síndrome do Túnel Carpal/diagnóstico por imagem , Síndrome do Túnel Carpal/cirurgia , Tecido Conjuntivo/diagnóstico por imagem , Humanos , Nervo Mediano , Tendões/diagnóstico por imagem , Tendões/cirurgia , UltrassonografiaRESUMO
BACKGROUND: The nerve autograft remains the gold standard when reconstructing peripheral nerve defects. However, although autograft repair can result in useful functional recovery, poor outcomes are common, and better treatments are needed. The purpose of this study was to evaluate the effect of purified exosome product on functional motor recovery and nerve-related gene expression in a rat sciatic nerve reverse autograft model. METHODS: Ninety-six Sprague-Dawley rats were divided into three experimental groups. In each group, a unilateral 10-mm sciatic nerve defect was created. The excised nerve was reversed and used to reconstruct the defect. Group I animals received the reversed autograft alone, group II animals received the reversed autograft with fibrin glue, and group III animals received the reversed autograft with purified exosome product suspended in the fibrin glue. The animals were killed at 3 and 7 days and 12 and 16 weeks after surgery. Evaluation included compound muscle action potentials, isometric tetanic force, tibialis anterior muscle wet weight, nerve regeneration-related gene expression, and nerve histomorphometry. RESULTS: At 16 weeks, isometric tetanic force was significantly better in group III (p = 0.03). The average axon diameter of the peroneal nerve was significantly larger in group III at both 12 and 16 weeks (p = 0.015 at 12 weeks; p < 0.01 at 16 weeks). GAP43 and S100b gene expression was significantly up-regulated by purified exosome product. CONCLUSIONS: Local administration of purified exosome product demonstrated improved nerve regeneration profiles in the reverse sciatic nerve autograft rat model. Thus, purified exosome product may have beneficial effects on nerve regeneration, gene profiles, and motor outcomes.
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Exossomos , Regeneração Tecidual Guiada/métodos , Traumatismos dos Nervos Periféricos/cirurgia , Nervo Isquiático/transplante , Neuropatia Ciática/cirurgia , Animais , Autoenxertos/fisiologia , Modelos Animais de Doenças , Humanos , Masculino , Regeneração Nervosa , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Nervo Isquiático/fisiologiaRESUMO
Nerve area and motion in carpal tunnel syndrome (CTS) are currently under investigation in terms of prognostic potential. Therefore, there is increasing interest in non-invasive measurement of the nerve using ultrasound. Manual segmentation is time consuming and subject to inter-rater variation, providing an opportunity for automation. Dynamic ultrasound images (nâ¯=â¯5560) of carpal tunnels from 99 clinically diagnosed CTS patients were used to train a U-Net-shaped neural network. The best results from the U-Net were achieved with a location primer as initial region of interest for the segmentations during finger flexion (Dice coefficientâ¯=â¯0.88). This is comparable to the manual Dice measure of 0.92 and higher than the resulting automated Dice measure of wrist flexion (0.81). Although there is a dependency on image quality, a trained U-Net can reliably be used in the assessment of ultrasound-acquired median nerve size and mobility, considerably decreasing manual effort.
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Síndrome do Túnel Carpal/diagnóstico por imagem , Nervo Mediano/diagnóstico por imagem , Redes Neurais de Computação , Síndrome do Túnel Carpal/fisiopatologia , Humanos , Nervo Mediano/fisiopatologia , Amplitude de Movimento Articular , Ultrassonografia/métodos , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/fisiopatologiaRESUMO
OBJECTIVE: The incidence of carpal tunnel syndrome (CTS) is higher in women, and peaks around the age of menopause. Therefore, we investigated whether bilateral oophorectomy is associated with an increased risk of severe CTS. METHODS: We included all of the 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication between 1988 and 2007, and a random sample of 1,653 age-matched referent women who did not undergo bilateral oophorectomy in Olmsted County, MN. Diagnoses of CTS assigned to women over their entire lifetime were identified in these two cohorts. The risk of de novo severe CTS after bilateral oophorectomy (or index date) was evaluated using Cox proportional hazards models adjusted for potential confounders. RESULTS: Bilateral oophorectomy was associated with an increased risk of severe CTS (adjusted hazard ratio 1.65, 95% confidence interval 1.20-2.25). The risk was suggestively greater in women with lower body mass index, nulliparity, and with a benign ovarian indication for oophorectomy (nonsignificant interactions). We did not observe a protective effect of estrogen therapy after the oophorectomy. The findings were similar in secondary analyses considering the incidence of CTS of any severity or idiopathic CTS. CONCLUSIONS: The risk of severe CTS, common in perimenopausal women, is increased after bilateral oophorectomy. The association may be causal or due to confounding. Therefore, the precise biological mechanisms explaining the association and the absence of a mitigating effect of estrogen therapy should be further investigated.
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Síndrome do Túnel Carpal , Fatores Etários , Síndrome do Túnel Carpal/epidemiologia , Síndrome do Túnel Carpal/etiologia , Síndrome do Túnel Carpal/cirurgia , Estudos de Coortes , Feminino , Humanos , Ovariectomia , Fatores de RiscoRESUMO
BACKGROUND: The suture-tendon interface turned out to be the weak point of a repaired rotator cuff. A double rip-stop (DRS) technique was developed to enhance the strength of the suture-tendon interface. The first aim of this study was to compare the suture-tendon interface strength between mesh suture and the No. 2 FiberWire (FW), which is commonly used in the clinic. The second aim was to compare the biomechanical properties of rotator cuff repair between mesh suture and No. 2 FiberWire using a typical suture-bridge (SB) and DRS techniques. METHODS: Eighteen porcine subscapularis tendon (SST) was randomly assigned to the Mesh-tendon group and FiberWire-tendon group. A single suture loop was passed through the SST with a Mesh suture or FiberWire. Thirty-two infraspinatus tendons (ISTs) were randomly assigned to four groups: SB-Mesh group: SB technique with Mesh suture, SB-FW group: SB technique with FiberWire, DRS-Mesh group: DRS technique with Mesh suture, and DRS-FW group: DRS technique with FiberWire. All repaired specimens were underwent failure testing. Failure modes, load to create a 3-mm gap, failure load, and stiffness were compared. RESULTS: There were no significant differences between the Mesh-tendon group and FiberWire-tendon group regarding the failure load, stiffness, and ultimate stress. When the same technique was used, the rotator cuff repaired with a mesh suture had the similar load to create a 3-mm gap, failure load, and stiffness compared with FiberWire. When the same suture was used, the DRS technique had a significantly higher load to create a 3-mm gap formation and failure load compared with the SB technique. CONCLUSIONS: The repair failure strength and stiffness using the mesh suture were similar to the FiberWire suture regardless of the repair techniques. However, the repair strength in the DRS technique was significantly stronger than the SB technique when the same suture material was used.
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Carpal tunnel syndrome (CTS) is a disorder that affects the median nerve at the wrist sufficient to cause impairment of nerve function. Elevated carpal tunnel pressure (CTP) leads to median nerve pathology, sensory, and motor changes in CTS patient. The techniques to quantify CTP used in clinic are invasive. This study aimed to investigate the feasibility of a noninvasive ultrasound vibro-elastography (UVE) to predict CTP in CTS patients and healthy individuals. The magnitudes of shear wave speed ratio (rSWS) of the 10 CTS patients (10 hands) and 6 healthy individuals (12 hands), and 10 cadaveric hands were compared using UVE. The ratios of intra to extra-carpal tunnel SWS in CTS patients was significantly higher than those in the healthy individuals (p = 0.0008) and cadaveric hands (p = 0.0015) with 500-g tendon tension. We estimated the CTP in the carpal tunnel using the mean rSWS of each group obtained from the present study and the linear approximation obtain from cadaveric hands data with 500-g tendon tension (y = 0.0036x + 1.1413). These results indicated that the elevated pressure applied to the 3rd flexor digitorum superficialis tendon in the carpal tunnel of CTS patients resulted in faster shear wave propagation. These results show that UVE was useful to indirectly estimate the CTP by measuring the rSWS; thus, they are potentially useful for the early diagnosis and assessment of CTS.
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Síndrome do Túnel Carpal , Técnicas de Imagem por Elasticidade , Síndrome do Túnel Carpal/diagnóstico por imagem , Humanos , Nervo Mediano/diagnóstico por imagem , Tendões/diagnóstico por imagem , PunhoRESUMO
OBJECTIVES: The mobility (transverse movement) of the median nerve (MN) is decreased in patients with carpal tunnel syndrome and can be measured noninvasively by ultrasound. To date, there are few prognostic features to help predict the outcome of 2 commonly performed treatments: surgical carpal tunnel release and corticosteroid injection. This study aimed to assess the changes in nerve mobility after the intervention and to correlate this with treatment and the disease severity. METHODS: A total of 181 patients with carpal tunnel syndrome with different electrophysiologic severities were recruited and assessed by dynamic ultrasound scanning of the MN before and after treatment. The dynamic ultrasound images were collected while the patients performed finger and wrist flexion. RESULTS: For both injection and carpal tunnel release, the nerve displacement increased with wrist flexion, from a mean ± SD of 7.0 ± 2.4 to 7.9 ± 2.7 mm (P < .005). Patients who underwent surgery showed greater improvement (P < .005) in nerve mobility compared to those who underwent injection. We also observed that the increase in nerve mobility was predominantly in patients with more nerve damage at baseline. CONCLUSIONS: This study shows that the dynamic behavior of the MN changes in response to treatment and lays a foundation for future studies to assess the prognostic potential of nerve mobility measurement.
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Síndrome do Túnel Carpal , Nervo Mediano , Síndrome do Túnel Carpal/diagnóstico por imagem , Síndrome do Túnel Carpal/cirurgia , Humanos , Nervo Mediano/diagnóstico por imagem , Ultrassonografia , Punho/diagnóstico por imagem , Articulação do Punho/diagnóstico por imagemRESUMO
BACKGROUND: The purpose of this study was to determine the effect of fibrinogen concentration on cell viability and migration in a tissue culture tendon healing model. METHODS: Forty-eight canine flexor digitorum profundus tendons were randomly divided into three groups. In each group the tendons were lacerated and repaired augmented with a canine bone marrow stromal cell seeded fibrin interposition patch using either 5 mg/ml fibrinogen and 25 U/ml thrombin (physiological as a control), 40 mg/ml fibrinogen and 250 U/ml thrombin (low adhesive), or 80 mg/ml fibrinogen and 250 U/ml thrombin (high adhesive). The sutured tendons were cultured for two or four weeks. RESULTS: Failure load was not significantly different among the groups. Cell-labeling staining showed that the stromal cells migrated across the gap in the control and low adhesive groups, but there was no cell migration in the high adhesive group at two weeks. CONCLUSION: A high fibrinogen concentration in a fibrin patch or glue may impede early cell migration. LEVEL OF EVIDENCE: Not applicable because this study was a laboratory study.
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Procedimentos de Cirurgia Plástica , Traumatismos dos Tendões , Animais , Cães , Movimento Celular , Fibrina , Traumatismos dos Tendões/tratamento farmacológico , Traumatismos dos Tendões/cirurgia , Tendões/cirurgiaRESUMO
BACKGROUND: Carpal Tunnel Syndrome (CTS) is an idiopathic fibrotic disorder. Fibrosis in the subsynovial connective tissues (SSCT) of CTS and many other fibrotic diseases is mediated by Transforming growth factor ß (TGF-ß). Recently monocyte chemoattractant protein-1 (MCP-1) a cytokine involved in cellular recruitment has been suggested to regulate TGF-ß activity. It is related to the onset of diseases which are caused by fibrosis, such as idiopathic pulmonary fibrosis, renal fibrosis, and systemic scleroderma. In this study, we evaluated the effect of the MCP-1 synthesis inhibitor, Bindarit, on primary cultures of fibroblasts from the SSCT of five CTS patients. METHODS: Fibroblasts were treated with Bindarit (10 µM, 50 µM, 100 µM, or 300 µM). Responses to inhibitors were evaluated by regulation of CTS fibrosis-associated genes, fibrosis gene array and Smad luciferase reporter assay. We also assessed the combination effect of Bindarit and SD208, a TGF-ß receptor type 1 inhibitor on TGF-ß signaling. RESULTS: Collagen type III A1 (Col3), connective tissue growth factor (CTGF), and SERPINE1 expression were significantly down-regulated by Bindarit (300 µM) compared to vehicle control. In the fibrosis array, expression of inhibin beta E chain precursor (INHBE), beta actin (ACTB), endothelin 1 (EDN1) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) were significantly down-regulated, and integrin beta-3 (ITGB3) was significantly up-regulated by Bindarit (300 µM). Smad signal transduction activation was significantly down-regulated by Bindarit (300 µM) and/or SD208 (1 µM) with TGF-ß1 compared to vehicle control with TGF-ß1. CONCLUSIONS: These results suggest that Bindarit in combination with SD208 may be beneficial as medical therapy for the SSCT fibrosis associated with CTS.
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Síndrome do Túnel Carpal , Quimiocina CCL2 , Síndrome do Túnel Carpal/tratamento farmacológico , Quimiocina CCL2/antagonistas & inibidores , Colágeno Tipo III , Fibroblastos , Fibrose , Humanos , Fator de Crescimento Transformador beta , Fator de Crescimento Transformador beta1RESUMO
Reducing tendon failure after repair remains a challenge due to its poor intrinsic healing ability. The purpose of this study is to investigate the effect of a novel tissue-engineered purified exosome product (PEP) patch on tendon healing in a canine ex vivo model. Lacerated flexor digitorum profundus (FDP) tendons from three canines' paws underwent simulated repair with Tisseel patch alone or biopotentiated with PEP. For the ex vivo model, FDP tendons were randomly divided into three groups: FDP tendon repair alone group (Control), Tisseel patch alone group, and the Tisseel plus PEP (TEPEP) patch group. Following 4 weeks of tissue culture, the failure load, stiffness, histology, and gene expression of the healing tendon were evaluated. Transmission electron microscopy revealed that in exosomes of PEP the diameters ranged from 93.70 to 124.65 nm, and the patch release test showed this TEPEP patch could stably release the extracellular vesicle over 2 weeks. The failure strength of the tendon in the TEPEP patch group was significantly higher than that of the Control group and Tisseel alone group. The results of histology showed that the TEPEP patch group had the smallest healing gap and the largest number of fibroblasts on the surface of the injured tendon. Quantitative reverse transcription polymerase chain reaction showed that TEPEP patch increased the expression of collagen type III, matrix metallopeptidase 2 (MMP2), MMP3, MMP14, and reduced the expression of transforming growth factor ß1, interleukin 6. This study shows that the TEPEP patch could promote tendon repair by reducing gap formation and inflammatory response, increasing the activity of endogenous cells, and formation of type III collagen.