The effects of NF-κB suppression on the early healing response following intrasynovial tendon repair in a canine model.

The highly variable clinical outcomes noted after intrasynovial tendon repair have been associated with an early inflammatory response leading to the development of fibrovascular adhesions. Prior efforts to broadly suppress this inflammatory response have been largely unsuccessful. Recent studies have shown that selective inhibition of IkappaB kinase beta (IKK-ß), an upstream activator of nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) signaling, mitigates the early inflammatory response and leads to improved tendon healing outcomes. In the current study, we test the hypothesis that oral treatment with the IKK-ß inhibitor ACHP (2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinenitrile an inhibitor) will modulate the postoperative inflammatory response and improve intrasynovial flexor tendon healing. To test this hypothesis, the flexor digitorum profundus tendon of 21 canines was transected and repaired within the intrasynovial region and assessed after 3 and 14 days. Histomorphometry, gene expression analyses, immunohistochemistry, and quantitative polarized light imaging were used to examine ACHP-mediated changes. ACHP led to reduction in phosphorylated p-65, indicating that NF-κB activity was suppressed. ACHP enhanced expression of inflammation-related genes at 3 days and suppressed expression of these genes at 14 days. Histomorphometry revealed enhanced cellular proliferation and neovascularization in ACHP-treated tendons compared with time-matched controls. These findings demonstrate that ACHP effectively suppressed NF-κB signaling and modulated early inflammation, leading to increased cellular proliferation and neovascularization without stimulating the formation of fibrovascular adhesions. Together, these data suggest that ACHP treatment accelerated the inflammatory and proliferative phases of tendon healing following intrasynovial flexor tendon repair. Clinical Significance: Using a clinically relevant large-animal model, this study revealed that targeted inhibition of nuclear factor kappa-light chain enhancer of activated B cells signaling with ACHP provides a new therapeutic strategy for enhancing the repair of sutured intrasynovial tendons.

Metabolic regulation of intrasynovial flexor tendon repair: The effects of dichloroacetate administration on early tendon healing in a canine model.

Enriched in glycolytic enzymes, paucicellular and hypovascular intrasynovial flexor tendons fail to mount an effective healing response after injury and repair. In contrast, well-vascularized extrasynovial flexor tendons possess high levels of oxidative phosphorylation (OXPHOS) enzymes and have a markedly improved healing capacity. This study was designed to compare the metabolic profiles of the two types of tendons and to evaluate the impact of metabolic reprogramming on early intrasynovial tendon healing in a clinically relevant canine model. Results showed that healthy intrasynovial tendons expressed higher levels of PDK1 and GAPDH and lower levels of SCX and IGF1 than did extrasynovial tendons. PDK1 encodes a subtype of pyruvate dehydrogenase kinase (PDK) that inhibits OXPHOS. Consistently, ATP production via glycolysis was favored in intrasynovial tendon cells whereas OXPHOS was the preferred pathway in extrasynovial tendon cells. Inhibition of glycolysis in vitro increased SCX expression in intrasynovial tendon cells. Therefore, dichloroacetate (DCA), a PDK1 inhibitor, was used in vivo to shift intrasynovial tendon ATP production from glycolysis to OXPHOS. Oral DCA administration reduced serum lactate concentration and increased acetyl-CoA content in repaired intrasynovial tendons and led to reduced TLR4 and IL1B and increased IGF1, SCX, and TGFB3 expressions in treated intrasynovial tendons compared to controls. Immunohistochemistry staining with anti-Ki67 and anti-CD31 antibodies revealed marked increases in cellularity and neovascularization in treated intrasynovial tendons. Clinical significance: The findings of this experiment indicate that improved gene expression and histological outcomes can be achieved by regulating glucose metabolism in the early stages following intrasynovial tendon repair.

The Utility of the Carpal Tunnel Syndrome-6 for Predicting the Outcomes of Carpal Tunnel Release.

PURPOSE: Considering the cost of, discomfort with, and time required for nerve conduction testing, the Carpal Tunnel Syndrome-6 (CTS-6) is often used to determine the likelihood of the presence of carpal tunnel syndrome. We sought to determine whether the CTS-6, designed as a diagnostic instrument, could serve a dual purpose and predict the outcome of carpal tunnel release (CTR) based on postoperative changes in the Boston Carpal Tunnel Questionnaire (BCTQ) score. METHODS: This prospective observational study enrolled 118 adults before they underwent open CTR at a tertiary center. A primary regression analysis was used to determine the association between preoperative CTS-6 scores and changes in the BCTQ score at ≥6 months after surgery. Additional demographic, social, electrodiagnostic, and mental health variables were assessed for associations with changes in the BCTQ score. The secondary outcomes included single questions rating satisfaction with the result of CTR as well as symptom changes and the Decision Regret Scale. Noneffective CTR was defined as a BCTQ score change of <1.0 point or reported dissatisfaction. RESULTS: Postoperatively, the BCTQ score improvement averaged 1.38 ± 0.77. Although 102 of 109 patients (94%) noted symptom improvement, 94 of 109 (86%) were satisfied with the result of CTR, and 78 of 109 patients (72%) demonstrated a meaningful change in the BCTQ score. Preoperative CTS-6 scores were not correlated with changes in BCTQ scores. CTS-6 scores were not associated with Decision Regret Scale scores, reported satisfaction, or the single-question assessment of symptom changes. Satisfaction, decision regret, and the single symptom change question were correlated with changes in the BCTQ score and each other. Dissatisfied patients were distinguished by a differential improvement in the BCTQ score (1.5 vs 0.7), but no preoperative variable consistently predicted noneffective CTR. CONCLUSIONS: The CTS-6 score does not predict changes in BCTQ scores after CTR. Patient satisfaction with surgical results is associated with postoperative changes in carpal tunnel symptoms but is not predictable using preoperative information. A single question of symptom change may offer an efficient assessment of CTR outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

The use of connective tissue growth factor mimics for flexor tendon repair.

Intrasynovial flexor tendon lacerations of the hand are clinically problematic, typically requiring operative repair and extensive rehabilitation. The small-molecule connective tissue growth factor (CTGF) mimics, oxotremorine M (Oxo-M) and 4-PPBP maleate (4-PPBP), have been shown to improve tendon healing in small animal models by stimulating the expansion and differentiation of perivascular CD146+ cells. To enhance intrasynovial flexor tendon healing, small-molecule CTGF mimics were delivered to repaired canine flexor tendons via porous sutures. In vitro studies demonstrated that Oxo-M and 4-PPBP retained their bioactivity and could be released from porous sutures in a sustained manner. However, in vivo delivery of the CTGF mimics did not improve intrasynovial tendon healing. Histologic analyses and expression of tenogenic, extracellular matrix, inflammation, and remodeling genes showed similar outcomes in treated and untreated repairs across two time points. Although in vitro experiments revealed that CTGF mimics stimulated robust responses in extrasynovial tendon cells, there was no response in intrasynovial tendon cells, explaining the lack of in vivo effects. The results of the current study indicate that therapeutic strategies for tendon repair must carefully consider the environment and cellular makeup of the particular tendon for improving the healing response.

Flexor Tendon Injury and Repair. The Influence of Synovial Environment on the Early Healing Response in a Canine Model.

BACKGROUND: Environmental conditions strongly influence the healing capacity of connective tissues. Well-vascularized extrasynovial tendons typically undergo a robust wound-healing process following transection and repair. In contrast, avascular intrasynovial tendons do not mount an effective repair response. The current study tests the hypothesis that flexor tendons, as a function of their synovial environment, exhibit unique inflammatory, angiogenic, and metabolic responses to injury and repair. METHODS: Flexor tendons present a distinct opportunity to test the study hypothesis, as they have proximal regions that are extrasynovial and distal regions that are intrasynovial. In an internally controlled study design, the second and fifth forepaw flexor tendons were transected and repaired in either the extrasynovial or the intrasynovial anatomical region. Histological, gene expression, and proteomics analyses were performed at 3 and 7 days to define the early biological events that drive synovial environment-dependent healing responses. RESULTS: Uninjured intrasynovial tendons were avascular, contained high levels of proteoglycans, and expressed inflammatory factors, complement proteins, and glycolytic enzymes. In contrast, extrasynovial tendons were well vascularized, contained low levels of proteoglycans, and were enriched in inflammation inhibitors and oxidative phosphorylation enzymes. The response to injury and repair was markedly different between the 2 tendon regions. Extrasynovial tendons displayed a robust and rapid neovascularization response, increased expression levels of complement proteins, and an acute shift in metabolism to glycolysis, whereas intrasynovial tendons showed minimal vascularity and muted inflammatory and metabolic responses. CONCLUSIONS: The regional molecular profiles of intact and healing flexor tendons revealed extensive early differences in innate immune response, metabolism, vascularization, and expression of extracellular matrix as a function of the synovial environment. These differences reveal mechanisms through which extrasynovial tendons heal more effectively than do intrasynovial tendons. CLINICAL RELEVANCE: To improve outcomes after operative repair, future treatment strategies should promote features of extrasynovial healing, such as enhanced vascularization and modulation of the complement system and/or glucose metabolism.

Stem cell-derived extracellular vesicles attenuate the early inflammatory response after tendon injury and repair.

Adipose-derived stem cells (ASCs) have the potential to enhance tendon repair via paracrine regulation of the inflammatory response to injury. Extracellular vesicles (EVs), which are secreted by ASCs, have shown promise in mediating this process. This study was designed to evaluate the effect of ASC EVs on early tendon healing using a mouse Achilles tendon injury and repair model. EVs were isolated from the conditioned medium of naïve and interferonγ-primed ASCs and applied to the repair site via a collagen sheet. Tendon healing was assessed in nuclear factor-κB (NF-κB)-luciferase reporter mice up to 7 days after suture repair. As anticipated, repair site NF-κB activity increased greater than twofold following tendon repair. Treatment with EVs from primed but not naïve ASCs effectively suppressed the response. Accordingly, the pro-inflammatory genes Il1b and Ifng were both dramatically increased in repaired tendons, while primed, but not naïve ASC EVs attenuated the response. Compared with control repairs, primed ASC EVs further reduced the rate of post-repair tendon gap formation and rupture and facilitated collagen formation at the injury site. Additional experiments demonstrated that EVs target macrophages and that primed ASC EVs were most effective in blocking macrophage NF-κB activity. Collectively, the findings of this study demonstrate that primed ASC EVs, similar to ASCs, attenuate the early tendon inflammatory response after injury via modulation of the macrophage inflammatory response. Statement of clinical significance: These findings introduce a new cell-free therapy, derived from stem cells, for tendon repair with the potential for improved therapeutic efficacy and safety. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:117-127, 2020.

The Academic Chair: Achieving Success in a Rapidly Evolving Health-Care Environment: AOA Critical Issues.

There is a growing consensus that an accomplished curriculum vitae and prior achievement as an academician may not correlate with success as a chairperson of a contemporary academic orthopaedic department. As surgeons, formal professional education, research expertise, and clinical experience often are inadequate to foster the necessary skills and experience in executive leadership, change management, business administration, and strategy. The recruiting and hiring processes to fill academic leadership roles have been slow to adapt and recognize the skills that are necessary to be a successful chairperson. Recent research has identified emotional competency, resiliency, leadership, communication, results orientation, and personnel development as skills that correlate with success in academic leadership. Formal courses and training in executive leadership and business management may be helpful in enhancing knowledge and skills in these disciplines.

The effect of modified locking methods and suture materials on Zone II flexor tendon repair-An ex vivo study.

The failure rate of intrasynovial tendon repair is high due to substantial elongation at the repair site and to the development of adhesions between the tendon's surface and the surrounding digital sheath. To minimize these complications, we sought to reduce the incidence of gapping and to facilitate the initiation of early motion by improving the time zero structural properties of repair. The Winters-Gelberman 8-strand repair technique was modified by adding surface lock loops and by using Fiberwire suture material. Forty-eight canine flexor digitorum profundus tendons were transected and repaired with one of three 8-strand techniques (Pennington modified Kessler, half hitch loops, or surface locking Kessler) using either 3-0 Supramid or 4-0 Fiberwire suture. Biomechanical testing was performed to determine the physiologic and failure mode properties of the repairs. The surface locking Kessler technique improved repair maximum load, load necessary to create a 2 mm repair site gap, and yield force compared to the modified Kessler and half hitch loop techniques. Fiberwire suture improved maximum load, the load necessary to create a 2 mm repair site gap, stiffness, and yield force compared to Supramid suture. Failure occurred by both suture pull out and by suture breakage in the modified Kessler, Supramid suture repair group. Failure occurred consistently by suture breakage in the surface locking Kessler, Supramid suture repair group. These results reveal that a novel locking Kessler repair is significantly stronger than the current state-of-the art flexor tendon suture repair technique. The use of a surface locking Kessler technique with Fiberwire suture markedly improves the mechanical properties of intrasynovial tendon repair by reducing the risk of post-operative gapping and rupture.

Academic Orthopaedic Leadership: Current Challenges and Lessons Learned: AOA Critical Issues.

Health-care reform, market competition, cost containment, and pressure for productivity have dramatically impacted the practice of orthopaedic surgery and academic surgical training. Orthopaedic leaders and training programs are striving to identify and solve these contemporary challenges. Herein, we focus on 4 areas that currently pose important challenges to modern orthopaedic surgical departments and academic hospital systems, including the demanding and evolving skill sets that are required of physician leaders, the effects of the changing medical-legal environment on academic medicine, the impact of increased clinical productivity emphasis on surgical education, and departmental leadership transitions.

The effect of adipose-derived stem cell sheets and CTGF on early flexor tendon healing in a canine model.

Intrasynovial tendon injuries are among the most challenging in orthopedics. Despite significant improvements in operative and rehabilitation methods, functional outcomes continue to be limited by adhesions, gap formation, and rupture. Adhesions result from excessive inflammation, whereas tendon gapping and rupture result from inflammation-induced matrix degradation and insufficient regeneration. Therefore, this study used a combined treatment approach to modulate inflammation with adipose-derived mesenchymal stromal cells (ASCs) while stimulating tendon regeneration with connective tissue growth factor (CTGF). ASCs were applied to the repair surface via cell sheets and CTGF was delivered to the repair center via porous sutures. The effect of the combined treatment was assessed fourteen days after repair in a canine flexor tendon injury model. CTGF, either alone or with ASCs, reduced inflammatory (IL1B and IL6) and matrix degrading (MMP3 and MMP13) gene expression, while increasing anti-inflammatory gene (IL4) expression and collagen synthesis compared to control repairs. The combined treatment was more effective than CTGF treatment alone, reducing the inflammatory IFNG and scar-associated COL3A1 gene expression and increasing CD146+ tendon stem/progenitor cells at the tendon surface and interior along the core suture tracks. Therefore, the combined approach is promising in promoting early flexor tendon healing and worthy of further investigation.

Surgical transposition for chronic instability of the extensor carpi ulnaris tendon.

Painful extensor carpi ulnaris tendon instability has various treatments with limited available outcome data. We treated 12 wrists of 11 patients (including eight collegiate or professional athletes) with dorsal transposition of the extensor carpi ulnaris tendon to lie over the 5th compartment, stabilized with a retinacular sling from 2010-2015. All patients had symptom resolution and returned to sport at the pre-injury level by 3 months after surgery. Mean post-surgical Patient Reported Outcomes Measurement Information System (PROMIS) upper extremity score was 56, and PROMIS pain interference score was 42. Patient overall satisfaction averaged 9.8 points on a 10-point scale for the procedure and pain decreased by 6 points on a 10-point scale from before surgery to final follow-up. We conclude that surgical treatment of the extensor carpi ulnaris tendon instability via dorsal transposition of the extensor carpi ulnaris tendon is an effective surgical option for all patients including the high level athlete. Level of evidence: IV.

Effect of connective tissue growth factor delivered via porous sutures on the proliferative stage of intrasynovial tendon repair.

Recent growth factor, cell, and scaffold-based experimental interventions for intrasynovial flexor tendon repair have demonstrated therapeutic potential in rodent models. However, these approaches have not achieved consistent functional improvements in large animal trials due to deleterious inflammatory reactions to delivery materials and insufficient induction of targeted biological healing responses. In this study, we achieved porous suture-based sustained delivery of connective tissue growth factor (CTGF) into flexor tendons in a clinically relevant canine model. Repairs with CTGF-laden sutures were mechanically competent and did not show any evidence of adhesions or other negative inflammatory reactions based on histology, gene expression, or proteomics analyses at 14 days following repair. CTGF-laden sutures induced local cellular infiltration and a significant biological response immediately adjacent to the suture, including histological signs of angiogenesis and collagen deposition. There were no evident widespread biological effects throughout the tendon substance. There were significant differences in gene expression of the macrophage marker CD163 and anti-apoptotic factor BCL2L1; however, these differences were not corroborated by proteomics analysis. In summary, this study provided encouraging evidence of sustained delivery of biologically active CTGF from porous sutures without signs of a negative inflammatory reaction. With the development of a safe and effective method for generating a positive local biological response, future studies can explore additional methods for enhancing intrasynovial tendon repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2052-2063, 2018.

Combined Administration of ASCs and BMP-12 Promotes an M2 Macrophage Phenotype and Enhances Tendon Healing.

BACKGROUND: Outcomes after intrasynovial tendon repair are highly variable. An intense inflammatory cascade followed by a delayed healing response can cause adhesion formation and repair-site failure that severely impair the function of repaired digits. No effective remedies exist to fully address these issues. Cell- and growth factor-based therapies have been shown to modulate inflammation and improve cell proliferation and matrix synthesis and therefore are promising treatment approaches for intrasynovial tendon repair. QUESTIONS/PURPOSES: (1) Can autologous adipose-derived mesenchymal stromal cells (ASCs) and recombinant bone morphogenetic protein-12 (rBMP-12) be effectively delivered to an intrasynovial flexor tendon repair without adverse effects? (2) Do autologous ASCs modulate the inflammatory response after intrasynovial tendon injury and repair? (3) Does the combined application of autologous ASCs and rBMP-12 modulate the proliferative and remodeling responses after intrasynovial tendon injury and repair? METHODS: Sixteen 1- to 2-year-old female canines were used in this study. Autologous ASC sheets, with and without rBMP-12, were applied to the surface of sutured flexor tendons. Fourteen days after repair, the effects of treatment were determined using quantitative PCR (six per group) for the expression of genes related to macrophage phenotype or inflammation (IL-4, CD163, VEGF, NOS2, IL-1B, and IFNG), cell proliferation (CCND1), and tendon formation (SCX, TNMD, COL1A1 and COL3A1). Proteomics analysis (four per group) was performed to examine changes in tendon protein abundances. CD146 immunostaining and hematoxylin and eosin staining (four per group) were used to detect tendon stem or progenitor cells and to semiquantitatively evaluate cellularity at the tendon repair; analyses were done blinded to group. RESULTS: Gross inspection and cell tracing showed that autologous ASCs and rBMP-12 were delivered to the flexor tendon repair site without the deleterious effects of adhesion and repair-site gap formation. Quantitative assessment of gene and protein expression showed effects of treatment: ASC-sheet treatment modulated the postrepair inflammatory response and facilitated healing by increasing regenerative M2 macrophages (M2 marker CD204, twofold of normal, p = 0.030), inflammatory inhibitor (prostaglandin reductase 1 [PTRG1], 1.6-fold of normal, p = 0.026), and proteins involved in tendon formation (periostin [POSTN], 1.9-fold of normal, p = 0.035). Consistently, semiquantitative and qualitative evaluations of repaired tissue showed that ASC-sheet treatment reduced mononuclear cell infiltration (12% less than nontreated tendons, p = 0.021) and introduced CD146+ stem or progenitor cells to the repair site. The combined administration of ASCs and rBMP-12 further stimulated M2 macrophages by increasing IL-4 (116-fold of normal, p = 0.002) and led to the increase of M2 effector matrix metalloproteinase-12 involved in matrix remodeling (twofold of normal, p = 0.016) and reduction of a negative regulator of angiogenesis and cell migration (StAR-related lipid transfer domain protein13 [STARD13]; 84% of normal, p = 0.000), thus facilitating the proliferative stage of tendon repair. CONCLUSIONS: ASCs and BMP-12 accelerated the progression of healing in the proliferative stage of tendon repair. The effects of ASCs and BMP-12 on tendon functional recovery should be evaluated in future studies. CLINICAL RELEVANCE: The cell sheet approach is an effective, biocompatible, and surgeon-friendly approach for cell and growth factor delivery during tendon repair. Combined application of ASCs and BMP-12 may accelerate intrasynovial tendon healing while suppressing the adverse inflammatory response.

Long-Term Effectiveness of Repeat Corticosteroid Injections for Trigger Finger.

PURPOSE: To quantify the long-term success of repeat injections for trigger fingers and to identify predictors of treatment outcomes. METHODS: This retrospective case series analyzed 292 repeat corticosteroid injections for trigger fingers administered by hand surgeons at a single tertiary center between January 2010 and January 2013. One hundred eighty-seven patients (64%) were female, 139 patients (48%) had multiple trigger fingers, and 63 patients (22%) were diabetic. The primary outcome, treatment failure, was defined as receiving a subsequent injection or surgical treatment. Patients without either documented failure or a return office visit in 2015 or 2016 were surveyed by telephone to determine if they had required subsequent treatment. Kaplan-Meier analyses with log-rank testing assessed the median time to treatment failure and the effect of demographic and disease-specific characteristics on injection success rate and predictors of injection outcome (success vs failure) were assessed with multivariable logistic regression. RESULTS: Second injections provided long-term treatment success in 39% (111 of 285) of trigger fingers with 86 receiving an additional injection and 108 ultimately undergoing surgical release. Thirty-nine percent (24 of 62) of third injections resulted in long-term success, with 22 receiving an additional injection, and 23 ultimately undergoing surgery. Median times-to-failure for second and third injections were 371 and 407 days, respectively. Success curves did not differ significantly according to any patient or disease factor. Logistic regression identified that advancing patient age and injection for trigger thumb were associated with success of second injections. CONCLUSIONS: Thirty-nine percent of second and third corticosteroid injections for trigger finger yield long-term relief. Although most patients ultimately require surgical release, 50% of patients receiving repeat trigger injections realize 1 year or more of symptomatic relief. Repeat injections of trigger fingers should be considered in patients who prefer nonsurgical treatment. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Locking Plate Arthrodesis Compares Favorably with LRTI for Thumb Trapeziometacarpal Arthrosis: Early Outcomes from a Longitudinal Cohort Study.

BACKGROUND: Trapeziometacarpal arthrodesis (TMA) has been complicated by nonunion and hardware failure. QUESTIONS/PURPOSES: We hypothesized that modification of the TMA technique with a locking cage plate construct would afford reliable bony union while producing greater hand function than trapeziectomy with ligament reconstruction and tendon interposition (LRTI) at early follow-up. METHODS: We enrolled 36 consecutive patients with trapeziometacapal osteoarthritis (14 TMA patients (15 thumbs), 22 LRTI patients (22 thumbs)). The study was powered to detect a minimal clinically important difference on the QuickDASH questionnaire between groups. Secondary outcomes included Michigan Hand Questionnaire (MHQ), VAS-pain, and EQ-5D-3L scores. Patients were examined to evaluate thumb motion and strength. TMA patients were evaluated clinically and radiographically for union. RESULTS: Mean follow-up was 15.6 months, and the mean age was 59.2 years. Union was achieved in 14/15 (93%) of TMA thumbs. Improvement in QuickDASH scores was similar after TMA and LRTI (49 to 28 and 50 to 18, respectively). Postoperative patient-rated upper extremity function, health status, and pain were similar between groups. Pinch strength was significantly greater after TMA (5.9 vs 4.7 kg). No differences in thumb or wrist range of motion were observed postoperatively with the exception of greater total metacarpophalangeal joint motion after TMA. Complications after TMA included nonunion (7%), development of symptomatic scaphotrapezotrapezoidal (STT) arthrosis (7%), symptomatic hardware (7%), and superficial branch of the radial nerve (SBRN) paresthesia (7%). Complications after LRTI included subsidence (5%), MP hyperextension deformity (5%), and SBRN paresthesias (5%). CONCLUSIONS: At early follow-up, patient-rated function was similar among patients undergoing TMA and LRTI. TMA produced 25% greater pinch strength compared with LRTI. Despite historical concerns regarding global loss of ROM with arthrodesis, motion was similar between groups. Our observed TMA nonunion rate of 7% is low relative to historically reported nonunion rates (7-16%). Locking cage plate technology affords rigid fixation for TMA with promising early results noting reliable bony union while minimizing complications.

The effect of mesenchymal stromal cell sheets on the inflammatory stage of flexor tendon healing.

BACKGROUND: The clinical outcomes following intrasynovial flexor tendon repair are highly variable. Excessive inflammation is a principal factor underlying the formation of adhesions at the repair surface and affecting matrix regeneration at the repair center that limit tendon excursion and impair tendon healing. A previous in-vitro study revealed that adipose-derived mesenchymal stromal cells (ASCs) modulate tendon fibroblast response to macrophage-induced inflammation. The goal of the current study was therefore to explore the effectiveness of autologous ASCs on the inflammatory stage of intrasynovial tendon healing in vivo using a clinically relevant animal model. METHODS: Zone II flexor tendon transections and suture repairs were performed in a canine model. Autologous ASC sheets were delivered to the surface of repaired tendons. Seven days after repair, the effects of ASCs on tendon healing, with a focus on the inflammatory response, were evaluated using gene expression assays, immunostaining, and histological assessments. RESULTS: ASCs delivered via the cell sheet infiltrated the host tendon, including the repair surface and the space between the tendon ends, as viewed histologically by tracking GFP-expressing ASCs. Gene expression results demonstrated that ASCs promoted a regenerative/anti-inflammatory M2 macrophage phenotype and regulated tendon matrix remodeling. Specifically, there were significant increases in M2-stimulator (IL-4), marker (CD163 and MRC1), and effector (VEGF) gene expression in ASC-sheet treated tendons compared with nontreated tendons. When examining changes in extracellular matrix expression, tendon injury caused a significant increase in scar-associated COL3A1 expression and reductions in COL2A1 and ACAN expression. The ASC treatment effectively counteracted these changes, returning the expression levels of these genes closer to normal. Immunostaining further confirmed that ASC treatment increased CD163+ M2 cells in the repaired tendons and suppressed cell apoptosis at the repair site. CONCLUSIONS: This study provides a novel approach for delivering ASCs with outcomes indicating potential for substantial modulation of the inflammatory environment and enhancement of tendon healing after flexor tendon repair.

Simultaneous Bilateral Versus Staged Bilateral Carpal Tunnel Release: A Cost-effectiveness Analysis.

The purpose of this study was to determine if simultaneous bilateral carpal tunnel release (CTR) is a cost-effective strategy compared with bilateral staged CTR for the treatment of bilateral carpal tunnel syndrome. METHODS: A decision analytic model was created to compare the cost effectiveness of three strategies (ie, bilateral simultaneous CTR, bilateral staged CTR, and no treatment). Direct medical costs were estimated from 2013 Medicare reimbursement rates and wholesale drug costs in US dollars. Indirect costs were derived from consecutive patients undergoing unilateral or simultaneous bilateral CTR at our institution and from national average wages for 2013. Health state utility values were derived from a general population of volunteers using the Short Form-6 dimensions (SF-6D) health questionnaire. RESULTS: Both surgical strategies were cost effective compared with the no-treatment strategy. Bilateral simultaneous CTR had lower total costs and higher total effectiveness than bilateral staged CTR, and had an incremental cost-effectiveness ratio of $921 per quality-adjusted life year compared with the no-treatment strategy. The conclusions of the analysis remained unchanged though all sensitivity analyses, displaying robustness against parameter uncertainty. CONCLUSIONS: Surgical management is cost effective for the treatment of bilateral carpal tunnel syndrome. Bilateral simultaneous CTR, however, has lower total costs and higher total effectiveness compared with bilateral staged CTR. LEVEL OF EVIDENCE: Economic and Decision Analysis I.

Enhanced Zone II Flexor Tendon Repair through a New Half Hitch Loop Suture Configuration.

This study evaluated the impact of a new half hitch loop suture configuration on flexor tendon repair mechanics. Cadaver canine flexor digitorum profundus tendons were repaired with 4- or 8-strands, 4-0 or 3-0 suture, with and without half hitch loops. An additional group underwent repair with half hitch loops but without the terminal knot. Half hitch loops improved the strength of 8-strand repairs by 21% when 4-0, and 33% when 3-0 suture was used, and caused a shift in failure mode from suture pullout to suture breakage. 8-strand repairs with half hitch loops but without a terminal knot produced equivalent mechanical properties to those without half hitch loops but with a terminal knot. 4-strand repairs were limited by the strength of the suture in all groups and, as a result, the presence of half hitch loops did not alter the mechanical properties. Overall, half hitch loops improved repair mechanics, allowing failure strength to reach the full capability of suture strength. Improving the mechanical properties of flexor tendon repair with half hitch loops has the potential to reduce the postoperative risk of gap formation and catastrophic rupture in the early postoperative period.

Cell and Biologic-Based Treatment of Flexor Tendon Injuries.

The two primary factors leading to poor clinical results after intrasynovial tendon repair are adhesion formation within the digital sheath and repair-site elongation and rupture. As the outcomes following modern tendon multi-strand repair and controlled rehabilitation techniques are often unsatisfactory, alternative approaches, such as the application of growth factors and mesenchymal stem cells (MSCs), have become increasingly attractive treatment options. Successful biological therapies require carefully controlled spatiotemporal delivery of cells, growth factors, and biocompatible scaffold matrices in order to simultaneously (1) promote matrix synthesis at the tendon repair site leading to increased biomechanical strength and stiffness and (2) suppress matrix synthesis along the tendon surface and synovial sheath preventing adhesion formation. This review summarizes recent cell and biologic-based experimental treatments for flexor tendon injury, with an emphasis on large animal translational studies.