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.

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.

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.

The Management of Cubital Tunnel Syndrome.

Symptomatic cubital tunnel syndrome is a condition that frequently prompts patients to seek hand surgical care. Although cubital tunnel syndrome is readily diagnosed, achieving complete symptom resolution remains challenging. This article reviews related anatomy, clinical presentation, and current management options for cubital tunnel syndrome with an emphasis on contemporary outcomes research.

Trapeziometacarpal Arthritis: A Prospective Clinical Evaluation of the Thumb Adduction and Extension Provocative Tests.

PURPOSE: To determine the diagnostic performance (ie, sensitivity, specificity, interrater reliability) of the thumb metacarpal adduction and extension tests against traditional examination maneuvers for trapeziometacarpal (TMC) arthritis. METHODS: This cross-sectional study recruited 129 patients from 2 outpatient offices at a tertiary institution. All patients had radiographic wrist examinations and completed a standardized physical examination consisting of the thumb adduction and extension tests as well as standard examination maneuvers for radial wrist and thumb pain. The physical examinations were performed by 1 of 2 attending physicians and an independent examiner. Patients were recruited for 3 diagnostic groups: TMC arthritis, radial wrist or hand pain, and nonradial wrist pain controls. Statistical analysis calculated the sensitivity, specificity, and interrater reliability of each physical examination maneuver for detecting TMC arthritis. RESULTS: The thumb adduction maneuver was found to have a sensitivity of 0.94 (confidence interval [CI], 0.82-0.98) and a specificity of 0.93 (CI, 0.86-0.97). The thumb extension maneuver had a sensitivity of 0.94 (CI, 0.82-0.98) and a specificity of 0.95 (CI, 0.87-0.98). The interrater reliability was excellent for both the adduction (κ = 0.79) and the extension tests (κ = 0.84). The grind test had a sensitivity of 0.44 (CI, 0.30-0.59), a specificity of 0.92 (CI, 0.84-0.97), and poor interrater reliability (0.31). Point tenderness at the TMC joint had a sensitivity of 0.94 (CI, 0.82-0.98), a specificity of 0.81 (CI, 0.71-0.88) and fair interrater reliability (κ = 0.63). CONCLUSIONS: The adduction and extension tests each proved to be more sensitive than the grind test for the detection of TMC arthritis. Further, these provocative tests were more specific for basal joint arthrosis than was the elicitation of point tenderness at the joint. The metacarpal adduction and extension maneuvers demonstrated excellent utility as screening tests for the identification of TMC arthritis. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

The Impact of Uninterrupted Warfarin on Hand and Wrist Surgery.

PURPOSE: To determine the impact of uninterrupted use of warfarin on hand and wrist surgery. METHODS: This single-center, prospective cohort trial enrolled adult patients undergoing hand and wrist surgery. Between May 2009 and August 2014, 47 surgical patients receiving uninterrupted warfarin (50 procedures) were enrolled and matched as a group by age and procedure type to 48 surgical patients (50 procedures) who were not prescribed warfarin. Complications, defined as bleeding, infection, or wound dehiscence requiring reoperation, were recorded for each group. Surgical outcome measures were composed of objective findings affected by surgical site bleeding (ie, ecchymosis extent, hematoma presence, 2-point discrimination) and standardized patient-rated assessments (Quick-Disabilities of the Arm, Shoulder, and Hand, and visual analog scales: pain and swelling). We collected data preoperatively and at 2 and 4 weeks postoperatively. Statistical analyses contrasted complications and outcomes data between patient groups. RESULTS: One procedure (2%; 95% confidence interval, 0% to 11%) in a patient taking warfarin was complicated by hematoma requiring reoperation resulting from an elevated postoperative international normalized ratio of 5.4. There were no complications among controls (0%; 95% confidence interval, 0% to 7%). At 2 weeks postoperatively, patients receiving warfarin more frequently had hematomas (28% vs 10%) and demonstrated a greater extent of ecchymosis from the surgical incision (50 vs 19 mm). At 4 weeks, no differences existed in hematoma presence or extent of ecchymosis between groups. The incidence of transiently elevated 2-point discrimination was not different between groups (10% warfarin; 6% controls). Visual analog scores for pain and swelling were not significantly different between groups at any time. Differences in Quick-Disabilities of the Arm, Shoulder, and Hand scores between groups did not exceed a minimal clinically important difference. CONCLUSIONS: Uninterrupted use of warfarin in patients undergoing surgery of the hand and wrist was associated with an infrequent risk of bleeding complication requiring reoperation. Increased rates of hematoma and ecchymosis in patients taking warfarin normalized by 4 weeks postoperatively. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

The effect of suture caliber and number of core suture strands on zone II flexor tendon repair: a study in human cadavers.

PURPOSE: To compare the tensile properties of a 3-0, 4-strand flexor tendon repair with a 4-0, 4-strand repair and a 4-0, 8-strand repair. METHODS: Following evaluation of the intrinsic material properties of the 2 core suture calibers most commonly used in tendon repair (3-0 and 4-0), we tested the mechanical properties of 40 cadaver flexor digitorum profundus tendons after zone II repair with 1 of 3 techniques: a 3-0, 4-strand core repair, a 4-0, 8-strand repair, or a 4-0, 4-strand repair. We compared results across suture caliber for the 2 sutures and across tendon repair methods. RESULTS: Maximum load to failure of 3-0 polyfilament caprolactam suture was 49% greater than that of 4-0 polyfilament caprolactam suture. The cross-sectional area of 3-0 polyfilament caprolactam was 42% greater than that of 4-0 polyfilament caprolactam. The 4-0, 8-strand repair produced greater maximum load to failure when compared with the 2 4-strand techniques. Load at 2-mm gap, stiffness, and work to yield were significantly greater in the 4-0, 8-strand repair than in the 3-0, 4-strand repair. CONCLUSIONS: In an ex vivo model, an 8-strand repair using 4-0 suture was 43% stronger than a 4-strand repair using 3-0 suture, despite the finding that 3-0 polyfilament caprolactam was 49% stronger than 4-0 polyfilament caprolactam. These results suggest that, although larger-caliber suture has superior tensile properties, the number of core suture strands across a repair site has an important effect on time zero, ex vivo flexor tendon repair strength. CLINICAL RELEVANCE: Surgeons should consider using techniques that prioritize multistrand core suture repair over an increase in suture caliber.

Outcomes following modified oblique medial epicondylectomy for treatment of cubital tunnel syndrome.

PURPOSE: To quantify and define objective and patient-rated outcomes after our modification of medial epicondylectomy for the treatment of cubital tunnel syndrome. Although medial epicondylectomy has been previously studied, data are lacking regarding elbow-specific outcomes after our technique that aims to minimize complications historically associated with medical epicondylectomy. METHODS: A total of 27 subjects with clinical and electrodiagnostic evidence of cubital tunnel syndrome underwent a modified oblique medial epicondylectomy that was designed to minimize bony resection and preserve the origin of the ulnar collateral ligament of the elbow. Average age was 57 years, mean duration of symptoms was 24 months, and mean postoperative follow-up was 29 months. Eight patients had McGowan stage I disease, 14 had stage II, and 5 had stage III. Preoperatively, we measured intrinsic hand strength, 2-point discrimination, and residual medial elbow pain, and assessed for continuing signs and symptoms of nerve compression. Postoperatively, we added to the clinical examination elbow stability testing, elbow range of motion, and assessment of medial antebrachial cutaneous nerve injury. We collected patient-reported outcomes, including Quick Disabilities of the Shoulder, Arm, and Hand; Levine-Katz Severity Score; and Patient-Rated Elbow Evaluation. RESULTS: We noted improvement of at least 1 McGowan grade in 20 of 27 patients (74%). Three of the 7 patients who had no change in McGowan grade still reported excellent patient-rated outcomes. Good to excellent results were achieved in 25 of 27 patients (93%). One patient had long-term severe medial elbow pain. Three patients had postoperative medial elbow pain that resolved with a single corticosteroid injection. One patient had a 30° flexion contracture; preoperative motion was not available for comparison. No patients had signs of elbow instability or numbness in the medial antebrachial cutaneous nerve distribution. CONCLUSIONS: Modified oblique medial epicondylectomy was effective in improving symptoms in cubital tunnel syndrome. This medial collateral ligament sparing technique minimized complications previously associated with the original technique. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Outcomes of rigid night splinting and activity modification in the treatment of cubital tunnel syndrome.

PURPOSE: To prospectively analyze, using validated outcome measures, symptom improvement in patients with mild to moderate cubital tunnel syndrome treated with rigid night splinting and activity modifications. METHODS: Nineteen patients (25 extremities) were enrolled prospectively between August 2009 and January 2011 following a diagnosis of idiopathic cubital tunnel syndrome. Patients were treated with activity modifications as well as a 3-month course of rigid night splinting maintaining 45° of elbow flexion. Treatment failure was defined as progression to operative management. Outcome measures included patient-reported splinting compliance as well as the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire and the Short Form-12. Follow-up included a standardized physical examination. Subgroup analysis included an examination of the association between splinting success and ulnar nerve hypermobility. RESULTS: Twenty-four of 25 extremities were available at mean follow-up of 2 years (range, 15-32 mo). Twenty-one of 24 (88%) extremities were successfully treated without surgery. We observed a high compliance rate with the splinting protocol during the 3-month treatment period. Quick Disabilities of the Arm, Shoulder, and Hand scores improved significantly from 29 to 11, Short Form-12 physical component summary score improved significantly from 45 to 54, and Short Form-12 mental component summary score improved significantly from 54 to 62. Average grip strength increased significantly from 32 kg to 35 kg, and ulnar nerve provocative testing resolved in 82% of patients available for follow-up examination. CONCLUSIONS: Rigid night splinting when combined with activity modification appears to be a successful, well-tolerated, and durable treatment modality in the management of cubital tunnel syndrome. We recommend that patients presenting with mild to moderate symptoms consider initial treatment with activity modification and rigid night splinting for 3 months based on a high likelihood of avoiding surgical intervention. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

The impact of antiplatelet medication on hand and wrist surgery.

PURPOSE: To quantify the impact of maintaining antiplatelet medication during hand and wrist surgery on bleeding and functional outcomes. METHODS: This prospective cohort trial compared operative outcomes and complications of hand and wrist surgery in patients without interruption of daily antiplatelet medications (n = 107 procedures) with control patients (n = 107 procedures). We determined rates of complications requiring reoperation for each group. We compared measures of surgical site bleeding (extent of ecchymosis or hematoma formation), patient-rated outcome assessment (Quick Disabilities of the Arm, Shoulder, and Hand score and visual analog scales of pain and swelling), and 2-point discrimination between groups. Data were collected preoperatively and postoperatively at 2 and 4 weeks. We confirmed control and antiplatelet populations to be similar for data analysis according to health status (Short Form-12) and percentage of bony procedures. RESULTS: One patient receiving antiplatelet medication required reoperation for surgical site bleeding after wrist arthrodesis (0.9%). There were no complications in the control group. The extent of postoperative ecchymosis was similar in the antiplatelet and control patients at 2 weeks (16 vs 19 mm) and 4 weeks (1 vs 1 mm). Hematoma rates were not increased for patients receiving antiplatelet medication (17% vs 14% at 2 wk). Patient-rated function scores were equivalent at baseline and at follow-up between groups. A total of 22 control patients and 20 patients receiving antiplatelet medication had transiently increased 2-point discrimination (≥ 2-mm change) postoperatively. CONCLUSIONS: Bleeding-related perioperative complications were rare when continuing antiplatelet medications without interruption for hand and wrist surgery. Maintenance of antiplatelet medication does not appear to negatively affect patient-rated or objective measures of function, although surgical-site bleeding may be greatest in patients taking higher-dose antiplatelet medication and undergoing bony procedures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Ligamentous hyperlaxity and dorsal wrist ganglions.

PURPOSE: To determine whether symptomatic dorsal wrist ganglions are associated with generalized ligamentous hyperlaxity. METHODS: Ninety-six patients (61 females) presenting to hand surgeons for a symptomatic dorsal wrist ganglions were prospectively enrolled in this case-control investigation. Beighton scores were calculated to quantify generalized ligamentous laxity in each patient, and a scaphoid shift test (scapholunate capsuloligamentous laxity evaluation) was performed. A positive scaphoid shift test was defined by both pain and a palpable clunk. Ninety-six individuals without ganglions were then enrolled to form an age and sex frequency-matched control cohort. The control group was similarly assessed for Beighton score and scaphoid shift test. Binary logistical regression was performed to assess the association of ganglions with generalized ligamentous hyperlaxity (Beighton score ≥ 4) while accounting for effects of age and sex. RESULTS: Patients with symptomatic dorsal wrist ganglions demonstrated significantly increased rates of generalized ligamentous hyperlaxity. Among those with ganglions, 27 of 96 (28%) patients exhibited generalized ligamentous hyperlaxity, compared with 12 of the 96 (13%) age- and sex-matched individuals in the control group. Patients with symptomatic dorsal wrist ganglions were also significantly more likely to demonstrate localized scapholunate hyperlaxity with a positive scaphoid shift test (25% positive scaphoid shift test with ganglions vs 1% in controls). In logistical modeling, patients with dorsal wrist ganglions had 2.9 (95% confidence interval [CI] 1.3-6.2) times greater odds of generalized ligamentous hyperlaxity compared with patients without a dorsal wrist ganglion after accounting for patient age and sex. CONCLUSIONS: Symptomatic dorsal wrist ganglions were associated with both generalized ligamentous hyperlaxity and a positive scaphoid shift test. Although an association between wrist ganglions and ligamentous hyperlaxity does not prove causation, the possibility of the same underlying pathological entity causing both can be envisioned (ie, abnormal formation or organization of dense regular connective tissue). TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic III.

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 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.

The effect of core and epitendinous suture modifications on repair of intrasynovial flexor tendons in an in vivo canine model.

PURPOSE: To determine in vivo effects of modifications to core and epitendinous suture techniques in a canine intrasynovial flexor tendon repair model using clinically relevant rehabilitation. Our null hypothesis was that gap formation and rupture rates would remain consistent across repair techniques. METHODS: We evaluated gap formation and rupture in 75 adult mongrel dogs that underwent repair of intrasynovial flexor tendon lacerations followed by standardized postoperative therapy. The current suture technique was a 4-0, 8-strand core suture with a purchase of 1.2 cm and a 5-0, epitendinous suture repair with a 2-mm purchase length and depth. We compared gap and failure by chi-square analysis to a historical group of in vivo repairs (n = 76) from the same canine model using 8-strand core suture repair with purchase of 0.75 cm and 6-0 epitendinous suture with a 1-mm purchase length and depth. RESULTS: A total of 93% of tendons (n = 70) demonstrated gapping of less than 3 mm using the current suture technique. Five percent of tendons (n = 4) had a gap of 3 mm or greater, and there was 1 repair site failure. This was significantly improved over the comparison group of historical 8-strand core repair technique, which resulted in 82% (n = 62) of repairs with a gap of less than 3 mm and 7 failures (9%). CONCLUSIONS: In an in vivo model, current modifications to suture techniques for intrasynovial flexor tendon repair demonstrated significant improvements in gap formation and rupture compared with a similar technique using shorter purchase lengths and shallower purchase depth. CLINICAL RELEVANCE: Suggested repair modifications for the treatment of zone II flexor tendon transections demonstrate improvements in gap formation and tendon rupture in vivo.

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.

Technical and biological modifications for enhanced flexor tendon repair.

Clinical outcomes after intrasynovial flexor tendon repair have been substantially improved over the past 2 decades through advances in tendon suture techniques and postoperative rehabilitation methods. Nevertheless, complications such as repair site elongation (i.e., gap formation) and rupture continue to occur frequently. Experimental studies have shown that repair site strength fails to increase in the first 3 weeks after tendon suture. After 3 weeks, the strength and rigidity of the repair site improve significantly, a process that continues for several months. Formation of a repair site gap during the early rehabilitation period has been shown to considerably delay the accrual of repair site strength over time. Thus, it is of prime importance that the method of tendon suture achieves and maintains a stiff and strong repair site during the early healing interval by maintaining close approximation of the tendon stumps and by stimulating, where possible, the intrinsic repair response. In this review, we describe recent efforts to enhance the integrity of the immature repair site. We focus on 2 major areas of advancement: surgical technique modifications and manipulation of the biologic and biochemical environment.

Joint leveling for advanced Kienböck's disease.

PURPOSE: The use of joint leveling procedures to treat Kienböck's disease have been limited by the degree of disease advancement. This study was designed to compare clinical and radiographic outcomes of wrists with more advanced (stage IIIB) Kienböck's disease with those of wrists with less advanced (stage II/IIIA) disease following radius-shortening osteotomy. METHODS: This retrospective study enrolled 31 adult wrists (30 patients; mean age, 39 y), treated with radius-shortening osteotomy at 2 institutions for either stage IIIB (n = 14) or stage II/IIIA (n = 17) disease. Evaluation was performed at a mean of 74 months (IIIB, 77 mo; II/IIIA, 72 mo). Radiographic assessment determined disease progression. Clinical outcomes were determined by validated patient-based and objective measures. RESULTS: Patient-based outcome ratings of wrists treated for stage IIIB were similar to those with stage II/IIIA (shortened Disabilities of the Arm, Shoulder, and Hand score, 15 vs 12; modified Mayo wrist score, 84 vs 87; visual analog scale pain score, 1.2 vs 1.7; visual analog scale function score, 2.6 vs 2.1). The average flexion/extension arc was 102° for wrists with stage IIIB and 106° for wrists with stage II/IIIA Kienbock's. Grip strength was 77% of the opposite side for stage IIIB wrists versus 85% for stage II/IIIA. Postoperative carpal height ratio and radioscaphoid angle were worse for wrists treated for stage IIIB (0.46 and 65°, respectively) than stage II/IIIA (0.53 and 53°, respectively) disease. Radiographic disease progression occurred in 7 wrists (6 stage II/IIIA, 1 stage IIIB). The one stage IIIB wrist that progressed underwent wrist arthrodesis. CONCLUSIONS: In this limited series, clinical outcomes of radius shortening using validated, patient-based assessment instruments and objective measures failed to demonstrate predicted clinically relevant differences between stage II/IIIA and IIIB Kienböck's disease. Given the high percentage of successful clinical outcomes in this case series of 14 stage IIIB wrists, we believe that static carpal malalignment does not preclude radius-shortening osteotomy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.