Workflow and Outcome of Thrombectomy in Late Time Window: A Pooled Multicenter Analysis.

BACKGROUND: We investigated the impact of workflow times on the outcomes of patients treated with endovascular thrombectomy (EVT) in the late time window. METHODS: Individual patients' data who underwent EVT in the late time window (onset to imaging >6 hours) were pooled from seven registries and randomized clinical trials. Multiple time intervals were analyzed. Mixed-effects logistic regression was used to estimate the likelihood of functional independence at 90 days (modified Rankin Scale 0-2). Mixed-effects negative binomial regression was used to evaluate the relationship between patient characteristics and workflow time intervals. RESULTS: 608 patients were included. The median age was 70 years (IQR: 58-71), 307 (50.5%) were female, and 310 (53.2%) had wake-up strokes. Successful reperfusion was achieved in 493 (81.2%) patients, and 262 (44.9%) achieved 90-day mRS 0-2. The estimated odds of functional independence decreased by 13% for every 30 minute delay from emergency department (ED) arrival to imaging time and by 7% from ED arrival to the end of EVT in the entire cohort. Also, the estimated odds of functional independence decreased by 33% for every 30 minute delay in the interval from arterial puncture to end of EVT, 16% in the interval from arrival in ED to end of EVT and 6% in the interval from stroke onset to end of EVT among patients who had a wake-up stroke. CONCLUSION: Faster workflow from ED arrival to end of EVT is associated with improved functional independence among stroke patients treated in the late window.

Patient gender and rotator cuff surgery: are there differences in outcome?

BACKGROUND: Although rotator cuff syndrome is common and extensively studied from the perspective of producing healed tendons, influence of gender on patient-reported outcomes is less well examined. As activity and role demands may vary widely between men and women, clarity on whether gender is an important factor in outcome would enhance patient education and expectation management. Our purpose was to determine if differences exist in patient-reported outcomes between men and women undergoing rotator cuff surgery. METHODS: One hundred forty-eight participants (76 W:72 M) aged 35-75 undergoing surgery for unilateral symptomatic rotator cuff syndrome were followed for 12 months after surgery. Demographics, surgical data, and the Western Ontario Rotator Cuff (WORC) scores were collected. Surgery was performed by two fellowship-trained shoulder surgeons at a single site. RESULTS: There were no gender-based differences in overall WORC score or subcategory scores by 12 months post-op. Pain scores were similar at all time points in men and women. Women were more likely to have dominant-arm surgery and had smaller rotator cuff tears than men. Complication rates were low, and satisfaction was high in both groups. CONCLUSION: Patient gender doesn't appear to exert an important effect on patient-reported rotator cuff outcomes in this prospective cohort. Further work examining other covariates as well as the qualitative experience of going through rotator cuff repair should provide greater insight into factors that influence patient-reported outcomes.

PrEvention of posttraumatic contractuRes with Ketotifen 2 (PERK 2) - protocol for a multicenter randomized clinical trial.

BACKGROUND: Injuries and resulting stiffness around joints, especially the elbow, have huge psychological effects by reducing quality of life through interference with normal daily activities such as feeding, dressing, grooming, and reaching for objects. Over the last several years and through numerous research results, the myofibroblast-mast cell-neuropeptide axis of fibrosis had been implicated in post-traumatic joint contractures. Pre-clinical models and a pilot randomized clinical trial (RCT) demonstrated the feasibility and safety of using Ketotifen Fumarate (KF), a mast cell stabilizer to prevent elbow joint contractures. This study aims to evaluate the efficacy of KF in reducing joint contracture severity in adult participants with operately treated elbow fractures and/or dislocations. METHODS/DESIGN: A Phase III randomized, controlled, double-blinded multicentre trial with 3 parallel groups (KF 2 mg or 5 mg or lactose placebo twice daily orally for 6 weeks). The study population consist of adults who are at least 18 years old and within 7 days of injury. The types of injuries are distal humerus (AO/OTA type 13) and/or proximal ulna and/or proximal radius fractures (AO/OTA type 2 U1 and/or 2R1) and/or elbow dislocations (open fractures with or without nerve injury may be included). A stratified randomization scheme by hospital site will be used to assign eligible participants to the groups in a 1:1:1 ratio. The primary outcome is change in elbow flexion-extension range of motion (ROM) arc from baseline to 12 weeks post-randomization. The secondary outcomes are changes in ROM from baseline to 6, 24 & 52 weeks, PROMs at 2, 6, 12, 24 & 52 weeks and impact of KF on safety including serious adverse events and fracture healing. Descriptive analysis for all outcomes will be reported and ANCOVA be used to evaluate the efficacy KF over lactose placebo with respect to the improvement in ROM. DISCUSSION: The results of this study will provide evidence for the use of KF in reducing post-traumatic joint contractures and improving quality of life after joint injuries. TRIAL REGISTRATION: This study was prospectively registered (July 10, 2018) with ClinicalTrials.gov reference: NCT03582176.

Reconstruction of medial collateral ligament defects with a flexor-pronator fascia patch in complete open release of stiff elbows.

BACKGROUND: Because medial elbow stability is essential for stiff elbow release, surgical techniques have been reported for reconstructing medial elbow stability. However, medial collateral ligament (MCL) defects, caused by inevitable detachment and resection performed for complete release, make the reconstruction more challenging. To our knowledge, no study has evaluated the outcomes after using a flexor-pronator fascia patch in medial elbow reconstruction for open release of stiff elbows. We hypothesized that this technique is effective for repairing MCL defects. METHODS: We retrospectively reviewed the records of 10 patients. The MCL defects were all reconstructed with a flexor-pronator fascia patch. An external fixator was used in all patients. One patient could not be contacted and was thus excluded from the study. Outcome measures included stability, range of motion, Mayo Elbow Performance Score, ulnar nerve symptoms, power grip, and radiographic findings. RESULTS: The mean follow-up period was 19.6 months; all elbows were stable by the last follow-up. One patient presented with moderate elbow instability and then regained stability 3 months after the external fixator was removed. The Mayo Elbow Performance Score improved from 58 points to 94 points, and the mean flexion arc improved from 40° to 133°. No radiographic manifestations of elbow dislocation or suture anchor looseness were observed. CONCLUSION: A flexor-pronator fascia patch provides sufficient stability for repairing MCL defects without restricting the range of motion gained during arthrolysis.

Open arthrolysis for elbow stiffness increases carrying angle but has no impact on functional recovery.

BACKGROUND: With the exception of normal anatomic changes in the medial collateral ligament and radial head, other factors related to carrying angle changes have not been systematically studied. We reviewed patients who underwent open arthrolysis of the elbow, and evaluated if open arthrolysis could change carrying angle. We then identified factors associated with carrying angle changes. METHODS: Fifty patients with a minimum of 24 months of follow-up after open arthrolysis were evaluated retrospectively. Preoperative and postoperative carrying angles were compared. RESULTS: The carrying angles of 36 elbows in 36 patients were unchanged after surgery (Group A), while the carrying angles of 14 elbows in 14 patients increased postoperatively (Group B). In Group A, mean postoperative extension and flexion were 7° (range 0-24°) and 125° (range 10-135°) respectively, while mean postoperative pronation and supination were 60° (range 50-80°) and 65° (range 30-85°), respectively. In Group B, mean postoperative extension and flexion were 25° (range 0-40°) and 128° (range 60-138°), while mean postoperative pronation and supination were 65° (range 45-85°) and 60° (range 45-75°), respectively. No significant difference in range of motion and Mayo Elbow Performance Score was observed between the two groups. CONCLUSIONS: During open arthrolysis, humeral trochlea debridement and techniques for improving forearm rotation could increase carrying angle. However, this had no impact on elbow functional recovery.

Subscapularis partial tear nodule causing shoulder rotational triggering.

UNLABELLED: Subscapularis nodules are rare causes of shoulder pain. There have been no reports of nodular swellings arising from the articular surface of the subscapularis tendon. We report two original cases of intra-articular subscapular nodules with reciprocal middle glenohumeral ligament thickening. In both cases, the patients had long standing deep-seated anterior shoulder pain with failed conservative treatments. Arthroscopy, magnetic resonance imaging and histology reports revealed nodules with underlying partial subscapularis tears. Arthroscopy may be needed to identify and successfully treat rare symptomatic nodules as causes of pain and clicking in the shoulder joint. LEVEL OF EVIDENCE: V.

Liberal or restrictive transfusion in high-risk patients after hip surgery.

BACKGROUND: The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial. We conducted a randomized trial to determine whether a higher threshold for blood transfusion would improve recovery in patients who had undergone surgery for hip fracture. METHODS: We enrolled 2016 patients who were 50 years of age or older, who had either a history of or risk factors for cardiovascular disease, and whose hemoglobin level was below 10 g per deciliter after hip-fracture surgery. We randomly assigned patients to a liberal transfusion strategy (a hemoglobin threshold of 10 g per deciliter) or a restrictive transfusion strategy (symptoms of anemia or at physician discretion for a hemoglobin level of <8 g per deciliter). The primary outcome was death or an inability to walk across a room without human assistance on 60-day follow-up. RESULTS: A median of 2 units of red cells were transfused in the liberal-strategy group and none in the restrictive-strategy group. The rates of the primary outcome were 35.2% in the liberal-strategy group and 34.7% in the restrictive-strategy group (odds ratio in the liberal-strategy group, 1.01; 95% confidence interval [CI], 0.84 to 1.22), for an absolute risk difference of 0.5 percentage points (95% CI, -3.7 to 4.7). The rates of in-hospital acute coronary syndrome or death were 4.3% and 5.2%, respectively (absolute risk difference, -0.9%; 99% CI, -3.3 to 1.6), and rates of death on 60-day follow-up were 7.6% and 6.6%, respectively (absolute risk difference, 1.0%; 99% CI, -1.9 to 4.0). The rates of other complications were similar in the two groups. CONCLUSIONS: A liberal transfusion strategy, as compared with a restrictive strategy, did not reduce rates of death or inability to walk independently on 60-day follow-up or reduce in-hospital morbidity in elderly patients at high cardiovascular risk. (Funded by the National Heart, Lung, and Blood Institute; FOCUS ClinicalTrials.gov number, NCT00071032.).

Low-Intensity Pulsed Ultrasound Versus Sham in the Treatment of Operatively Managed Scaphoid Nonunions: The SNAPU Randomized Controlled Trial.

BACKGROUND: The primary goal after open reduction and internal fixation of an established scaphoid nonunion is to achieve union. Low-intensity pulsed ultrasound (LIPUS) has been reported to increase the rate of union and to decrease the time to union for multiple fractures and nonunions in clinical and animal models. The evidence for LIPUS in the treatment of scaphoid nonunion, however, is sparse. The aim of this study was to assess whether active LIPUS (relative to sham LIPUS) accelerates the time to union following surgery for scaphoid nonunion. METHODS: Adults with a scaphoid nonunion indicated for surgery were recruited for a multicenter, prospective, double-blinded randomized controlled trial. After surgery, patients self-administered activated or sham LIPUS units beginning at their first postoperative visit. The primary outcome was the time to union on serial computed tomography (CT) scans starting 6 to 8 weeks postoperatively. Secondary outcomes included patient-reported outcome measures, range of motion, and grip strength. RESULTS: A total of 142 subjects completed the study (69 in the active LIPUS group and 73 in the sham group). The average age was 27 years, and the cohort was 88% male. There was no difference in time to union (p = 0.854; hazard ratio, 0.965; 95% confidence interval, 0.663 to 1.405). Likewise, there were no differences between the active LIPUS and sham groups with respect to any of the secondary outcomes, except for wrist flexion at baseline (p = 0.008) and at final follow-up (p = 0.043). CONCLUSIONS: Treatment with LIPUS had no effect on reducing time to union in patients who underwent surgical fixation of established scaphoid nonunions. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Posttraumatic elbow joint contractures: defining pathologic capsular mechanisms and potential future treatment paradigms.

The Andrew J. Weiland Medal is presented by the American Society for Surgery of the Hand to a midcareer researcher who is dedicated to advancing patient care in the field of hand surgery. This essay, awarded the Weiland Medal in 2012, focuses on posttraumatic elbow joint contractures. Joint contractures are well known to hand surgeons because they limit function of our patients. There is a thorough understanding of the pathoanatomy underlying joint contractures. However, the mechanisms leading to the pathoanatomy are either unknown or partially understood, depending on the etiology of the particular clinical condition. This review describes our research over the past 14 years on posttraumatic elbow joint contractures. It defines pathologic cellular, matrix, and growth factor changes in the joint capsule, elaborates on the development of an animal model of posttraumatic joint contractures, presents an evaluation of a potential prevention strategy based on our research, and outlines future plans to bring this work to the clinical realm for the benefit of patients.

A retrospective cohort study of displaced segmental radial head fractures: is 2 mm of articular displacement an indication for surgery?

HYPOTHESIS: Many investigators agree that 2 mm of articular displacement is a reasonable indication for open reduction and internal fixation of Mason type II fractures of the radial head. However, there is no evidence to support that this degree of articular displacement is predictive of poor outcomes in conservatively treated fractures. We hypothesized there would be no difference between conservatively treated radial head fractures with greater 2 mm of displacement and those with less than 2 mm of displacement in terms of patient-reported or clinical outcomes. MATERIALS AND METHODS: We reviewed databases of all radial head fractures in our region. The primary outcomes were the Patient-Rated Elbow Evaluation and Disabilities of the Arm, Shoulder and Hand questionnaires. Secondary outcomes included radiologic radiocapitellar arthritis and range of motion (ROM) at follow-up. Postinjury treatment protocols, as well as patient factors, were examined for their effects on outcome. RESULTS: The results showed no significant difference in any outcome for conservatively treated radial head fractures with 2 mm (P = .8) or even 3 mm (P = .6) of articular displacement over a mean follow-up of 4.4 years. Early ROM and physiotherapy showed no significant differences in any outcome measure. Dominant hand injury showed no significant difference in patient-reported outcomes; however, ROM was significantly decreased on examination. CONCLUSIONS: This retrospective review suggests that fracture displacement of 2 to 3 mm is not necessarily an indication for surgical fixation in isolated fractures of the radial head. In addition, it appears that postinjury ROM/physiotherapy does not play a large role in improving patient outcome.

Posttraumatic elbow contractures: targeting neuroinflammatory fibrogenic mechanisms.

Posttraumatic elbow stiffness remains a common and challenging clinical problem. In the setting of a congruent articular surface, the joint capsule is regarded as the major motion-limiting anatomic structure. The affected joint capsule is characterized by irreversible biomechanical and biochemical fibrogenic changes strikingly similar to those observed in many other fibroproliferative human conditions. Studies in humans and preclinical animal models are providing emergent evidence that neuroinflammatory mechanisms are critical upstream events in the pathogenesis of posttraumatic connective tissue fibrogenesis. Maladaptive recruitment and activation of mast cell infiltrates coupled with the aberrant expression of growth factors such as transforming growth factor-beta, nerve growth factor, and neuropeptides such as substance P are common observations in posttraumatic joint contractures and many other fibroproliferative disorders. Blockade of these factors is providing promising evidence that if treatment is timed correctly, the fibrogenic process can be interrupted or impeded. This review serves to highlight opportunities derived from these recent discoveries across many aberrant fibrogenic disorders as we strive to develop novel, targeted antifibrotic prevention and treatment strategies for posttraumatic elbow stiffness.

The credibility of subgroup analyses reported in stroke trials is low: A systematic review.

BACKGROUND: Subgroup analyses are widely used to evaluate the heterogeneity of treatment effects in randomized clinical trials. However, there is a limited investigation of the quality of prespecified and reported subgroup analyses in stroke trials. This study evaluated the credibility of subgroup analyses in stroke trials. METHODS AND ANALYSIS: We searched Medline/PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science from inception to 24 March 2021. Three reviewers screened, extracted, and analyzed the data from the publications. Primary publications of stroke trials that reported at least one subgroup effect and had published corresponding study protocols were included. The Instrument for Assessing the Credibility of Effect Modification Analyses (ICEMAN) was used to examine the quality of the subgroup effects reported, with each subgroup effect assigned a credibility rating ranging from very low to high. Subgroup effects with two or more "definitely no" responses received a low credibility rating. The risk of bias was assessed using the Cochrane Risk-of-Bias tool for randomized trials version 2. RESULTS: Seventy-four articles met the inclusion criteria and reported a combined total of 647 subgroup effects. The median sample size was 1264 (interquartile range (IQR): 380-3876), and the median number of subgroups prespecified in the protocol was 6 (IQR: 2-10). Sixty-one (82%) studies used the univariate test of interaction. Of the total 647 subgroup effects reported in these studies, 319 (49%) were reported in acute stroke trials, while 423 (65%) had low credibility. CONCLUSION: The quality of subgroup analysis reporting in stroke trials remains poor. More effort is needed to train trialists on the best methods for designing and performing subgroup analyses, and how to report the results. TRIAL REGISTRATION NUMBER: We prospectively registered the review with International Prospective Register for Systematic Reviews (registration number: CRD42020223133).

The mast cell stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures.

OBJECTIVES: Using a rabbit model of post-traumatic joint contractures, we investigated whether treatment with a mast cell stabilizer after joint injury would lessen the molecular manifestations of joint capsule fibrosis. METHODS: Surgical joint injury was used to create stable post-traumatic contractures of the knee in skeletally mature New Zealand white rabbits. Four groups of animals were studied: a non-operated control group (n = 8), an operated contracture group (n = 13) and two operated groups treated with the mast cell stabilizer, ketotifen, at doses of 0.5 mg/kg (n = 9) and 1.0 mg/kg (n = 9) twice daily. Joint capsule fibrosis was assessed by quantifying the mRNA and protein levels of α-SMA, tryptase, TGF-ß1, collagen I and collagen III. Significance was tested using an ANOVA analysis of variance. RESULTS: The protein and mRNA levels of α-SMA, TGF-ß1, tryptase and collagen I and III were significantly elevated in the operated contracture group compared to control (p < 0.01). In both ketotifen-treated groups, protein and mRNA levels of α-SMA, TGF-ß1 and collagen I were significantly reduced compared to the operated contracture group (p < 0.01). CONCLUSIONS: These data suggest an inflammatory pathway mediated by mast cell activation is involved in joint capsule fibrosis after traumatic injury.

An in vivo rabbit joint injury model to measure trauma-induced coagulopathy and the effect of timing of administration of ketotifen fumarate on posttraumatic joint contracture.

Objectives: Using a rabbit in vivo joint injury model, the primary objective of the study was to determine if a relationship exists between earlier time to initiation of ketotifen fumarate (KF) treatment and posttraumatic joint contracture (PTJC) reduction. The secondary objective was to determine if a coagulation response could be detected with serial thrombelastography (TEG) analysis following acute trauma in this model. Methods: PTJC of the knee were created in 25 skeletally mature, New Zealand White rabbits. Five groups of 5 animals were studied: a control group that received twice daily subcutaneous injections of normal saline and 4 treatment groups that received twice daily subcutaneous injections of KF (0.5 mg/kg) starting immediately, 1-, 2-, and 4-weeks post-injury. After 8 weeks of immobilization, flexion contractures were measured biomechanically. Serial TEG analysis was performed on the control group animals pre-injury and weekly post-injury. Results: The average joint contracture in the Control Group (43.1°â€Š±â€Š16.2°) was higher than all KF treatment groups; however, the differences were not statistically significant. The average joint contracture was lowest in the 2-week post-injury treatment group (29.4°â€Š±â€Š12.1°), although not statistically significant compared to the other treatment groups. Serial TEG analysis demonstrated significantly higher mean maximal amplitude (maximal amplitude = 68.9 ±â€Š1.7 mm; P < .001), alpha-angle (81.9°â€Š±â€Š0.9°; P < .001), and coagulation index (4.5 ±â€Š0.3; P < .001) 1-week post-injury, which normalized to pre-injury values by 5-weeks post-injury. Conclusions: The use of the mast cell stabilizer KF within 2 weeks of injury demonstrated a nonsignificant trend towards reducing joint contracture in a rabbit in vivo model of PTJC. TEG and the in vivo rabbit joint injury model may be valuable in future preclinical studies of venous thromboembolism prevention and furthering our understanding of the pathophysiology of posttraumatic hypercoagulability.

Elbow joint contracture after traumatic injury.

INTRODUCTION: The purpose of the study was to follow elbow range of motion for 1 year after injury and to document the rate of secondary intervention due to joint contracture. METHODS: We prospectively followed up 25 subjects with traumatic elbow injuries. Data were collected up to 52 weeks after injury. Injuries at the elbow included fractures, elbow dislocations, fracture-dislocations, and biceps tendon ruptures. Subjects were treated as their injury necessitated, with a rehabilitation protocol for each injury type. RESULTS: There was significant improvement for all range-of-motion measures for the time course to 1-year follow up (P < .05). At 1 year, 22 of 25 subjects achieved a flexion-extension arc greater than 100°. At 1 year, 24 of 25 subjects achieved a pronation-supination arc greater than 100°. Reoperation was performed in 5 of 25 subjects; in 3 of which, this was because of elbow joint contracture. CONCLUSIONS: Traumatic elbow injuries carry a risk of joint contracture, 12% of our subjects did not regain a functional range of motion, and 12% had a joint contracture that required reoperation. Range of motion continues to improve up to 1 year after injury; failure to progress 3 months after injury suggests impending elbow joint contractures.

Surgical outcomes and complications following distal biceps tendon reconstruction: a systematic review and meta-analysis.

BACKGROUND: Primary repair of chronic distal biceps tendon ruptures may not be possible because of tendon retraction, and there remains no clear consensus on the type of reconstruction technique used. The purpose of this study was to report the clinical outcomes and complication rates following reconstruction of chronic distal biceps tendon ruptures. METHODS: A systematic review was performed following PRISMA guidelines. The following databases were searched: Embase, MEDLINE, and Cochrane Central Register of Controlled Trials. The primary outcomes of interest included range of motion, strength, and functional outcome scores. Secondary outcomes included complication, reoperation, and revision rates. Outcomes and complication rates of each graft type and fixation technique were aggregated and compared with nonparametric Wilcoxon signed rank and rank sum tests. Spearman rank coefficients were calculated for time from injury to surgery on all outcomes. RESULTS: There were no significant differences found between the graft type or fixation technique for postoperative range of motion, strength, and patient-reported outcomes. Postoperative complications were substantially higher in the autograft group (34%) as compared to the allograft group (14%). The fixation technique used also demonstrated a significantly increased complication rate in the weave group compared with the onlay group (34% and 9%, respectively). CONCLUSION: Our results do not reveal any statistically significant differences between groups in the primary outcomes. However, substantially higher complication rates were observed in the autograft and weave cohorts; more than half of the complications related to the use of autograft were associated with donor site morbidity. No specific graft type was identified as superior, although this may be due to the small patient numbers included within this study.

The Dose-Response Effect of the Mast Cell Stabilizer Ketotifen Fumarate on Posttraumatic Joint Contracture: An in Vivo Study in a Rabbit Model.

Posttraumatic joint contracture is a debilitating complication following an acute fracture or intra-articular injury that can lead to loss of motion and an inability to complete activities of daily living. In prior studies using an established in vivo model, we found that ketotifen fumarate (KF), a mast cell stabilizer, was associated with a significant reduction in the severity of posttraumatic joint contracture. Our primary research question in the current study was to determine whether a dose-response relationship exists between KF and posttraumatic joint contracture reduction. METHODS: A standardized operative method to create posttraumatic joint contracture in a knee was performed on skeletally mature New Zealand White rabbits. The animals were randomly assigned to 1 of 5 groups (n = 10 per group): a nonoperative control group, an operative control group, or 1 of 3 experimental KF groups (0.01 mg/kg [the KF 0.01 group], 0.1 mg/kg [KF 0.1], or 5.0 mg/kg [KF 5.0]). Flexion contractures were measured following 8 weeks of knee immobilization using a hydraulic material-testing machine. The posterior knee joint capsules were then harvested for quantification of myofibroblast and mast cell numbers with immunohistochemistry analysis. RESULTS: Forty-five rabbits were used in the final analysis. Contracture severity was significantly reduced in the KF 0.1 group (p = 0.016) and the KF 5.0 group (p = 0.001) compared with the operative control group. When converted to a percent response, posttraumatic joint contracture reduction was 13%, 45%, and 63% for the KF 0.01, KF 0.1, and KF 5.0 groups, respectively. A half-maximal effective concentration (EC50) for KF of 0.22 mg/kg was established. There was also a decrease in myofibroblasts, mast cells, and substance P-containing nerve fiber counts with increasing doses of KF. CONCLUSIONS: Using a preclinical, rabbit in vivo model of posttraumatic joint contracture, increasing doses of KF were associated with decreasing biomechanical estimates of knee posttraumatic joint contracture as well as decreasing numbers of myofibroblasts, mast cells, and substance P-containing nerve fibers. CLINICAL RELEVANCE: KF has been used safely in humans for more than 40 years and, to our knowledge, is the first and only agent ready to be potentially translated into an effective treatment for posttraumatic joint contracture.

Is Immobilization Necessary for Early Return to Work Following Distal Biceps Repair Using a Cortical Button Technique?: A Randomized Controlled Trial.

BACKGROUND: Improvements in surgical fixation to repair distal biceps tendon ruptures have not fully translated to earlier postoperative mobilization; it is unknown whether earlier mobilization affords earlier functional return to work. This parallel-arm randomized controlled trial compared the impact of early mobilization versus 6 weeks of postoperative immobilization following distal biceps tendon repair. METHODS: One hundred and one male participants with a distal biceps tendon rupture that was amenable to a primary repair with use of a cortical button were randomized to early mobilization (self-weaning from sling and performance of active range of motion as tolerated during first 6 weeks) (n = 49) or 6 weeks of immobilization (splinting for 6 weeks with no active range of motion) (n = 52). Follow-up assessments were performed by a blinded assessor at 2 and 6 weeks and at 3, 6, and 12 months. At 12 months, distal biceps tendon integrity was verified with ultrasound. The primary outcome was return to work. Secondary outcomes were pain, range of motion, strength, shortened Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) score, and tendon integrity. Intention-to-treat analysis was performed. A linear mixed model for repeated measures was used to compare pain, range of motion, strength, and QuickDASH between the groups over time; return to work was assessed with use of independent t tests. RESULTS: The groups were similar preoperatively (p ≥ 0.16). The average age (and standard deviation) was 44.7 ± 8.6 years. Eighty-three participants (82%) were followed to 12 months. There were no differences between the groups in terms of return to work (p ≥ 0.83). Participants in the early mobilization group had significantly more passive forearm supination (p = 0.04), with passive forearm pronation (p = 0.06) and active extension and supination (p = 0.09) trending toward significantly greater range of motion in the early mobilization group relative to the immobilization group. Participants in the early mobilization group had significantly better QuickDASH scores over time than those in the immobilization group (p = 0.02). There were no differences between the groups in terms of pain (p ≥ 0.45), active range of motion (p ≥ 0.09), or strength (p ≥ 0.70). Two participants (2.0%, 1 in each group) had full-thickness tears on ultrasound at 12 months (p = 0.61). Compliance was not significantly different between the groups (p = 0.16). CONCLUSIONS: Early motion after distal biceps tendon repair with cortical button fixation is well tolerated and does not appear to be associated with adverse outcomes. No clinically important group differences were seen. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Neuropeptide, mast cell, and myofibroblast expression after rabbit deep flexor tendon repair.

PURPOSE: Increased numbers of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers have been found in a number of fibrotic processes in connective tissues. The purpose of the present study was to investigate the occurrence of factors implicated in a hypothesized profibrotic neuropeptide-mast cell-myofibroblast pathway in deep flexor tendon healing. METHODS: In a rabbit model of flexor tendon injury, with repair of the sharply transected deep flexor tendon using a modified Kessler and a running circumferential peripheral suture, segments of flexor tendons and sheaths were analyzed. The time points chosen-3, 6, 21, and 42 days after tendon repair-represent different stages in tendon healing. The messenger RNA levels of transforming growth factor-ß1 and α-smooth muscle actin were measured with conventional reverse transcription-polymerase chain reaction, and the numbers of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers were determined with immunohistochemistry. RESULTS: The messenger RNA levels for transforming growth factor-ß1 and the myofibroblast marker α-smooth muscle actin were significantly increased in deep flexor tendons after injury and repair, at all studied time points, but remained unchanged or even down-regulated in the sheaths. Myofibroblasts, mast cells, and neuropeptide-containing nerve fibers all increased significantly in the healing tendons, exhibiting similar patterns of change in percentages of total cell number over time, reaching levels resembling that of the tendon sheaths with 33% to 50% of the total cell population. CONCLUSIONS: After injury to the deep flexor tendon in a rabbit model, the proportion of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers increases significantly. These findings support the hypothesis that the profibrotic neuropeptide-mast cell-myofibroblast pathway is activated in deep flexor tendon healing.