Dupuytren's Contracture Recurrence and Treatment Following Collagenase Clostridium Histolyticum Injection: A Longitudinal Assessment in a Veteran Population.

INTRODUCTION: Dupuytren's contracture is a connective tissue disease characterized by an abnormal proliferation of collagen in the palm and fingers, which leads to a decline in hand function because of progressive joint flexion. In addition to surgical and percutaneous interventions, collagenase clostridium histolyticum (CCH, trade name Xiaflex) is an intralesional enzymatic treatment for adults with palpable cords. The objectives of this study are to evaluate factors predictive of recurrence following treatment with CCH and to review the outcomes of repeat treatments with CCH for recurrent contracture. MATERIALS AND METHODS: An institutional review board-approved retrospective chart review was conducted for patients between 2010 and 2017 who received CCH injections for Dupuytren's contracture at a Veterans Affairs hospital. Demographics, comorbidities, affected finger and joint, pre/posttreatment contracture, time to recurrence, and treatment of recurrence were recorded. Successful treatment was defined as contracture ≤5° following CCH, and improvement was defined as ≥20° reduction from baseline contracture. Study cohorts were followed after their secondary treatment, and time to recurrence was recorded and plotted using a Kaplan-Meier curve. A Cox proportional hazards model was used to compare treatment group risk factors for recurrence with a P-value less than .05 defined as statistical significance. RESULTS: Of 174 injections performed for the correction of flexion deformities in 109 patients, 70% (121) were successfully treated with CCH, and an additional 20% (35) had improvement. There was a recurrence of contractures in 43 joints (25%). Of these, 16 contractures were treated with repeat CCH, whereas another 16 underwent limited fasciectomy. In total, 75% (12 of 16) of the repeat CCH group and 75% of the fasciectomy group were successfully treated. Pre-injection contracture of ≥25° was found to be predictive of recurrence (P < .05). CONCLUSIONS: Initial treatment of contracture with CCH had a 70% success rate with 25% recurrence during the study period. Compared with limited fasciectomy, CCH had decreased efficacy. Based on the findings of this study, we believe that the treatment of primary and/or recurrent Dupuytren's contracture with CCH is a safe and less invasive alternative to fasciectomy in the era of telemedicine. CCH treatment requires no suture removal, which allows the ability to assess motion virtually, and the potential consequences of CCH treatment such as skin tears can be assessed and managed conservatively. In the veteran and active duty population, CCH can facilitate faster recovery and return to service. Strengths of this study include a large series of veteran populations with longitudinal follow-up to determine treatment efficacy for primary Dupuytren's contracture and recurrence. Limitations include a smaller sample size compared to previous trials, a lack of standardized follow-up, and the retrospective nature of our study that prohibits randomization to compare outcomes between CCH treatment and fasciectomy efficacy over time. Directions for future research include stratification of patients by joint and specific digit involvement as well as comparison with percutaneous needle fasciotomy, another minimally invasive technique that could benefit the veteran population at increased risk for developing Dupuytren's disease.

Altered patterning of trisomy 21 interneuron progenitors.

Individuals with Down syndrome (DS; Ts21), the most common genetic cause of intellectual disability, have smaller brains that reflect fewer neurons at pre- and post-natal stages, implicating impaired neurogenesis during development. Our stereological analysis of adult DS cortex indicates a reduction of calretinin-expressing interneurons. Using Ts21 human induced pluripotent stem cells (iPSCs) and isogenic controls, we find that Ts21 progenitors generate fewer COUP-TFII+ progenitors with reduced proliferation. Single-cell RNA sequencing of Ts21 progenitors confirms the altered specification of progenitor subpopulations and identifies reduced WNT signaling. Activation of WNT signaling partially restores the COUP-TFII+ progenitor population in Ts21, suggesting that altered WNT signaling contributes to the defective development of cortical interneurons in DS.

Early Experience With Locked Intramedullary Wrist Arthrodesis.

PURPOSE: The most common method of total wrist arthrodesis is dorsal compression plating, which can require revision for soft tissue or tendon irritation. A locked intramedullary system was developed to reduce this complication. The goal of this study was to investigate the complication rate of total wrist arthrodesis using this system in our center. METHODS: A retrospective chart review of all patients undergoing intramedullary wrist arthrodesis from January 2016 to February 2018 was performed. RESULTS: Nine wrist arthrodeses were performed with locked intramedullary wrist fusion in 5 women and 4 men. The indications for fusion included posttraumatic arthritis in 7 and inflammatory arthritis in 2. Two patients underwent primary arthrodesis and 7 had revision from prior partial wrist fusions. Local bone graft at the radiocarpal joint was used in all cases. The mean follow-up was 27 weeks. Radiocarpal fusion was achieved in 8 patients after the initial procedure and in the ninth patient after revision. There were 6 complications in 4 patients with revision reoperation required in 3. The complications were metacarpal locking screw migration in 3, metacarpal fracture in 1, radiocarpal nonunion in 1, and symptomatic middle finger carpometacarpal nonunion in 1. The revision surgeries include distal screw removal in 1, distal screw removal with replacement in 1, and bone grafting in the radiocarpal nonunion. CONCLUSIONS: Use of the locked intramedullary wrist fusion system yields high fusion rates. However, based on the high complication rate, particularly from distal screw migration, and the high revision rate in this series, we recommend caution with the use of this system. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

A Variant of Madelung Deformity: Management of the Distal Ulna Within the Carpal Canal.

Madelung deformity is a rare disease that affects the normal growth of the distal radius and occurs in 1.7% of all pediatric congenital hand deformities. It is characterized by progressive deformity and shortening of the radius at the distal radial physis owing to anomalous tethering of the ulnar-volar growth plate. The distal ulna overgrows the radius and usually displaces dorsally. As growth continues, the carpals assume a wedge shape. Deformity, pain, and functional limitations are the usual presenting problems. We report the case of a 9-year-old girl with bilateral Madelung deformity and pain, in whom initial radiographs of the right wrist showed that the right ulna was displaced volarly and in the carpal canal.

Ultrasound Imaging Improves Identification of Prominent Hardware in the Surgical Treatment of Distal Radius Fractures: A Cadaveric and Prospective Clinical Study.

Background Volarly applied locking plates are one of several current treatment options for displaced fractures of the distal radius. Presently, surgeons use intraoperative depth gauges and fluoroscopy to select and confirm proper screw length. The contour of the dorsal cortex beneath the extensor compartments along with fracture comminution may limit the accuracy of screw length selection. Question/Purpose To evaluate the accuracy of ultrasound (US) and fluoroscopy in the detection of dorsally prominent screws placed during volar plating of experimentally created distal radius fractures and extend this prospectively into the clinical setting. Patients and Methods Distal radius fractures were experimentally induced in fresh cadaveric arms. The fractures were then internally fixated with volar locking plates utilizing fluoroscopic imaging. US imaging of the dorsal surface of the radius was then performed followed by dorsal dissection and direct caliper measurements to quantitate screw tips as recessed, flush, or protruding from the dorsal cortex. A small, prospective clinical study was also conducted to validate the clinical usefulness of using US to provide additional information regarding screw tip prominence. Results Our study demonstrated that US was able to detect dorsally prominent screw tips not visible on fluoroscopy. Cadaveric dissection showed a higher statistical correlation between US imaging and actual prominence than between fluoroscopy and actual prominence. Conclusions US examination after volar plate fixation of comminuted distal radius fractures may detect dorsal screw tip prominence when screw lengths are selected to engage the dorsal cortex. Level of Evidence IV.

The "Thumbs-up" sign and trapeziometacarpal joint injection: a useful clinical indicator.

BACKGROUND: Several clinical studies investigating the accuracy and efficacy of trapeziometacarpal injection exist. Some studies utilize anatomical landmarks for proper injection placement while others utilize modalities including ultrasound and fluoroscopy. The changes of limb position that occur at the time of intra-articular injection can provide valuable visual and tactile feedback to the clinician. The purpose of this study is to investigate the occurrence of the "Thumbs-up" sign with injection of the thumb trapeziometacarpal joint as a useful and reliable clinical indicator of intra-articular trapeziometacarpal injection and correlate level and duration of pain relief. METHODS: Trapeziometacarpal joint injections were performed on twenty-seven thumbs utilizing anatomic landmarks. At the time of injection, the presence or absence of the "Thumbs-up" sign was noted, and needle location was verified after injection with orthogonal mini-C arm fluoroscopic images. Visual analog pain scale scores were obtained pre-injection and by follow-up telephone calls at 1 week, 6 weeks, and 3 months post injection. RESULTS: Twenty-four of twenty-seven injections demonstrated a positive "Thumbs-up" sign. There were three negative "Thumbs-Up" injections. The thumbs-up sign demonstrated a 92.3 % sensitivity. Eighteen of twenty-seven thumbs had sustained relief at 3 months post injection. CONCLUSIONS: The "Thumbs-up" sign is a practical clinical tool that gives the practitioner important visual feedback at the time of injection. Patient relaxation and joint compliance are limiting factors. The "Thumbs-up" sign is an inexpensive indicator of successful intra-articular injection and may obviate the need and expense of advanced imaging modalities at the time of injection.

Rat posterior facial vein interpositional graft: a more relevant training model.

Microvascular training models for vein grafting most often use the rat epigastric vein interpositioned to the femoral artery. We describe the rat posterior facial vein as an alternative vein graft model; it has at least a 2:1 diametric ratio to the femoral artery and a tougher connective tissue, making it more similar to clinical vein grafting for reconstructive microsurgery. A series of 24 grafts interpositioned to the femoral artery were done using 11-12 sutures per end-to-end anastomosis and yielded early patency rates of 96% at 20 min and 92% at 2 and 4 weeks for subsets of 12 grafts. As a training model the diametric disparity provides unique challenges with clinical relevance, for which a number of different techniques for matching arterial to venous circumferences can be done.

Thrombodynamics of microvascular repairs: effects of antithrombotic therapy on platelets and fibrin.

PURPOSE: To evaluate the hypothesis that platelets and fibrin differentially accrue at microvascular anastomoses in arteries versus veins and under different pharmacologic conditions. METHODS: We evaluated mouse arterial and venous anastomoses with intravital fluorescence imaging, using fluorophore-labeled platelets and anti-fibrin antibodies to measure the extent of thrombus component development in the intraluminal anastomotic site. We evaluated systemic heparin or eptifibatide (platelet aggregation inhibitor) to determine their relative influences on thrombus composition. RESULTS: Platelets accumulated rapidly in both arterial and venous repairs, and then fell in number after 10 to 30 minutes of reflow. Fibrin had a relatively steady development over 60 minutes in veins, with a more variable increase in arteries. Heparin reduced platelet accumulation in arteries and fibrin development in veins. Eptifibatide reduced platelets in both arteries and veins and had an apparent effect on lowering the amount of fibrin in veins. CONCLUSIONS: These findings show that platelets have a rapid, transient response, whereas fibrin has a slower, more sustained accrual in both arterial and venous anastomoses. Furthermore, inhibition of either coagulation or platelet aggregation can influence presumably non-targeted components of thrombosis in vascular repairs of both arteries and veins. CLINICAL RELEVANCE: Preventing replantation failure using antithrombotic therapies requires a better understanding of the effect of each pharmacologic compound on the various aspects of thrombogenesis.

Long-term BMP-2-induced bone formation in rat island and free flaps.

Ectopic osteoinduction by exogenous bone morphogenetic proteins (BMPs) is rapid but heretofore characterized as transient. A rat model of carrier-free recombinant human BMP-2 intramuscular implantation was used, followed by creation of either an island flap or transplantation of a free flap. BMP-2 injection into an unaltered gastrocnemius, thigh adductor, or cutaneous trunci (thoracic wall) muscle site led to bone resorption at 4 weeks. In contrast, creation of an island or free flap of the muscle/injection site caused the newly formed ossicle to maintain its bony composition with active osteoblastic presence, from 3-8 weeks. Muscle denervation or sectioning of the Achilles tendon (for gastrocnemius injections) did not prevent bone resorption at 4 weeks. There was little osteoclastic activity within de novo bone sites of island- and free flap-injected muscles at 4 and 8 weeks. These data demonstrate that simple injection of BMP-2 into a surgically isolated flap site results in the prolonged presence of de novo bone. These findings suggest that BMP-injected island or free muscle flaps may be used to generate new bone for reconstruction of a bony defect.

Modeled evidence of force reduction at the extensor carpi radialis brevis origin with the forearm support band.

PURPOSE: Although the forearm support band has been hypothesized to reduce force and thus inflammation and degeneration at the extensor carpi radialis brevis (ECRB) origin, little evidence exists to support an actual effect. We present both a cadaveric and clinical model that show the effect and principles of the forearm support band. METHOD: The cadaver model measured forces at the ECRB origin as various pressures were applied to the forearm support band and while the ECRB tendon was loaded distally. For clinical correlation support band pressure during rest and activity was measured in healthy individuals. RESULTS: Our results revealed an increased forearm support band effect with increased band pressure and a decreased relative effect with increased force applied distally. For clinical correlation the support band pressure during activity was measured in 21 healthy volunteers while controlling for the application pressure in 2 common support band designs. This resulted in activity pressures ranging from 43 to 192 mm Hg dependent on the starting pressure of application. CONCLUSIONS: Although further clinical evaluation is necessary to determine the most appropriate clinical indications and application pressures for the forearm support band these combined results suggest that the forearm support band may be most effective when applied to 30 to 50 mm Hg at rest, resulting in up to 120 mm Hg pressure during activity. According to our model this would result in a force reduction at the ECRB origin of approximately 13% to 15% throughout a range of activity levels.