Vincent R. Hentz

Injectable Collagenase Clostridium Histolyticum for Dupuytren's Contracture

BACKGROUND Dupuytrens disease limits hand function, diminishes the quality of life, and may ultimately disable the hand. Surgery followed by hand therapy is standard treatment, but it is associated with serious potential complications. Injection of collagenase clostridium histolyticum, an office-based, nonsurgical option, may reduce joint contractures caused by Dupuytrens disease. METHODS We enrolled 308 patients with joint contractures of 20 degrees or more in this prospective, randomized, double-blind, placebo-controlled, multicenter trial. The primary metacarpophalangeal or proximal interphalangeal joints of these patients were randomly assigned to receive up to three injections of collagenase clostridium histolyticum (at a dose of 0.58 mg per injection) or placebo in the contracted collagen cord at 30-day intervals. One day after injection, the joints were manipulated. The primary end point was a reduction in contracture to 0 to 5 degrees of full extension 30 days after the last injection. Twenty-six secondary end points were evaluated, and data on adverse events were collected. RESULTS Collagenase treatment significantly improved outcomes. More cords that were injected with collagenase than cords injected with placebo met the primary end point (64.0% vs. 6.8%, P < 0.001), as well as all secondary end points (P < or = 0.002). Overall, the range of motion in the joints was significantly improved after injection with collagenase as compared with placebo (from 43.9 to 80.7 degrees vs. from 45.3 to 49.5 degrees, P < 0.001). The most commonly reported adverse events were localized swelling, pain, bruising, pruritus, and transient regional lymph-node enlargement and tenderness. Three treatment-related serious adverse events were reported: two tendon ruptures and one case of complex regional pain syndrome. No significant changes in flexion or grip strength, no systemic allergic reactions, and no nerve injuries were observed. CONCLUSIONS Collagenase clostridium histolyticum significantly reduced contractures and improved the range of motion in joints affected by advanced Dupuytrens disease. (ClinicalTrials.gov number, NCT00528606.)

A virtual-reality-based telerehabilitation system with force feedback

A PC-based orthopedic rehabilitation system was developed for use at home, while allowing remote monitoring from the clinic. The home rehabilitation station has a Pentium II PC with a graphics accelerator, a Polhemus tracker and a multi-purpose haptic control interface. This novel interface is used to sample a patients hand positions and to provide resistive forces using the Rutgers Master II (RMII) glove. A library of virtual rehabilitation routines was developed using WorldToolKit software. At the present time, it consists of three physical therapy exercises (DigiKey, ball and Power Putty) and two functional rehabilitation exercises (peg board and ball game). These virtual reality exercises allow automatic and transparent patient data collection into an Oracle database. A remote Pentium II PC is connected with the home-based PC over the Internet and an additional video conferencing connection. The remote computer runs an Oracle server to maintain the patient database, monitor progress and change the exercise level of difficulty. This allows for patient progress monitoring and repeat evaluations over time. The telerehabilitation system is undergoing clinical trials at Stanford Medical School, with progress being monitored from Rutgers University. Other haptic interfaces currently under development include devices for elbow and knee rehabilitation connected to the same system.

Neurotization in brachial plexus injuries. Indication and results.

In neurotization or nerve transfer, a healthy but less valuable nerve or its proximal stump is transferred in order to reinnervate a more important sensory or motor territory that has lost its innervation through irreparable damage to its nerve. In brachial plexus injuries, extraplexal nerves such as the spinal accessory nerve, rami of the cervical plexus, or intercostal nerves are transferred onto trunks, cords, or individual nerves or else segments of the brachial plexus that maintain continuity with the spinal cord may be coapted to trunks or cords the surgeon wishes to innervate. This method is particularly indicated in root avulsion injuries that occur frequently following traction trauma to the brachial plexus. The authors convey their experience with neurotization using the long thoracic nerve in seven cases, the accessory nerve in 30 cases, intercostal nerves in 66 cases, and various nerve transfers within the plexus in 31 cases. Results of other authors are also reported. With these methods, it is possible to obtain good elbow flexion in more than one-half of patients; however, only limited shoulder function and no useful finger function are obtained.

Experience with the temporoparietal fascial free flap

The temporoparietal fascia is an ideal tissue source for free transfer to distant sites where ultrathin coverage is either desirable or mandatory. The fascias dependable vascular anatomy facilitates the technical aspects of microvascular transfer by means of its large vessels, ample pedicle, and ability to be grafted on either side. Furthermore, this highly vascular tissue is available in surprisingly large quantities, and its donor scar is hidden in the hair. The authors have found this flap useful (1) in covering exposed bone and tendon without adding unwanted bulk, (2) in providing thin flap coverage or lining in major facial reconstruction, (3) in covering vital structures such as exposed nerves and vessels, (4) in providing neovascularity both as a recipient graft bed and for control of chronic infection, and (5) in reestablishing gliding-tendon mechanisms. The authors have successfully employed this free flap in 15 cases which involved deformities of the ankle, foot, Achilles tendon, forearm, hand, nose, and contralateral ear and scalp. Seven cases are utilized to illustrate the broad application of this unique and versatile free flap.

Virtual reality-based orthopedic telerehabilitation

Rehabilitation interventions in remote areas are problematic because of distance and available resources. Orthopedic impairments acquired by individuals in remote areas can then lead to permanent disabilities/loss of function because of lack of appropriate rehabilitation. A system being developed by Rutgers and Stanford Universities provides therapy at the patients home, with remote monitoring and periodic re-assessment. This telerehabilitation system uses virtual reality and haptic interfaces, and a pair of networked PCs. It is intended for rehabilitation of patients with hand, elbow, knee and ankle impairments. Data from the first patient treated with the telerehabilitation system is encouraging.

Collagenase injection as nonsurgical treatment of Dupuytren's disease: 8-year follow-up.

PURPOSE Collagenase has been investigated in phase II and phase III clinical trials for the treatment of Dupuytrens disease. The purpose of this study is to report 8-year follow-up results in a subset of patients who had collagenase injection for the treatment of Dupuytrens contracture. METHODS Twenty-three patients who participated in the phase II clinical trial of injectable collagenase were contacted by letter and phone. Eight patients were enrolled, completed a Dupuytrens disease questionnaire, and had independent examination of joint motion by a single examiner. RESULTS Eight patients completed the 8-year follow-up study: 6 had been treated for isolated metacarpophalangeal (MCP) joint contracture, and 2 had been treated for isolated proximal interphalangeal (PIP) joint contracture. Average preinjection contracture was 57 degrees in the MCP group. Average contracture was 9 degrees at 1 week, 11 degrees at 1 year, and 23 degrees at 8-year follow-up. Four of 6 patients experienced recurrence, and 2 of 6 had no evidence of disease recurrence at 8-year follow-up. Average preinjection contracture was 45 degrees in the PIP group. Average contracture was 8 degrees at 1 weeks, 15 degrees at 1 year, and 60 degrees at 8-year follow-up. Both patients experienced recurrence at 8-year follow-up. No patients had had further intervention on the treated finger in either the MCP or the PIP group. Patients subjectively rated the overall clinical success at 60%, and 88% of patients stated that they would pursue further injection for the treatment of their recurrent or progressive Dupuytrens disease. CONCLUSIONS Enzymatic fasciotomy is safe and efficacious, with initial response to injection resulting in reduction of joint contracture to within 0 degrees -5 degrees of normal in 72 out of 80 patients. Initial evaluation of long-term recurrence rates suggests disease recurrence or progression in 4 out of 6 patients with MCP contractures and 2 patients with PIP contractures; however, recurrence was generally less severe than the initial contracture in the MCP group. In addition, patient satisfaction was high.

Quantification of fingertip force reduction in the forefinger following simulated paralysis of extensor and intrinsic muscles

Objective estimates of fingertip force reduction following peripheral nerve injuries would assist clinicians in setting realistic expectations for rehabilitating strength of grasp. We quantified the reduction in fingertip force that can be biomechanically attributed to paralysis of the groups of muscles associated with low radial and ulnar palsies. We mounted 11 fresh cadaveric hands (5 right, 6 left) on a frame, placed their forefingers in a functional posture (neutral abduction, 45 degrees of flexion at the metacarpophalangeal and proximal interphalangeal joints, and 10 degrees at the distal interphalangeal joint) and pinned the distal phalanx to a six-axis dynamometer. We pulled on individual tendons with tensions up to 25% of maximal isometric force of their associated muscle and measured fingertip force and torque output. Based on these measurements, we predicted the optimal combination of tendon tensions that maximized palmar force (analogous to tip pinch force, directed perpendicularly from the midpoint of the distal phalanx, in the plane of finger flexion-extension) for three cases: non-paretic (all muscles of forefinger available), low radial palsy (extrinsic extensor muscles unavailable) and low ulnar palsy (intrinsic muscles unavailable). We then applied these combinations of tension to the cadaveric tendons and measured fingertip output. Measured palmar forces were within 2% and 5 degrees of the predicted magnitude and direction, respectively, suggesting tendon tensions superimpose linearly in spite of the complexity of the extensor mechanism. Maximal palmar forces for ulnar and radial palsies were 43 and 85% of non-paretic magnitude, respectively (p<0.05). Thus, the reduction in tip pinch strength seen clinically in low radial palsy may be partly due to loss of the biomechanical contribution of forefinger extrinsic extensor muscles to palmar force. Fingertip forces in low ulnar palsy were 9 degrees further from the desired palmar direction than the non-paretic or low radial palsy cases (p<0.05).

Tumours of the hand

Hand tumours of soft-tissue and bony origin are frequently encountered, and clinicians must be able to distinguish typical benign entities from life-threatening or limb-threatening malignant diseases. In this Review, we present a diagnostic approach to hand tumours and describe selected cancers and their treatments. Soft-tissue tumours include ganglion cysts, giant-cell cancers and fibromas of the tendon sheath, epidermal inclusion cysts, lipomas, vascular lesions, peripheral-nerve tumours, skin cancers, and soft-tissue sarcomas. Bony tumours encompass enchondromas, aneurysmal bone cysts, osteoid osteomas, giant-cell lesions of bone, bone sarcomas, and metastases. We look at rates of recurrence and 5-year survival, and recommendations for adjunct chemotherapy and radiotherapy for malignant lesions.

Use of cyclosporin A in allotransplantation of rat limbs

An experimental model for limb transplantation as a composite tissue transfer has been developed using two genetically well defined strains of rats, BUF and LEW. The study shows that cyclosporin A (CyA) is very effective as an immunosuppressive agent in preventing refection of transplanted limbs in rats. It is found to suppress rejection of the homotransplants as long as treatment is continuous. No untoward side effects have been noted at the current experimental dosage of the medication. CyA is superior to the conventional agents, such as azathioprine and prednisolone, which allow rejection of the limbs while treatment is in progress. There is a period of immune tolerance following CyA treatment; however, this period becomes shorter as the length of the treatment is increased. This may indicate that CyA treatment should be continuous and not pulsed at the dosage used in this experimental model. Additional experiments are underway to further elucidate this phenomenon.

The nerve gap dilemma: A comparison of nerves repaired end to end under tension with nerve grafts in a primate model

The objective of this study was to compare, in a clinically relevant primate model, axon regeneration after epineurial repair under tension (15 mm gap) with interfascicular nerve grafts with the use of either standard microsuture techniques or a new interfascicular nerve graft technique termed fascicular tubulization that uses a hypoantigenic collagen membrane formed into a tube to approximate nerve ends. Electrophysiologic analysis demonstrated that the percentage of proximal axons that conducted across the repair site was greater in those nerves repaired under tension with epineurially placed sutures than in either of the tensionless repairs involving interfascicular graft techniques. The mean diameters of the regenerated axons repaired under tension with epineurial sutures were greater than those of the nerves repaired with interfascicular grafts, although the difference was not statistically significant. Interfascicular nerve grafting with tubulization using the current collagen tube resulted in regeneration equal to the sutured interfascicular nerve grafts. For modest defects (perhaps up to 3 to 4 cm in the adult), it seems advantageous to accept the modest tension associated with an epineurial repair rather than to use an autograft (or artificial graft) to achieve a tension-free repair.