Safety and tolerability of collagenase Clostridium histolyticum and fasciectomy for Dupuytren's contracture.

Safety was evaluated for collagenase Clostridium histolyticum (CCH) based on 11 clinical trials (N = 1082) and compared with fasciectomy data in a structured literature review of 48 European studies (N = 7727) for treatment of Dupuytren's contracture. Incidence of adverse events was numerically lower with CCH vs. equivalent complications from fasciectomy (median [range] incidence), including nerve injury (0% vs. 3.8% [0%-50+%]), neurapraxia (4.4% vs. 9.4% [0%-51.3%]), complex regional pain syndrome (0.1% vs. 4.5% [1.3%-18.5%]) and arterial injury (0% vs. 5.5% [0.8%-16.5%]). Tendon injury (0.3% vs. 0.1% [0%-0.2%]), skin injury (16.2% vs. 2.8% [0%-25.9%]) and haematoma (77.7% vs. 2.0% [0%-25%]) occurred at a numerically higher incidence with CCH than surgery. Adverse events in CCH trials not reported after fasciectomy included peripheral oedema; extremity pain; injection site pain, haemorrhage and swelling; tenderness; pruritus and lymphadenopathy. CCH-related adverse events were reported as predominantly injection-related and transient. These results may support clinical decision-making for treatment of Dupuytren's contracture.

Biomechanical effect of isolated capitate shortening in Kienbock's disease: an anatomical study.

Multiple operations have been proposed to slow the progression of osteonecrosis and secondary carpal damage in Kienböck's disease. To assess the biomechanical changes after capitate shorting, we inserted pressure-testing devices into the carpal and radiocarpal joints in an anatomical study. Pressure sensors were placed into eight thawed non-fixated human cadaver arms to measure the forces transmitted in physiological loading. Longitudinal 9.8 N and 19.6 N forces were applied before and after capitate shortening. After capitate shortening, significant load reduction on the lunate was evident in all specimens. An average decrease of 49% was seen under a 9.8 N load and 56% under a 19.6 N load. The load was transferred to the radial and ulnar intercarpal joints. More relief of pressure on the lunate after isolated capitate shortening is achieved with a shallow angle between the scaphoid and capitate in the posteroanterior radiograph.

Nonsurgical treatment of Dupuytren's contracture: 1-year US post-marketing safety data for collagenase clostridium histolyticum.

BACKGROUND: Collagenase clostridium histolyticum (CCH) is a Food and Drug Administration-approved treatment for adult patients with Dupuytren's contracture with a palpable cord that has been shown efficacious and safe in clinical trials. METHODS: This paper summarizes the most common post-marketing clinical adverse event (AE) reports received by the manufacturer of CCH and sponsor of the US Biologics License Application (Auxilium Pharmaceuticals, Malvern, PA, USA) during the first 12 months after drug approval and commercialization in the USA. RESULTS: Of the 115 AE reports describing 270 AEs voluntarily received from patients or health care providers after approximately 5,400 injections of CCH administered, the most common AEs involved local, nonserious reactions to treatment, including skin tears, peripheral edema, and contusion. There were few serious AEs observed (0.6% reporting rate per 1,000 injections), and two flexor tendon ruptures and one flexor pulley injury were reported. CONCLUSIONS: Analysis of post-marketing AEs received for CCH in the first year post-approval supports the safety profile reported earlier during clinical development and did not reveal additional clinical risks or concerns about CCH.

An experimental study on costal osteochondral graft.

OBJECTIVE: To investigate usefulness of osteochondral grafting from the costo-osteochondral junction as a repair technique for articular cartilage defects histologic and biochemical analysis of grafted cartilage in rabbit knees was evaluated up to 48 weeks after transplantation. METHODS: Twenty New Zealand White rabbits were used. A costal osteochondral plug was harvested from a middle rib. After trimming, it was transplanted into a cylindrical osteochondral 2.5 mm diameter and 5 mm deep defect created in the knee. The animals were sacrificed at 6, 12, 24, and 48 weeks after transplantation. Defect sites were inspected macroscopically, and then by light microscopy. Samples were evaluated for cell viability using a fluorescent in situ double-staining protocol with confocal laser microscopic analysis. Samples were also processed to assess type I & II collagen and aggrecan mRNA expression using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Histologically, bone union was achieved in all plugs. Confocal microscopic analysis revealed chondrocyte viability in the 48-week grafts; the distribution of chondrocytes was similar to surrounding articular cartilage. The expression of type II collagen and aggrecan mRNA in the grafted cartilage was consistent with normal articular cartilage and normal costal cartilage. These results were observed over 6-48 weeks. CONCLUSIONS: Our study revealed that chondrocytes in the grafted cartilage were viable at least up to 48 weeks and that mRNA expression of type II collagen and aggrecan was also similar to that of normal articular cartilage. These results suggest that costal osteochondral grafting can be a useful alternative in the treatment of osteochondral defects.

Manual Ability Measure (MAM-16): a preliminary report on a new patient-centred and task-oriented outcome measure of hand function.

The purpose of this study was to develop an easy-to-use and psychometrically sound outcome instrument that is task-oriented and patient-centred. One hundred fifteen patients with a variety of hand impairments completed a rating scale of perceived manual ability (i.e., the Manual Ability Measure). The first 70 patients also completed two other questionnaires about physical health and psychological well-being. Rasch Analyses were conducted to transform the ordinal ratings into linear measures; Rasch statistics were used to evaluate its measurement properties at both scale and item levels. Eighty-three original items were reduced to 16 common tasks; Rasch reliabilities were good; the easy-to-difficult item hierarchy makes sense clinically. Moderate correlations were found between manual ability, physical function and general sense of well-being. The results of this preliminary study suggest that the MAM is a promising outcome measure that has adequate psychometric properties and can be used to complement other objective clinical measurements.

Early versus delayed treatment of enchondroma.

Enchondromata are among the most common primary neoplasms of the hand, which often present as pathologic fractures. The purpose of this study is to determine whether there are any differences between cases in which both fracture and tumor were treated primarily and those in which tumor treatment was delayed. We reviewed a total of 16 cases; six were treated immediately, 10 were delayed. The immediate treatment group had four complications, the delayed group had one. The theoretical advantages of immediate treatment include a decrease in both the period of disability and delay of definitive diagnosis. This study supports that supposition. However, we did note a significantly higher complication rate for the immediate treatment group (67% versus 10%). Our results indicate that while there is an apparent decreased disability period, there may be reason for caution in immediate treatment of both the fracture and the tumor in pathologic fractures through enchondromata.

Functional assessment in the rat by ground reaction forces.

Although the rat sciatic nerve model is used extensively in the investigation of repair techniques, and a variety of evaluation methods utilized to assess the results, a means to measure directly and accurately the return of function in these animals is absent. Histologic, histomorphometric, and electrophysiologic methods can be reliable indicators of nerve regeneration but do not correlate to functional recovery. The purposes of this study were to develop apparatus to continuously measure ground reaction forces (GRF) and use GRF parameters in the assessment of gait parameters in normal rats preoperatively and following peripheral nerve severance and repair. Three neurorrhaphy methods: direct sciatic nerve repair, direct tibial nerve repair and double sciatic nerve repair simulating autograft, as well as a non-repaired tibial nerve transection were evaluated. The testing apparatus was designed to measure the spontaneous and voluntary effort of the rat with objective data. Three orthogonal components - vertical, craniocaudal (braking and propulsion), and mediolateral - of the ground reaction force were measured. Preoperative data showed that vertical forces were comparable among the four limbs but propulsion and braking forces displayed significant differences. At 12 weeks, functional recovery was most evident in the direct tibial nerve repair group and absent in the non-repaired tibial defect group. Direct sciatic nerve repairs and sciatic nerve grafts resulted in lesser degrees of improvement. Results indicated that the propulsive force is the optimal GRF parameter for evaluating recovery of useful function.

Adhesions from flexor tendon surgery: an animal study comparing surgical techniques.

Intraoperative and postoperative hemorrhage has long been considered a cause of tendon adhesion and, thus, scarring and poor surgical results. To prevent such problems bipolar coagulators are commonly used during surgery to help achieve hemostasis. Surgical lasers also have been reported to help limit bleeding and scar formation. Very little is known regarding the relationship between hemorrhage and/or direct tendon tissue effects and tendon adhesions with the use of these modalities. We compared 3 different surgical techniques (meticulous sharp scalpel dissection, scalpel dissection plus bipolar coagulation, and CO(2) laser dissection) and used chicken flexor tendons to biomechanically and histologically assess the amount of adhesion formation after each procedure. Our findings show that bipolar coagulation and CO(2) laser application are both associated with significantly increased adhesion formation in tendon surgery compared with sharp dissection alone and that the meticulous, conventional sharp dissection technique is the best method to control adhesion formation. These conclusions have relevance to clinical tendon surgery.

Changes in digital flexor tendon mechanics after endoscopic and open carpal tunnel releases in cadaver wrists.

Digital flexor tendon excursion due to isolated wrist motion was measured in 5 cadaver wrists. Five sequential experimental conditions were tested: (1) intact wrists, (2) after single-incision endoscopic carpal tunnel release, (3) after addition of a distal endoscopic portal, (4) after conversion to an open palm incision, and (5) after suturing of the palm incision. Combined tendon excursion increased 27.8% after 1-incision and 29.7% after 2-incision endoscopic release; both increases were significant. A further increase in combined excursion to 43.4% over the value in intact wrists was measured after conversion to an open palm incision. Combined flexor tendon excursion after open release was significantly greater than excursion after either type of endoscopic release. Increases in excursion were also significant when flexor digitorum superficialis and flexor digitorum profundus tendons were considered separately. Excursion did not change significantly after skin suturing. These findings suggest that digital flexor tendon mechanics are closer to normal after endoscopic carpal tunnel release than after open release. It remains to be shown whether the difference is an advantage of endoscopic release over open release in the clinical setting. (J Hand Surg 2000; 25A:112-119.

Hand function following single ray amputation.

We retrospectively studied primary and reconstructive single ray resection at 16 to 150 months after surgery (median, 41 months) in 25 patients (18 males) whose average age was 28 years. Cases were reviewed 16 to 154 months after surgery (median, 41 months). The injuries involved 14 dominant and 11 nondominant hands. Twelve patients had primary ray resection (< or =2 weeks after injury) and 13 had secondary/reconstructive amputation of 18 border and 7 central digits. Examinations and functional testing by Minnesota rate of manipulation and timed grooved pegboard tests were done and x-rays were reviewed. The majority of patients were subjectively satisfied with the appearance and function of the hand. Patients lost an average of 13 weeks of work (range, 2-24 weeks); those with primary resection were out of work 9 weeks (range, 2-17 weeks) and patients who had secondary resection lost a total of 16 weeks of work (range, 7-24 weeks). Twenty-one of the 25 patients returned to their preinjury occupation. Evaluation of nonwork plus settled workers' compensation cases versus nonsettled compensation/litigation cases showed that there were statistically significant differences in grip strength, key pinch, oppositional pinch, and Minnesota rate of manipulation test results. Primary ray removal limits the total costs associated with injury and disability; unsettled compensation/litigation issues produce statistically disparate and otherwise physically inexplicable differences.

Comparative results of resection of the distal ulna in rheumatoid arthritis and post-traumatic conditions.

The purpose of this study was to determine whether the results of resection of the distal ulna differed depending upon the underlying aetiology of the condition. Patients with rheumatoid arthritis were compared with patients with post-traumatic wrist complaints. Fifty resections in 40 patients (eight male, 32 female) were assessed with respect to pain, range of motion, and grip strength. Of the 23 rheumatoid wrists, 86% were pain-free following surgery; however, only 36% of the patients in the trauma group reported pain relief postoperatively. Pain relief in post-traumatic patients was more predictable when distal radioulnar joint arthrosis was identified as the sole cause of wrist pain.

Distal interphalangeal joint implant arthroplasty in a musician.

Degenerative joint disease commonly affects the distal interphalangeal (DIP) joints, causing articular destruction and marginal bone formation. Treatment for pain relief and function is most often done through arthrodesis. The case of a 70-year-old concert violinist with left index finger DIP joint osteoarthritis is presented. Arthritis in the involved joint caused pain and deformity and interfered with the patient's ability to play music. Trial arthrodesis with K-wires proved impossible because of the patient's need for continued mobility. Swanson hinge implant arthroplasty was performed on the affected DIP joint. The patient eventually achieved an excellent result and was able to return to playing the violin professionally. Treatment and therapy guidelines are presented.

Pediatric hand disease. Diagnosis and treatment.

Proper care of the pediatric hand requires a careful, systematic history, and physical examination, and is facilitated by recognizing common disease patterns, making it easier to determine which conditions require specialty referral, and the timing of those referrals. The article outlines pertinent details of examination and discusses diagnosis and treatment of a number of common diseases entities of the hand.

Salvaging the "unsalvageable" digit.

Establishing soft-tissue coverage adequate to retain an injured digit (preserve length) is not always possible or advisable. Careful evaluation combined with the skillful application of various reconstructive procedures (at the expense of length) may salvage the function and aesthetics of the injured hand.

Pressure changes in Guyon's canal after carpal tunnel release.

We measured pressure changes in Guyon's canal and the carpal tunnel before and after endoscopic (11 cases) and open (10) carpal tunnel release. We found that release of the flexor retinaculum by endoscopic and open techniques measurably decreased pressure in both the carpal tunnel and Guyon's canal. This study provides an explanation for relief of ulnar tunnel syndrome symptoms following carpal tunnel release and may indicate that carpal tunnel release alone may be sufficient to provide symptomatic relief for most patients with carpal and ulnar tunnel syndromes.

Effect of high-energy phosphates and free radical scavengers on replant survival in an ischemic extremity model.

In replantation surgery, preoperative and intraoperative ischemia can lead to irreversible changes that prevent reperfusion during the subsequent re-establishment of circulation. These changes are termed the no-reflow phenomenon. Ischemic phase damage was addressed by comparing the dose-response effects of controls vs. five different high-energy phosphate compounds on replanted limb survival. Reperfusion damage was evaluated via comparisons of controls with superoxide dismutase (SOD). Ischemic hindlimbs treated with high-energy phosphates displayed improved survival compared with controls. Limbs treated with SOD demonstrated no change in survival at 4 hours and improved survival at 8 hours. Combining adenosine and SOD had no improved effect on survival. Adenosine was the most effective high-energy phosphate in limiting ischemic damage. The free radical scavenger (SOD) was beneficial only at the later stages of ischemia. In this experimental model, there appears to be a role for both phosphates and free radical scavengers in enhancing ischemic tissue survival.

Long-term results of carpal tunnel release.

To determine the long-term results of carpal tunnel release, we retrospectively reviewed 60 cases, an average of 5.5 years after surgery. 87% reported a good or excellent overall outcome; the average time to maximum improvement of symptoms was 9.8 months. However, 30% reported poor to fair strength and long-term scar discomfort, and 57% noted a return of some pre-operative symptoms, most commonly pain, beginning an average of 2 years after surgery. We found no correlation between pre-operative symptoms or extent of surgical dissection (internal neurolysis) and outcome. Carpal tunnel syndrome was job related in 42%; of these, 26% changed from heavy to lighter work following surgery. Although occupational cases were slower to improve and remained off work longer, the long-term subjective results were the same for both groups. We found significant morbidity from the surgical scar and decreased strength, and often considerable delay until ultimate improvement, especially in patients with job-related carpal tunnel syndrome.

Endoscopic carpal tunnel release: a prospective study of complications and surgical experience.

A 63-center prospective study of endoscopic carpal tunnel release using the Agee Carpal Tunnel Release System was conducted in 1049 procedures in 988 patients. Prior experience with endoscopic release varied significantly among surgeon participants. Surgeons evaluated the newly redesigned system for blade visibility, blade height, and mechanical function. Data on patient complications were collected at the time of surgery and 3-4 weeks postoperative. The results indicated minimal complications and no confirmed injuries to vessels or nerves; the symptoms from one possible digital nerve injury eventually resolved completely. Surgeons were able to observe the point of entry of the blade into the transverse carpal ligament in 97.5% of procedures. Introduction of the blade assembly into the carpal tunnel was rated easy or adequate in 90.6% of procedures, and blade height was rated adequate in 97.4% of procedures.

Morphologic changes following endoscopic and two-portal subcutaneous carpal tunnel release.

This study describes the morphologic changes that occur following single incision endoscopic and two-portal subcutaneous carpal tunnel release. Seventeen patients were studied preoperatively and an average of 24 weeks postoperatively. Canal volume, carpal arch width, and median nerve palmar displacement and cross-sectional area were measured by use of multiplanar reformation and three-dimensional reconstruction of magnetic resonance images. Both methods produced a marked increase in canal volume and median nerve cross-sectional area; neither resulted in a significant change in carpal arch width. These data provide a morphologic basis for the belief that endoscopic or subcutaneous carpal tunnel release will produce clinical relief equivalent to open carpal tunnel release.

Mallet finger: results of early versus delayed closed treatment.

The efficacy of continuous splinting was retrospectively compared in two populations of 40 patients with soft tissue and bony mallet finger whose treatment was initiated within 2 weeks after injury (early) or more than 4 weeks after trauma (delayed). Splint treatment was successful in restoring active extension (with no more than 10 degrees extensor lag) in 17 of 21 patients in the early group and 15 of 19 patients in the delayed group. Neither the presence or absence of dorsal lip fracture less than one third of the articular surface of the distal phalanx nor the type of splint used affected the final outcome. Splinting was as effective in the delayed treatment population as it was in the early treatment population.