[Current Trends in the Implantation of the Touch Prosthesis at the Thumb Carpometacarpal Joint: Results of the 1st German-Speaking User Meeting]. / Aktuelle Trends bei der Implantation der Touch-Prothese am Daumensattelgelenk: Ergebnisse des 1. deutschsprachigen Anwendertreffens.

The introduction of the new generation of thumb carpometacarpal (CMC I) joint implants for the treatment of CMC I osteoarthritis has significantly broadened the scope of hand surgery in recent years. However, the technical demands of the procedure and the many details that need to be considered require appropriate training and a learning curve. To share experiences with the Touch CMC I prosthesis, we held the first German-speaking CMC I joint prosthetics user meeting in Zurich. After some basic introductory lectures on biomechanics and the principles of prosthetic fitting of the CMC I joint, the various challenges associated with CMC I joint prosthetics were discussed in interactive expert panels. Subsequently, cases were discussed in small groups under expert guidance and the respective conclusions were discussed in plenary. The main results of this symposium are summarised in this manuscript.

FOXO1 gene involvement in a non-rhabdomyosarcomatous neoplasm.

Myoepithelial neoplasms of soft tissue are rare tumors with clinical, morphological, immunohistochemical, and genetic heterogeneity. The morphological spectrum of these tumors is broad, and the diagnosis often requires immunostaining to confirm myoepithelial differentiation. Rarely, tumors show a morphology that is typical for myoepithelial neoplasms, while the immunophenotype fails to confirm myoepithelial differentiation. For such lesions, the term "myoepithelioma-like" tumor was introduced. Recently, two cases of myoepithelioma-like tumors of the hands and one case of the foot were described with previously never reported OGT-FOXO gene fusions. Here, we report a 50-year-old woman, with a myoepithelial-like tumor localized in the soft tissue of the forearm and carrying a OGT-FOXO1 fusion gene. Our findings extend the spectrum of mesenchymal tumors involving members of the FOXO family of transcription factors and point to the existence of a family of soft tissue tumors that carry the gene fusion of the OGT-FOXO family.

[Scapholunate lesions and instabilities--how to recognize and treat them?]. / Lésions et instabilités scapho-lunaires: les reconnaître et les traiter.

The lesions of the scapholunate ligament are some of the most frequently encountered in the wrist. Left untreated, the complete rupture of the ligament is followed by degenerative arthritis according to a well-defined pattern of progression through the wrist, eventually leading to multifocal arthrosis, a condition described as scapholunate advanced collapse (SLAC wrist). The scapholunate lesions are classified in stages according to the degree of the lesion established by imaging studies or arthroscopy and to the chronicity of the lesion. Both together essentially determine the healing potential and the prognosis, which rapidly decrease after six weeks from the initial trauma, thus indicating the importance of recognizing the acute or subacute lesion and directing the patient to the hand surgeon early enough. The therapeutic options are notably reduced and often of palliative nature in case of chronic lesions with secondary changes in the wrist mechanics or cartilage damage.

Midterm Outcome of Bone-Ligament-Bone Graft and Dorsal Capsulodesis for Chronic Scapholunate Instability.

PURPOSE: To assess midterm outcomes of our bone-ligament-bone (BLB) grafts for chronic scapholunate (SL) instability and better define criteria for their use. METHODS: We conducted a retrospective review of 26 patients treated with BLB grafts and dorsal capsulodesis between 1997 and 2009. Twenty-four patients were reviewed. Mean follow-up was 8.2 years. Two patients had dynamic lesions, 7 had SL dissociation, 14 had a dorsal intercalated segment instability lesion, and 1 had SL advanced collapse stage 1. Mean age at surgery was 46 years. All patients presented with pain and 14 had lack of strength. Results were reviewed clinically and radiologically. Images were assessed by 4 surgeons and 1 radiologist for radial styloid, radioscaphoid, radiolunate, midcarpal, and scaphotrapeziotrapezoid degenerative changes. RESULTS: Five patients needed subsequent 4-corner arthrodesis. Of the remaining 19 patients at follow-up, both extension and flexion decreased to 73% of the contralateral side. Postoperative grip strength improved from 78% to 90% of the nonsurgical wrist. Quick Disabilities of the Arm, Shoulder, and Hand score was 10 of 100 and the Patient-Rated Wrist Evaluation score was 10 of 100. Radiologically, the SL gap was improved and maintained at follow-up. The SL angle (mean before surgery, 79°) was initially corrected to 69° but returned to preoperative values at follow-up. Eleven of the 19 cases had signs of midcarpal arthritis. CONCLUSIONS: Bone-ligament-bone grafts with SL dorsal capsulodesis were able to restore and maintain an improved SL interval in all patients. The technique achieved good clinical results and high patient satisfaction, but it did not stop the progression of arthritis, particularly at the midcarpal level. This technique is an option for isolated unrepairable lesion of the dorsal SL ligament with an easily correctable lunate and especially when restoration of grip strength is important. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

[When and which treatment for scapho-lunate ligament lesions?]. / Wann, welche Behandlung bei scapho-lunären Bandverletzungen?

The lesions of the scapholunate ligament are some of the most frequently encountered in the wrist. Left untreated, the complete rupture of the ligament is followed by degenerative arthritis according to a well-defined pattern of progression through the wrist, eventually leading to multifocal arthrosis, a condition described as scapholunate advanced collapse (SLAC wrist). The scapholunate lesions are classified in stages according to the degree of the lesion established by imaging studies or arthroscopy and to the chronicity of the lesion. Both together essentially determine the healing potential and the prognosis, which rapidly decrease after six weeks from the initial trauma, thus indicating the importance of recognizing the acute or subacute lesion and directing the patient to the hand surgeon early enough. The therapeutic options are notably reduced and often of palliative nature in case of chronic lesions with secondary changes in the wrist mechanics or cartilage damage.

Effect of controlled co-delivery of synergistic neurotrophic factors on early nerve regeneration in rats.

Present interventions to repair severed peripheral nerves provide slow and poor early axonal regeneration, which may cause unsatisfactory functional reinnervation. To improve early axonal regeneration in a 10 mm rat sciatic nerve gap model, we developed collagen nerve conduits loaded with the synergistically acting glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). For controlling the concomitant GDNF and NGF release, the collagen tubes were cross-linked by a dehydro-thermal treatment (110 degrees C; 20 mbar; 5 days) prior to impregnating the tubes with GDNF and NGF and by coating drug-loaded tubes with layers of poly(lactide-co-glycolide). The conduits made of cross-linked collagen released low initial amounts of GDNF and NGF (2% of both during first 3 days) and enhanced significantly the early (2 weeks) nerve regeneration in terms of axonal outgrowth and Schwann cell migration in a 10 mm rat sciatic nerve gap model, as compared to the conduits made of non-cross-linked collagen releasing higher initial amounts of GDNF and NGF (12-16% within 3 days), or those releasing GDNF alone. The enhancement of early axonal regeneration using controlled co-delivery of multiple synergistic neurotrophic factors is an important requisite for eventually establishing functional connections with the target organ.

Collagen nerve conduits releasing the neurotrophic factors GDNF and NGF.

Artificial nerve conduits (NC) can clinically be instrumental for facilitating the surgery of damaged peripheral nerves. To improve axonal regeneration of injured peripheral nerves, we have developed collagen nerve conduits (NC) releasing glial cell line-derived neurotrophic factor (GDNF) alone or in combination with nerve growth factor (NGF), which exert synergistic action on axonal growth. Degradation of the NC and their mechanical and drug release properties were controlled by two means: (i) cross-linking the collagen tubes by physical means, through a dehydro-thermal treatment (DHT), before loading with the neurotrophic factors (NTFs) GDNF or GDNF/NGF; and (ii) coating the drug-loaded collagen tubes with layers of poly(lactide-co-glycolide) (PLGA). Non-cross-linked collagen NC (C-NC) released high amounts of NTFs during the initial 2-3 days of incubation, whereas the DHT-treated collagen NC (C(dht)-NC) did not show a prominent burst effect. The release kinetics was similar for GDNF alone and GDNF co-delivered with NGF. Within 30 days, the C-NC released 78% and 83% of the total doses of GDNF and NGF, respectively, whereas the C(dht)-NC released only 68% of GDNF and 56% of NGF. The bioactivity of the NTFs released up to 30 days was confirmed by an in vitro bioassay using chicken embryonic dorsal root ganglion (DRG) explants. The C(dht)-NC also possessed adequate mechanical resistance against radial compression, the pull-out of a suture thread, and loss of patency upon bending. Modulus and pull-out strength increased in the order of C-NC, C(dht)-NC approximately Neuragen, and Neurolac, with the latter two products being commercially available collagen and polyester NC, respectively. In vitro degradation time upon incubation with collagenase increased in the same order for the collagen-based NC. In conclusion, co-delivery of synergistically acting GDNF and NGF from structurally improved NC may be a promising tool for the successful repair of peripheral nerve defects.

Synergistic effect of GDNF and NGF on axonal branching and elongation in vitro.

There is a clinical need to enhance functional recovery of injured peripheral nerves. Local administration of neurotrophic factors (NTFs) after surgical repair has been proposed for this purpose. Little is known, however, on the optimal local dose and dosing frequency of NTFs in a peripheral nerve defect. For increasing our knowledge on biologically relevant local NTFs concentrations and for making available an in vitro assay for assessing the bioactivity of NTFs in connection with implantable localized delivery systems, we developed in this study a bioassay for NTFs, which is based on dorsal root ganglion (DRG) explants from E9 (9 days old) chicken embryos. Axonal elongation and extent of axonal branching was analyzed microscopically after addition of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF), each alone and in combination. GDNF significantly promoted axonal elongation, but only little axonal branching, whereas NGF induced extensive axonal branching with modest axonal elongation. The combination of GDNF and NGF exerted a synergistic effect on the axonal elongation, axonal branching and growth kinetics. GDNF and NGF also enhanced the expression of their respective functional receptors Ret and TrkA on the DRG neurons. This information should be relevant for the development of implants containing NTFs and on drug therapy of damaged peripheral nerves.

Controlled nerve growth factor release from multi-ply alginate/chitosan-based nerve conduits.

The delivery kinetics of growth factors has been suggested to play an important role in the regeneration of peripheral nerves following axotomy. In this context, we designed a nerve conduit (NC) with adjustable release kinetics of nerve growth factor (NGF). A multi-ply system was designed where NC consisting of a polyelectrolyte alginate/chitosan complex was coated with layers of poly(lactide-co-glycolide) (PLGA) to control the release of embedded NGF. Prior to assessing the in vitro NGF release from NC, various release test media, with and without stabilizers for NGF, were evaluated to ensure adequate quantification of NGF by ELISA. Citrate (pH 5.0) and acetate (pH 5.5) buffered saline solutions containing 0.05% Tween 20 yielded the most reliable results for ELISA active NGF. The in vitro release experiments revealed that the best results in terms of reproducibility and release control were achieved when the NGF was embedded between two PLGA layers and the ends of the NC tightly sealed by the PLGA coatings. The release kinetics could be efficiently adjusted by accommodating NGF at different radial locations within the NC. A sustained release of bioactive NGF in the low nanogram per day range was obtained for at least 15days. In conclusion, the developed multi-ply NGF loaded NC is considered a suitable candidate for future implantation studies to gain insight into the relationship between local growth factor availability and nerve regeneration.

Variations in glial cell line-derived neurotrophic factor release from biodegradable nerve conduits modify the rate of functional motor recovery after rat primary nerve repairs.

Accelerating axonal regeneration to shorten the delay of reinnervation and improve functional recovery after a peripheral nerve lesion is a clinical demand and an experimental challenge. We developed a resorbable nerve conduit (NC) for controlled release of glial cell line-derived neurotrophic factor (GDNF) with the aim of assessing motor functional recovery according to the release kinetics of this factor in a short gap model. Different types of resorbable NCs were manufactured from a collagen tube and multiple coating layers of poly(lactide-coglycolide), varying in poly(lactide-coglycolide) type and coating thickness to afford three distinct release kinetics of the neurotrophic factor. GDNF release was quantified in vitro. End-to-end suture and GDNF-free NC served as controls. Thirty-five Wistar rats underwent surgery. Motor recovery was followed from 1 to 12 weeks after surgery by video gait analysis. Morphometrical data were obtained at mid-tube level and distal to the NC. NCs were completely resorbed within 3 months with minimal inflammation. GDNF induced a threefold overgrowth of fibers at mid-tube level. However, the number of fibers was similar in the distal segment of all groups. The speed of recovery was inversely proportional to the number of fibers at the NC level but the level of recovery was similar for all groups at 3 months. The resorbable conduits proved their ability to modulate axonal regrowth through controlled release of GDNF. In relation to the dose delivered, GDNF strikingly multiplied the number of myelinated fibers within the NC but this increase was not positively correlated with the return of motor function in this model.

Silk fibroin matrices for the controlled release of nerve growth factor (NGF).

Nerve conduits (NC) for peripheral nerve repair should guide the sprouting axons and physically protect the axonal cone from any damage. The NC should also degrade after completion of its function to obviate the need of subsequent explanation and should optionally be suitable for controlled drug release of embedded growth factors to enhance nerve regeneration. Silk fibroin (SF) is a biocompatible and slowly biodegradable biomaterial with excellent mechanical properties that could meet the above stated requirements. SF material (films) supported the adherence and metabolic activity of PC12 cells, and, in combination with nerve growth factor (NGF), supported neurite outgrowth during PC12 cell differentiation. NGF-loaded SF-NC were prepared from aqueous solutions of NGF and SF (20%, w/w), which were air-dried or freeze-dried (freezing at -20 or -196 degrees C) in suitable molds. NGF release from the three differently prepared SF-NC was prolonged over at least 3 weeks, but the total amount released depended on the drying procedure of the NC. The potency of released NGF was retained within all formulations. Control experiments with differently dried NGF-lactose solutions did not evidence marked protein aggregation (SEC, HPLC), loss of ELISA-reactivity or PC12 cell bioactivity. This study encourages the further exploitation of SF-NC for growth factor delivery and evaluation in peripheral nerve repair.

Nerve conduits and growth factor delivery in peripheral nerve repair.

Peripheral nerves possess the capacity of self-regeneration after traumatic injury. Transected peripheral nerves can be bridged by direct surgical coaptation of the two nerve stumps or by interposing autografts or biological (veins) or synthetic nerve conduits (NC). NC are tubular structures that guide the regenerating axons to the distal nerve stump. Early synthetic NC have primarily been made of silicone because of the relative flexibility and biocompatibility of this material and because medical-grade silicone tubes were readily available in various dimensions. Nowadays, NC are preferably made of biodegradable materials such as collagen, aliphatic polyesters, or polyurethanes. Although NC assist in guiding regenerating nerves, satisfactory functional restoration of severed nerves may further require exogenous growth factors. Therefore, authors have proposed NC with integrated delivery systems for growth factors or growth factor-producing cells. This article reviews the most important designs of NC with integrated delivery systems for localized release of growth factors. The various systems discussed comprise NC with growth factors being released from various types of matrices, from transplanted cells (Schwann cells or mesenchymal stem cells), or through genetic modification of cells naturally present at the site of injured tissue. Acellular delivery systems for growth factors include the NC wall itself, biodegradable microspheres seeded onto the internal surface of the NC wall, or matrices that are filled into the lumen of the NC and immobilize the growth factors through physical-chemical interactions or specific ligand-receptor interactions. A very promising and elegant system appears to be longitudinally aligned fibers inserted in the lumen of a NC that deliver the growth factors and provide additional guidance for Schwann cells and axons. This review also attempts to appreciate the most promising approaches and emphasize the importance of growth factor delivery kinetics.

Hydrogel nerve conduits produced from alginate/chitosan complexes.

Nerve conduits (NCs) represent a promising alternative to conventional treatments for peripheral nerve repair. Materials for NC production should be biodegradable, possess adequate mechanical properties, and allow for exchange of nutrients. To this aim, we developed biodegradable NC made of a hydrogel that consisted of the oppositely charged polysaccharides alginate and chitosan. Swelling and permeation studies, as well as rheological measurements, served to characterize the NC. The alginate/chitosan NC showed high water uptake (84% w/w) and permitted permeation of fluorescent-labeled dextrans in a molecular weight dependent manner. The NC fulfilled the mechanical specifications without further crosslinking. The soft NC can be expected to preclude nerve compression (storage modulus of about 40 kPa), but possess sufficient mechanical strength. In combination with remarkable tear resistance, the NC affords easy surgical handling.

Accessory extensor pollicis longus.

Phylogenetically the accessory extensor pollicis longus in man seems to find its origin in the deep extensor layer, and this has largely been described in primates. I describe a case and present a comprehensive review of other publications on the subject.

Development of neuropathic pain in the rat spared nerve injury model is not prevented by a peripheral nerve block.

BACKGROUND: The mechanisms responsible for initiation of persistent neuropathic pain after peripheral nerve injury are unclear. One hypothesis is that injury discharge and early ectopic discharges in injured nerves produce activity-dependent irreversible changes in the central nervous system. The aim of this study was to determine whether blockade of peripheral discharge by blocking nerve conduction before and 1 week after nerve injury could prevent the development and persistence of neuropathic pain-like behavior in the spared nerve injury model. METHODS: Bupivacaine-loaded biodegradable microspheres embedded in fibrin glue were placed in a silicone tube around the sciatic nerve to produce a conduction block. After sensory-motor testing of block efficacy, a spared nerve injury procedure was performed. Development of neuropathic pain behavior was assessed for 4 weeks by withdrawal responses to stimulation (i.e., von Frey filaments, acetone, pinprick, radiant heat) in bupivacaine microspheres-treated animals (n = 12) and in controls (n = 11). RESULTS: Bupivacaine microspheres treatment produced conduction blockade with a complete lack of sensory responsiveness in the sural territory for 6 to 10 days. Once the block wore off, the degree of hypersensitivity to stimuli was similar in both groups. CONCLUSIONS: Peripheral long-term nerve blockade has no detectable effect on the development of allodynia or hyperalgesia in the spared nerve injury model. It is unlikely that injury discharge at the time of nerve damage or the early onset of ectopic discharges arising from the injury site contributes significantly to the persistence of stimulus-evoked neuropathic pain in this model.

A mechanical comparison of bone-ligament-bone autografts from the wrist for replacement of the scapholunate ligament.

A study was performed to compare the mechanical properties of two intracarpal ligaments with those of the dorsal component of the scapholunate interosseous ligament (SLIL). Trapezoid-to-second metacarpal, capitate-to-trapezoid ligaments, and the dorsal part of the SLIL were obtained as bone-ligament-bone grafts from fresh frozen cadavers. Their respective load to failure and stiffness were measured under uniaxial load on a servohydraulic machine and compared. The capitate-to-trapezoid ligament closely approximated the load to failure and stiffness of the dorsal SLIL, whereas the trapezoid-to-second metacarpal ligament was significantly stronger and stiffer than the dorsal SLIL. These 2 intracarpal bone-ligament-bone grafts share similar mechanical properties with the dorsal component of the scapholunate ligament and might be used clinically to replace it.

GDNF and NGF released by synthetic guidance channels support sciatic nerve regeneration across a long gap.

The present work was performed to determine the ability of neurotrophic factors to allow axonal regeneration across a 15-mm-long gap in the rat sciatic nerve. Synthetic nerve guidance channels slowly releasing NGF and GDNF were fabricated and sutured to the cut ends of the nerve to bridge the gap. After 7 weeks, nerve cables had formed in nine out of ten channels in both the NGF and GDNF groups, while no neuronal cables were present in the control group. The average number of myelinated axons at the midpoint of the regenerated nerves was significantly greater in the presence of GDNF than NGF (4942 +/-1627 vs. 1199 +/-431, P < or = 0.04). A significantly greater number of neuronal cells in the GDNF group, when compared to the NGF group, retrogradely transported FluoroGold injected distal to the injury site before explantation. The total number of labelled motoneurons observed in the ventral horn of the spinal cord was 98.1 +/-23.4 vs. 20.0 +/-8.5 (P < or = 0.001) in the presence of GDNF and NGF, respectively. In the dorsal root ganglia, 22.7% +/- 4.9% vs. 3.2% +/-1.9% (P +/-0.005) of sensory neurons were labelled retrogradely in the GDNF and NGF treatment groups, respectively. The present study demonstrates that, sustained delivery of GDNF and NGF to the injury site, by synthetic nerve guidance channels, allows regeneration of both sensory and motor axons over long gaps; GDNF leads to better overall regeneration in the sciatic nerve.

Complications of plate fixation in metacarpal fractures.

BACKGROUND: The objective of this study is to assess the complications after open reduction and plate fixation of extra-articular metacarpal fractures. METHODS: We retrospectively reviewed the clinical and radiologic records of 129 consecutive patients with 157 metacarpal fractures treated by open reduction and internal fixation with plates between 1993 and 1999. Intra-articular fractures and fractures of the thumb metacarpal were excluded. Eighty-one patients (64 men and 17 women) with 104 fractures were available for review, at an average follow-up of 13.6 months (range, 6-27 months). RESULTS: Twenty-eight patients (35%) and 33 fractures (32%) had one or more complications, including difficulty with fracture healing (12 patients [15%]), stiffness (eight patients [10%]), plate loosening or breakage (seven patients [8%]), complex regional pain syndrome (two patients), and one patient who developed a deep infection. CONCLUSION: Despite technical advances in implant material, design, and instrumentation, plate fixation of metacarpal fractures remains fraught with complications and unsatisfactory results.