Local delivery of the Neuregulin1 receptor ecto-domain (ecto-ErbB4) has a positive effect on regenerated nerve fiber maturation.

The Neuregulin/ErbB system plays an important role in the peripheral nervous system, under both normal and pathological conditions. We previously demonstrated that expression of soluble ecto-ErbB4, the released extracellular fragment of the ErbB4 receptor, stimulated glial cell migration in vitro. In this study we examined the possibility of manipulating this system in vivo in order to improve injured peripheral nerve regeneration. Transected rat median nerves of adult female Wistar rats were repaired with a 10-mm-long graft made by muscle-in-vein combined nerve guide previously transduced with either the adeno-associated viral (AAV) vector AAV2-LacZ or AAV2-ecto-ErbB4. Autologous nerve grafts were used as control. Both stereological and functional analyses were performed to assess nerve regeneration. Data show that delivery of soluble ecto-ErbB4 by gene transfer in the muscle-in-vein combined nerve guide has a positive effect on fiber maturation, suggesting that it could represent a potential tool for improving peripheral nerve regeneration.

Step-by-step surgical technique for mandibular reconstruction with fibular free flap: application of digital technology in virtual surgical planning.

At present, mandibular reconstruction with a fibular free flap is the gold standard for functional and esthetic rehabilitation after oncological surgery. The purpose of this study was to describe the computer-assisted mandibular reconstruction procedure adopting the customized solution Synthes ProPlan CMF. The study reports five consecutive patients with benign or malignant disease requiring mandibular reconstruction using a microvascular fibular free flap, pre-operative virtual planning, construction of cutting guides and customized laser pre-bent titanium plates. The surgical technique is discussed in a step-by-step fashion. The average post-operative hospital stay was 18 ± 3 days. Ischemia time was recorded in all five cases, with an average of 75 ± 8 min. No problems were encountered in any surgical step and there were no major complications. Excellent precision of cutting guides and a good fit of pre-bent plates were found on both the mandible and fibula. There was excellent precision in bone to bone contact and position between mandible and fibula graft. Measurement data from the pre-operative and post-operative CT scans were compared. The average difference (Δ) between programed segment lengths and CT control segment lengths was 0.098 ± 0.077 cm. Microsurgical mandibular reconstruction using a virtual surgical planning yields significantly shorter ischemia times and allows more precise osteotomies. The technology is becoming increasingly recognized for its ability to optimize surgical outcomes and minimize operating time. Considering that the extent of resection can be wider than predicted, this results in safer modeling of the fibula only after frozen sections have demonstrated the radicality of resection.

Surgical treatment of acute fingernail injuries.

The fingernail has an important role in hand function, facilitating the pinch and increasing the sensitivity of the fingertip. Therefore, immediate and proper strategy in treating fingernail injuries is essential to avoid aesthetic and functional impairment. Nail-bed and fingertip injuries are considered in this review, including subungual hematoma, wounds, simple lacerations of the nail bed and/or matrix, stellate lacerations, avulsion of the nail bed, ungual matrix defect, nail-bed injuries associated with fractures of the distal phalanx, and associated fingertip injuries. All these injuries require careful initial evaluation and adequate treatment, which is often performed under magnification. Delayed and secondary procedures of fingernail sequelae are possible, but final results are often unpredictable.

Experimental and clinical employment of end-to-side coaptation: our experience.

The last 15 years have seen a growing interest regarding a technique for nerve repair named end-to-side coaptation. Since 2000, we have carried out experimental studies on end-to-side nerve repair as well as employed this technique to a series of selected clinical cases. Here we report on the results of this experience.For experimental studies, we have used the model represented by median nerve repair by end-to-side coaptation either on the ulnar (agonistic) or the radial (antagonistic) nerve. For time course assessment of median nerve functional recovery we used the grasping test, a test which permits to assess voluntary control of muscle function. Repaired nerves were processed for resin embedding to allow nerve fibre stereology and electron microscopy. Results showed that, in either experimental group, end-to-side-repaired median nerves were repopulated by axons regenerating from ulnar and radial donor nerves, respectively. Moreover, contrary to previously published data, our results showed that voluntary motor control of the muscles innervated by the median nerve was progressively recovered also when the antagonistic radial nerve was the donor nerve.As regards our clinical experience, results were not so positive. We have treated by end-to-side coaptation patients with both sensory (n = 7, collateral digital nerves) and mixed (n = 8, plexus level) nerve lesions. Results were good, as in other series, in sensory nerves whilst they were very difficult to investigate in mixed nerves at the plexus level.Take together, these results suggest that clinical employment of end-to-side coaptation should still be considered at the moment as the ultima ratio in cases in which no other repair technique can be attempted. Yet, it is clear that more basic research is needed to explain the reasons for the different results between laboratory animal and humans and, especially, to find out how to ameliorate the outcome of end-to-side nerve repair by adequate treatment and rehabilitation.

Impact of COVID-19 on hand surgery in Italy: A comparison between the Northern and the Southern regions.

The aims of this study were to evaluate the impact of the COVID-19 pandemic on emergency and elective hand surgery in four Italian regions that had either a high (Lombardy and Piemonte) or a low (Sicilia and Puglia) COVID-19 case load to discuss problems and to elaborate strategies to improve treatment pathways. A panel of hand surgeons from these different regions compared and discussed data from the centers they work in. The COVID-19 pandemic had an enormous impact on both elective and emergency surgery in Italy, not only in highly affected regions but also - and paradoxically even at a higher extent - in regions with a low COVID-19 case load. A durable and flexible redesign of hand surgery activities should be promoted, while changing and hopefully increasing human resources and enhancing administrative support. Telematics must also be implemented, especially for delivering rehabilitation therapy.

A simple sterile polypropylene fingernail substitute.

Traumatic nail injuries are often observed in clinical practice. Usually the fingernail can be preserved, cleaned and disinfected in order to use it in the reconstructive procedure. However, in some cases the nail can be avulsed and lost or too damaged to be used. In cases when the nail is not available it should be replaced by a substitute in order to protect nail bed and avoid adherences along the proximal nail bed and the nail fold. Furthermore the substitute serves to protect the tender nail bed from painful stimuli during the healing process. We used, as fingernail substitute, a polypropylene sheet in eight patients with fingernail avulsion or disruption. The polypropylene foil was trimmed reproducing the profile of the avulsed fingernail and thinned at the proximal edge to reduce thickness in order to ease the insertion into the nail fold. A small hole was then created in the center of the foil to allow blood drainage. The substitute was usually removed one month after the application. In our clinical experience we had not complications related to the polypropylene device. The new fingernail had good cosmetic appearance in most cases and all the patients reported a good protection of the fingertip during the healing period. The substitute used in this series is sterile, inexpensive and easily available in emergency and elective operatory theater. This polypropylene foil is flexible and can be shaped and adapted to the nail curvature radius. The substitute used in our clinical series protected the nail bed during healing until the growth of the new fingernail and respected our functional expectations.

Employment of the mouse median nerve model for the experimental assessment of peripheral nerve regeneration.

The experimental investigation of nerve regeneration after microsurgical repair is usually carried out in rats, rather than mice, because of the larger sized peripheral nerves. Today however, the availability of genetically modified mice makes the use of this laboratory animal very intriguing for investigating nerve regeneration at a molecular level. In this study we aimed to provide a standardization of the experimental model based on microsurgical direct repair, by 12/0 suture, of the left median nerve in adult male mice. Postoperative recovery was regularly assessed by the grasping test. At day-75 postoperative, regenerated median nerve fibers were analyzed by design-based quantitative morphology and electron microscopy. Yet, sections were immuno-labelled using two axonal antibodies commonly employed for rat nerve fibers. Results indicated that functional recovery begun at day-15 and progressively increased reaching values not significantly different from normal by day-50. Quantitative morphology showed that, at day-75, the number of regenerated nerve fibers was not significantly different in comparison to controls. In contrast, differences were detected in fiber density, mean axon and fiber diameter and myelin thickness which were all significantly lower than controls. Immunohistochemistry showed that axonal markers commonly used for rat nerves studies are effective also for mouse nerves. Similar to the rat, the mouse median nerve model is superior to sciatic nerve model for the minimal impact on animal well-being and the effectiveness of the grasping test for motor function evaluation. The main limitation is the small nerve size which requires advanced microsurgical skills for performing 12/0 epineurial suturing.

Lack of topographic specificity in nerve fiber regeneration of rat forelimb mixed nerves.

Multiple nerve repair by means of a Y-shaped nerve guide represents a good model for studying the specificity of peripheral nerve fiber regeneration. Here we have used it for investigating the specificity of axonal regeneration in mixed nerves of the rat forelimb model. The left median and ulnar nerves, in adult female rats, were transected and repaired with a 14-mm Y-shaped conduit. The proximal end of the Y-shaped conduit was sutured to the proximal stump of either the median nerve or the ulnar nerve. Ten months after surgery, rats were tested for functional recovery of each median and ulnar nerve. Quantitative morphology of regenerated myelinated nerve fibers was then carried out by the two-dimensional disector technique. Results showed that partial recovery of both median and ulnar nerve motor function was regained in all experimental groups. Performance in the grasping test was significantly lower when the ulnar nerve was used as the proximal stump. Ulnar test assessment showed no significant difference between the two Y-shaped repair groups. The number of regenerated nerve fibers was significantly higher in the median nerve irrespectively of the donor nerve, maintaining the same proportion of myelinated fibers between the two nerves (about 60% median and 40% ulnar). On the other hand, nerve fiber size and myelin thickness were significantly larger in both distal nerves when the median nerve was used as the proximal donor nerve stump. G-ratio and myelin thickness/axon diameter ratio returned to normal values in all experimental groups. These results demonstrate that combined Y-shaped-tubulization repair of median and ulnar nerves permits the functional recovery of both nerves, independently from the proximal donor nerve employed, and that tissue, and not topographic, specificity guides nerve fiber regeneration in major forelimb mixed nerves of rats.

Alternative techniques for peripheral nerve repair: conduits and end-to-side neurorrhaphy.

Nowadays new techniques may help the surgeon in difficult cases of nerve tissue loss: when a gap is produced in a mixed nerve, the use of conduits can be an alternative to nerve grafts, which still represent the "gold standard" for this kind of lesions. We have applied biologic conduits (muscle inside a vein) in more than 40 cases since 1993 with 85% of good functional results for both sensory and mixed nerves up to 5 cm. The advantages of this technique are: (1) all graft material is easily withdrawn in the lesion area and thus is not necessary to perform any new incision; (2) the possibility of reconstructing nerve gaps up to 5 cm avoids secondary damage created by the withdrawal of healthy nerves; (3) the possibility for spontaneous orientation of regenerating nerve fibers is offered as fibers are allowed to search for their final target (chemiotropism). Furthermore, when the tissue loss is important or the proximal nerve stump is not available, so jeopardizing the possibility of recovery with traditional reconstruction, the use of end-to-side neurorrhaphy has been described to solve the problem. However the use of end-to-side neurorrhaphy in the clinical setting for motor recovery remains controversial. In our experience we had satisfying results only in 20% of cases and thus motor reconstruction in the absence of an available proximal nerve may be best handled by nerve to nerve transfers. By contrast we had good results in sensory nerve reconstruction (especially digital nerves) by end-to-side coaptation.

Functional, morphological and biomolecular assessment of posttraumatic neuro-muscular recovery in the rat forelimb model.

Over the last five years, we have used the rat forelimb model for investigating neuromuscular recovery after microsurgical nerve reconstruction of median and ulnar nerves by end-to-side neurorrhaphy and muscle-vein-combined tubulization (using both straight and Y-shaped guides). The outcome of nerve repair at different postoperative times was assessed by functional, morphological and biomolecular analysis. Results showed that both end-to-side and tubulization repair of rat median and ulnar nerves led to successful axonal regeneration along the severed nerve trunk as well as to a partial recovery of the lost function as assessed by grasping test. Biomolecular analysis by means of reverse transcription polymerase chain reaction (RT-PCR) demonstrated early overexpression during nerve regeneration of the gliotrophic factor NRG1 and two of its receptors: erbB2 and erbB3. Finally, our experience also suggests that the rat forelimb experimental model is particularly appropriate for the study of microsurgical reconstruction of major mixed nerve trunks. Furthermore, since the forelimb model is less compromising for the animal, it should be preferred to the hindlimb model for many research purposes.

Fibular osteofasciocutaneous flap in computer-assisted mandibular reconstruction: technical aspects in oral malignancies.

Virtual surgical planning technology in head and neck surgery is witnessing strong growth. In the literature, the validity of the method from the point of view of accuracy and clinical utility has been widely documented, especially for bone modelling. To date, however, with its increased use in head and neck oncology, and consequently the increased need for bone and soft tissue reconstruction, is important to carry out the virtual programme considering not only bone reconstruction but also all aspects related to the reconstruction of soft tissue using composite flaps. We describe our approach to virtual planning in the case of composite flaps. The study reports six consecutive patients with malignant disease requiring mandibular bone and soft tissue reconstruction using fibular osteocutaneous flaps. In all six patients, the resection and reconstruction were planned virtually focusing on the position of cutaneous perforator vessels in order to schedule fibula cutting guides. There were no complications in all six cases. The technique described allowed us to schedule composite fibula flaps in mandibular reconstruction virtually with good accuracy of the position of the bone segment in relation to the cutaneous paddle, important for soft tissue reconstruction. Despite the limited number of cases, the preliminary results of the study suggest that this protocol is useful in virtual programmes using composite flaps in mandibular reconstruction. Further investigations are needed.

Chitosan crosslinked flat scaffolds for peripheral nerve regeneration.

Chitosan (CS) has been widely used in a variety of biomedical applications, including peripheral nerve repair, due to its excellent biocompatibility, biodegradability, readily availability and antibacterial activity. In this study, CS flat membranes, crosslinked with dibasic sodium phosphate (DSP) alone (CS/DSP) or in association with the γ-glycidoxypropyltrimethoxysilane (CS/GPTMS_DSP), were fabricated with a solvent casting technique. The constituent ratio of crosslinking agents and CS were previously selected to obtain a composite material having both adequate mechanical properties and high biocompatibility. In vitro cytotoxicity tests showed that both CS membranes allowed cell survival and proliferation. Moreover, CS/GPTMS_DSP membranes promoted cell adhesion, induced Schwann cell-like morphology and supported neurite outgrowth from dorsal root ganglia explants. Preliminary in vivo tests carried out on both types of nerve scaffolds (CS/DSP and CS/GPTMS_DSP membranes) demonstrated their potential for: (i) protecting, as a membrane, the site of nerve crush or repair by end-to-end surgery and avoiding post-operative nerve adhesion; (ii) bridging, as a conduit, the two nerve stumps after a severe peripheral nerve lesion with substance loss. A 1 cm gap on rat median nerve was repaired using CS/DSP and CS/GPTMS_DSP conduits to further investigate their ability to induce nerve regeneration in vivo. CS/GPTMS_DSP tubes resulted to be more fragile during suturing and, along a 12 week post-operative lapse of time, they detached from the distal nerve stump. On the contrary CS/DSP conduits promoted nerve fiber regeneration and functional recovery, leading to an outcome comparable to median nerve repaired by autograft.

Can an adipofascial flap be used to prevent adhesions after plating of the proximal phalanx? A case report.

Tendon adhesions in zone IV after proximal phalangeal fractures are common and may lead to loss of range of motion at the proximal interphalangeal joint. The type of fracture, surgical technique and rehabilitation strategy also influence the final functional outcome. Plate fixation is a reliable solution in cases of comminuted phalangeal fracture. This article describes how adhesions between the plate and extensor apparatus in cases of comminuted fractures of the proximal phalanx can be reduced by using an adipofascial flap.

Methodological issues in size estimation of myelinated nerve fibers in peripheral nerves.

Size estimation of myelinated nerve fibers in peripheral nerves is a very common task in neuromorphology and different dedicated morpho-quantitative procedures have been devised and used to date. Unfortunately, many reports on experimental nerve studies lack comprehensive information on the procedures that have been designed and applied for myelinated fiber size estimation. This paper addresses the issue in the light of the recent advances in quantitative morphology that have recognized the concept of unbiased estimates as the key methodological issue to be addressed in morpho-quantitative studies. The potential foundations of bias at various study levels are analysed together with indications on how to cope with them. In addition, the issue of the precision of size estimates is addressed and the various geometrical parameters that can be selected for myelinated nerve fiber size assessment are outlined. Taken together, information provided in this paper is expected to help investigators conduct an appropriate preliminary study design phase, the key step for setting up the most adequate morpho-quantitative procedure for any given research goal.

Morphological analysis of peripheral nerve regenerated by means of vein grafts filled with fresh skeletal muscle.

Clinical data have shown that a vein segment filled with fresh skeletal muscle can be considered a good autologous grafting conduit for the repair of peripheral nerve lesions. In this study, the long-term morphological organization of rat sciatic nerve fibers regenerated along a muscle-vein-combined graft conduit is further analysed by light and electron microscopy. Regenerated nerve fibers were organized into fascicles of various sizes that were clearly delimited by perineurial-like shells made by long and thin cytoplasmic processes of perineurial-like bipolar cells and by densely packed collagen fibrils. Grafted skeletal muscle fibers were still detectable among nerve fiber fascicles. However, in spite of the persistence of skeletal muscle along the graft, regenerated nerve fibers showed a good morphological pattern of regeneration, providing further evidence that the muscle-vein-combined grafting technique represents an effective surgical alternative to the classical fresh nerve autograft for the repair of peripheral nerve defects.

Sutureless microvascular anastomoses by a biodegradable laser-activated solid protein solder.

A new sutureless technique to successfully anastomose the abdominal aorta of rats (1.3 mm in diameter) by using a fully biodegradable, laser-activated protein solder is presented. A total of 90 rats were divided into two groups randomly. In group one, the anastomoses were performed by using conventional microsuturing technique, whereas in group two, the anastomoses were performed by using a new laser welding technique. In addition, each of the two groups were divided into five subgroups and evaluated at different follow-up periods (10 minutes, 1 hour, 1 day, 1 week, and 6 weeks). At these intervals, the anastomoses were evaluated for patency and tensile strength. Three anastomoses in each subgroup were processed for light and electron microscopy. All anastomoses were found to be patent. The mean clamp time of the anastomoses performed with conventional suturing was 20.6 minutes compared with 7.2 minutes for the laser-activated welded anastomoses (p < 0.001). The strain measurements showed a stronger mechanical bond of the sutured anastomoses in the initial phase. However, at 6 weeks the tensile strength of the laser-welded anastomoses was higher compared with the conventional suture technique. Histologic evaluations revealed a near complete resorption of the solder after 6 weeks. The junction site of the vessel ends cannot be determined on the luminal side of the artery. In conclusion, a resorbable protein used as a solder, activated by a diode laser, can provide a reliable, safe, and rapid arterial anastomosis, which could be performed by any microsurgeon faster than conventional suturing after a short learning curve.

Verification of the two-dimensional disector, a method for the unbiased estimation of density and number of myelinated nerve fibers in peripheral nerves.

Quantification of the number of myelinated fibers in peripheral nerves is a common requirement in quantitative morphology. This parameter provides important information on the consequences of various physiological, pathological and experimental conditions on the nerve structure and is one of the main indicators of success of peripheral nerve repair. In this paper, the theoretical rationale for the application of stereological principles to obtain unbiased estimates of the density and total number of myelinated fibers in peripheral nerves is discussed and a simple stereological method is described. The method is applied together with a systematic random sampling scheme, that was optimized for the purposes of the present study, and with sampling scheme analysis by calculating the coefficient of error (CE). The stereological method, which consists of a two-dimensional variation of the classical disector procedure (two-dimensional disector), and the sampling scheme are verified by comparing estimates with the true density and total number of myelinated fibers in peripheral nerve trunks where true values have been accurately determined by extensive counting. The verification of the 2-D disector method, both of normal and regenerated nerves, showed that estimates of density and total number of myelinated nerve fibers are unbiased. The method also proved to be efficient (time-saving): Estimation of density and total number of myelinated fibers in a single nerve takes about 2-3 hours.

Reconstruction of traumatic losses of substance at the elbow.

Traumatic lesions at the elbow involving great loss of substance are uncommon, but represent a significant problem when such cases are referred to a trauma department. Most of these injuries may cause severe final functional impairment, thereby jeopardising future activities, particularly in cases where treatment was delayed or inappropriate. The timing and method of treatment are critical. The trauma may involve soft tissues only, or bone and joint, or several structures at the same time, which results in combined complex tissue defects. Each type of tissue loss should be managed by choosing the most suitable technique from the armamentarium of reconstructive surgery, taking into account different priorities and the optimum timing (immediate or delayed, one- or two-stages). The authors describe a spectrum of indications and techniques that can be useful tools in managing these injuries.

Secondary repair of flexor tendon injuries.

Tendon adhesions or even secondary ruptures causing severe hand functional impairment still represent a frequent complication after repair of flexor tendon injuries. Secondary treatment of these problems includes tenolysis, one or two stages flexor tendons reconstruction by grafts or even the use of tendon prosthesis. The mechanism and severity of injury, the status of the surrounding tissues and injured finger, the presence of associated lesions, the age of the patient, post-operative management, patient motivation and the surgeon's skill, may all have implications in the final outcome of the tendon reconstruction. A correct evaluation of the problem by means of classifications such as the one described by Boyes, may help the surgeon in choosing the appropriate technique.