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Lichen sclerosus (LS) is a chronic inflammatory disease of the skin, and the gold standard for treatment is the use of the very potent topical steroids, but they can have side effects. Previously, we demonstrated that OZOILE (stable ozonides) were effective in children affected by LS, reducing the inflammatory process and stimulating tissue regeneration of the foreskin, showing a similar efficacy to steroid treatment. In this study, the modulation of inflammatory and oxidative stress pathways was evaluated by qRT-PCR and Western blotting in foreskins affected by LS removed from patients untreated or treated with OZOILE or corticosteroid cream formulations for 7 days before circumcision. OZOILE induced a significant increase in NRF2 and SOD2 levels, while it did not produce change in MIF, NF-kB subunits, and MMPs in comparison to untreated foreskins. Conversely, steroid topical treatment produced a significant reduction in the expression of p65, MIF, and MMP9, but it did not cause variation in NRF2 and SOD2 levels. These results demonstrate that the use of OZOILE as cream formulation exhibits effects on NRF2 signaling, and it does not induce NF-κB activation, unlike corticosteroids. On the basis of our biochemical data, further studies evaluating the role of NRF2 signaling cascade are necessary.

Background and Objectives: Choosing the correct site for a nerve biopsy remains a challenge due to nerve sacrifice and major donor site complications, such as neuroma, as seen in sural nerve biopsy. Selecting a deeper donor nerve can help in burying nerve stumps in deep soft tissues, preventing neuroma. Moreover, using an expendable, deeply situated motor nerve can aid indiagnosis when a motor neuropathy is suspected. The authors propose using the pronator quadratus (PQ) branch for this purpose, as it is located deep between the bellies of the flexor muscles and the interosseous membrane in the forearm. This branch is expendable since the denervation of the PQ has a negligible effect on forearm pronation, which is primarily sustained by the pronator teres., Methods: The surgical approach is the same as the approach for anterior interosseous nerve transfer to the motor component of the ulnar nerve in the distal forearm: access is in the midline in the middle third of the forearm under local anesthesia Blunt dissection is performed, separating and retracting the flexor musculotendinous junction to reach the interosseous membrane where the PQ branch is identified. A careful dissection of the nerve branch is performed, allowing a 2 cm long segment to be cut and removed. The proximal stump is then buried into an adjacent muscle belly and the surgical site is closed., Results: The technique is safe and reproducible in experienced hands., Conclusion: This technique may be especially applicable in cases where neurologists need to study motor neuropathies. Contraindications of the technique include wrist instability and high median nerve palsies., (Copyright © 2024. Published by Elsevier B.V.)

BACKGROUND The absence of valid vessels for the anastomosis constitutes a contraindication to replantation, but the need for arterial vessels in good condition has recently been questioned and some authors have proposed the arterialization of the veins with promising results. However, this method is not routine in replantation and it is unclear what conditions can establish venous congestion and loss of the replanted segment. CASE REPORT We detail a case where indocyanine green aids in evaluating arterialization of a vein during thumb replantation in a 40-year-old smoker following a crush injury. Multiple attempts to anastomose the princeps pollicis and its collateral vessel failed due to a thrombus formation, leaving the finger non-perfused despite urokinase treatment. To confirm the absence of reperfusion, we administered 0.3 mg/kg of indocyanine green through an upper limb peripheral vein. Observing no reperfusion, we located a suitable radial dorsal vein and performed an arteriovenous anastomosis at the proximal phalanx level. Indocyanine Green Angiography (IGA) revealed a slightly delayed reperfusion but a effective venous outflow. We did not consider it necessary to perform additional venous anastomoses other than the single dorsal radial venous anastomosis. CONCLUSIONS This single case report shows the potential of indocyanine green as a valid aid to evaluate the perfusion of the replantation and also any early venous congestion, being able to modify the operative plan accordingly.

BACKGROUND Fracture of the fifth metacarpal of the hand is due to trauma to the clenched fist. The non-displaced fracture can be treated by splinting and immobilization, but fracture dislocation requires individualized management to ensure the return of function. The Jahss maneuver for reduction of volar displaced metacarpal neck fractures involves flexion of the metacarpophalangeal and proximal interphalangeal joint at 90°, with the proximal phalanx used to reduce the metacarpal head. This report is of a 25-year-old male Italian pianist with a displaced fifth metacarpal neck fracture successfully treated by reduction using the Jahss maneuver and K-wire attachment of subchondral bone to the metacarpal. CASE REPORT A pianist presented with a trauma to his right hand due to punching a wall. Radiograph images demonstrated an angulated, displaced right fifth neck fracture. A specific approach was decided, considering the complexity of the musical movements and the patient's performance needs. After fracture's reduction by the Jahss maneuver, 2 retrograde cross-pinning K-wires were inserted at the subchondral bone of the metacarpal head. Healing under splinting was uneventful, and the K-wires were removed after 45 days. At 4 months after surgery, the patient had complete recovery of both range of motion and strength. CONCLUSIONS Our technique avoided piercing the metacarpophalangeal joint capsule, preventing extensor tendon damage, dislocation, instability, and pain and retraction of the extensor cuff. This novel mini-invasive technique successfully achieved early metacarpophalangeal joint motion, joint stability, and complete recovery of movements in all planes.

Background: Peripheral nerve injuries (PNIs) include several conditions in which one or more peripheral nerves are damaged. Trauma is one of the most common causes of PNIs and young people are particularly affected. They have a significant impact on patients' quality of life and on the healthcare system, while timing and type of surgical treatment are of the utmost importance to guarantee the most favorable functional recovery. To date, several different classifications of PNIs have been proposed, most of them focusing on just one or few aspects of these complex conditions, such as type of injury, anatomic situation, or prognostic factors. Current classifications do not enable us to have a complete view of this pathology, which includes diagnosis, treatment choice, and possible outcomes. This fragmentation sometimes leads to an ambiguous definition of PNIs and the impossibility of exchanging crucial information between different physicians and healthcare structures, which can create confusion in the choice of therapeutic strategies and timing of surgery., Materials: The authors retrospectively analyzed a group of 24 patients treated in their center and applied a new classification for PNI injuries. They chose (a) five injury-related factors, namely nerve involved, lesion site, nerve type (whether motor, sensory or mixed), surrounding tissues (whether soft tissues were involved or not), and lesion type-whether partial/in continuity or complete. An alphanumeric code was applied to each of these classes, and (b) four prognostic codes, related to age, timing, techniques, and comorbidities., Results: An alphanumeric code was produced, similar to that used in the AO classification of fractures., Conclusions: The authors propose this novel classification for PNIs, with the main advantage to allow physicians to easily understand the characteristics of nerve lesions, severity, possibility of spontaneous recovery, onset of early complications, need for surgical treatment, and the best surgical approach., Level of Evidence: according to the Oxford 2011 level of evidence, level 2., (© 2023. The Author(s).)

Objective: Surgical reconstruction of soft tissue defects in the distal third of the lower limbs has always been challenging for surgeons. The adipofascial flaps are made up of vascularized adipose tissue, which plastically conforms to the site to be reconstructed with its rich presence of stem cells. In this study, we resumed our case history of reverse neuroadipofascial sural flap, and we evaluated the stability of the scar to verify if this type of reconstruction can ensure long-term results and its regenerative power., Patients and Methods: In this retrospective cohort study, we analyzed 32 patients who had undergone lower limb reconstruction with the sural neuroadipovenous flap., Results: A total of 32 patients were included in the study. The average age was 62.2 years. Chronic skin ulcer was the cause of the defects in 13 (40.6%) patients, chronic wound after trauma in 7 (21.9%) patients, wheel bedsores in 4 (12.5%) patients, osteomyelitis in 5 (15.6%) patients, exposed internal hardware in 2 (6.3%) patients, dog bite in 1 (3.1%). The site defect comprised 11 heels (34.4%), 4 external malleoli (12.5%), three medial malleoli (9.4%), 12 lower third of the leg (37.5%), and two dorsa of the foot (6.3%). In all cases, defects were covered with reverse sural island flap. The dimension of the flap ranged from 5 to 9 cm in length and from 3 to 7 in width. Six patients showed early or later postoperative complications., Conclusions: The neuroadipofascial sural flap is versatile, fast, and easy-to-perform to cover a chronic defect in the distal part of the lower limb, including both the malleoli and the heel, due to its long vascular pedicle. Consistent with the studies carried out in other districts, the present study confirms the remarkable regenerative power of the vascularized adipose tissue at the level of complex wounds of the lower third of the leg.

The lack of meticulous knowledge concerning the topographical anatomy of the deep branch of the ulnar nerve (DUN) may pose difficulties, leading to a delay or a misdiagnosis of a DUN injury. Identification of the DUN is quite difficult without precise anatomical landmarks as reference points. The current study investigates the topography of the DUN between genders, taking as a reference point a well-known landmark, the Kaplan line, used in hand surgery for carpal tunnel release. Twenty-two (15 males and 7 female) fresh frozen adult cadaveric hands were dissected by using magnifying loupes (3.5 and 5.0 x). We marked values proximal to the Kaplan line as positive (+), while we marked distal ones as negative (-). The mean distance DUN-Kaplan line was 1.69 ± 4.45 mm. In male hands, the mean distance was 4.17 ± 1.88 mm, distal to the Kaplan line, while in females, the mean distance was -4.92 ± 0.69 mm proximal to the Kaplan line. Gender dimorphism was detected, with higher statistically significant values in male hands ( p  = 0.001). Cadaveric studies of the DUN topography, course, and distribution pattern are uncommon. The current study provides an accurate description of the DUN topography, taking the Kaplan line as a reference point, emphasizing gender differences. The DUN is located distally in males and proximally in females. Knowledge of these predictable anatomical relations may help hand surgeons intraoperatively when dealing with a DUN lesion, because of hand trauma or during the decompression of the DUN.

The posterior interosseous flap (PIOF), as fasciocutaneous flap, represents an interesting option in reconstructive surgery of the upper limb. The PIOF allows coverage of losses of substance of the dorsal side of the hand and, with technical modifications, up to the proximal interphalangeal (PIP) joint without any need of microsurgical technique or the sacrifice of the main vascular axes for the hand. Its dimensions can reach up to 22 cm x12 cm and have excellent versatility since it can incorporate vascularized bone grafts and tendon grafts for complex substance losses. Despite the above-mentioned advantages, among the factors that limit its diffusion, indeed, there is the complex dissection technique originally described. Several authors also report a variable incidence of venous congestion, attributing it to the reverse flow vascularity of the flap. However, in the hands of experienced surgeons, this flap has a negligible incidence of complications. For these reasons, the authors performed a systematic review of the literature to organize the various technical updates over the years to extend the indications of the PIOF and reduce the incidence of complications, thus providing a valuable tool for reconstructive surgeons., Competing Interests: Conflict of Interest The authors report no conflicts of interest to disclose., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Lumbrical muscles originate in the palm from the 4 tendons of the flexor digitorum profundus and course distally along the radial side of the corresponding metacarpophalangeal joints, in front of the deep transverse metacarpal ligament. The first and second lumbrical muscles are typically innervated by the median nerve, and third and fourth by the ulnar nerve. A plethora of lumbrical muscle variants has been described, ranging from muscles' absence to reduction in their number or presence of accessory slips. The current cadaveric study highlights typical and variable neural supply of lumbrical muscles., Materials: Eight (3 right and 5 left) fresh frozen cadaveric hands of 3 males and 5 females of unknown age were dissected. From the palmar wrist crease, the median and ulnar nerve followed distally to their terminal branches. The ulnar nerve deep branch was dissected and lumbrical muscle innervation patterns were noted., Results: The frequency of typical innervations of lumbrical muscles is confirmed. The second lumbrical nerve had a double composition from both the median and ulnar nerves, in 12.5% of the hands. The thickest branch (1.38 mm) originated from the ulnar nerve and supplied the third lumbrical muscle, and the thinnest one (0.67 mm) from the ulnar nerve and supplied the fourth lumbrical muscle. In 54.5%, lumbrical nerve bifurcation was identified., Conclusion: The complex innervation pattern and the peculiar anatomy of branching to different thirds of the muscle bellies are pointed out. These findings are important in dealing with complex and deep injuries in the palmar region, including transmetacarpal amputations.

Background: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of UV radiation-induced damage repair that is characterized by photosensitivity and a propensity for developing, among many others, skin cancers at an early age. This systematic review focused on the correlation between the clinical, pathological, and genetic aspects of XP and skin cancer., Methods: A systematic review was conducted through a literature search of online databases PubMed, Cochrane Library, SciELO, and Google Scholar. Search terms were "Xeroderma pigmentosum", "XP", "XPC", "Nucleotide excision repair", "NER", "POLH", "Dry pigmented skin", and "UV sensitive syndrome" meshed with the terms "Skin cancer", "Melanoma", and "NMSC"., Results: After 504 abstracts screening, 13 full-text articles were assessed for eligibility, and 3 of them were excluded. Ten articles were selected for qualitative assessment., Conclusions: Patients with XP usually suffer shorter lives due to skin cancer and neurodegenerative disease. Deletion/alteration of a distinct gene allele can produce different types of cancer. The XPC and XP-E variants are more likely to have skin cancer than patients in other complement groups, and the most common cause of death for these patients is skin cancer (metastatic melanoma or invasive SCC). Still, aggressive preventative measures to minimize UV radiation exposure can retard the course of the disease and improve the quality of life., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Tito Brambullo et al.)

Background: The possible relationships between breast and thyroid diseases have been reported in the literature. The purpose of our study was to evaluate the occurrence of histologically verified thyroid pathologies in women who were diagnosed with breast cancer and, after mastectomy/quadrantectomy complemented by oncological treatment, were thyroidectomized based on their periodic thyroid evaluation., Patients and Methods: Our series consist of 31 women with a mean age of 62.9 ± 10.9 years (range, 45-81) treated for breast cancer (18 right-sided, 11 left-sided, and 2 bilateral), of whom 29 were thyroidectomized, since two women who developed Graves' disease refused thyroidectomy. These 31 women belong to a cohort of 889 women who referred to the Breast Surgery Unit of our university hospital during the period January 2010 through December 2020., Results: The mean time interval between breast cancer and thyroid pathologies was 48.1 ± 23.4 months (range, 12-95). The final diagnosis at histopathology was infiltrating ductal breast carcinoma in 26 women (with 2/26 patients having bilateral carcinoma) and infiltrating lobular breast carcinoma in the other 5 women. Ten of the twenty-nine thyroidectomized women (34.5%) had a thyroid malignancy on histology: five papillary carcinomas, three papillary micro-carcinomas and two follicular carcinomas. Two of the five women with papillary carcinoma also had histological evidence of chronic lymphocytic thyroiditis/Hashimoto's thyroiditis, which was also detected in another five women with benign thyroid diseases., Conclusions: We suggest that breast cancer survivors should be made aware of the possible increased risk of thyroid pathologies (including thyroid malignancy) so that they can undergo screening and follow-up.

The normal wound healing process is characterized by a complex, highly integrated cascade of events, requiring the interactions of many cell types, including inflammatory cells, fibroblasts, keratinocytes and endothelial cells, as well as the involvement of growth factors and enzymes. However, several diseases such as diabetes, thermal injury and ischemia could lead to an impaired wound healing process characterized by wound hypoxia, high levels of oxygen radicals, reduced angiogenesis, decreased collagen synthesis and organization. Polydeoxyribonucleotide (PDRN) has been used to improve wound healing through local and systemic administration thanks to its ability to promote cell migration and growth, angiogenesis, and to reduce inflammation on impaired wound healing models in vitro, in vivo and clinical studies. In light of all these observations, the aim of this review is to provide a full overview of PDRN applications on skin regeneration. We reviewed papers published in the last 25 years on PubMed, inserting "polydeoxyribonucleotide and wound healing" as the main search term. All data obtained proved the ability of PDRN in promoting physiological tissue repair through adenosine A 2A receptor activation and salvage pathway suggesting that PDRN has proven encouraging results in terms of healing time, wound regeneration and absence of side effects.

Axonal count is the base for efficient nerve transfer; despite its capital importance, few studies have been published on human material, most research approaches being performed on experimental animal models of nerve injury. Thus, standard analysis methods are still lacking. Quantitative data obtained have to be reproducible and comparable with published data by other research groups. To share results with the scientific community, the standardization of quantitative analysis is a fundamental step. For this purpose, the experiences of the Italian, Austrian, German, Greek, and Iberian-Latin American groups have been compared with each other and with the existing literature to reach a consensus in the fiber count and draw up a protocol that can make future studies from different centers comparable. The search for a standardization of the methodology was aimed to reduce all the factors that are associated with an increase in the variability of the results. All the preferential methods to be used have been suggested. On the other hand, alternative methods and different methods have been identified to achieve the same goal, which in our experience are completely comparable; therefore, they can be used indifferently by the different centers according to their experience and availability., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The cornea's intense innervation is responsible for corneal trophism and ocular surface hemostasis maintenance. Corneal diabetic neuropathy affects subbasal nerve plexus, with progressive alteration of nerves' morphology and density. The quantitative analysis of nerve fibers can be performed with in vivo corneal confocal microscopy considering the main parameters such as corneal nerve fibers length, corneal nerve fibers density, corneal nerve branching density, tortuosity coefficient, and beadings frequency. As the nerve examination permits the detection of early changes occurring in diabetes, the invivo corneal confocal microscopy becomes, over time, an important tool for diabetic polyneuropathy assessment and follow-up. In this review, we summarize the actual evidence about corneal nerve changes in diabetes and the relationship between the grade of alterations and the duration and severity of the disease. We aim at understanding how diabetes impacts corneal nerves and how it correlates with sensorimotor peripheral polyneuropathy and retinal complications. We also attempt to analyze the safety of the most common surgical procedures such as cataract and refractive surgery in diabetic patients and to highlight the specific risk factors. We believe that information about the corneal nerve fibers' condition obtained from the in vivo subbasal nerve plexus investigation may be crucial in monitoring peripheral small fiber polyneuropathy and that it will help with decision-making in ophthalmic surgery in diabetic patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The appearance of a symptomatic neuroma following finger amputation is a devastating consequence for patient's quality of life. It could be cause of chronic neuropathic pain. The prevention of neuroma formation is a challenging effort for hand surgeons. The biological mechanisms leading to neuroma formation are mostly unknown and different preventing procedures have been tried without certain results. In this paper, a panel of Italian hand surgeons have been asked to express appropriateness about potentially preventive techniques of neuroma formation following the RAND/UCLA appropriateness protocol., Methods: A literature review was preliminarily performed identifying the most employed methods to reduce the pathologic nerve scar. Afterwards, the selected panelists were asked to score the appropriateness of each procedure in a double scenario: in case of a sharp amputation or in a tear injury. The appropriateness was evaluated according to RAND/UCLA protocol., Results: Nine Italian hand surgeons were included in the panel. Of them 5 were orthopaedic surgeons, 4 plastic surgeons. The identified appropriate procedures were: revision amputation should be done in operating room, the neurovascular bundles should be identified and is mandatory to treat surrounding soft tissues. Only in case of clean-cut amputation, it is appropriate to perform a proximal extension of the dissection, to use diathermocoagulation and coverage with local flaps. Procedures such as shortening in tension of the nerve stump, bone shortening, implantation of the nerve end in the soft tissue, treatment in the emergency room and, in both scenarios, certain results are evaluated as uncertain., Discussion: In order to prevent the formation of a distal stump neuroma few methods were judged appropriate. It is mandatory to identify the neurovascular bundles and treat also the surrounding tissues, but no certain results could be obtained with local flap, bone shortening and other ancillary surgical acts. Moreover, it is not possible to guarantee the non arising of neuroma in any cases, also when every procedure has been temped., Conlusions: The prevention of distal neuroma is actually a challenge, without a well known strategy due to the variability of response of nervous tissue to injury., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Cortical plasticity is a finely regulated process that allows the central nervous system (CNS) to change in response to internal and external stimuli. While these modifications occur throughout normal brain development, interestingly, they are also elicited after peripheral nerve injury and surgery. This article provides an overview of the principle mechanisms of synaptic, neuronal, cortical and subcortical neuroplasticity, with special attention to cortical and subcortical modifications-as suggested by modern neuroimaging techniques-after peripheral nerve surgery. The main nerve transfer techniques for the superior extremities and their effect on cortical plasticity are also described.

Background:  Preclinical training in perforator flap harvesting is typically conducted on living animal models; however, repeated training is not possible with these models because of ethical and/or economical constraints. We describe an anterolateral thigh flap (ALT flap) training model using chicken thigh that seems to be an appropriate training model prior, for example, to raise a perforator flap in a living rat or swine model., Methods:  A total of 10 chicken legs were used in this study. Six chicken legs were anatomically dissected to confirm the presence of the perforator and to identify the main vascular tree. In four chicken legs, a skin flap was planned based on the perforator and intramuscular dissection was performed under magnification., Results:  The perforator was identified in all dissections and was consistently found 3 cm above the line extending from the patella to the head of the femur in its third proximal. Proximally, the mean diameter of the artery and vein was 0.56 (σ = 0.04) and 0.84 (σ = 0.06) mm, respectively. The mean dissection time to raise the flap was 88 (σ = 7) min., Conclusion:  This is the first description of a nonliving biological simulation model for training in perforator flap dissection that mimics an ALT flap. As an ex vivo chicken model, it is a cost effective and readily accessible model suitable for repeated practice., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: The aim of the current study is to investigate the first and second lumbrical nerves as potential fibers donors to the deep motor branch of the ulnar nerve to avoid intrinsic atrophy in high ulnar nerve injuries., Methods: Sixteen fresh frozen cadaveric hands were dissected, the radial lumbrical nerves accessed, and a coaptation, either in reverse end-to-side or in double end-to-side through a bridge nerve graft, was created to the deep motor branch of ulnar nerve. Semithin sections were taken from samples of donor and recipient nerves for qualitative (nerve architecture) and quantitative studies (fiber count and donor/recipient ratio)., Results: The first lumbrical showed a robust trunk and a superior axon density (9,126.50 ± 2,923.41 axons/mm 2 ) to the ulnar motor branch (7,506.50 ± 1,137.50 axons/mm 2 distal to the opponens tunnel and 7,947.75 ± 1,741.24 axons/mm 2 before its terminal branching); the ulnar motor branch showed a higher axon number (2,633.51 ± 410.00 distal to the opponens tunnel and 2,345.75 ± 2,101.56 before its terminal branching) than the first lumbrical (1,410.56 ± 823.89); section areas occupied by axons were higher in proximal (0.20 ± 0.16) and distal (0.26 ± 0.20) ulnar samples than the first lumbrical (0.17 ± 0.16). Donor/recipient ratio first lumbrical/deep motor branch of the ulnar nerve were 1:1.86 (distal to the opponens tunnel) and 1:1.67 (at its terminal branching); data about the second lumbrical were ruled out because of bias., Conclusions: A transfer from the first lumbrical nerve to the deep motor branch of the ulnar nerve in palm is suitable to avoid intrinsic atrophy., (© 2018 Wiley Periodicals, Inc.)

Introduction: The aim of this research was to test, in an animal model, the nerve regeneration technique with a hypoallergenic acellular dermal matrix used to wrap the microsurgical neural suture., Materials and Methods: Two groups of rats received the cut of limb right median nerves. The regeneration technique considers for both groups an end-to-end nerve suture. In the experimental group (A) was used also a wrapping protocol by a conduit of collagen matrix currently used in oral surgery. The animals underwent functional grasping tests (at 1, 3, 5, and 7 months) and a histological and quantitative analysis of distal nerve was performed at the end of experimental time., Result: After seven months, the grasping test reveals functional recovery in each tested animal; this improvement is more evident in Group A. The fibers appear well organized with restored myelin sheaths in both groups. Group A showed a great quantity of connective tissue surrounding the nerve. The quantitative morphology analysis in both groups shows a similar fibers density, fiber diameter, and myelin thickness. The differences between the groups in axon mean diameter are significant. In Group A M/d, D/d, and g-ratio is significantly higher compared to control group., Conclusions: Histological and functional assessments show a functional recovery of the injured nerve in the test groups, stressed by the results of the grasping tests and the meaningful increasing in fiber diameter and higher g-ratio. Moreover, a connective tissue cuff distinguishes the distal portion of the injured nerve. Considering the easy availability and handling of the material used in this study we can conclude that this experimental technique can be considered as a valid alternative to protect nerves in nerve wrap surgery.

Objectives: "Form and function restoration" is the ultimate goal of reconstructive surgery, which is oriented toward regeneration rather than reparation. Recently, research in reconstructive surgery has focused on the regenerative potential of the adipose tissue. The aim of the study is to illustrate the surgical methods and show the functional and aesthetic results achieved by the reconstruction of finger soft-tissue defects using homodigital dorsal adipofascial reverse flap (HDARF)., Materials and Methods: A total of 63 cases (45 acute and 18 elective) were included between September 2010 and August 2016. In each case, we preliminarily performed surgical debridement and then harvested an adipofascial flap from the back of the finger. Nine injured thumbs that were repaired with the flap as emergency cases were also included. The average age of the patients was 46 (range: 4-69) years., Results: All flaps survived without any complications during the 24-month follow-up. Good nail regrowth through the flap and full regeneration were observed in approximately all cases. Sensitivity tests and histological analysis of biopsy samples of the regenerated fingers confirmed full regeneration of the epidermis, dermis, cutaneous adnexa, and nerves. All the patients were satisfied with the hand functionality and aesthetic appearance., Conclusion: The HDARF represents a very useful alternative for the reconstruction of nailbed crushes, achieving regeneration of injured segments in deformities caused by trauma or infection., (© 2018 The Authors.)

Purpose: Although communications between branches and cords of the brachial plexus have been extensively published, there is a scarcity of reports concerning radial and ulnar nerve (RN-UN) communication in the arm. The current study aims to demonstrate the incidence, topography, and length of communicating branches between RN and UN. Any additional coexisted variations were also recorded., Materials and Methods: Two hundred and sixty-six upper limbs collected from one hundred and thirty-three (81 males and 52 females) Greek cadavers were dissected., Results: Three out of one hundred and thirty-three cadavers, accounting for an incidence of up to 2.3%, were found to have an atypical communicating branch originating at a high humeral level from RN towards UN. In two cadavers, communicating branches were detected on the left side and in one cadaver bilaterally., Conclusions: The study of atypical communications between RN and UN attracts great attention for its clinical importance, mainly in cases of peripheral neuropathies with diagnostic dilemma or upper limb nerve injury producing an otherwise unexpected symptomatology due to the aberrant nerve supply. Familiarity with these variations is crucial in avoiding misdiagnosis and preserving valuable communicating branches, thus achieving an uneventful outcome in cases of upper limb nerve injury repair.

Diabetes is characterized by poor wound healing which currently lacks an efficacious treatment. The innate repair receptor (IRR) is a master regulator of tissue protection and repair which is expressed as a response injury or metabolic stress, including in diabetes. Activation of the IRR might provide benefit for diabetic wound healing. A specific IRR agonist cibinetide was administered in an incisional wound healing model performed mice with genetic diabetes (db + /db + ) and compared to the normal wild-type. Animals were treated daily with cibinetide (30μg/kg/s.c.) or vehicle and euthanized 3, 7, and 14days after the injury to quantitate vascular endothelial growth factor (VEGF), malondialdehyde (MAL), phospho-Akt (pAkt), phospho e-NOS (p-eNOS), and nitrite/nitrate content within the wound. Additional evaluations included quantification of skin histological change, angiogenesis, scar strength, and time to complete wound closure. Throughout the wound healing process diabetic animals treated with vehicle exhibited increased wound MAL with reduced VEGF, pAkt, peNOS and nitrite/nitrate, all associated with poor re-epitheliziation, angiogenesis, and wound breaking strength. Cibenitide administration significantly improved these abnormalities. The results suggest that cibinetide-mediated IRR activation may represent an interesting strategy to treat diabetes-associated wound healing., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Nerve fibers are attracted by sutureless end-to-side nerve coaptation into the recipient nerve. Opening a window in the epineurium enhances axon attraction and myelination. The authors analyze the features of nerve repair by end-to-side coaptation. They highlight the known mechanisms of axon sprouting and different hypotheses of start up signals (presence or absence of an epineurial window, role of Schwann cells, signaling from the distal trunk). The clinical literature is also presented and differences between experimental and clinical applications are pointed out. The authors propose their point of view and perspectives deriving from recent experimental and clinical experiences., Competing Interests: Conflicts of interest: None declared.

End-to-side nerve coaptation brings regenerating axons from the donor to the recipient nerve. Several techniques have been used to perform coaptation: microsurgical sutures with and without opening a window into the epi(peri)neurial connective tissue; among these, window techniques have been proven more effective in inducing axonal regeneration. The authors developed a sutureless model of end-to-side coaptation in the rat upper limb. In 19 adult Wistar rats, the median and the ulnar nerves of the left arm were approached from the axillary region, the median nerve transected and the proximal stump sutured to the pectoral muscle to prevent regeneration. Animals were then randomly divided in two experimental groups (7 animals each, 5 animals acting as control): Group 1: the distal stump of the transected median nerve was fixed to the ulnar nerve by applying cyanoacrylate solution; Group 2: a small epineurial window was opened into the epineurium of the ulnar nerve, caring to avoid damage to the nerve fibres; the distal stump of the transected median nerve was then fixed to the ulnar nerve by applying cyanoacrylate solution. The grasping test for functional evaluation was repeated every 10-11 weeks starting from week-15, up to the sacrifice (week 36). At week 36, the animals were sacrificed and the regenerated nerves harvested and processed for morphological investigations (high-resolution light microscopy as well as stereological and morphometrical analysis). This study shows that a) cyanoacrylate in end-to-side coaptation produces scarless axon regeneration without toxic effects; b) axonal regeneration and myelination occur even without opening an epineurial window, but c) the window is related to a larger number of regenerating fibres, especially myelinated and mature, and better functional outcomes.

Five years after both right ulnar and median nerve decompression for paraesthesias and palsy, a patient, coming from Nigeria but living in Italy, came to our unit claiming to have persistent pain and combined median and ulnar palsy. Under suspicion of leprosy, skin and left sural nerve biopsy were performed. Skin tests were negative, but Schwann cells resulted as positive for acid-fast bacilli (AFB), leading to the diagnosis of Pure Neuritic Leprosy (PNL). The patient was given PB multidrug therapy and recovered from pain in two months. After nine months both High Resolution Ultrasonography (HRUS) and Magnetic Resonance Imaging (MRI) were performed, revealing thickening of the nerves. Since demyelination is common in PNL, the Authors started to use Diffusion Tensor Imaging Tractography (DTIT) to get better morphological and functional data about myelination than does the traditional imaging. DTIT proved successful in showing myelin discontinuity, reorganization, and myelination, and the Authors suggest that it can give more information about the evolution of the disease, as well as further indications for surgery (nerve decompression, nerve transfers, and babysitting for distal effector protection), and should be added to traditional imaging tools in leprosy., Competing Interests: The authors declare that they have no competing interests.

Aim: The aim of this study is to clearly define the vascularisation of the lateral paratibial septum of the leg, defining the basis for a vertical pedicled adipofascial flap harvested from the anterolateral aspect of the leg to cover pretibial soft tissue defects., Materials and Methods: Twelve cadaver legs (eight fixed with formalin and four fresh) were dissected. The vessels running into the lateral paratibial septum were identified. The number of vessels were noted and evaluated at the lateral border of the proximal, middle and distal thirds of the leg. In addition, an angiographic study was performed on two limbs to confirm the connection between tibialis anterior artery and the overlaying fascia through these septal vessels., Results: All the specimens had periosteo-septal vessels running in the lateral aspect of the tibia. The average number was 6.6. The distribution was constant in all the thirds of the leg., Conclusion: These data are useful to propose the harvesting technique for adipofascial flap with vertical pedicle as a suitable reconstructive option to cover pretibial soft tissue defects., (Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

In regenerative medicine, new approaches are required for the creation of tissue substitutes, and the interplay between different research areas, such as tissue engineering, microsurgery and gene therapy, is mandatory. In this article, we report a modification of a published model of tissue engineering, based on an arterio-venous loop enveloped in a cross-linked collagen-glycosaminoglycan template, which acts as an isolated chamber for angiogenesis and new tissue formation. In order to foster tissue formation within the chamber, which entails on the development of new vessels, we wondered whether we might combine tissue engineering with a gene therapy approach. Based on the well-described tropism of adeno-associated viral vectors for post-mitotic tissues, a muscular flap was harvested from the pectineus muscle, inserted into the chamber and transduced by either AAV vector encoding human VEGF165 or AAV vector expressing the reporter gene β-galactosidase, as a control. Histological analysis of the specimens showed that muscle transduction by AAV vector encoding human VEGF165 resulted in enhanced tissue formation, with a significant increase in the number of arterioles within the chamber in comparison with the previously published model. Pectineus muscular flap, transduced by adeno-associated viral vectors, acted as a source of the proangiogenic factor vascular endothelial growth factor, thus inducing a consistent enhancement of vessel growth into the newly formed tissue within the chamber. In conclusion, our present findings combine three different research fields such as microsurgery, tissue engineering and gene therapy, suggesting and showing the feasibility of a mixed approach for regenerative medicine.

Reconstructive surgery of complex hair-bearing skin defects often represents a challenge for the plastic surgeon; indeed, a multistage procedure is to be planned, including a first reconstructive step including local flaps, even if pre-expanded, or for larger defects, microsurgical flaps. To date, the implant of dermal regeneration templates has been proven an effective alternative. The authors relate their results of a complex hair-bearing reconstruction of a scalp and brow defect after a friction road burn with those reported in literature, concluding that a 3-staged reconstruction (dermal template implantation, skin grafting, and finally hair micrografting) can achieve good results in this complex kind of reconstruction. Histological specimens taken 2 years later confirmed a full anatomical reconstruction of the hair-bearing areas. Finally, this paper reports the first case of brow reconstruction performed with these techniques.

Deep second-degree burns are characterized by delayed formation of granulation tissue and impaired angiogenesis. Erythropoietin (EPO) is able to stimulate angiogenesis and mitosis, activating vascularization and cell cycle. The aim of our study was to investigate whether two biosimilar recombinant human erythropoietins, EPO-α and EPO-Z, may promote these processes in an experimental model of burn injury. A total of 84 mice were used and a scald burn was produced on the back after shaving, in 80°C water for 10 seconds. Mice were then randomized to receive EPO-α (400 units/kg/day/sc) or EPO-Z (400 units/kg/day/sc) or their vehicle (100 μL/day/sc 0.9% NaCl solution). After 12 days, both EPO-α and EPO-Z increased VEGF protein expression. EPO-α caused an increased cyclin D1/CDK6 and cyclin E/CDK2 expression compared with vehicle and EPO-Z (p<0.001). Our study showed that EPO-α and EPO-Z accelerated wound closure and angiogenesis; however EPO-α resulted more effectively in achieving complete skin regeneration. Our data suggest that EPO-α and EPO-Z are not biosimilars for the wound healing effects. The higher efficacy of EPO-α might be likely due to its different conformational structure leading to a more efficient cell proliferation and skin remodelling.

Craniofacial duplication is a very rare malformation. The phenotype comprises a wide spectrum, ranging from partial duplication of few facial structures to complete dicephalus. We report the case of a newborn with an accessory oral cavity associated to duplication of the tongue and the mandible diagnosed by multi-row detector Computed Tomography, few days after her birth. Our case of partial craniofacial duplication can be considered as Type II of Gorlin classification or as an intermediate form between Type I and Type II of Sun classification. Our experience demonstrates that CT scan, using appropriate reconstruction algorithms, permits a detailed evaluation of the different structures in an anatomical region. Multi-row CT scan is also the more accurate diagnostic procedure for the pre-surgical evaluation of craniofacial malformations., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Type 2 diabetes impairs the healing process because of an exaggerated and persistent inflammatory response, and an altered expression pattern of angiogenic molecules. We investigated the effects of inflammasome blockade in diabetes-related wound-healings defects, in genetically diabetic mice., Experimental Approach: An incisional skin wound model was produced on the back of female diabetic C57BL/KsJ-m +/+ Lept(db) mice (db⁺ /db⁺) and their normal littermates (db⁺ /m⁺). Animals were treated daily with two inflammasome blocking agents, BAY 11-7082 (20  mg·kg⁻¹ i.p.), or Brilliant Blue G (BBG, 45.5 mg·kg⁻¹ i.p.), or vehicle. Mice were killed on 3, 6 and 12 days after skin injury to measure expression of the NOD-like receptor NLRP3, caspase-1, VEGF, the inflammasome adapter protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and the chemokine CXCL12. Wound levels of IL-1β and IL-18 were also measured, along with histological assessments of wound tissue and the time to complete wound closure., Key Results: During healing, the diabetic mice exhibited increased activation of NLRP3, caspase-1, ASC, IL-1β and IL-18. They also showed a reduced expression of VEGF and CXCL12.Treatment with BAY 11-7082 or BBG, to block activation of the inflammasome, decreased the levels of pro-inflammatory molecules. Histological evaluation indicated that inflammasome blockade improved the impaired healing pattern, at day 12 in diabetic mice, along with a decreased time to complete skin healing., Conclusions and Implications: These data strongly suggest that activation of the NLRP3 inflammasome is one of the key contributors to the delayed healing of wounds in diabetic mice., (© 2013 The British Pharmacological Society.)

Defects of the dorsum of the foot can be challenging to reconstruct, none more so than the dorsum of the toe. The reverse Dorsalis Pedis Adipofascial Perforator (DPAP) flap is one possible reconstructive option for defects in this region. The aim of this study was to first demonstrate the anatomy of this flap, particularly the consistency of the perforators arising from the dorsalis pedis artery. Second, we present a clinical series based on this flap to demonstrate how it can be used. For the anatomical studies, 22 fresh cadaveric lower extremities were dissected, and injection studies were used to delineate the vascular territories. The presence of the distal perforator, distance to the first metatarso-phalangeal joint and diameter of each perforator were recorded. The cadaveric studies confirmed the presence of distal perforators to the first metatarso-phalangeal joint in 100% of limbs examined. The clinical study demonstrated the feasibility of the use of the adipofascial turn-over perforator flap for dorsal foot reconstruction. These anatomic findings provide an alternative method of reconstruction of great toe defects using the reverse DPAP flap., (Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: The Authors point out the interest of differential diagnosis and conservative surgical treatment of a rare case of digital and ulnar side of the hand gigantism, with massive fatty infiltration of soft tissues and a neurovascular bundle, to be included into Macrodystrophia Lipomatosa with fibrolipomatous hamartomata., Patients and Methods: Excision of the mass included 4th ray disarticulation (the fifth had been amputated several years ago) as well as microsurgical external and internal neurolysis of the ulnar nerve, the ulnar neurovascular bundle being exposed and covered with dermal substitute INTEGRATM, with a good result both from a cosmetic and functional point of view at three year follow up., Results: This is the first report of INTEGRATM covering of a neurovascular bundle. Samples taken from the dermal substitute matrix interface at day 6 and day 25 were examined with transmission Electron Microscopy: a newly formed tissue, rich in precursor cells, was detected., Conclusions: Conservative surgery, requiring particular microsurgical skills and use of dermal templates, plays an outstanding role in treatment of these rare but aggressive soft tissues masses of the upper limb.

Objectives: Lipostructure has been reported as a successful ancillary tool for surgery in tenolysis procedures, but to date no reports of its capability to resolve tendon adherence without further surgery have been reported. The aim of this study is to highlight the role of lipografting in the treatment of tendon and joint adherences., Patients and Methods: In our experience, we started treating important tendon adherences together with nerve entrapment on the dorsal aspect of the foot in two cases and in a severe burned hand., Results: We achieved good results both in terms of function and sensory recovery. A twenty four month follow up showed good maintenance of the ROM. We also reported gaining of almost 30-40 degrees of a flexion contracure in the second finger of a burned hand, minimizing further surgery for scar contracture and tenoarthrolysis, with a stable follow up., Conclusions: We suggest that prior to refer to surgery scars involving tendons as well as joints should be considered for lipografting.

A case of capitate fracture in a 28-year-old man, with a 180-degree rotation (volar dislocation) of the proximal fragment is reported. Due to a late diagnosis, the patient presented 2 weeks after trauma. Open reduction and internal fixation with Kirschner wires provided good bone alignment, uneventful healing and a good range of wrist motion was achieved. The authors remind the reader the possibility of capitate fracture, a rare but troublesome event among wrist traumas, requiring a prompt diagnosis and treatment to relief important wrist pain and to restore function. Moreover, in consideration of important vascular complications, producing non-union and arthritis, the emerging role of imaging in detecting even minor signs of bone necrosis, leading to correct surgical indications, has to be taken into account., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Sub-muscular positioning of breast implants requires interrupting as well as disinserting both the abdominal and sterno-chondral fibers of the pectoral muscle; this can produce a muscular strength reduction which reveal bothering and is often detected in some daily motions, such as cutting bread into slices., Material and Methods: The revision of anatomy and literature induced the authors to search for a conservative approach for breast augmentation. They describe a new technique defined "Tri-plane" where the muscular fibers are not cut but simply split to create the pocket for breast implants., Results: Our experience evidenced that this technique gave good aesthetic results together with a more significant projection of the NAC without any strength diminution either in adduction or abduction of the arms., Conclusions: This technique is a valid alternative to other techniques of breast augmentation as it conjugates the advantages of sub-glandular and sub-muscular implants without muscular deficit.

Dorsal adipofascial flaps have been used in the surgical reconstruction of complex injuries distal to the eponychial fold. Such injuries produce nail matrix devascularization/necrosis so that nail bed reconstruction can be a challenging technical problem. Irregular scarring of the nail bed and regrowth anomalies of the nail lamina can result, with both functional and cosmetic impairment of the finger. This study aimed to define the precise vascular anatomy of the dorsal adipofascial flap that has previously been used to reconstruct such complex soft tissue defects. Specifically, the purpose was to identify the key points of safe dissection for these flaps. Anatomical dissections were performed on 32 long fingers. The vascular tree was injected with suitable contrast and the distal dorsal region of the long fingers was studied.

A case of challenging microsurgical reconstruction of a difficult defect in a radiated upper limb is reported. A difficult wound, with tendon and bone exposition, developed on the dorsum of the forearm in a 76-year-old patient; she had been radiated since almost 50 years and her left hand had also been revascularized twice with venous grafts between the humeral artery and the superficial palmar arch. After failure of a local flap, an anterior-lateral thigh perforator flap was successfully transferred with end-to-side anastomoses on the arterialized venous graft. Up to date follow-up shows a good outcome. The Authors discuss the case and review the indications for microsurgical reconstruction in difficult wounds after radiation and ischemic limb conditions., (Copyright 2009 Wiley-Liss, Inc. Microsurgery 2009.)

Introduction: : Neuroma formation is a major problem in nerve surgery and consensus about its prevention has not been reached. It has been suggested that vein covering can reduce neuroma formation in transected nerves. In this article, the Authors propose an easy and novel method of covering by nerve stump capping with a free vein graft., Methods: : Neuroma-like lesions were created on the rat thigh sectioning the femoral nerve above its division in 16 animals. The proximal nerve stump was invaginated into the lumen of a 1.5 cm long femoral free vein graft on the right side, and the vein was closed on itself by microsurgical sutures to form a cap for the nerve stump. On the left side acting as the control neuroma, the nerve was cut and left uncovered. Histological and immunohistochemical assessment was used to quantify the degree of neuroma formation., Results: : Significant differences were found in both neuroma size and axon-glia organization between the treated and control sides indicating that free vein graft capping reduced neuroma formation in comparison to uncovered nerve stumps., Conclusions: : Our results confirm that vein-covering of a transected nerve stump can be effective in reducing neuroma formation. Moreover, unlike previous works that buried the nerve into an adjacent vein left in place, our experiments showed that also the use of a free vein graft cap can hinder neuroma formation. Although translation of rat experiments to the clinics should be dealt with caution, our data suggest a careful clinical use of the technique. (c) 2009 Wiley-Liss, Inc. Microsurgery, 2009.

Background: Squamous cell carcinoma (SCC) is the second most common skin cancer in humans. Because the incidence of metastasis from SCC of the skin is rare, regional lymphadenectomy is generally not recommended for the patients with clinically node-negative disease. However, in patients with an intermediate and high risk of metastasis, evaluation of the lymph nodes to detect the absence of metastatic nodal disease is a difficult task., Patients and Methods: The authors reviewed the pertinent demographic and surgical data in a consecutive series of six patients with squamous cell carcinoma who underwent sentinel lymph node staging. The tumour size was greater than 2 cm (T2) and the patients had clinically non-palpable regional lymph nodes (N0). All nodes were examined using haematoxylin-eosin staining. Sentinel Lymph Node Biopsy (SLNB) and Selective Lymphadenectomy (SL) using preoperative lymphoscintigraphy and intraoperative radiolymphoscintigraphy and vital dye injections was used to identify the sentinel lymph node avoiding complete axillary node dissection., Results: No false-negative results were observed. At a median follow-up of 10 months (mean 15 months), neither local or regional recurrences in sentinel node-negative basins have been noted., Conclusions: Sentinel node biopsy is a minimally invasive staging procedure useful in identifying occult regional lymph node disease in selected patients with squamous cutaneous malignancies of the arm. Furthermore sentinel lymph node histology is possibly the most important negative predictor of early recurrence and survival in patients with American Joint Committee on Cancer stage I and II squamous cell carcinoma. Although sentinel node-negative patients are a prognostically favourable group, this small series of patients demonstrates that further studies to verify these findings and develop formal guidelines are indicated