Development of Autologous Platelet-Rich Plasma Mixed-Microfat as an Advanced Therapy Medicinal Product for Intra-Articular Injection of Radio-Carpal Osteoarthritis: From Validation Data to Preliminary Clinical Results.

Wrist osteoarthritis (OA) is one of the most common conditions encountered by hand surgeons with limited efficacy of non-surgical treatments. The purpose of this study is to describe the Platelet-Rich Plasma (PRP) mixed-microfat biological characteristics of an experimental Advanced Therapy Medicinal Product (ATMP) needed for clinical trial authorization and describe the clinical results obtained from our first three patients 12 months after treatment (NCT03164122). Biological characterization of microfat, PRP and mixture were analysed in vitro according to validated methods. Patients with stage four OA according to the Kellgren Lawrence classification, with failure to conservative treatment and a persistent daily painful condition >40 mm according to the visual analog scale (VAS) were treated. Microfat-PRP ATMP is a product with high platelet purity, conserved viability of stromal vascular fraction cells, chondrogenic differentiation capacity in vitro and high secretion of IL-1Ra anti-inflammatory cytokine. For patients, the only side effect was pain at the adipose tissue harvesting sites. Potential efficacy was observed with a pain decrease of over 50% (per VAS score) and the achievement of minimal clinically important differences for DASH and PRWE functional scores at one year in all three patients. Microfat-PRP ATMP presented a good safety profile after an injection in wrist OA. Efficacy trials are necessary to assess whether this innovative strategy could delay the necessity to perform non-conservative surgery.

Soft Tissue Coverage in Distal Lower Extremity Open Fractures: Comparison of Free Anterolateral Thigh and Free Latissimus Dorsi Flaps.

BACKGROUND: When microsurgical transfers are required in posttraumatic lower limb reconstruction, surgeons must choose among many types of free flaps. Historically, surgeons have advocated muscular flaps for coverage of open lower extremity wounds, but fasciocutaneous free flaps are now often used with good results. This study aimed to compare the functional and aesthetic outcome of reconstruction by free muscular latissimus dorsi (LD) flap and free fasciocutaneous anterolateral thigh (ALT) flap used for soft tissue coverage of distal lower extremity open fractures. METHODS: We performed a single-center, retrospective study of subjects with distal lower limb open fractures treated with LD flaps or ALT flaps between 2008 and 2014. Patients with limited follow-up or incomplete data were excluded from the analysis. Donor and recipient sites, early complications and long-term outcomes (functional and aesthetic) were studied and compared according to the type of flap. RESULTS: A total of 47 patients were included: 27 patients in the LD flap group and 20 patients in the ALT flap group. No significant difference was found regarding early and late complications and long-term functional outcomes (bone healing, infectious bone complications, flap healing). As for aesthetic outcome and donor-site morbidity, reconstruction using the ALT free flap had significantly better results (p < 0.05). CONCLUSIONS: In posttraumatic lower limb injury, either LD or ALT free flaps can be used for wound coverage with comparable long-term functional outcomes. The ALT flap provides better cosmetic results than LD.

Immediate Proximal Row Carpectomy for Severe Perilunate Dislocation Injuries: A Minimum 5-Year Follow-Up.

Background: In patients with perilunate injuries (PLI) with multiple ligamentous and bony injuries involving the proximal carpal row, open reduction and internal fixation (ORIF) can be difficult and lead to poor functional outcomes. Proximal row carpectomy (PRC) is an alternative procedure that has been used for severely comminuted fractures. The aim of our study is to evaluate the long-term functional outcome (minimum 5 years) of patients that underwent an emergency PRC for PLI. Methods: We conducted a retrospective study of patients who underwent PRC at our centre between 2001 and 2016. Only patients with follow-up data of more than 5 years were included in the study. We evaluated range of motion, grip strength, Mayo Modified Wrist Score (MMWS) and Quick Disabilities of Arm, Shoulder and Hand (Quick-DASH). Radiographic analyses were performed to assess the presence of radiocarpal osteoarthritis and the space between the radius and capitate. Results: Thirteen patients were included, with an average follow-up of 78.07 months (6.5 years). The MMWS was 65 points (four excellent and good, four fair and five poor results) and the Quick-DASH score was 30 points. X-ray analysis reported only 15.3% of patients with radiocarpal arthrosis and an average radio-capitate joint space of 1.92 mm. Conclusions: The outcomes of PRC in the management of PLI are comparable to the results reported in literature for conventional ORIF. PRC is a simpler procedure that minimises the need for re-intervention. Level of Evidence: Level IV (Therapeutic).

Free Fibula Flap in Traumatic Femoral Bone Reconstruction: A 10-year Review.

Introduction: The loss of femoral bone substance represents a major therapeutic issue. When the loss of bone substance is extensive, or the local condition is unfavourable, there are few satisfactory solutions. In this study, we share our experience of large femoral bone reconstruction by free fibula flap. Materials and methods: A retrospective monocentric chart review (2007-2017) was performed for 26 patients after receiving a pure bone-free fibula flap operation. The times of consolidation and hypertrophy of the graft were analysed according to the fixation with a 2-year follow-up. Results: The time to consolidation was 8.7 months (range, 6-15) for double plates, 7.2 months (range, 5-11) for locked plates, 6 months (range, 5-7) for external fixators and plate blades and 8 months (range, 7-9) for intramedullary nails.Full weight-bearing was resumed at an average of 6.5 months (range, 5-10) postoperatively. It was authorised at 7 months (range, 5-10) for patients fixed by double plate, at 6.3 months (range, 5-9) for those fixed by a locked plate, at 5.5 months (range, 5-6) for those fixed by an external fixator or plate blade and at 7 months for those fixed by an intramedullary nail. Conclusion: Free fibula flap remains reliable in the face of a great loss of bone material after trauma, with high consolidation rates. The choice of fixation must be reasoned and should offer a compromise between stability, allowing consolidation and hypertrophy of the graft, and rigidity, exposing the risk of massive osteosynthesis dismantling. Other multicentric studies, including more patients, should be carried out to compare the techniques of fixation. How to cite this article: Viaud-Ambrosino S, Bargemon JBV, Kachouh N, et al. Free Fibula Flap in Traumatic Femoral Bone Reconstruction: A 10-year Review. Strategies Trauma Limb Reconstr 2023;18(1):44-50.

Human nasal olfactory stem cells, purified as advanced therapy medicinal products, improve neuronal differentiation.

Background: Olfactory ecto-mesenchymal stem cells (OE-MSC) are mesenchymal stem cells derived from the lamina propria of the nasal mucosa. They display neurogenic and immunomodulatory properties and were shown to induce recovery in animal models of spinal cord trauma, hearing loss, Parkinsons's disease, amnesia, and peripheral nerve injury. As a step toward clinical practice, we sought to (i) devise a culture protocol that meets the requirements set by human health agencies and (ii) assess the efficacy of stem cells on neuron differentiation. Methods: Nasal olfactory mucosa biopsies from three donors were used to design and validate the good manufacturing process for purifying stem cells. All processes and procedures were performed by expert staff from the cell therapy laboratory of the public hospital of Marseille (AP-HM), according to aseptic handling manipulations. Premises, materials and air were kept clean at all times to avoid cross-contamination, accidents, or even fatalities. Purified stem cells were cultivated for 24 or 48 h and conditioned media were collected before being added to the culture medium of the neuroblastoma cell line Neuro2a. Results: Compared to the explant culture-based protocol, enzymatic digestion provides higher cell numbers more rapidly and is less prone to contamination. The use of platelet lysate in place of fetal calf serum is effective in promoting higher cell proliferation (the percentage of CFU-F progenitors is 15.5%), with the optimal percentage of platelet lysate being 10%. Cultured OE-MSCs do not show chromosomal rearrangement and, as expected, express the usual phenotypic markers of mesenchymal stem cells. When incorporated in standard culture medium, the conditioned medium of purified OE-MSCs promotes cell differentiation of Neuro2a neuroblastoma cells. Conclusion: We developed a safer and more efficient manufacturing process for clinical grade olfactory stem cells. With this protocol, human OE-MSCs will soon be used in a Phase I clinical based on their autologous transplantation in digital nerves with a neglected injury. However, further studies are required to unveil the underlying mechanisms of action.

Intra Articular Injection of Autologous Microfat and Platelets-Rich Plasma in the Treatment of Wrist Osteoarthritis: A Pilot Study.

No injection treatment has been proven to be effective in wrist osteoarthritis. When conservative measures fail, its management involves invasive surgery. Emergence of biotherapies based on adipose derived stem cells (ADSC) offers promising treatments for chondral degenerative diseases. Microfat (MF) and platelets-rich plasma (PRP) mixture, rich in growth factors and ADSC could be a minimally invasive injectable option in the treatment of wrist osteoarthritis. The aim of this uncontrolled prospective study was to evaluate the safety of a 4 mL autologous MF-PRP intra-articular injection, performed under local anesthesia. The secondary purpose was to describe the clinical and MRI results at 12 months of follow-up. Patients' data collected were: occurrence of adverse effects, Visual analog scale (VAS), Disabilities of the Arm, Shoulder and Hand score (DASH) and Patient-Rated Wrist Evaluation (PRWE) scores, wrist strength, wrist range of motion and 5-level satisfaction scale. No serious adverse event was recorded. A statistically significant decrease in pain, DASH, PRWE and force was observed at each follow-up. Our preliminary results suggest that intra-articular autologous MF and PRP injection may be a new therapeutic strategy for wrist osteoarthritis resistant to medical symptomatic treatment prior to surgical interventions.

Accidental section of the ulnar nerve in the wrist during arthroscopy.

Arthroscopy of the wrist is a frequently performed procedure. Its role in diagnosis and treatment is significant. The complications of arthroscopy are well known and are described in the literature. We describe a case of accidental section of the ulnar nerve during repair of the triangular fibrocartilage complex during arthroscopy. The nerve section was caused by the trocar used for drainage in the 6U portal. We propose to establish the injury mechanism and describe a safe procedure for this examination.

Outcomes of secondary trapeziectomy after revision of trapeziometacarpal implants: a retrospective comparative matched study.

We evaluated secondary trapeziectomy for revision of trapeziometacarpal implants and compared this to primary trapeziectomy with a matched retrospective single centre study performed between October 2003 and February 2015. Thirty-one patients with trapeziometacarpal prosthesis failure who had a secondary trapeziectomy were matched with a primary trapeziectomy regarding sex, date of the operation and age. We evaluated function, mobility, autonomy, pain, strength, complications and shortening of the thumb on radiographs. The median time until removal of the implant was 37 months. The median age in both groups was similar. Median follow-up was more than 7 years in both groups. There was no statistically significant difference in terms of function, mobility, autonomy, pain, strength, complications and shortening of the thumb. Secondary trapeziectomy after revision of trapeziometacarpal implants provides results comparable with primary trapeziectomy.Level of evidence: III.

Free vascularized medial femoral condyle corticoperiosteal flap with non-vascularized iliac crest graft for the treatment of recalcitrant clavicle non-union.

Clavicle non-union is a challenging problem. Open reduction with internal fixation and autologous bone grafting is usually the first line treatment. In case of failure, the medial femoral condyle corticoperiosteal flap in association with a non-vascularized bone graft is one of the therapeutic options, which is well adapted to the clavicle anatomical characteristics. We performed a retrospective study of all patients treated with this technique in our department. Between 2014 and 2017, five patients with recalcitrant post traumatic clavicle non-unions received this surgical treatment. The average nonunion time period was 50.2 month (range 10 to 108 months), and the mean defect length was 3.4 cm (between 2 and 5 cm), defects were all located in the medial third of the clavicle Three patients achieved full consolidation with an average time of consolidation of 8,7 months (range 6 to12 months). Patients with radiological consolidation had better functional improvement and pain reduction with an average DASH score improved from 53,6 before surgery to 19,6 after consolidation (at the last follow up visit). There was one donor site complications (hematoma). The medial femoral condyle corticoperiosteal flap with non-vascularized iliac crest graft is a good option for the management of recalcitrant clavicle non-union, especially when the bone defect is small.

Vitamin D2 potentiates axon regeneration.

To date, the use of autograft tissue remains the "gold standard" technique for repairing transected peripheral nerves. However, the recovery is suboptimal, and neuroactive molecules are required. In the current study, we focused our attention on vitamin D, an FDA-approved molecule whose neuroprotective and neurotrophic actions are increasingly recognized. We assessed the therapeutic potential of ergocalciferol--the plant-derived form of vitamin D, named vitamin D2--in a rat model of peripheral nerve injury and repair. The left peroneal nerve was cut out on a length of 10 mm and immediately autografted in an inverted position. After surgery, animals were treated with ergocalciferol (100 IU/kg/day) and compared to untreated animals. Functional recovery of hindlimb was measured weekly, during 10 weeks post-surgery, using a walking track apparatus and a numerical camcorder. At the end of this period, motor and sensitive responses of the regenerated axons were calculated and histological analysis was performed. We observed that vitamin D2 significantly (i) increased axogenesis and axon diameter; (ii) improved the responses of sensory neurons to metabolites such as KCl and lactic acid; and (iii) induced a fast-to-slow fiber type transition of the Tibialis anterior muscle. In addition, functional recovery was not impaired by vitamin D supplementation. Altogether, these data indicate that vitamin D potentiates axon regeneration. Pharmacological studies with various concentrations of the two forms of vitamin D (ergocalciferol vs. cholecalciferol) are now required before recommending this molecule as a potential supplemental therapeutic approach following nerve injury.

Results of the modified Brunelli tenodesis for treatment of scapholunate instability: a retrospective study of 19 patients.

PURPOSE: Management of chronic scapholunate (SL) instability without osteoarthritis remains controversial. In order to recreate an SL interosseous linkage, some surgeons opt for a limited wrist arthrodesis, whereas others use soft tissue stabilization. The purpose of the current study was to review and assess the therapeutic benefit of the modified Brunelli tenodesis that used the flexor carpi radialis tendon to replicate the stabilizing ligaments of the scaphoid. METHODS: Between 2001 and 2005, 19 tenodesis procedures have been performed to correct dynamic or static SL instability without osteoarthritis. On average, patients had surgery 15 months after injury. The mean follow-up was 37 months. RESULTS: After surgery, 15 patients had no to mild pain with a mean visual analog scale score of 3 of 10. The average wrist motion was 50 degrees extension, 41 degrees flexion, 24 degrees radial deviation, and 29 degrees ulnar deviation (75%, 73%, 68%, and 86% of the uninvolved wrists, respectively). The grip strength was 78% of the uninvolved wrists. On radiographs, the mean static SL distance was 2.4 mm (2.8 mm before surgery). There was no widening of the SL gap compared to the immediate postoperative gap. The SL angle improved from a mean preoperative value of 61 degrees to 53 degrees immediately after surgery and rose again to 62 degrees at the time of the review. One patient developed a scapholunate advanced collapse wrist stage 2. CONCLUSIONS: Ligament reconstruction using tendon grafts gave satisfactory results to correct reducible chronic SL instability without osteoarthritis. This repair technique achieved a relatively pain-free wrist, with acceptable grip strength and normal SL distance but with a loss in the arc of motion and a loss of correction of SL angle. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Saccharomyces cerevisiae osteomyelitis in an immunocompetent baker.

Invasive infection caused by Saccharomyces cerevisiae is rare. We report the first case of osteomyelitis caused by S. cerevisiae (baker's yeast) in a post-traumatic patient. The clinical outcome was favorable after surgical debridement, prolonged antifungal treatment and hyperbaric oxygen therapy.

Nosocomial Infections with Aeromonas hydrophila from Leeches.

The manner in which leeches are maintained before they are used for therapy has not been studied as a factor contributing to nosocomial infections. A 5-year retrospective survey of Aeromonas hydrophila nosocomial infections at a hospital in Marseille, France, revealed infections in 5 (4.1%) of an estimated 122 patients treated with leeches in the Hand Surgery Unit and 2 (2.4%) of an estimated 85 patients treated with leeches in other hospital units. The retrospective survey showed that the Hand Surgery Unit was the only unit that had its own aquarium for maintaining leeches; this aquarium was filled with tap water contaminated with Aeromonas species and was not regularly disinfected or cleaned. Leeches used in other units were maintained in noncarbonated water in a transport device. Use of leeches kept in aquariums that are filled with tap water and not disinfected or cleaned regularly may be linked to A. hydrophila infections.

Cholecalciferol (vitamin D3) improves myelination and recovery after nerve injury.

Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form - ergocalciferol versus cholecalciferol - and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or spinal cord repair.

Isolated capitate shortening osteotomy for the early stage of Kienböck disease with neutral ulnar variance.

BACKGROUND: Kienböck disease is an aseptic necrosis of the lunate for which the treatment is still debated, particularly in the rare cases with neutral ulnar variance. One option is to perform a capitate shortening osteotomy associated with a capitate-hamatum arthrodesis. The aim of this study was to evaluate a simple capitate osteotomy without arthrodesis. METHODS: This is a retrospective study of 11 cases. All patients had a mild form of Kienböck disease (stage I to IIIA according to the classification of Lichtman). A shortening capitate osteotomy was performed through a dorsal medial approach and fixed with staples. RESULTS: At the final follow-up evaluation (mean, 67.4 months), the mean visual analogue scale score was 1.7 (range, 0 to 7). Based on the Nakamura score, the authors obtained six good, two fair, and three poor results. Mean strength improvement was 25 percent compared with the healthy side, and the authors observed no change in range of motion. The radiologic follow-up showed no difference in either the Stahl or the Youm index between preoperative and postoperative measurements. No complication was observed; however, in two cases, the result was evaluated as poor and a revision procedure was performed. CONCLUSION: This technique is a simple and reliable method with which to manage the early stages of Kienböck disease with neutral ulnar variance.