Distinct roles of vaccine-induced SARS-CoV-2-specific neutralizing antibodies and T cells in protection and disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing antibodies (NAbs) lack cross-reactivity between SARS-CoV species and variants and fail to mediate long-term protection against infection. The maintained protection against severe disease and death by vaccination suggests a role for cross-reactive T cells. We generated vaccines containing sequences from the spike or receptor binding domain, the membrane and/or nucleoprotein that induced only T cells, or T cells and NAbs, to understand their individual roles. In three models with homologous or heterologous challenge, high levels of vaccine-induced SARS-CoV-2 NAbs protected against neither infection nor mild histological disease but conferred rapid viral control limiting the histological damage. With no or low levels of NAbs, vaccine-primed T cells, in mice mainly CD8+ T cells, partially controlled viral replication and promoted NAb recall responses. T cells failed to protect against histological damage, presumably because of viral spread and subsequent T cell-mediated killing. Neither vaccine- nor infection-induced NAbs seem to provide long-lasting protective immunity against SARS-CoV-2. Thus, a more realistic approach for universal SARS-CoV-2 vaccines should be to aim for broadly cross-reactive NAbs in combination with long-lasting highly cross-reactive T cells. Long-lived cross-reactive T cells are likely key to prevent severe disease and fatalities during current and future pandemics.

A first-in-human trial on the safety and immunogenicity of COVID-eVax, a cellular response-skewed DNA vaccine against COVID-19.

The COVID-19 pandemic and the need for additional safe, effective, and affordable vaccines gave new impetus into development of vaccine genetic platforms. Here we report the findings from the phase 1, first-in-human, dose-escalation study of COVID-eVax, a DNA vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Sixty-eight healthy adults received two doses of 0.5, 1, or 2 mg 28 days apart, or a single 2-mg dose, via intramuscular injection followed by electroporation, and they were monitored for 6 months. All participants completed the primary safety and immunogenicity assessments after 8 weeks. COVID-eVax was well tolerated, with mainly mild to moderate solicited adverse events (tenderness, pain, bruising, headache, and malaise/fatigue), less frequent after the second dose, and it induced an immune response (binding antibodies and/or T cells) at all prime-boost doses tested in up to 90% of the volunteers at the highest dose. However, the vaccine did not induce neutralizing antibodies, while particularly relevant was the T cell-mediated immunity, with a robust Th1 response. This T cell-skewed immunological response adds significant information to the DNA vaccine platform and should be assessed in further studies for its protective capacity and potential usefulness also in other therapeutic areas, such as oncology.

Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications.

Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.

Signaling pathways involved in anti-inflammatory effects of Pulsed Electromagnetic Field in microglial cells.

Literature studies suggest important protective effects of low-frequency, low-energy pulsed electromagnetic fields (PEMFs) on inflammatory pathways affecting joint and cerebral diseases. However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown. Therefore the aim of this study was to identify the molecular targets of PEMFs anti-neuroinflammatory action. The effects of PEMF exposure in cytokine production by lipopolysaccharide (LPS)-activated N9 microglial cells as well as the pathways involved, including adenylyl cyclase (AC), phospholipase C (PLC), protein kinase C epsilon (PKC-ε) and delta (PKC-δ), p38, ERK1/2, JNK1/2 mitogen activated protein kinases (MAPK), Akt and caspase 1, were investigated. In addition, the ability of PEMFs to modulate ROS generation, cell invasion and phagocytosis, was addressed. PEMFs reduced the LPS-increased production of TNF-α and IL-1ß in N9 cells, through a pathway involving JNK1/2. Furthermore, they decreased the LPS-induced release of IL-6, by a mechanism not dependent on AC, PLC, PKC-ε, PKC-δ, p38, ERK1/2, JNK1/2, Akt and caspase 1. Importantly, a significant effect of PEMFs in the reduction of crucial cell functions specific of microglia like ROS generation, cell invasion and phagocytosis was found. PEMFs inhibit neuroinflammation in N9 cells through a mechanism involving, at least in part, the activation of JNK MAPK signalling pathway and may be relevant to treat a variety of diseases characterized by neuroinflammation.

Pulsed electromagnetic field and relief of hypoxia-induced neuronal cell death: The signaling pathway.

Low-energy low-frequency pulsed electromagnetic fields (PEMFs) exert several protective effects, such as the regulation of kinases, transcription factors as well as cell viability in both central and peripheral biological systems. However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown. In this study, we have characterized in nerve growth factor-differentiated pheochromocytoma PC12 cells injured with hypoxia: (i) the effects of PEMF exposure on cell vitality; (ii) the protective pathways activated by PEMFs to relief neuronal cell death, including adenylyl cyclase, phospholipase C, protein kinase C epsilon and delta, p38, ERK1/2, JNK1/2 mitogen-activated protein kinases, Akt and caspase-3; (iii) the regulation by PEMFs of prosurvival heat-shock proteins of 70 (HSP70), cAMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), and Bcl-2 family proteins. The results obtained in this study show a protective effect of PEMFs that are able to reduce neuronal cell death induced by hypoxia by modulating p38, HSP70, CREB, BDNF, and Bcl-2 family proteins. Specifically, we found a rapid activation (30 min) of p38 kinase cascade, which in turns enrolles HSP70 survival chaperone molecule, resulting in a significant CREB phosphorylation increase (24 hr). In this cascade, later (48 hr), BDNF and the antiapoptotic pathway regulated by the Bcl-2 family of proteins are recruited by PEMFs to enhance neuronal survival. This study paves the way to elucidate the mechanisms triggered by PEMFs to act as a new neuroprotective approach to treat cerebral ischemia by reducing neuronal cell death.

Is Treatment With Dithiothreitol More Effective Than Sonication for the Diagnosis of Prosthetic Joint Infection?

BACKGROUND: Prosthetic joint infection (PJI) is among the most-severe complications of a total joint arthroplasty. Identification of the causal organism is of paramount importance for successful treatment, and sonication of implants may aid in this identification. Dithiothreitol (DTT) treatment has been proposed as an alternative to sonication to improve diagnosis, reduce costs, and improve reliability of the procedure, but its efficacy remains poorly characterized. QUESTIONS/PURPOSES: (1) Are DTT and sonication more sensitive and/or more specific than standard cultures of tissue samples for the diagnosis of PJI? (2) Which test (DTT or sonication) is more sensitive when the clinician does not suspect infection before surgery? (3) Which test (DTT or sonication) is more sensitive when the clinician suspects infection before surgery? METHODS: Two hundred thirty-two patients undergoing revision of a knee or hip arthroplasty were prospectively evaluated in this randomized study. Cultures were performed on five tissue samples from each patient and on fluid obtained by prosthesis treatment in patients randomly assigned to sonication (117 patients) or DTT (115 patients). The reference standard against which cultures (on tissue samples and on fluids from sonication or DTT) were compared was the Musculoskeletal Infection Society definition of PJI. RESULTS: Cultures on sonication and DTT fluids provided higher sensitivity (89% and 91%, respectively) than those on standard cultures of tissue samples (79%; p < 0.001). Among patients in whom infection was not suspected before surgery, the sensitivity of DTT was greater than that for sonication and cultures on tissue samples (100% versus 70% and 50%; p < 0.001). Among patients in whom infection was suspected before surgery, the sensitivity of DTT and sonication were not greater than that for standard cultures (89% and 94% versus 86%). CONCLUSIONS: In this randomized study, we found no difference in sensitivity between DTT and sonication for the detection of PJI, and both of those tests were more sensitive than standard tissue cultures. Thus, cultures of sonication or DTT fluid should be considered important additional tools to standard cultures for definition of PJI and should be considered together with other criteria, especially in settings where infection is not suspected before revision surgery.Level of Evidence Level I, diagnostic study.

Biophysical stimulation improves clinical results of matrix-assisted autologous chondrocyte implantation in the treatment of chondral lesions of the knee.

PURPOSE: The purpose of the present study was to evaluate the effects of pulsed electromagnetic fields (PEMFs) on clinical outcome in patients who underwent arthroscopic matrix-assisted autologous chondrocyte implantation (MACI) for chondral lesions of the knee. METHODS: Thirty patients affected by grade III and IV International Cartilage Repair Society chondral lesions of the knee underwent MACI. After surgery, patients were randomly assigned to either experimental group (PEMFs 4 h per day for 60 days) or control group . Clinical outcome was evaluated through International Knee Documentation Committee (IKDC) subjective knee evaluation form, Visual Analog Scale, Short Form-36 (SF-36) and EuroQoL before surgery and 1, 2, 6, and 60 months postoperative. RESULTS: Mean size of chondral lesion was 2.4 ± 0.6 cm2 in the PEMFs group and 2.5 ± 0.5 cm2 in the control one. No differences were found between groups at baseline. IKDC score increased in both groups till 6 months, but afterward improvement was observed only in the experimental group with a significant difference between groups at 60 months (p = 0.001). A significant difference between groups was recorded at 60 months for SF-36 (p = 0.006) and EuroQol (p = 0.020). A significant pain reduction was observed in the experimental group at 1-, 2- and 60-month follow-up. CONCLUSION: Biophysical stimulation with PEMFs improves clinical outcome after arthroscopic MACI for chondral lesions of the knee in the short- and long-term follow-up. Biophysical stimulation should be considered as an effective tool in order to ameliorate clinical results of regenerative medicine. The use of PEMFs represents an innovative therapeutic approach for the survival of cartilage-engineered constructs and consequently the success of orthopaedic surgery. LEVEL OF EVIDENCE: II.

Postoperative wound management with negative pressure wound therapy in knee and hip surgery: a randomised control trial.

OBJECTIVE: To compare the effectiveness in wound healing of negative pressure wound therapy (NPWT) versus a standard dressing in patients who underwent hip or knee revision surgery. METHOD: Participating patients scheduled for hip and knee prosthetic revision were randomised into two groups: one receiving standard povidone-iodine gauze and patch wound dressing (control group) and the other NPWT over the sutured wound area (NPWT group). Patients were evaluated by means of ASEPSIS score, occurrence of blisters, visual analogue scale (VAS) and dressing changes seven days after surgery. We hypothesised a five-point difference in ASEPSIS scores as clinically relevant. RESULTS: A total of 110 patients were enrolled in the study. Mean ASEPSIS score was 5.1 for the control group and 3.0 for the NPWT group, with a significant difference in the ASEPSIS score between groups (p<0.001), although this was not clinically relevant. Considering patients with more than three risk factors for healing complication, a statistical difference of >5 points ASEPSIS score was recorded (p<0.0005). Blister occurrence, VAS score and number of dressing changes were significantly lower in the NPWT group. CONCLUSION: The results of this study do not support the routine use of NPWT after hip and knee revision. However, it could be beneficial for selected patients once specific risk factors for wound healing complications have been determined.

A Human 3D In Vitro Model to Assess the Relationship Between Osteoporosis and Dissemination to Bone of Breast Cancer Tumor Cells.

Despite consistent improvements in diagnostic and therapeutic strategies for breast cancer, up to 40% of patients will develop bone metastases. To reduce the morbidity and complications related with bone metastases, it is imperative to reduce their etiological factors. Osteoporosis, being characterized by a sudden estrogen deficiency, may provide a favorable condition for bone metastasis. This work, using a humanized 3D in vitro model, aims at evaluating the relationship between osteoporosis and breast cancer-derived bone metastases. Bone tissue discarded from total hip replacement surgery of healthy and osteoporotic patients was cultured in a rolling apparatus system in hypoxic environment. Protein levels (i.e., vascular endothelial growth factor (VEGF), VEGF receptor 1, VEGF receptor 2, interleukin (IL)-6, IL-1ß, IL-8 IL-10, tumor necrosis factor α (TNF-α), osteoprotegerin (OPG), receptor activator for nuclear factor KB ligand (RANKL)) and histological and immunohistochemical (i.e., cytokeratin 8 and 18) analyses showed a noticeable specificity of breast cancer cells for the colonization of osteoporotic bone. These data are the first to demonstrate that using humanized 3D in vitro systems, which individually model the pre- and postmenopausal bone microenvironment, it is possible to recognize major differences in tumor growth and colonization between healthy and osteoporotic status. Thus, this system might help to develop a shared system between basic and clinical sciences where a personalized diagnosis is associated to a therapeutic strategy designed for a single patient: a model able to achieve a translational research approach in the clinical setting, which may lead to the application and dissemination of personalized medicine. J. Cell. Physiol. 232: 1826-1834, 2017. © 2016 Wiley Periodicals, Inc.

Adenosine Receptors as a Biological Pathway for the Anti-Inflammatory and Beneficial Effects of Low Frequency Low Energy Pulsed Electromagnetic Fields.

Several studies explored the biological effects of low frequency low energy pulsed electromagnetic fields (PEMFs) on human body reporting different functional changes. Much research activity has focused on the mechanisms of interaction between PEMFs and membrane receptors such as the involvement of adenosine receptors (ARs). In particular, PEMF exposure mediates a significant upregulation of A2A and A3ARs expressed in various cells or tissues involving a reduction in most of the proinflammatory cytokines. Of particular interest is the observation that PEMFs, acting as modulators of adenosine, are able to increase the functionality of the endogenous agonist. By reviewing the scientific literature on joint cells, a double role for PEMFs could be hypothesized in vitro by stimulating cell proliferation, colonization of the scaffold, and production of tissue matrix. Another effect could be obtained in vivo after surgical implantation of the construct by favoring the anabolic activities of the implanted cells and surrounding tissues and protecting the construct from the catabolic effects of the inflammatory status. Moreover, a protective involvement of PEMFs on hypoxia damage in neuron-like cells and an anti-inflammatory effect in microglial cells have suggested the hypothesis of a positive impact of this noninvasive biophysical stimulus.

Intraoperative diagnosis of Staphylococcus aureus and coagulase-negative Staphylococcus using Xpert MRSA/SA SSTI assay in prosthetic joint infection.

The aim of this prospective study was to evaluate the performance of the Polymerase Chain Reaction (PCR) tool Xpert MRSA/SA SSTI test (Cepheid, Sunnyvale, CA, USA) on periprosthetic samples from a cohort of patients with suspected prosthetic joint infection (PJI). Seventy adult patients were included in this prospective study. On the basis of the preoperative evaluation, 39 patients were clinically considered to have a PJI, whereas 31 were presumed to suffer from an aseptic mobilization of the implant. Xpert MRSA/SA SSTI identified 4 out of 4 MRSA, 7 out of 7 MSSA, and 14 out of 16 methicillin resistant CoNS. Among the 31 patients not having a PJI, the rapid PCR did not find any bacteria among those identifiable, thus demonstrating an excellent performance in terms of specificity. Statistical analysis of the analytical performance showed a high correlation (p<0.001) between the result of Xpert MRSA/SA SSTI and culture. Xpert MRSA/SA SSTI assay is a novel, yet well known, rapid and accurate method for the identification of different species of staphylococci. The test can be used with peri-operative samples thus dramatically improving the diagnostic sensitivity. In addition, thanks to the very short turnaround time the use of Xpert assay can modify the clinical management of patients suffering from PJI during the ongoing operative procedure.

A 2- to 7-Year Follow-Up of a Modular Iliac Screw Cup in Major Acetabular Defects: Clinical, Radiographic and Survivorship Analysis With Comparison to the Literature.

BACKGROUND: Inadequate acetabular bone stock is a major issue in total hip arthroplasty, and several treatment options are available. Stemmed cups have been used in this scenario with variable results. A novel modular polyaxial uncemented iliac screw cup (HERM-BS-Sansone cup-Citieffe s.r.l., Calderara di Reno, Bologna, Italy) has been recently introduced to overcome the drawbacks of stemmed cups. In this retrospective study, we report the results of this cup in patients with large acetabular bone defects at 2- to 7-year follow-up. METHODS: We evaluated a consecutive series of 121 hips (118 revisions and 3 complex primary arthroplasties) treated with this novel cup at a mean follow-up of 46 months. Kaplan-Meier survival analysis was performed with implant revision for any reason as a primary end point. Further survival analysis was performed excluding septic failures. Clinical outcome was assessed with the Harris Hip Score. RESULTS: There had been 7 reoperations: 1 for aseptic loosening, 5 for deep infection, and 1 for recurrent dislocation. In 5 cases, the cup was removed; estimated survival rate at 5-year follow-up with implant removal for any reason was 95.6% (95% confidence interval = 91-99), and 98.3% (95% CI = 96-100) excluding those failed for infection. Mean Harris Hip Score at latest follow-up was 77 points (range, 44-95; standard deviation = 11.9). CONCLUSION: The present findings show the short-term efficacy of the iliac screw cup with respect to implant survival. A longer follow-up and a larger number of patients are necessary to confirm the encouraging preliminary results.

Fluoroscopic and Gait Analyses for the Functional Performance of a Custom-Made Total Talonavicular Replacement.

The present study evaluated the restoration of joint function in a special clinical case: a professional rock climber who underwent an original total talonavicular replacement with a custom-made prosthesis after a complex articular fracture. Full body gait analysis and 3-dimensional joint kinematics using single-plane fluoroscopy were performed on the same day at the 30-month follow-up examination. Gait analysis was performed using stereophotogrammetric, dynamometric, electromyographic, and baropodometric systems. Gait analysis showed good restoration of rotation, as well as moment patterns in the main lower limb and foot joints in the operated leg. At the artificial tibiotalar joint, videofluoroscopic analysis revealed a flexion capability of about 20°, together with a few degrees of motion in the frontal and transverse planes. The neighboring joints of the foot did not present with severe kinematic abnormalities. A full talonavicular replacement can be a viable and effective solution for complex ankle injury sequelae, even in patients with highly demanding functionality.

Bioabsorbable Calcaneo-Stop Implant for the Treatment of Flexible Flatfoot: A Retrospective Cohort Study at a Minimum Follow-Up of 4 Years.

Arthroereisis of the subtalar joint is a common surgical technique in Europe for the management of flexible flatfoot in the pediatric population. In most cases, it is performed using a calcaneo-stop metallic screw. Despite the good clinical results, screw removal is always advised after 2 to 3 years. The use of a bioabsorbable screw might overcome the need for a second operation to remove a nonabsorbable device. We report the results of a biodegradable calcaneo-stop screw at a minimum of 4 years of follow-up. Eighty-eight procedures were performed on 44 children. All patients were clinically and radiologically evaluated preoperatively and at a minimum 4-year follow-up period. Patient satisfaction and plantar collapse using Viladot's classification were recorded. Meary's talus-first metatarsal angle and talocalcaneal angle were measured on radiographs preoperatively and at the last follow-up visit. The presence of the device at the last follow-up examination was assessed by magnetic resonance imaging. The mean follow-up duration was 56 months. Of the 44 patients, 33 (75%) reported excellent clinical outcomes, 9 (20.5%) good outcomes, and 2 (4.5%) poor. Foot print improvement was registered for all patients. The mean Meary's talus-first metatarsal angle had improved from 160.6° ± 7.7° preoperatively to 170.6° ± 6.5° at the last follow-up visit (p < .001). The talocalcaneal angle had decreased from 39.9° ± 5.2° preoperatively to 29.4° ± 4° at the last follow-up examination (p < .001). At the 4-year follow-up point, the implant could be seen to have almost completely biodegraded on magnetic resonance imaging. Two screw breakages occurred. The bioabsorbable calcaneo-stop screw seems to be an effective solution for flexible flatfoot in pediatric patients. Also, owing to its biodegradable composition, the need of a second operation for implant removal will not always be necessary.

Results at a minimum follow-up of 5 years of a ligaments-compatible total ankle replacement design.

BACKGROUND: A new design of 3-part ankle replacement was developed to achieve compatibility with the natural ligaments by allowing certain fibers to remain isometric during passive motion. METHODS: We evaluate 75 ankle prostheses implanted from July 2003 to December 2008, at a mean follow-up 6.5±1.1years (range 5-9 years). The mean age at surgery was 62±13years (range 29-82). RESULTS: The mean AOFAS scores achieved at pre-op and at last follow-up were respectively 37±5 (23-45) and 78±8 (64-98). (p<0.001). Clinical range of motion of the ankle measured by goniometer pre op was 1°±2 of dorsiflexion and 12°±4° of plantarflexion; at last follow-up range of motion increased to 6°±5° in dorsiflexion (p<0.01) and 18°±7° in plantarflexion (p<0.05). Radiographs showed no loosening and little signs of radiolucency. Two revisions necessitated component removal, neither for implant loosening. The overall survival rate was 97.3%. CONCLUSIONS: Function and Range-of-motion showed significant improvements. These results demonstrate that ligaments-compatible shaped talar and tibial components, with a fully conforming interposed meniscal bearing, can provide satisfactory survival rates and clinical outcomes in the middle term.

Is there a role of pulsed electromagnetic fields in management of patellofemoral pain syndrome? Randomized controlled study at one year follow-up.

Patellofemoral pain syndrome (PFPS) is a common cause of recurrent or chronic knee pain in young adults, generally located in the retropatellar region. Etiology is controversial and includes several factors, such as anatomical defects, muscular imbalance, or joint overuse. Good results have been reported with exercise therapy, including home exercise program (HEP). Joint inflammation with increase of pro-inflammatory cytokines levels in the synovial fluid might be seen especially when chondromalacia becomes evident. Biophysical stimulation with pulsed electromagnetic fields (PEMFs) has shown anti-inflammatory effects and anabolic chondrocyte activity. The purpose of this randomized controlled study was to evaluate if the combination of HEP with PEMFs was more effective than HEP alone in PFPS treatment. Thirty-one PFPS patients were enrolled in this study. All patients were instructed to train with HEP. Patients in the PEMFs group associated HEP with PEMFs. Function and pain were assessed with Victorian Institute of Sport Assessment score (VISA), Visual Analog Scale (VAS), and Feller's Patella Score at baseline at 2, 6, and 12 months of follow-up. Drug assumption was also recorded. Increase in VISA score was significantly higher in PEMFs group compared to controls at 6 and 12 months, as well as the increase in the Feller's Patella Score at 12 months. VAS score became significantly lower in the PEMFs group with respect to control group since 6 month follow-up. Pain reduction obtained with PEMFs enhanced practicing therapeutic exercises leading to a better recovery process; this is extremely important in addressing the expectations of young patients, who wish to return to sporting activities.

Custom-Made Total Talonavicular Replacement in a Professional Rock Climber.

Professional athletes are often eager to resume sporting activities at preinjury levels. When facing the challenge of restoring joint function after a complex articular fracture, innovative solutions must be explored. We describe the results of what we believe to be the first custom-made talonavicular prosthesis implanted in a professional rock climber who had developed post-traumatic ankle and talonavicular arthritis as sequelae of a complex talar and navicular fracture. Using computed tomography scan reconstruction of the contralateral healthy ankle and direct metal laser sintering, a custom-made talonavicular prosthesis was obtained and implanted using an anteromedial approach. The patient was clinically and radiographically evaluated every 6 months after surgery for 30 months. A 3-dimensional videofluoroscopic analysis was performed to assess the range of motion about the prosthesis. At the last follow-up visit, the functional scores were excellent (Tegner activity scale score of 9 of 10), and he had completely resumed his sporting activity. The American Orthopaedic Foot and Ankle Society score had increased from 36 to 81 points, and no signs of radiolucency were observed on the radiographs. The 3-dimensional videofluoroscopic analysis showed 15° of dorsiflexion and 4° of plantar flexion at the ankle. A customized solution is an option when the patient's expectations are not likely to be met by standard treatment, such as arthrodesis. A custom-made talonavicular prosthesis can be an effective solution for complex ankle injury sequelae in patients demanding high functionality.

Surgical prevention of femoral neck fractures in elderly osteoporotic patients. A literature review.

Fragility fractures of the femur are one of the major causes of morbidity and mortality worldwide. The incidence of new contralateral hip fractures in elderly osteoporotic patients ranges from 7 to 12% within 2 years after the first fracture. Secondary prevention can be divided in: pharmacological therapy based on the prescription of anti-osteoporotic drugs with different mechanism of action and non-pharmacological therapy which is based on modification of environmental risk factors, on a healthy diet with daily supplements of calcium and vitamin D and calcium and on the use of hip protectors. Recently a new form of prevention is becoming achievable: surgical prevention; the rationale of surgical reinforcement is the need to increase the resistance of the femoral neck to the compression and distraction forces acting on it. In this paper we analyse all the experimental and "on the market" device available for the surgical prevention of femoral neck fracture.

Pulsed electromagnetic fields combined with a collagenous scaffold and bone marrow concentrate enhance osteochondral regeneration: an in vivo study.

BACKGROUND: The study aimed to evaluate the combined effect of Pulsed Electromagnetic Field (PEMF) biophysical stimulation and bone marrow concentrate (BMC) in osteochondral defect healing in comparison to the treatment with scaffold alone. METHODS: An osteochondral lesion of both knees was performed in ten rabbits. One was treated with a collagen scaffold alone and the other with scaffold seeded with BMC. Half of the animals were stimulated by PEMFs (75 Hz, 1.5 mT, 4 h/day) and at 40 d, macroscopic, histological and histomorphometric analyses were performed to evaluate osteochondral defect regeneration. RESULTS: Regarding cartilage, the addition of BMC to the scaffold improved cell parameters and the PEMF stimulation improved both cell and matrix parameters compared with scaffold alone. The combination of BMC and PEMFs further improved osteochondral regeneration: there was an improvement in macroscopic, cartilage cellularity and matrix parameters and a reduction in the percentage of cartilage under the tidemark. Epiphyseal bone healing improved in all the osteochondral defects regardless of treatment, although PEMFs alone did not significantly improve the reconstruction of subchondral bone in comparison to treatment with scaffold alone. CONCLUSIONS: Results show that BMC and PEMFs might have a separate effect on osteochondral regeneration, but it seems that they have a greater effect when used together. Biophysical stimulation is a non-invasive therapy, free from side effects and should be started soon after BMC transplantation to increase the quality of the regenerated tissue. However, because this is the first explorative study on the combination of a biological and a biophysical treatment for osteochondral regeneration, future preclinical and clinical research should be focused on this topic to explore mechanisms of action and the correct clinical translation.