The gender role in the publishing of Authorships in high-impact orthopedic journals.

To evidence the existence of a gender gap in the orthopedic scientific literature by including also differences between some specific orthopedic surgery specialities, such as hands and feet. Then, we also considered gender role in the Authorship linked with the economic wealth of each country belonging to each Author. The gender of the first Authors of journals on orthopedics and sports medicine indexing in the Scopus database with the highest impact factor (IF) related to the year 2019, for the period from January 1, 2015, to December 31, 2020, were considered. A total of 11 journals were considered, including a total of 5474 articles, 1087 (19.86%) had a woman as the first Author and 4387 (80.14%) a man. During the studied period, the trend seems to be the same (p = 0.906): Men were significantly more producing than women in the orthopedic field both by considering the topic of the journal (p = .003), all the most impacted orthopedic journals (p < 0.001) and economies (p < 0.001). There was therefore a strong significance: In the orthopedic field, there were significantly more male researchers who presented their first name in scientific publications compared to females in all orthopedic subspecialties. The economically poorer countries published less and the role of women became almost absent.

One-shot platelet-rich plasma (PRP) injection is non-inferior to extracorporeal shockwave therapy in the management of supraspinatus tendinosis.

PURPOSE: Supraspinatus tendinosis (ST) refers to the intratendinous degeneration of the supraspinatus tendon. Platelet-Rich Plasma (PRP) is one of the possible conservative treatments for supraspinatus tendinosis. This prospective observational study aims to evaluate the efficacy and safety of a single ultrasound-guided PRP injection in the treatment of supraspinatus tendinosis and to assess its non-inferiority to the widely used shockwave therapy. METHODS: Seventy-two amateur athletes (35 male, mean age: 43.75 ± 10.82, range 21-58 years old) with ST were finally included in the study. All the patients underwent clinical evaluation at baseline, (T0) and at 1-month (T1), 3-month (T2) and 6-month (T3) follow-up using the following clinical scales: the Visual Analogue Scale for pain (VAS), Constant Score and the Disabilities of the Arm, Shoulder and Hand Score (DASH). A T0 and T3 ultrasound examination was also performed. The findings observed in the recruited patients were compared to the clinical results observed in a retrospective control group made up of 70 patients (32 male, mean age = 41.29 ± 13.85, range 20-65 years old) treated by extracorporeal shockwave therapy (ESWT). RESULTS: VAS, DASH and Constant scores significantly improved from T0 to T1; the improvement in clinical scores was kept until T3. No local nor systemic adverse events were observed. An improvement in the tendon structure was observed on ultrasound examination. PRP showed a non-statistical inferiority, in terms of efficacy and safety, compared to ESWT. CONCLUSION: The PRP one-shot injection is a valid conservative treatment to reduce pain, and improve both quality of life and functional scores in patients with supraspinatus tendinosis. Furthermore, the PRP intratendinous one-shot injection showed a non-inferiority in terms of efficacy at the 6-month follow-up, compared to ESWT.

Novel directions in the study of osteoporosis: focus on gut microbiota as a potential therapeutic target.

Osteoporosis is a significant social health problem, not only in terms of pain and disability but also in terms of mortality rate. In recent years, there is an increasing interest in studying the relationship between gut dysmicrobiosis, immune system and bone health, therefore the term "osteomicrobiology" has been recently coined. This review aims to summarize the current knowledge about the link between gut dysbiosis and osteoporosis, in order to define a potential preventive and therapeutic strategy. Gut microbiota (GM) plays a major role in maintaining body homeostasis, since it is involved in several physiological processes; in recent years, the gut microbiota has shown to modulate not only local processes but also systemic responses including bone metabolism. Several potential mechanisms may explain how gut microorganisms could affect bone metabolism, i.e. influencing the host metabolism, immune system and hormone secretion. The relationship between gut dysbiosis, immunological dysfunction and bone loss could be explained by mainly focusing on T cells. Moreover, it should be noted that the relationship between GM and the endocrine system could also explicate how the microbiome influences bone status. In this context, Insulin-Like Growth Factor-1 (IGF-1), vitamin D, serotonin and leptin might play a central role. GM could have a significant impact on bone metabolism, therefore future clinical studies are necessary to develop a new multidisciplinary approach for osteoporosis treatment and prevention.

The limits and potentials of presepsin in orthopaedic surgery: state of the art and future directions.

Presepsin, i.e. the soluble cluster of differentiation 14-SubType (sCD14-ST), is an emerging biomarker for the diagnosis and evaluation of sepsis and infection. In 2004, Yaegashi et al. originally described presepsin as a potential biomarker; since then, several studies have investigated the role of presepsin in different infectious conditions, including neonatal sepsis, severe acute pancreatitis, infections in patients with haematological malignancies, severe community-acquired pneumonia, pacemaker and implantable cardioverter-defibrillator (ICD) pocket infections, surgical site infections (SSIs) and periprosthetic joint infects (PJIs). Moreover, presepsin has been also studied in the risk stratification in cardiac surgery patients, and as a biomarker in the perioperative management of patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). This review aims to summarize the current knowledge about presepsin, focusing on the limits and potentials that the use of this biomarker could have in daily clinical practice. Presepsin is could be useful in daily clinical practice in orthopaedic surgery in the diagnosis and prevention of SSIs and PJIs. It is a cost-effective biomarker, but to improve its accuracy, it is important to carefully recalculate presepsin circulating values in patients with chronic kidney disease. However, further studies with larger patients' samples are needed to better validate the use of this biomarker in orthopaedics. In the future, synovial fluid presepsin might be a useful biomarker in the diagnosis of septic arthritis and PJIs.

Bridging the gap between serum biomarkers and biomechanical tests in musculoskeletal ageing.

Musculoskeletal ageing is a major public health interesting and strain due to the significant demographic modifications in the population, and it is linked to high risk of falls, loss of autonomy in elderly individuals and institutionalization with small health outcomes. Thus, this pathological status is related to high morbidity and health care rates. Bone mass and muscle mass and strength increase during late adolescence and early adulthood but start to reduce noticeably from the fifth decade of life and are closely linked. Preclinical and clinical data strongly support the muscle-bone cross-talk showing the presence of many tissue-specific factors released by the muscle that modulate bone, such as insulin-like growth factor-1 (IGF- 1), IL-6, IL-15, myostatin and irisin. Bone and muscle tissues were increasingly recognized as endocrine target organs and endocrine organs themselves, interacting through paracrine and endocrine signals. It is then plausible that laboratory parameters could be involved in sarcopenia and osteoporosis diagnosis and treatment monitoring. This narrative review raises the possibility of whether this poor correlation between different muscle/lean mass assessment methods and muscle function tests could suggest that each parameter evaluates different aspects of "muscle status" or "muscle quality". If this is true, no one test can be used to assess muscle status but rather a battery of tests is necessary for a comprehensive assessment. More research is required to provide information for researchers to optimally design studies by using the muscle assessment method that is best associated with selected specific outcomes.

Gait analysis in the postoperative assessment of intertrochanteric femur fractures.

Proximal femur fractures (PFFs) are an increasing public health concern. Improving gait and mobility after surgical fixation of intertrochanteric femur fractures (IFFs) is the most important target of research efforts. The purpose of this study is to investigate the role of gait analysis in the functional assessment of over-65 patients with stable and unstable IFFs, at a minimum 6-month follow-up. Fourteen patient's over-65 with IFFs (AO/OTA 31-A) treated with intramedullary nailing (EBA-2, Citieffe Srl, Italy) were enrolled. The patients were divided into two groups according to the fracture stable or unstable pattern, according to AO/OTA classification. At follow-up appointments, clinical outcomes [Harris Hip Score (HHS)], Western Ontario and McMaster University (WOMAC) and gait parameters were assessed. Radiographs were analyzed at the time of surgery and at each follow-up visit. At 3-month follow-up, both groups showed a significantly different gait patterns, compared with control subjects. At 6-month follow-up, a significant improvement of both mean HHS score (p=0.43) and mean WOMAC score was observed (p=0.43) within groups. Nonetheless, patients with stable fractures showed a comparable gait pattern, compared with control subjects, while patients with unstable fractures still presented a worse gait pattern, compared with control subjects. Therefore, in presence of an unstable IFF, a more aggressive rehabilitative program is needed. The data provided by postoperative gait analysis, therefore, could be useful to customize the patients' rehabilitative protocol, to quickly improve their walking ability and autonomy, thus reducing the post-operative re-fall risks.

Posterior approaches in malleolar fracture: when, why and how.

The treatment of posterior malleolus fractures has radically changed over the last few years, therefore this study aims to summarize the current evidence on the usefulness of posterior approaches in the management of malleolar fractures. The main elements that suggest the use of a posterior approach to the ankle are the posterior malleolus fragment shape and size, the presence of loose bodies at the fracture site: the possibility to obtain an anatomic fixation of the fracture; the presence of a posterior ankle subluxation; the eventually osteochondral impaction of the tibial plafond and the mechanical stability of the joint. The postero-lateral approach has been widely used to treat these fractures, but the posteromedial approach should be considered in specific cases. The anatomic reduction of these fractures lead to joint stability, with a consequent lesser occurrence of post-traumatic arthritis and better functional outcomes.

Humeral shaft butterfly fractures managed with intramedullary nail: could the third fragment features predict the fracture healing time?

To assess the impact of the radiological features of the third fragment on the outcome of humeral shaft fractures type 12-B managed with endomedullary nails. We retrospectively evaluated a series of 80 patients, divided into 3 groups, according to the fracture healing time: within 6 months (group-A), between 6 and 12 months (group-B) or fracture non-union after 12 months (group-C). In 26 patients out of 80 the fracture healing was observed at 6 months follow-up; in 47 out of 80 at 12 months after trauma and in 7 out of 80 no fracture healing was observed at 12 months follow-up. Regression analysis showed that the third fragment displacement and angulation are the most important features that affect the fracture healing. The mean third fragment dislocation (cut-off: 12 mm) is the main parameter to influence the fracture healing within or in more than six months.

Gut microbiota and osteoarthritis: a deep insight into a new vision of the disease.

Osteoarthritis (OA) is a multifactorial disease, whose exact pathogenesis is still unclear. In recent years, the gut microbiota (GM) has shown to modulate not only local processes but also systemic responses. This narrative review aims to summarize the recent evidence about the link between gut dysbiosis and OA onset and define a potential preventive and therapeutic strategy. OA symptomatic expression, resulting from the complex interplay between mechanical and biological factors, might be enhanced by systemic lowgrade inflammation. It is reported several OA-related risk factors are linked to a systemic inflammatory status and potential GM dysfunctions. Moreover, recent studies have demonstrated the presence of lipopolysaccharides, proteoglycan and bacterial nucleic acids in the synovial fluid of patients undergoing total knee arthroplasty. In the future, microbiota profiling could help predict OA progression and, at the same time, GM could be a potential target in the treatment and prevention of OA.

The role of biophysical stimulation with pemfs in fracture healing: from bench to bedside.

Clinical biophysics investigates the relationship between non-ionizing physical energy and the human body. This narrative review aims to summarize the current evidence on the efficacy of PEMF-therapy in the promotion of fracture healing. The effectiveness of PEMFs has been deeply investigated in preclinical in vitro ed in vivo studies and level-I clinical studies. All these studies depicted only PEMF-devices with specific physical wave features - i.e. pulse shape, frequency and amplitude- could significantly promote bone repair. Moreover, the dose-response relationship was also defined in preclinical studies, thus providing the minimum exposure time needed in PEMF-therapy. PEMFs are currently employed in the management several bone injuries, including acute fractures at non-union risk, non-unions, osteotomies, stress fractures and osteonecrosis. Moreover, several ongoing studies are investigating the effectiveness of PEMFs on emerging clinical conditions, thus the indications to PEMF-therapy could potentially raise in future years.

Serum biomarkers in the diagnosis of periprosthetic joint infection: consolidated evidence and recent developments.

Periprosthetic Joint Infection (PJI) represents one of the leading causes of revision prosthetic surgery, accounting for 25% of failed Total Knee Replacement (TKR) and 15% of failed Total Hip Replacement (THR). The search for a biomarker that, together with clinical and radiological findings, could improve the management of such a kind of patients is currently a big challenge for orthopaedic surgeons. This review aims (1) to assess the accuracy and the limitations of the traditional (Serum Erythrocytes Sedimentation Rate, C-reactive Protein, Procalcitonin, Interleukin 6, Tumor Necrosis Factor alpha), (2) and to analyse the emerging serum biomarkers (Presepsin, Toll-like Receptor 2, soluble urokinase-type Plasminogen Activator Receptor, Chemokine Ligand 2 and Osteopontin) in the diagnosis of PJI. A special attention will be given to the emerging serum biomarkers, that could play an important role as first-line investigations, in the screening of PJI in a close future.

New insights into the treatment of non-healing diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are one of the most serious and devastating complication of diabetes mellitus, affecting about 15% of diabetic patients. This review describes the innovative treatment options currently available in the treatment of non-healing DFUs. The use of Platelet-Rich-Plasma (PRP) is a safe and valid approach in the treatment of DFUs. However, the methods used to obtain and prepare autologous PRP vary between the studies, thus further evidences are eagerly awaited. Adipose tissue-derived mesenchymal stem cells (ADSCs) are a promising tool in the treatment of DFUs, but additional largescale and long-term follow-up clinical trials are needed. Bone marrow mesenchymal stem cells (BM-MSCs) transplantation, on the other hand, revealed effective in reducing incidents and improving the quality of life of patients with amputations. Autologous Peripheral Blood Mononuclear Cells (A-PBMNCs) showed a good efficacy in the treatment of diabetic patients with CLI, but further RCTs are awaited to best investigate this new therapeutic approach. Photobiomodulation (PBM) therapy revealed effective in the treatment of DFUs in two RCTs, but a standardization of therapeutic protocols as well as level-I studies are needed.

Multi-omics analysis of synovial fluid: a promising approach in the study of osteoarthritis.

Osteoarthritis (OA), affecting 250 million individuals worldwide, is a significant social health problem. Therefore, the search for synovial fluid (SF) biomarkers that could anticipate the diagnosis of OA is gaining increasing importance in orthopaedics. This review summarizes the recent progresses preformed in the multi-omics approach to OA, mainly focusing on proteome and metabolome analysis of SF. Proteomics of the SF has shown the up-regulation of several components of the classic complement pathway in OA samples, including C1, C2, C3, C4A, C4B, C5 and C4 C4BPA, thus depicting that complement is involved in the pathogenesis of OA. Moreover, proteomics has displayed that some pro-inflammatory cytokines, namely IL-6, IL-8 and IL-18, have a role in OA. The metabolomic profiling of the SF in OA has identified some metabolites as potential biomarkers of OA and has shown the existence of metabolically different OA subgroups. However, further studies with larger samples sizes and matched-control groups are needed to identify SF biomarkers that could be useful in the diagnosis, treatment and follow-up of OA.

Biophysical stimulation of the knee with PEMFs: from bench to bedside.

Clinical biophysics investigates the relationship between non-ionizing physical energy and the human body. Although several types of electrical stimulation devices have received US FDA approval for orthopaedic application, the use of Pulsed Electromagnetic Field (PEMFs) play a central role in joint biophysics. This narrative review aims to summarize the current evidences on the efficacy of PEMF-therapy in the treatment of knee articular diseases. Preclinical studies have assessed the effects of PEMFs on chondrocytes, synoviocytes, articular cartilage explants and animal models, showing positive effects of PEMF-therapy on cells proliferation, extracellular matrix (ECM) production, chondrocytes apoptosis and inflammatory cytokines down-regulation. Currently, PEMF-therapy is a valid option in the conservative management of several knee articular diseases, including early OA, patellofemoral pain syndrome and SONK. PEMFs could be also used as an adjunct after an arthroscopic knee procedure or TKA implantation, in order to control the joint post-operative inflammatory state.

Perioperative plasmatic presepsin levels in patients undergoing total hip or knee replacement: a preliminary study.

Presepsin (sCD14-ST) is an emerging biomarker in the diagnosis of sepsis. In the field of orthopaedics, it could be useful in the diagnosis and management of periprosthetic joint infections (PJI). The aim of this study is to define the normal perioperative plasmatic levels of presepsin in patients undergoing primary cementless total hip replacement (THR) or primary cemented total knee replacement (TKR). For this purpose, 50 patients (19 male, 31 female, mean age= 64.04±8.88) were recruited. The patients were divided into two groups: Group A patients underwent cementless THR, whereas Group B patients underwent cemented TKR. On recruitment, anthropometric data, smocking status, osteoarthritis stage according to Kellgren and Lawrence, Harris Hip Score (HHS) for Group A patients and Knee Society Score (KSS) for Group B patients, drugs assumption and comorbidities were recorded. All the patients underwent serial blood tests, including complete blood count, presepsin (PS), C-reactive protein (CRP) and procalcitonin (PCT) 24 hours before arthroplasty (T0) and at 24 (T1), 48 (T2), 72 (T3) and 96 (T4) hours postoperatively. Body temperature (θ) was recorded every six hours in the time lapse T0-T4. Presepsin plasmatic concentration was comparable at baseline in both groups. After surgery, however, a significant increase of presepsin was observed in Group A, whereas in Group B no significant changes of presepsin were recorded. A comparable trend of this biomarker was found in the two groups, i.e. presepsin increased from T0 to T3, when it reached its maximum value, and its decrease started at T4. Finally, presepsin resulted more accurate than CRP in the evaluation of perioperative inflammatory response in patients undergoing THR or TKR. These data will be helpful in defining a reference interval for presepsin in patients with prosthetic joint implants, and a cut-off of this biomarker for the diagnosis of PJI.

CAPACITIVE COUPLING ELECTRIC FIELDS IN THE TREATMENT OF VERTEBRAL COMPRESSION FRACTURES.

Positive effects of Capacitive Coupling Electric Field (CCEF) stimulation are described for several orthopedic indications such as the healing of recent fractures, non-unions and spinal fusion, due to the capacity to involve the up-regulation of osteopromotive factors. In vitro studies on MC3T3-E1 bone cells showed that CCEF acts opening the plasma membrane voltage gated calcium channels, thus increasing the cytosolic calcium concentration and the phospholipase A2 (PLA2) activity. Cytosolic calcium activates the calmodulin pathway, thus resulting in an up-regulated expression of osteogenic genes, such as transforming growth factor-ß superfamily genes (TGF-ß1, -ß2 -ß3, bone morphogenetic protein-2 and -4), fibroblast growth factor (FGF)-2, osteocalcin (BGP) and alkaline phosphatase (ALP). PLA2 acts increasing the synthesis of Prostaglandin E2 (PGE2), which promotes osteogenesis by raising the cellular L-ascorbic acid uptake through the membrane carrier sodium vitamin C transporter-2 (SVCT-2). In vivo, Brighton et al. in a castration-induced osteoporosis animal model, demonstrated that CCEF was able to restore bone mass/unit volume in the rat vertebral body. To investigate the role of CCEF stimulation in vertebral bone marrow edema (VBME) its percentage was assessed in 24 patients with 25 acute vertebral compression fractures (VCFs) conservatively treated with CCEF (group A) or without CCEF (group B) using serial MR imaging follow-up at 0, 30, 60, 90 days. Pain and quality of life were assessed by visual analog scale (VAS) and Oswestry Low Back Disability Index (ODI) in the same periods. At 90 day follow-up the complete resolution of VBME was found only in group A (p=0.0001). A significant improvement of VAS (p=0.007) and ODI (p=0.002) was also observed in group A. This preliminary observational study shows that patients treated with CCEF stimulation present an improvement of clinical symptoms with faster fracture healing and a complete VBME resolution.