The BrAID study protocol: integration of machine learning and transcriptomics for brugada syndrome recognition.

BACKGROUND: Type 1 Brugada syndrome (BrS) is a hereditary arrhythmogenic disease showing peculiar electrocardiographic (ECG) patterns, characterized by ST-segment elevation in the right precordial leads, and risk of Sudden Cardiac Death (SCD). Furthermore, although various ECG patterns are described in the literature, different individual ECG may show high-grade variability, making the diagnosis problematic. The study aims to develop an innovative system for an accurate diagnosis of Type 1 BrS based on ECG pattern recognition by Machine Learning (ML) models and blood markers analysis trough transcriptomic techniques. METHODS: The study is structured in 3 parts: (a) a retrospective study, with the first cohort of 300 anonymized ECG obtained in already diagnosed Type 1 BrS (75 spontaneous, 150 suspected) and 75 from control patients, which will be processed by ML analysis for pattern recognition; (b) a prospective study, with a cohort of 11 patients with spontaneous Type 1 BrS, 11 with drug-induced Type 1 BrS, 11 suspected BrS but negative to Na + channel blockers administration, and 11 controls, enrolled for ECG ML analysis and blood collection for transcriptomics and microvesicles analysis; (c) a validation study, with the third cohort of 100 patients (35 spontaneous and 35 drug-induced BrS, 30 controls) for ML algorithm and biomarkers testing. DISCUSSION: The BrAID system will help clinicians improve the diagnosis of Type 1 BrS by using multiple information, reducing the time between ECG recording and final diagnosis, integrating clinical, biochemical and ECG information thus favoring a more effective use of available resources. Trial registration Clinical Trial.gov, NCT04641585. Registered 17 November 2020, https://clinicaltrials.gov/ct2/show/NCT04641585.

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.

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.

Unlocked versus dynamic and static distal locked femoral nails in stable and unstable intertrochanteric fractures. A prospective study.

INTRODUCTION: Few clinical studies have analyzed the utility of distal interlocking screws in stable and unstable intertrochanteric fractures treated with intramedullary devices. We performed a prospective analysis comparing short unlocked versus short dynamic and short static distal locked intramedullary nails. MATERIALS AND METHODS: Nine level-II trauma centres were involved in the study. 240 patients over the age of 65 with a stable (AO/OTA 31-A1) or unstable intertrochanteric fracture (AO/OTA 31-A2) were prospectively investigated. The same type of nail was used in every patient. Patients were randomly divided into 3 groups according to the type of distal locking used. Intra-operative variables were examined and patients were followed clinically and radiographically at 1, 3, 6, 12 months postoperatively. All complications were recorded. RESULTS: A total of 212 patients completed 1 year of follow-up visits. In the Unlocking Group (UG) the operation time, blood loss, fluoroscopy time, total length of incision were significantly decreased compared to both the Dynamic Group (DG) and the Static Group (SG) (p < 0.05). Conversely, no reliable differences in intraoperative variables were noted between the Dynamic Group and the Static Group (p > 0.05). In terms of time of fracture union we found no differences among the three Groups (p > 0.05). Moreover, no cases of limb shortening >1 cm or varus collapse were detected in any group. The 3 Groups were similar in terms of HHS, SF-12 and Barthel index results at 1-year follow-up (p > 0.05). Finally, no significant differences were demonstrated across the three Groups in terms of major complications. CONCLUSIONS: This clinical study further confirms the hypothesis that short intramedullary nails do not need to be locked for stable and unstable intertrochanteric fractures.

Acetabular fractures: Is it possible to regain the same patient's related quality of life before trauma?

INTRODUCTION: acetabular fractures are difficult to treat with often an unsatisfactory results for patients. The aim of this study is to investigate about the health-related quality-of-life outcome of patients with a traumatic acetabular fracture, as recorded at least 24 months after their surgery. METHODS: a cohort of patients underwent a dedicated acetabular surgical reconstruction for a pelvic trauma between November 2011 and May 2016, were enrolled to investigate, at least two years after injury, their midterm quality of life; SF-36 and LiSat-11 were used. RESULTS: 35 patients were enrolled but only 28 patients were revisited, 20 males (714%) and 8 females (286%) with a mean age of 43 years (19-73). The most common cause was motor vehicle accident (655%). Lower score after trauma are reported in both tests, SF-36 and LiSat 11, for all items. DISCUSSION: comparing the SF-36 score in the Italian normative sample with our SF-36 score before the trauma there is no statistically significant difference (p = 0.1661) underlining how the patients before the trauma were healthy and in good health. Both scores, SF-36 and LiSat-11, before and after trauma are statistically different with respectively p = 0,0002 and p = 0,049 which proves the lower quality of life after trauma in comparison to their life before trauma. CONCLUSIONS: Although the treatment protocols of acetabular fractures have greatly improved over the years, these continue to have disabling consequences that hardly allow to recover a good quality of life two years after the trauma.

Evaluation of long-term postoperative outcomes between mini-open and arthroscopic repair for isolated supraspinatus tears: a retrospective analysis.

BACKGROUND: Despite arthroscopic repair of the rotator cuff is an increasingly popular procedure, the mini-open (MO) repair still remains a viable and appreciated technique. The purpose of the study was to analyze the long-term clinical outcomes of patients with isolated supraspinatus tear undergoing MO or arthroscopic surgery (AS) repair. PATIENTS AND METHODS: Forty-six patients underwent supraspinatus repair with anchors: 24 with MO technique and 22 with AS procedure. They were evaluated postoperatively at 3, 6, 12 months and 2 years. RESULTS: The mean surgery time, the mean hospital stay and the average costs were shorter in the MO patients respect to the AS group. Despite an initial better Disabilities of Arm, Shoulder and Hand and Constant Murley Score in the first 6 months of follow-up in the AS group, no differences were detected at 24 months. CONCLUSION: This study suggests that isolated supraspinatus tears can be treated with a MO or arthroscopic repair procedure with similar clinical outcome in the long-term postoperative period. The mean surgery time and the average costs are less in the MO group respect to the AS group.

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.

Autologous lipotransfer versus stromal vascular fraction enriched lipoinjection for diabetic foot wounds healing: a pilot study.

Chronic ulcers of the lower limbs represent a significant social and economic burden. Diabetes is a strong risk factor for development of chronic lesions. Adult stem cells and growth factors derived from the adipose tissue are among the most promising therapeutic strategies for hard to heal wounds. Fat grafts have been used for several decades to treat soft tissue deformities, but despite its excellent characteristics, the outcome was unpredictable, due to partial necrosis and resorption of the graft. Stem cells' enrichment of these grafts or their injection into the edges of the ulcers have shown encouraging results in various experimental settings. In this pilot study, we compared the standard of care to autologous lipotransfer and stromal vascular fraction (SVF) enriched lipoinjection in 30 patients with diabetic foot ulcers, showing clear superiority of SVF enriched lipoinjection in terms of percentage of reduction of ulcers size and healing time.

Ceramic Total Knee Arthroplasty: Ready to Go?

Total knee arthroplasty (TKA) is a well-established surgical procedure in the late stages of knee osteoarthritis. Nevertheless, this procedure is associated with a percentage of unsatisfactory results and biomechanical failures, with aseptic loosening being the most common cause of revision. Beside these problems, cutaneous and systemic hypersensitivity reactions to metals have arisen as an increasing concern after joint arthroplasties, even if allergies against implant materials are still a quite rare and not well-known problem. Ceramic composites have been recently used in prosthetic components, showing minimum wear and excellent long-term results in total hip replacement, due to their high resistance to scratching and their better wettability with respect to cobalt-chromium alloy. Furthermore, the biologic response to debris generated from these bearings is less aggressive. Knee joint simulator tests and clinical results demonstrate promising results of TKAs with ceramic components that should led to benefit for the patients.

Restoring the femoral offset prevent early migration of the stem in total hip arthroplasty: an EBRA-FCA study.

The use of modular stems is still debated and controversial. Some authors have highlighted a number of disadvantages of modular prostheses including high costs, the tendency to fracture, the fretting and corrosion and the increased production of debris. Other authors have emphasized several advantages to adapt the prosthesis to the morphometric differences of patients, to allow better accuracy in restoring the anatomy and biomechanics of hip joint. The advantages of the modular devices appear to be more evident in patients with developmental dysplasia of the hip (DDH). In our study we compared 96 patients, operated for arthritis of the hip with 55 modular neck prostheses (PROFEMUR®, Wright® Arlington, Tennesse, USA) and 41 standard femoral stems (SYMAX®, Striker® Kalamazoo, Michigan, USA). The precision of restoring the natural offset during surgery was correlated with the clinical outcome and the radiological early migration of each stem measured using the computer-assisted EBRA-FCA method. The average preoperative HHS (Harris Hip Score) was 44 (23-66); the postoperative 86.56 in the 55 patients operated with modular prostheses and 81.70 in the 41 patients with monoblock stem. The worst HH Scores were seen in patients in whom the offset was not restored properly. On the contrary, the best scores have been reached in patients in which that value is closer to the “target” value (offset value of the contralateral hip). Restoring the proper offset seems to determine an appropriate tension of the abductor muscles of the hip and implies a better functioning of the joint and a better primary stability of the implant, with less early migration. This has to be a primary objective of THA surgery.

The treatment of distal third humeral diaphyseal fractures: Is there still a place for the external fixation?

INTRODUCTION: The treatment for humeral diaphyseal fractures is still controversial. The purpose of this study was to evaluate the clinical and radiographic outcomes of treating humeral distal third diaphyseal fractures by using external fixation technique. MATERIALS AND METHODS: We retrospectively review 65 cases of diaphyseal humeral fractures (31 type A, 23 type B and 11 type C of the AO/OTA classification) treated with external fixation (Orthofix FAD small) between 2008 and 2013. The mean follow-up was 48 months (24-72 months). There were 12 open fractures; however, no cases of concomitant vascular injury were described. The transolecranic traction was always applied to promote partial reduction through ligamentotaxis. In case of interposition of soft tissues impeding reduction, a small incision was performed allowing mobilization of bone ends. RESULTS: All fractures resulted healed at a mean of 11 weeks (range 9-13 weeks); the average time of removal of the external fixator was 88 days (range 65-95 days). At the last follow-up, the mean elbow flexion was 132.6° (Min 126°-Max 137°) and the mean elbow extension was 6.4° (Max 0°-Min 13°). The Cassebaum's index rated as excellent in 47.8 % (31 patients), good in 37 % (24 patients), fair in 9.2 % (6 patients) and poor in 6 % (4 patients). The mean DASH score at the final follow-up was 14.7 (range 0-33); 15 patients had a range score between 10 and 20, 43 had less than 10, and seven had more than 20. We observed three cases of superficial infections and two cases of acute radial nerve palsy recovered within 3 months. CONCLUSION: According to the excellent clinical results and full rate of consolidation, we state external fixation as a valid option in the treatment of distal third humeral diaphyseal fractures.

Thyroid and shoulder diseases: the bases of a linked channel.

The association between thyroid disorders and musculoskeletal diseases has long been suspected, but it is still debated whether they have a role in the pathogenesis of shoulder diseases. In vivo and in vitro studies describe the role of thyroid hormones in bone, cartilage and tendon biology. Retrospective studies and case reports suggest that thyroid diseases should be considered as risk factors and hold prognostic value in some of the most common causes of shoulder pain. Thus, it is advisable to search for underlying thyroid disorders in these patients. The pathophysiologic mechanisms by which thyroid hormone imbalance affects the onset, progression and response to treatment of these diseases are yet to be thoroughly defined and demand further studies.

Is distal locking with short intramedullary nails necessary in stable pertrochanteric fractures? A prospective, multicentre, randomised study.

We investigated whether a proximal femoral nail can be implanted without a distal locking screw in AO/OTA 31-A1 and 31-A2 pertrochanteric stable femur fractures. A multicentre, randomised study was conducted in six level-two trauma centres in our area (Puglia, Italy). A total of 333 patients received their allocated intervention (162 in the locking group [LG] and 171 in the unlocking group [UG]) and 266 patients were included in the final analysis at 1year. Our data showed no statistically significant difference between the two groups at 1-year follow-up for ability to walk, SF-36 questionnaire results, residual pain (visual analogue scale [VAS] score) and level of overall satisfaction. There were also no statistically significant differences between groups for mortality and length of hospital stay. Conversely, the UG was associated with shorter operation and fluoroscopy times, shorter surgical incision length, and less blood loss and residual thigh pain. Pertrochanteric stable fractures (31-A1, 31-A2) can be treated successfully with intramedullary nails without distal locking, reducing patient and clinical personnel radiation exposure and sanitary costs (surgery time and screws costs).