Mesenchymal Stem Cells and Secretome as a New Possible Approach to Treat Cartilage Damage: An In Vitro Study.

Introduction: Osteoarthritis is a degenerative condition of the cartilage, often common among the population and occurs frequently with aging. Many factors are decisive for the development of its pathogenesis such as age, obesity, trauma, mechanical load, and modification of synovial biology. The main features of osteoarthritis are chondrocytes and cartilage matrix loss, which lead to pain, loss of function of the whole joint, and disability, representing a relevant health problem. Recently, a new therapeutic approach based on cell therapy has been studying the regenerative ability of mesenchymal stem cells for osteoarthritic chondrocytes. Aim: This in vitro study clarifies the regenerative effects of multipotent adipose-derived stem cells and the pluripotent amniotic epithelial stem cells on arthrosis chondrocytes by performing co-culture experiments. Methods: We studied the regenerative potential of secretome (soluble factors and extracellular vesicles), mesenchymal stem cells, and the adipose stromal vascular fraction. The regenerative effects were evaluated by gene and protein expression analysis of articular cartilage-specific genes and proteins like col2a1, acan, and sox9. Results: Mesenchymal stem cells, secretome, and adipose stromal vascular fractions influenced the cartilage genes and protein expression. Conclusions: The results indicate that the treatment with mesenchymal stem cells could be the best biological approach for cartilage regenerative medicine.

The use of a large diameter glenosphere in Reverse Shoulder Arthroplasty for proximal humeral fractures in elderly patients undergoing tuberosity removal.

BACKGROUND AND AIM: Prosthetic replacement with reverse shoulder arthroplasty (RSA) is commonly indicated for complex proximal humerus fractures (PHFs) in elderly patients. Aim of this study was to evaluate the clinical and radiological outcomes of RSA performed for comminuted PHFs, without periprosthetic reconstruction of the tuberosities. Our hypothesis was that a large diameter glenosphere could ensure satisfactory RSA mobility and stability, regardless of tuberosity removal. METHODS: We selected 32 patients (4 men, 28 women) with comminuted PHFs who underwent RSA with tuberosity excision and implantation of a 44-mm glenosphere between 2009 and 2015. Active range of motion (ROM), stability, Constant-Murley Score (CMS) (1) and Subjective Shoulder Value (SSV) (2) were assessed one year and four years after surgery. RESULTS: Clinical and radiological information were collected for 23 patients (72%). At one-year follow-up, active anterior elevation (AE) was 96±28 degrees, external rotation with adducted arm (ER1) 9±7 degrees, external rotation with abducted arm (ER2) 14±10 degrees, internal rotation (IR) to L4; CMS was 56±10 and SSV 65±22. Clinical assessment at 4-year follow up showed a decrease in active ROM (AE was 88±20 degrees, ER1 8±2 degrees, ER2 12±10 degrees, IR to L4), CMS (52±9) and SSV (62±8). No RSA dislocation occurred during the study. In 4 patients, grade I glenoid notching without any sign of component loosening was observed 4 years after surgery. CONCLUSIONS: A large diameter glenosphere does not ensure results comparable to those achieved after RSA with tuberosity reconstruction. However, the 44-mm glenosphere was effective in preventing RSA instability.

The Role of PEMFs on Bone Healing: An In Vitro Study.

Bone responses to pulsed electromagnetic fields (PEMFs) have been extensively studied by using devices that expose bone cells to PEMFs to stimulate extracellular matrix (ECM) synthesis for bone and cartilage repair. The aim of this work was to highlight in which bone healing phase PEMFs exert their action. Specifically, we evaluated the effects of PEMFs both on human adipose mesenchymal stem cells (hASCs) and on primary human osteoblasts (hOBs) by testing gene and protein expression of early bone markers (on hASCs) and the synthesis of late bone-specific proteins (on hOBs) as markers of bone remodeling. Our results indicate that PEMFs seem to exert their action on bone formation, acting on osteogenic precursors (hASCs) and inducing the commitment towards the differentiation pathways, unlike mature and terminally differentiated cells (hOBs), which are known to resist homeostasis perturbation more and seem to be much less responsive than mesenchymal stem cells. Understanding the role of PEMFs on bone regenerative processes provides important details for their clinical application.

Detection of SARS-CoV-2 in Cancellous Bone of Patients with COVID-19 Disease Undergoing Orthopedic Surgery: Laboratory Findings and Clinical Applications.

An emerging issue for orthopedic surgeons is how to manage patients with active or previous COVID-19 disease, avoiding any major risks for the surgeons and the O.R. personnel. This monocentric prospective observational study aims to assess the prevalence of SARS-CoV-2 viral RT-PCR RNA in cancellous bone samples in patients with active or previous COVID-19 disease. We collected data about 30 consecutive patients from our institution from January 2021 to March 2021 with active or previous COVID-19 disease. The presence of SARS-CoV-2 in the samples was determined using two different PCR-based assays. Eighteen of the thirty patients included in the study had a positive nasopharyngeal swab at the time of surgery. Twelve patients had a negative nasopharyngeal swab with a mean days since negativization of 138 ± 104 days, ranging from 23 to 331 days. Mean days of positivity to the nasal swab were 17 ± 17. Twenty-nine out of thirty (96.7%) samples were negative for the presence of SARS-CoV-2 RNA. In one sample, low SARS-CoV-2 load (Cycle threshold (Ct) 36.6.) was detected but not confirmed using an additional confirmatory assay. The conducted study demonstrates the absence of the viral genome within the analyzed cancellous bone. We think that the use of personal protection equipment (PPE) to only protect from aerosol produced during surgery, both in active and recovered patients, is not strictly necessary. We think that the use of PPE should not be employed by surgeons and the O.R. personnel to protect themselves from aerosols produced from the respiratory tract. Moreover, we think that our results could represent a valid basis for further studies related to the possibility of bone donation in patients that suffered and recovered from COVID-19.

Fast Functional Rehabilitation Protocol versus Plaster Cast Immobilization Protocol after Achilles Tendon Tenorrhaphy: Is It Different? Clinical, Ultrasonographic, and Elastographic Comparison.

BACKGROUND: the incidence of Achilles tendon (AT) rupture is rising; however, there is no clear consensus regarding the optimal treatment. The aim of this retrospective study was to compare instrumental and patient-reported outcome scores after fast functional rehabilitation (group A) versus plaster cast immobilization (group B) programs in patients who underwent AT tenorrhaphy. METHODS: 33 patients, with similar clinical and demographic features, underwent open AT tenorrhaphy between January and July 2018. Of these, 15 patients were treated with fast functional rehabilitation program (group A), and 18 patients were treated with plaster cast immobilization protocol (group B). Sural triceps hypotrophy and functional scores (American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score, and Achilles tendon Total Rupture Score (ATRS)) were recorded at a 12-month follow-up. Ultrasonography (US) and elastosonography (ES) were used to compare the characteristics of the tendons after surgery. RESULTS: At 12 months, no significant differences in any of the patient-reported outcomes or the instrumental measurement tests were seen between the two groups. CONCLUSIONS: fast functional rehabilitation after AT surgical repair is safe, effective, and may be the first choice of treatment, especially in young, collaborative, and active patients.

Functional outcome of arthroscopic debridement for massive, irreparable rotator cuff tears.

Rotator cuff tears are a common cause of shoulder pain in the middle-aged population. The treatment of these lesions must be individualized on the basis of the type of patient, the clinical and anatomical picture. Arthroscopic debridement is indicated in painful massive tears, in the absence of severe functional impairment of the shoulder. The aim of this study is the evaluation of the medium term clinical results of this procedure.  We retrospectively assessed patients who underwent arthroscopic debridement surgery for massive rotator cuff injury in the period between January 2011 and December 2016 at our institution. A group of patients underwent a follow-up evaluation during which the Constant Score, Oxford Shoulder Score and NRS pain score were compiled. Those who were unable to attend the evaluation were assessed through a telephone questionnaire aimed at investigating pain and degree of satisfaction with the  treatment.  93% of patients were satisfied with the results obtained, with an average NRS of 1.31 for patients undergoing the medical examination and 0.68 for patients contacted by telephone. The mean Constant score of the evaluated patients was 75.6 ± sd, with a mean strength of 3.92 ± sd, while the mean value of the Oxford Shoulder Score was 16.8 ± sd.  The study suggests that arthroscopic debridement is a viable option for the surgical treatment of massive rotator cuff tears. The clinical results and patient satisfaction are conditioned by the preoperative functional status: an optimal outcome can be expected for painful shoulders with sufficiently preserved active mobility.

Optimization of transdisciplinary management of elderly with femur proximal extremity fracture: A patient-tailored plan from orthopaedics to rehabilitation.

Fractures of femur proximal extremity (FFPE) are the most common fragility fractures requiring hospitalization, with a high risk of mortality, low independence in the activities of daily living and severe consequences on health-related quality of life. Timing for surgery has a key role in the management of elderly patients with FFPE as recommended by the Australian and New Zealand guidelines and the National Institute for Health and Care Excellence guidelines. Early surgery (within 48 h from hospital admission) allows significant benefits in terms of lower rates of postoperative complications and risk of death and can provide better functional outcomes. Therefore, time for surgery could be considered as a comorbidity marker. The choice between conservative or surgical approach surprisingly seems to be still not strongly supported by available literature, but it seems that both 30 d and 1 year risk of mortality is higher with the conservative treatment rather than with surgery. In light of these considerations, the optimization of FFPE management care is mandatory to improve functional outcomes and to reduce sanitary costs. Albeit it is widely accepted that transdisciplinary approach to patients suffering from FFPE is mandatory to optimize both short-term and long-term outcomes, the feasibility of a comprehensive approach in clinical practice is still a challenge. In particular, the large variability of figures involved could be considered both a resource and an additional disadvantage taking into account the difficulty to coordinate multidisciplinary approach covering care in all settings. Therefore, the aim of the present article was to summarize current evidence supporting transdisciplinary management of patients with FFPE, highlighting the benefits, feasibility and limitations of this approach.

Osteosynthesis devices in absorbable Magnesium alloy in comparison to standard ones: a Systematic Review on effectiveness and safety.

BACKGROUND AND AIM OF THE WORK: Magnesium (Mg) is a metal physiologically present in bone tissue and essential for bone health. Mg-based-alloys exhibit mechanical properties, namely density and strength, similar to human cortical bone. These features have been exploited for the development of osteosynthesis devices in biodegradable Mg-based-alloys. Accordingly, the aim of this study was to rank the effectiveness and safety of Mg-based alloys applied in bone surgery in comparison to other suitable metals, focusing in particular on Mg superior biocompatibility and biodegradability. METHODS: a systematic-review of the literature was conducted including only primary research studies dealing with patients suffering from fractured or osteotomized bones fixed using Mg-based osteosynthesis-devices. RESULTS: literature revision suggested Mg-alloys holding comparable properties and side effects in comparison with titanium (Ti) screws, thus showing similar efficacy and safety. In particular, the gas formation in the carpal bones was identified as the main side effect of the Mg-alloys, during the corrosion/degradation phase of Mg. CONCLUSIONS: according to the considered literature, the main advantages exploiting Mg-alloys for bone implants are related to their biocompatibility, bio-absorbability/-degradability, the lack of surgical removal, osteoconductivity and antibacterial activity. On the opposite, the main limitation of Mg-alloys is due to the poor mechanical resistance of small devices for internal fixation of bone fragments that lack of sufficient strength to withstand high forces. Therefore, an important future prospect could rely in the development of innovative hybrid systems aimed at fixing high load-bearing fractures, as well as in regenerative-medicine by developing new Mg-based engineered scaffolds.

Arthroscopically-assisted Reduction and Internal Fixation (ARIF) of tibial plateau fractures: clinical and radiographic medium-term follow-up.

BACKGROUND AND AIM OF THE WORK: Tibial plateau fractures include a wide spectrum of lesions with potentially disabling sequelae. Arthroscopically-assisted Reduction and Internal Fixation (ARIF) is an alternative to traditional ORIF. The aim of this retrospective single centre study is to evaluate medium-term clinical and radiographic outcomes achieved in a consecutive series of patients treated with ARIF. METHODS: 21 patients, with a mean age of 52.2 ± 13.4 years at surgery, were included. According to Schatzker classification, there were 9 type II, 10 type III, 2 type IV fractures. Associated intra-articular injuries (meniscal tears, tibial spine fractures, chondral lesions) were detected in 8 patients. At follow up, patients were clinically and radiographically evaluated according to knee ROM, KOOS, OKS and Rasmussen Clinical and Radiological Scores. RESULTS: At an average follow-up of 84 ± 22.5 months, 18 patients were evaluated. Mean values recorded were the following: knee ROM 1° - 135°, OKS 41.6 / 48 ± 8.18, subscale KOOS scores ranged from 75% ± 25.4 (Quality of Life) to 91.1% ± 11.2 (Pain), Rasmussen Clinical e Radiological 27.2 ± 2.64 (14 excellent, 3 good, 1 fair) and 9.1 ± 0.64 (15 excellent, 3 good) respectively. Worse results were observed in 5 patients with pre-existing degenerative chondropathy. CONCLUSIONS: ARIF revealed to be an effective technique for surgical treatment of unicondylar tibial plateau fractures. Our findings support the favourable results reported by other authors. ARIF is not a simple technique and requiresspecific experience in knee arthroscopy and a steep learning curve.(www.actabiomedica.it).

Indications and results of osteosynthesis for proximal humerus fragility fractures in elderly patients.

Proximal humerus fractures (PHF) are common injuries in the elderly population. Conservative treatment is indicated for undisplaced and stable fractures, which account for almost 80% of the cases. More complex fracture patterns might need surgery, with a wide variety of indication criteria and surgical techniques described in the literature. Surgical treatment should be reserved for patients in good clinical conditions, autonomous in daily living activities and able to adhere to postoperative rehabilitation protocols. In the elderly population with severe osteoporosis, cognitive impairment and clinical comorbidities, the risk of surgical failures is high. In these patients, the choice between surgical and conservative treatment, as well as for the type of procedure, is even more difficult, with no general consensus in the literature. Final indication is usually conditioned by surgeon's experience and preference. Two independent reviewers (B.H and G.G) independently extracted studies on proximal humeral fractures. All selected studies were screened independently (B.H and G.G) based on title and abstract. Then the full text of any article that either judged potentially eligible was acquired and reviewed again. Any disagreement was resolved by discussing the full text manuscripts. Aim of the present paper is to review the literature about indications and results of osteosynthesis for proximal humerus fragility fractures in the elderly population.

Short-Term Outcomes of the Grammont Reverse Shoulder Arthroplasty: Comparison between First and Second Generation Delta Prosthesis.

Purpose This article compares short-term outcomes of two series of patients, who underwent reverse total shoulder arthroplasty (RTSA) with two different implants, both based on Grammont's principles: the Delta III (D-3) and the Delta Xtend (D-XT) prostheses. Methods The D-3 group included a consecutive series of 26 patients (mean age 75 years), that were treated between 2000 and 2006; the D-XT group included a consecutive series of 31 patients (mean age 72.5 years), for a total of 33 implants performed between 2011 and 2015. In both groups the most common diagnoses were cuff tear arthropathy (18 and 22 shoulders, respectively) and malunion of proximal humerus fractures (3 and 5). All procedures were performed by the same surgeon. Constant-Murley score (CMS) was used to assess clinical and functional outcomes. Radiographic evaluation included the true anteroposterior and axillary views. Results Twenty-three patients of the D-3 group and 22 patients (24 shoulders) of the D-XT group were evaluated at a mean follow-up of 42 months (range 26-84) and 44 months (range 26-66), respectively. Four complications occurred in the D-3 group (1 partial deltoid detachment, 1 dislocation, and 2 glenoid component loosening), while one early postoperative infection occurred in the D-XT group. Increases in elevation and CMS between preoperative and postoperative period were observed in both groups; only the D-XT group showed a slight improvement in rotations. The incidence of scapular notching was significantly different between the two groups: 100% for D-3 and 22.2% for D-XT in patients with a minimum follow-up of 5 years. Conclusion Prosthetic design evolution and greater acquaintance with this surgery have undoubtedly led to an improvement in short-term outcomes with second generation implants of RTSA. Future studies will have to ascertain whether newer implants, relying on biomechanical solutions alternative to Grammont's original concept, might provide additional advantages and minimize drawbacks.

Minimally Invasive Plate Osteosynthesis for Proximal Humerus Fractures: A Retrospective Study Describing Principles and Advantages of the Technique.

BACKGROUND: The aim of this study was to evaluate the clinical and radiographic results after minimally invasive plate osteosynthesis (MIPO) for proximal humerus fractures. Potential advantages of this approach include the easier exposure of the greater tuberosity and the limited surgical dissection around the fracture site. MATERIALS AND METHODS: From October 2011 to March 2016, thirty-nine patients (32 women, 7 men) with a mean age of 64.9 years (range: 48-80) were surgically treated with the MIPO technique for proximal humeral fractures. According to Neer classification, there were 12 two-part, 24 three-part, and 2 four-part fractures and 1 two-part fracture-dislocation; the AO/OTA system was also used to categorize the fractures. The Constant-Murley (CMS) and the Oxford Shoulder (OSS) Scores were used to evaluate shoulder function. RESULTS: Thirty-four patients were available for clinical and radiographic evaluation at a mean follow-up of 31.8 months (range: 12-54 months). All fractures healed and no postoperative complications occurred. Full recovery of pretrauma activities was reported by 27 patients, while 7 patients presented mild functional limitations. The mean absolute CMS was 75.2 (range: 55-95), the mean normalized CMS was 90.5 (range: 69-107), and the mean OSS was 43.7 (range: 31-48). The only statistically significant correlation was found between the female gender and lower absolute CMS and OSS. Radiographic evaluation revealed varus malunion in 4 cases and valgus malunion in 1 case, while incomplete greater tuberosity reduction was detected in 4 cases. All malunions were related to inadequate reduction at time of surgery and not to secondary displacement. CONCLUSIONS: MIPO for proximal humeral fractures is an effective and safe surgical procedure. The limited tissue dissection allows minimizing the incidence of nonunion, avascular necrosis, and infection. The technique is not easy, requires experience to achieve mastery, and should be reserved for selected fracture patterns. In our experience, the main advantage of this approach consists in the direct access to the greater tuberosity, thus facilitating its anatomic reduction and fixation.

Role of low field MRI in detecting knee lesions.

Objective The aim of this work is to evaluate the diagnostic accuracy of 0.3T sectoral MR imaging, compared with arthroscopy, for meniscal, cruciate ligaments and chondral knee lesions. Materials and Methods We conducted a retrospective study analyzing all the consecutive knees subjected to arthroscopy at our institution between January 2014 and June 2017 and preceded within 3 months by knee MR examination at our institution with 0.3 T equipment. Patients with history of a new trauma in the time interval between MR exam and arthroscopy were excluded from the study. Two independent experienced radiologists evaluated in double blind the MR findings of menisci, cruciate ligaments and articular cartilage. Both radiological findings were independently compared with those of the arthroscopic report considered as gold standard. For each of the examined targets we calculated the following parameters: sensitivity, specificity, accuracy, positive and negative predictive value; interobserver concordance statistically calculated using Cohen's Kappa test. Results 214 knees (95R/119L) of 214 patients (143M/71F) aged from 18 to 72 years (mean 44) were included and analyzed. We found a good diagnostic accuracy of the low field MR in identifying the injuries of the menisci (93%) and the crossed ligaments (96%), but a lower accuracy for the articular cartilage (85%). Sensitivity resulted 90% for menisci, 73% for ligaments and 58% for cartilage. Specificity was 91% for menisci, 97% for ligaments and 92% for cartilage. Inter-observer concordance resulted to be excellent for cruciate ligaments (K of Cohen's test = 0.832), good (K = 0.768) for menisci, modest to moderate for articular cartilage (K from 0.236 to 0.389) with worse concordance for tibial cartilage. Conclusions Low-field MR sectoral device with dedicated joint equipment confirms its diagnostic reliability for the evaluation of meniscal and cruciate ligaments lesions but is weak in evaluating low grade chondral lesions.

Six-year experience with the Delta III reverse shoulder prosthesis.

PURPOSE: To report the clinical and radiographic results and complications of the Delta III reverse prosthesis. METHODS: 24 women and 2 men aged 62 to 84 (mean, 75) years underwent total shoulder replacement using the Delta III reverse prosthesis. Patient diagnoses were massive rotator cuff tear (n=20), disabling sequelae of proximal humeral fractures (n=3), and failure of an unconstrained arthroplasty (n=3). Clinical and functional results were assessed using the Constant scale. Active range of motion (ROM) was measured. Scapular notching and radiolucent lines around the humeral component were evaluated using radiographs. Patient satisfaction of the treatment was evaluated by a direct interview. RESULTS: 23 patients were followed up for 26 to 84 (mean, 42) months. Two patients had loosening of the glenoid component (at 6 months and 5 years) and underwent revision surgery. There were no instances of infection, instability, or acromial fracture. Only active elevation improved significantly after surgery, as did both the absolute and adjusted Constant scores. 12 patients were completely pain-free, 9 complained of slight pain, and one of moderate pain. The severity of scapular notching progressed with time. 15 patients were satisfied with the treatment, 6 were partially satisfied, and 2 were not satisfied. CONCLUSION: The Delta III prosthesis restores shoulder function but has biomechanical limits. Its use should be limited to elderly patients with severe impairment of the glenohumeral joint. Scapular notching is a main concern for the long-term survival of the implant.

Tissue engineering techniques for the treatment of a complex knee injury.

We report and discuss the use of and rationale for tissue engineering techniques in a 40-year-old sportsman who suffered simultaneous anterior cruciate ligament (ACL) rupture, irreparable medial meniscal tear, and chondral lesion of the medial femoral condyle. A 2-step treatment was adopted to address all lesions. The first procedures consisted of ACL reconstruction and collagen meniscus implant (CMI), followed 6 months later by autologous chondrocyte implantation on a collagen membrane (MACI). A CMI biopsy was performed 6 months after implantation. Histologic and ultrastructural analysis documented scaffold invasion by cells and newly synthesized connective tissue. At 2-year follow up, the clinical and functional results were good and magnetic resonance imaging showed integration of the meniscal and cartilage implants. In this patient, each lesion needed to be addressed to achieve an optimal outcome. The primary goal was to restore normal joint biomechanics by performing CMI and ACL reconstruction. MACI was an adequate solution for the management of the large (5 cm(2)) chondral defect.