Enhanced molecular release from elderly bone samples using collagenase I: insights into fatty acid metabolism alterations.

BACKGROUND: Bone is a metabolically active tissue containing different cell types acting as endocrine targets and effectors. Further, bone is a dynamic depot for calcium, phosphorous and other essential minerals. The tissue matrix is subjected to a constant turnover in response to mechanical/endocrine stimuli. Bone turnover demands high energy levels, making fatty acids a crucial source for the bone cells. However, the current understanding of bone cell metabolism is poor. This is partly due to bone matrix complexity and difficulty in small molecules extraction from bone samples. This study aimed to evaluate the effect of metabolite sequestering from a protein-dominated matrix to increase the quality and amount of metabolomics data in discovering small molecule patterns in pathological conditions. METHODS: Human bone samples were collected from 65 to 85 years old (the elderly age span) patients who underwent hip replacement surgery. Separated cortical and trabecular bone powders were treated with decalcifying, enzymatic (collagenase I and proteinase K) and solvent-based metabolite extraction protocols. The extracted mixtures were analyzed with the high-resolution mass spectrometry (HRMS). Data analysis was performed with XCMS and MetaboAnalystR packages. RESULTS: Fast enzymatic treatment of bone samples before solvent addition led to a significantly higher yield of metabolite extraction. Collagenase I and proteinase K rapid digestion showed more effectiveness in cortical and trabecular bone samples, with a significantly higher rate (2.2 folds) for collagenase I. Further analysis showed significant enrichment in pathways like de novo fatty acid biosynthesis, glycosphingolipid metabolism and fatty acid oxidation-peroxisome. CONCLUSION: This work presents a novel approach for bone sample preparation for HRMS metabolomics. The disruption of bone matrix conformation at the molecular level helps the molecular release into the extracting solvent and, therefore, can lead to higher quality results and trustable biomarker discovery. Our results showed ß-oxidation alteration in the aged bone sample. Future work covering more patients is worthy to identify the effective therapeutics to achieve healthy aging.

Low-density cultured cartilage cells expanded in platelet lysate present distinct features to develop an innovative clinical treatment for diffuse cartilage lesions.

PURPOSE: Chondrocyte-based cell therapies are effective for the treatment of chondral lesions, but remain poorly indicated for diffuse lesions in the context of early osteoarthritis (OA). The aim of this study was to develop a protocol to obtain chondroprogenitor cells suitable for the treatment of diffuse chondral lesions within early OA. METHODS: Cartilage cells were expanded at low density in human platelet lysate (hPL). A test was performed to exclude senescence. The expression of surface cluster of differentiation 146, cluster of differentiation 166, major histocompatibility complex (MHC)-I and MHC-II and of genes of interest were evaluated, as well as the trophic potential of these cells, by the assessment of lubricin and matrix production. The immunomodulatory potential was assessed through their co-culture with macrophages. RESULTS: Cartilage cells expanded at low density in hPL showed higher proliferation rate than standard-density cells, no replicative senescence, low immunogenicity and expression of lubricin. Moreover, they presented an increased expression of chondrogenic and antihypertrophic markers, as well as a superior matrix deposition if compared to cells cultured at standard density. Cartilage cells induced on macrophages an upregulation of CD206, although a higher increase of CD163 expression was observed in the presence of low-density cells. CONCLUSIONS: These findings lay the grounds to explore the clinical usefulness of low-density cultured cartilage cells to treat diffuse lesions in early OA joints for both autologous and allogenic use. LEVEL OF EVIDENCE: Not applicable.

Men and women undergoing total hip arthroplasty have different clinical presentations before surgery and different outcomes at 1-year follow-up.

PURPOSE: The purpose of this study was to investigate the influence of sex on patients undergoing total hip arthroplasty (THA) for hip osteoarthritis (HOA), aiming to assess the clinical and functional outcomes using patient-reported outcome measures (PROMs). METHODS: A retrospective analysis of patients undergoing THA at Ospedale Galeazzi-Sant'Ambrogio between 2016 and 2022 was conducted. Inclusion criteria encompassed Kellgren-Lawrence grade III or IV HOA, with preoperative and 12-month postoperative PROMs. Enroled patients have been selected from a larger cohort without matching design for confounders. The analyses were performed using R software v4.0.3 (R Core Team) and data distributions were assessed using the Shapiro-Wilk normality test. RESULTS: One hundred ninety patients (72 male and 118 female) who had both preoperative and postoperative PROMs have been analysed from our institutional prosthesis registry (Datareg). Baseline and 12-month post-THA PROMs showed significant improvements overall. VAS score dropped notably from baseline to 3 months postsurgery (7.1 ± 2.1 vs. 0.9 ± 1.7). Functional and mental PROMs, including Harris Hip Score-functional (HHS-F), Harris Hip Score-total (HHS-t), SF-12PS and SF-12MS, exhibited substantial improvements post-THA. Stratifying by sex, males had lower baseline VAS, higher HHS-F, SF-12MS and hip disability and osteoarthritis outcome score-physical function short form (HOOS-PS). At 12 months, males displayed significantly better VAS, HHS-F, SF-12PS and HOOS-PS scores. Complication rates were minimal (1.5%), with stable rates across genders, mostly involving dislocation and periprosthetic fractures. Implant survival at 12 months reached an impressive 99%. CONCLUSION: THA remains an effective treatment for severe HOA. However, females presented with worse baseline conditions and showed relatively less improvement at 1-year postsurgery compared to males. This difference could be attributed to physiological and psychosocial factors associated with sex, including hormonal changes, muscle mass decline and perception of pain. Longer follow-ups and prospective studies are necessary to validate these findings and facilitate personalised approaches in HOA treatment, emphasising the need for careful consideration of sex-related variables in clinical decision-making for THA patients. LEVEL OF EVIDENCE: Level III.

High incidence of RAMP lesions and a nonnegligible incidence of anterolateral ligament and posterior oblique ligament rupture in acute ACL injury.

PURPOSE: The purpose of this study was to assess the frequency of medial collateral ligament (MCL), posterior oblique ligament (POL) and anterolateral ligament (ALL) tears and different types of RAMP lesions of patients with verified acute anterior cruciate ligament (ACL) tears by magnetic resonance imaging (MRI). METHODS: MRI was performed on patients with a clinical diagnosis of acute ACL injury. Patients were eligible for inclusion if they had an initially clinically noted ACL tear confirmed on MRI within 30 days of trauma. RESULTS: A total of 146 patients were included in the study, 42 (28.8%) females and 104 (71.2%) males. The mean age at MRI was 27.2 ± 9.4 years, and the mean time from injury to MRI was 15.7 ± 7.8 days. Thirty-four (23.3%) patients had a complete MCL lesion, 32 (21.9%) had a complete POL lesion and 28 (19.2%) had a complete ALL lesion. One hundred and fourteen patients (78.1%) presented with RAMP lesions, while 20 (13.7%) patients reported other meniscal lesions. The mean medial and lateral tibial slopes were 4.0° ± 2.7° and 4.0° ± 3.1°, respectively. Only 10 (6.8%) patients reported no lesions associated with ACL rupture. The most common injuries were isolated RAMP type 3 (18-12.3%) and isolated RAMP type 1 (17-11.6%). Thirteen (8.9%) patients had a combination of MCL, POL and ALL rupture. CONCLUSIONS: Isolated lesions of the ACL are extremely rare. In most cases, a single RAMP lesion should be investigated. In the presence of MCL injury, POL injury should always be suspected as well, while nearly 20% of patients present a rupture of the ALL. About one in 10 patients had three lesions (MCL, ALL and POL), and most of them had a combined RAMP lesion. LEVEL OF EVIDENCE: Level IV.

A high level of scientific evidence is available to guide treatment of primary shoulder stiffness: The SIAGASCOT consensus.

PURPOSE: Shoulder stiffness (SS) is a condition characterised by active and passive restricted glenohumeral range of motion, which can occur spontaneously in an idiopathic manner or be associated with a known underlying aetiology. Several treatment options are available and currently no consensus has been obtained on which treatment algorithm represents the best choice for the patient. Herein we present the results of a national consensus on the treatment of primary SS. METHODS: The project followed the modified Delphi consensus process, involving a steering, a rating and a peer-review group. Sixteen questions were generated and subsequently answered by the steering group after a thorough literature search. A rating group composed by professionals specialised in the diagnosis and treatment of shoulder pathologies rated the question-answer sets according to the scientific evidence and their clinical experience. RESULTS: Recommendations were rated with an average of 8.4 points out of maximum 9 points. None of the 16 answers received a rating of less than 8 and all the answers were considered as appropriate. The majority of responses were assessed as Grade A, signifying a substantial availability of scientific evidence to guide treatment and support recommendations encompassing diagnostics, physiotherapy, electrophysical agents, oral and injective medical therapies, as well as surgical interventions for primary SS. CONCLUSIONS: A consensus regarding the conservative and surgical treatment of primary SS could be achieved at a national level. This consensus sets basis for evidence-based clinical practice in the management of primary SS and can serve as a model for similar initiatives and adaptable guidelines in other European countries and potentially on a global scale. LEVEL OF EVIDENCE: Level I.

Italian research on anterior cruciate ligament: a bibliometric analysis.

INTRODUCTION: This study analysed the trend of publications on anterior cruciate ligament (ACL) in Italy. It was hypothesised that publications on this topic have quickly increased in recent years due to increased knowledge of both clinical and radiological pathology. METHODS: PubMed and Scopus were accessed on 29/11/2023. This retrieved 838 articles from PubMed and 1050 from Scopus. We analysed the top 10 authors, and journals in publication numbers, citation numbers, and citations per year. We have also looked at the top 10 institutions publishing on anterior cruciate ligament from Scopus as PubMed does not give this information in the output. Data mining was performed using the Orange software, Mac version 3.32.0 ( https://orangedatamining.com/ ) from the titles of all articles. A word cloud analysis of titles, authors, journals and universities was performed. RESULTS: The peak of citations was in 2017 with 1529, whilst the peak of publications was in 2019 with 59 articles published. Analysing the number of publications and citations for the journal, the most impacted journal is Knee Surgery, Sports Traumatology, Arthroscopy with 5472 citations and 183 articles, followed by The American Journal of Sports Medicine, with 2722 citations and 56 articles and Arthroscopy with 1990 citations and 62 articles. Considering also international collaborations, the most cited author is Della Villa F. in 2020 with 43.67 citations per year. The Italian author with the major number of publications is Zaffagnini S. with 39 articles, whilst the author with the higher number of citations is Aglietti P. with 1612 citations. CONCLUSIONS: ACL reconstruction has gained growing interest amongst the scientific community. Publications and citations presented a rising trend, the majority of the highly cited papers were contributed by few centres, and clinical trials were the most cited study designs. The long-term outcomes of ACL lesions have attracted interest. The authors hypothesised that shortly there will be an increase in articles analysing the results of ACL revisions, the use of lateral extra-articular tenodesis, and meniscus transplants. LEVEL OF EVIDENCE IV: Cross-Sectional Study.

One-stage vs two-stage bilateral THA in Lombardy: a cost-effectiveness analysis.

BACKGROUND: Total hip arthroplasty (THA) is the most common treatment for primary and secondary end-stage hip osteoarthritis (OA). Almost 20% of all patients undergoing primary THA suffer from bilateral hip OA and, consequently, will need a contralateral procedure to be performed in the following years. The aim of this study is to evaluate the cost-effectiveness and the reliability of one-stage bilateral THA (1-BTHA) compared to two-stage bilateral THA (2-BTHA), in low-risk patients, performed with anterior minimally invasive surgery (AMIS). METHODS: Single patient's costs were obtained by dividing the annual costs report by the number of hospitalizations, considering the diagnosis related group (DRG) of the two procedures. Then, 16 patients undergoing 1-BTHA and 8 undergoing 2-BTHA were examined. Hemoglobin (Hb) values before surgery and before discharge, transfusion rate and the occurrence of post-operative complications were observed. RESULTS: Procedural costs were divided in different subgroups: pre-hospitalization, operating room, hospital stay, post-operative follow-up and other costs. 1-BTHA total costs amount to 5.754,82€, while performing 2-BTHA costs 7.624,32€. However, considering DRG reimbursement, the hospital's profit margin following 1-BTHA is lower than that following 2-BTHA (6.346,18€ versus 9.261,68€). Surgical time was found not to be significantly different between 1-BTHA and 2-BTHA (141,13 ± 26,1 min vs 164,8 ± 44,3 min; p = 0,111). The two groups showed a statistically significant difference in Hb decrease (4,8 ± 1,3 g/dl vs 3,3 ± 0,9; p = 0,001), despite no variances in transfusion rate. No further complications were observed in either group. CONCLUSIONS: This study demonstrates how, in carefully selected patients, 1-BTHA performed with AMIS is a cost-effective and safe technique compared to 2-BTHA, resulting in a shorter OR time, LOS and lower overall costs. LEVEL OF EVIDENCE: III.

Good results after treatment of RAMP lesions in association with ACL reconstruction: a systematic review.

PURPOSE: This study aimed to systematically evaluate the clinical, functional, and radiological outcomes, complications, and rate of return to sports among patients with RAMP lesion of the medial meniscus encountered during anterior cruciate ligament (ACL) reconstruction. METHODS: A systematic review was conducted based on the PRISMA guidelines. Two independent reviewers searched the PubMed, Scopus, Embase, and Cochrane Library databases using the terms "ACL" or "anterior cruciate ligament," and "RAMP lesion." The outcome measures extracted from the studies were the Short Form-12 (SF-12) in its mental and physical component (MCS and PCS), Lysholm score, Subjective IKDC, Marx Score, WOMAC Score, Tegner, Radiological changes, complications, failures and/or revision surgery, and rate of return to sports. RESULTS: The cohort of patients consisted of 1,243 participants with a mean age of 28.6 ± 2.6. The mean postoperative follow-up was 40.9 ± 6.3 months. A total of 1145 (92.1%) RAMP lesions were repaired with concomitant ACL reconstruction, while only 98 (7.9%) lesions were left untreated (or treated with abrasion only). The Lysholm score was used in 6 studies (in one only at final follow-up), with a significant improvement in all the studies (Lysholmpre 60.03 ± 6.12; Lysholmpost 89.9 ± 5.0). Eight studies out of nine reported Subjective IKDC score, and a significant improvement was noted in all cases (IKDCpre 56.2 ± 5.8. IKDCpost 84.9 ± 3.7). Of 18 (1.4%) complications reported, 15 (1.2%) were related to RAMP/ACL surgery, and of the remaining three (0.2%) two (0.2%) were hematomas and one (0.1%) a contralateral ACL lesion. Of the 106 (8.5%) revision surgeries required, 5 (0.4%) were in non-treated lesions [two (0.2%) ACL re-ruptures and three (0.2%) medial meniscus re-injury]. In treated patients, the revision occurred for the following reasons: 75 (6.0%) meniscectomy, 14 (1.1%) meniscal suture revisions, 11 (0.9%) ACL failures and one (0.1%) arthrolysis. CONCLUSIONS: It is not yet clear if, in all cases of ACL reconstruction in which a medial meniscal RAMP lesion is encountered, the lesion needs to undergo surgical repair. Accordingly, it is recommended that in the repair of all unstable medial meniscal RAMP lesions during an ACL reconstruction in cases associated with a stable RAMP lesion, the surgeon may decide on repair based on the patient profile. LEVEL OF EVIDENCE: Level IV.

In elite athletes with meniscal injuries, always repair the lateral, think about the medial! A systematic review.

PURPOSE: This study aimed to evaluate and compare the time required to return to sports (RTS) after surgery, the rate of revision surgery and the time required for RTS after revision surgery in elite athletes undergoing meniscal repair or partial meniscectomy, particularly analysing the difference between medial and lateral menisci. It was hypothesised that both procedures would entail similar, high rates of RTS, with the lateral meniscus exhibiting higher potential healing postprocedure compared to the medial meniscus. METHODS: A systematic review was conducted based on the PRISMA guidelines. Quality assessment of the systematic review was performed using the AMSTAR-2 checklist. The following search terms were browsed in the title, abstract and keyword fields: 'meniscus' or 'meniscal' AND 'tear,' 'injury' or 'lesion' AND 'professional,' 'elite' or 'high-level' AND 'athletes,' 'sports,' 'sportsman,' 'soccer,' 'basketball,' 'football' or 'handball'. The resulting measures extracted from the studies were the rate of RTS, level of RTS, complications, revision surgery and subsequent RTS, Tegner, International Knee Documentation Committee (IKDC) and Visual Analogue Scale (VAS). RESULTS: In this study, the cohort consisted of 421 patients [415 (98.6%) men and 6 (1.4%) women] with a mean age of 23.0 ± 3.0 years. All patients were elite athletes in wrestling, baseball, soccer, rugby or handball. While 327 (77.7%) patients received partial meniscectomy at a mean age of 23.3 ± 2.6 years, 94 (22.3%) patients received meniscal repair at a mean age of 22.1 ± 4.0 years. After partial meniscectomy, 277 patients (84.7%) returned to their competitive sports activity and 256 (78.3%) returned to their pre-injury activity levels. A total of 12 (3.7%) patients required revision surgery because of persistent pain [5 (1.5%) patients], chondrolysis [2 (0.7%) patients] or both chondrolysis and lateral instability [5 (1.5%) patients]. Ten (83.3%) of the twelve patients had involvement of the lateral meniscus, whereas the location of injury was not specified in the remaining two patients. After revision surgery, all patients (100%) resumed sports activity. However, after meniscal repair, 80 (85.1%) athletes returned to their competitive sports activity and 71 (75.5%) returned to their pre-injury activity levels. A total of 16 (17.0%) patients required partial meniscectomy in cases of persistent pain or suture failure. Of these, 4 (25%) patients involved lateral and medial menisci each and 8 (50%) patients were not specified. After revision surgery, more than 80.0% of the patients (13) resumed sports activity. CONCLUSIONS: In elite athletes with isolated meniscal injury, partial meniscectomy and meniscal suture exhibited similar rates of RTS and return to pre-injury levels. Nonetheless, athletes required more time for RTS after meniscal repair and exhibited an increased rate of revision surgery associated with a reduced rate of RTS after the subsequent surgery. For lateral meniscus tears, meniscectomy was associated with a high rate of revision surgery and risk of chondrolysis, whereas partial medial meniscectomy allowed for rapid RTS but with the potential risk of developing knee osteoarthritis over the years. The findings of this systematic review suggested a suture on the lateral meniscus in elite athletes because of the high healing potential after the procedure, the reduced risk of developing chondrolysis and the high risk of revision surgery after partial meniscectomy. Furthermore, it is important to evaluate several factors while dealing with the medial meniscus. If rapid RTS activity is needed, a hyperselective meniscectomy is recommended; otherwise, a meniscal suture is recommended to avoid accelerated osteoarthritis. LEVEL OF EVIDENCE: Level IV. STUDY REGISTRATION: PROSPERO-CRD42022351979 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=351979 ).

Similar rate of return to sports activity between posterior-stabilised and cruciate-retaining primary total knee arthroplasty in young and active patient.

PURPOSE: Cruciate-retaining and posterior-stabilised implant designs are available for primary total knee arthroplasty. However, whether the implant design is associated with a difference in the level of activity still remains unclear. This clinical trial compared posterior-stabilised and cruciate-retaining implants in sport-related patient-reported outcome measures, range of motion, rate of return to sport, and weekly time dedicated to sport in active adults. It was also hypothesised that in young and active patients both implants lead to a similar rate of return to sport in terms of hours per week, type of sport, and joint mobility. METHODS: All patients were evaluated preoperatively and for a minimum of 36 months follow-up. The University of California Los Angeles activity scores, High-Activity Arthroplasty Score, and Visual Analogue Scale were administered preoperatively and at the last follow-up. The range of motion was investigated at admission and the last follow-up. Data concerning the hours per week dedicated to sports and the type of sport practiced were also collected at admission and at the last follow-up. The Kaplan-Meier Curve was performed to compare implant survivorship. RESULTS: Data from 227 procedures (cruciate-retaining: 109, posterior-stabilised: 118) were prospectively collected. At the last follow-up, no difference was reported in The University of California Los Angeles activity scores (p = 0.6), High-Activity Arthroplasty Score (p = 0.1), Visual Analogue Scale (p = 0.9), flexion (p = 0.7) and extension (p = 0.4). No difference was found in the rate of return (p = 0.1) and weekly hours dedicated to sport (p = 0.3). The Kaplan-Meier curve evidenced no statistically significant difference in implant survivorship (p = 0.6). CONCLUSIONS: At approximately five years of follow-up, no difference was reported between cruciate-retaining and posterior-stabilised implants in active adults in sport-related patient-reported outcomes measures, range of motion, pain, weekly time dedicated to sport, rate of return to sport, and implant survivorship. LEVEL OF EVIDENCE: Level II, prospective study.

Management of the first episode of traumatic patellar dislocation: an international survey.

PURPOSE: This international survey aimed to evaluate the potential controversies regarding the management of first patellar dislocation amongst experienced knee surgeries in the treatment of the first episode of patellar dislocation without osteochondral fragments. METHODS: An online survey was conducted from February 2021 to December 2021 to assess the global trend in the diagnosis and management of first-time patellar dislocation without osteochondral fragments. The online survey was accessible on the homepage of the website of the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA). The questionnaire consisted of multiple-choice questions and was divided into three sections. The first section consisted of eight questions regarding demographic information, professional activity, and responder experience. The second section consisted of 13 questions regarding the approach to a first patellar dislocation (clinical examination, imaging, and rehabilitation). The third section contained 2 questions concerning the relevance of patient characteristics to the therapeutic algorithm (age, sports, and pathoanatomical predisposing risk factors). RESULTS: A total of 438 orthopaedic surgeons worldwide completed the questionnaire. At the first approach to diagnose a first-time patellar dislocation, 251 (57%) of the surgeons requested plain radiographs, and 158 (36%) requested magnetic resonance imaging (MRI). In conservatively treated patients, 368 (84%) of the respondents recommended the use of a knee brace. Amongst them, 14 (3%) advocated its use for one week, 75 (17%) for two weeks, 123 (28%) for three weeks, 105 (24%) for four weeks, and 97 (22%) for six weeks. In conservatively treated patients, 215 (49%) of the surgeons recommended load to tolerance, 148 (34%) recommended 30% to 60% of the bodyweight, and 75 (17%) advised against weight-bearing. More than half of the surgeons considered a patient aged less than 35 years practising contact sports to be a candidate for the medial patello-femoral ligament (MPFL) procedure. In addition, a tibial tuberosity to trochlear groove distance (TT-TG) distance of 15 to > 20 mm (for > 75% of the surgeons) and a trochlea types C and D (for > 70% of the surgeons) were considered possible indications for direct surgical management. CONCLUSION: At the first approach to diagnose a first-time patellar dislocation, plain radiographs and MRI should be performed. In conservatively treated patients, most of the surgeons recommend weight-bearing to tolerance and a knee brace during the first four weeks, with range of motion of full extension to 30° during the first 15 days and up to 60° for an additional 15 days. Surgical management should be performed in patients in the second and third decades of life practising contact sports and in those patients who present types C and D trochlea dysplasia and patella alta. LEVEL OF EVIDENCE: IV.

Micro-fragmented adipose tissue (mFAT) associated with arthroscopic debridement provides functional improvement in knee osteoarthritis: a randomized controlled trial.

PURPOSE: Current conservative treatments for knee OA provide limited benefits, with symptoms relief for a short amount of time. Regenerative medicine approaches such as the use of microfragmented adipose tissue (mFAT) showed promising results in terms of durable effects and the possibility to enhance tissue healing and counteract the progression of the pathology. Nevertheless, up to today, the large part of clinical data about mFAT use refers to uncontrolled studies, especially in the surgical setting. The purpose of this study was to evaluate the effectiveness of mFAT applied in association with arthroscopic debridement (AD) for the treatment of knee OA, in terms of symptoms relief and tissue healing. METHODS: This study is a prospective, randomized controlled clinical trial. 78 patients affected by knee OA grade 3-4 according to KL classification were randomly assigned to AD or AD + mFAT treatment groups. Clinical, radiological and serological assessments were performed at 6 months after treatment. Additional clinical evaluation was performed at the end of the study with an average follow-up of 26.1 ± 9.5 months. VAS, KOOS, WOMAC and SF-12 were also collected at both timepoints, KSS only at 6 months. RESULTS: Treatment with AD + mFAT improved functional scores at both 6 months (KOOS-PS: + 11.7 ± 20.2 vs + 24.4 ± 22.5, in AD and AD + mFAT, respectively, p = 0.024; KSS: + 14.9 ± 15.9 vs + 24.8 ± 23.5, in AD and AD + mFAT, respectively, p = 0.046) and 24-month follow-ups (KOOS-PS Functional subscale: - 2.0 ± 3.5 vs - 4.7 ± 4.2, in AD and AD + mFAT, respectively, p = 0.012). Lower T2-mapping scores were obtained in AD + mFAT-treated group in medial and lateral condyle compartments (p < 0.001). Slight increase was observed in the levels of a serum biomarker of cartilage deposition (PIIINP) in both groups at 6-month follow-up (p = 0.037). CONCLUSION: mFAT improves functional outcome and MRI appearance when used in association with AD, therefore supporting its use in the treatment of knee OA in an arthroscopic setting.

Regulation of Satellite Cells Functions during Skeletal Muscle Regeneration: A Critical Step in Physiological and Pathological Conditions.

Skeletal muscle regeneration is a complex process involving the generation of new myofibers after trauma, competitive physical activity, or disease. In this context, adult skeletal muscle stem cells, also known as satellite cells (SCs), play a crucial role in regulating muscle tissue homeostasis and activating regeneration. Alterations in their number or function have been associated with various pathological conditions. The main factors involved in the dysregulation of SCs' activity are inflammation, oxidative stress, and fibrosis. This review critically summarizes the current knowledge on the role of SCs in skeletal muscle regeneration. It examines the changes in the activity of SCs in three of the most common and severe muscle disorders: sarcopenia, muscular dystrophy, and cancer cachexia. Understanding the molecular mechanisms involved in their dysregulations is essential for improving current treatments, such as exercise, and developing personalized approaches to reactivate SCs.

Knee Osteoarthritis: Epidemiology, Pathogenesis, and Mesenchymal Stem Cells: What Else Is New? An Update.

Osteoarthritis (OA) is a chronic disease and the most common orthopedic disorder. A vast majority of the social OA burden is related to hips and knees. The prevalence of knee OA varied across studies and such differences are reflected by the heterogeneity of data reported by studies conducted worldwide. A complete understanding of the pathogenetic mechanisms underlying this pathology is essential. The OA inflammatory process starts in the synovial membrane with the activation of the immune system, involving both humoral and cellular mediators. A crucial role in this process is played by the so-called "damage-associated molecular patterns" (DAMPs). Mesenchymal stem cells (MSCs) may be a promising option among all possible therapeutic options. However, many issues are still debated, such as the best cell source, their nature, and the right amount. Further studies are needed to clarify the remaining doubts. This review provides an overview of the most recent and relevant data on the molecular mechanism of cartilage damage in knee OA, including current therapeutic approaches in regenerative medicine.

In Vitro and In Vivo Biocompatibility Assessment of a Thermosensitive Injectable Chitosan-Based Hydrogel for Musculoskeletal Tissue Engineering.

Musculoskeletal impairments, especially cartilage and meniscus lesions, are some of the major contributors to disabilities. Thus, novel tissue engineering strategies are being developed to overcome these issues. In this study, the aim was to investigate the biocompatibility, in vitro and in vivo, of a thermosensitive, injectable chitosan-based hydrogel loaded with three different primary mesenchymal stromal cells. The cell types were human adipose-derived mesenchymal stromal cells (hASCs), human bone marrow stem cells (hBMSCs), and neonatal porcine infrapatellar fat-derived cells (IFPCs). For the in vitro study, the cells were encapsulated in sol-phase hydrogel, and then, analyzed via live/dead assay at 1, 4, 7, and 14 days to compare their capacity to survive in the hydrogel. To assess biocompatibility in vivo, cellularized scaffolds were subcutaneously implanted in the dorsal pouches of nude mice and analyzed at 4 and 12 weeks. Our data showed that all the different cell types survived (the live cell percentages were between 60 and 80 at all time points in vitro) and proliferated in the hydrogel (from very few at 4 weeks to up to 30% at 12 weeks in vivo); moreover, the cell-laden hydrogels did not trigger an immune response in vivo. Hence, our hydrogel formulation showed a favorable profile in terms of safety and biocompatibility, and it may be applied in tissue engineering strategies for cartilage and meniscus repair.

No difference in mobile and fixed bearing partial knee arthroplasty in octogenarians: a clinical trial.

BACKGROUND: A clinical trial comparing MB (mobile-bearing) versus FB (fixed-bearing) in medial partial knee arthroplasty (PKA) in octagenarians has been conducted. The focus of the present study was on PROMs, range of motion (ROM), implant positioning and implants survivorship. The hypothesis of the present study was that MB implants performed better than FB in PKA in octogenarians. METHODS: The first group received FB PKA-PPK®; the second received MB PKA-Oxford. Patients were not randomly allocated. The following PROMs were administered at T0 (pre-operatively), T1 (1 year after surgery), and T2 (3 years after surgery): visual analogue scale (VAS), Knee Society Score (KSS) and Oxford Knee Score (OKS). Data regarding the implant survivorship and ROM were also collected. Furthermore, the following radiographic parameters were measured: Femoral component varus/valgus; Tibial component varus/valgus; Anteroposterior slope. RESULTS: At T0, 28 patients were included in the FB and 33 in the MB group. The surgical time was shorter in the FB group (p < 0.001). No difference between FB and MB in ROM, VAS, KSS, and OKS at each follow-up (p > 0.05). No difference was found in implant positioning (p > 0.05). At last follow-up, FB group reported three failures caused by aseptic loosening. Four failures were observed in the MB cohort: two for bearing dislocation and two for aseptic loosening. The Kaplan-Meier Curve found no differences in implant survivorship. CONCLUSIONS: According to the main findings of the present clinical trial, MB implants performed similar to FB in PKA in octogenarians. The FB group demonstrated shorted surgical time. No difference was found in patient reported outcome measures, ROM, implant positioning, and survivorship. LEVEL OF EVIDENCE: Level II, prospective study.

Successful salvage strategy using anterior retroperitoneal approach in failed posterior lumbar interbody fusion. A retrospective analisys on lumbar lordosis and clinical outcome.

OBJECTIVE: Posterior and transforaminal lumbar interbody fusion (PLIF, TLIF) are among the most popular surgical options for lumbar interbody fusion. If non-union occurs with consequent pain and reduced quality of life, revision surgery should correct any previous technical errors, avoiding further complications. The aim of this study was to analyze technical advantages, radiological and clinical outcomes of anterior approaches (ALIF) in case of failed PLIF or TLIF. METHODS: Retrospective analysis of consecutive patients with persistent low back pain after failed PLIF/TLIF where salvage ALIF through an anterior retroperitoneal miniopen video-assisted technique was performed. Surgical, clinical and radiological data were analysed. Uni and multivariate statistical analysis were applied. RESULTS: Thirty-six patients (average age: 47.1 years) were included. Mean follow-up was 34.4 months. In 30 patients (83.3%) a posterior surgical step was necessary. Non-union (86.1%), cage migration (5.5%), infection (8.3%) were the causes of revision surgery. In 22 patients (61.1%) the involved level was L5-S1, in 12 patients (33.4%) L4-L5, in 1 patient (2.7%) L3-L4. One patient (2.7%) had two levels (L4-L5 and L5-S1) involved. No major intraoperative complications were recorded. Significant correlation between clinical and radiological outcomes (L4-S1 and L5-S1 lordosis improvement) were observed (postoperative VAS and L5-S1, p = 0.038). CONCLUSIONS: Salvage ALIF is a safe option that can significantly ameliorate residual pain achieving primary interbody stability with an ideal segmental lordosis according to pelvic parameters. The advantages of a naive anterior approach fulfils the main objectives of a revision surgery in order to significantly increase the chances of definitive fusion.

Long spine fusions to the sacrum-pelvis are associated with greater post-operative proximal junctional kyphosis angle in sitting position.

STUDY DESIGN: A single-centre retrospective study. BACKGROUND AND PURPOSE: Although adult patients spend most of their time in sitting positions, the assessment of spinopelvic parameters in adult deformity surgery is commonly performed in standing X-rays. Our study compares the standing and sitting sagittal alignment parameters in subjects who underwent thoracolumbar fusion. METHODS: Patients who underwent corrective surgery for adult scoliosis with at least five instrumented vertebra were stratified according to the upper instrumented vertebra (UIV) and pelvic fixation. Group A:UIV proximal to T6 with pelvis fixation. B:UIV lower than T6 and pelvic fixation. Group C: thoracolumbar fusion without pelvic fixation. Post-operative spinopelvic sagittal parameters were measured in both standing and sitting X-rays. RESULTS: A total of 51 patients were enrolled in the study (11:Males and 40:Females). The mean age was 52.3 ± 21.7y/o. The comparison of post-operative standing and sitting X-ray within the group A and B showed that a significant change was observed in terms of JA-Junctional Angle-(Group A 6.3 ± 4.3 vs. 8.1 ± 3.3, p value = 0.03) (Group B 8.5 ± 6.4 vs. 10.9 ± 6.4, p value = 0.02). Group C showed statistically significant difference in terms of PT (15.6 ± 11.2 vs. 19.3 ± 9.2, p value = 0.04), AVA-Acetabular Version Angle-(41.1 ± 5.9 vs. 48.3 ± 6.6, p value < 0.01) and LL (- 51.3 ± 16.0 vs. - 42.6 ± 10.7, p value < 0.01). CONCLUSION: In our series, the post-operative sagittal alignment showed peculiar behaviours and adaptations in sitting position, depending on the length and the site of the instrumented area. If the pelvis is included, the JA tends to significantly increase in sitting position. These findings can improve the knowledge of pathologies as proximal junctional kyphosis or specific cases of anterior hip impingement. LEVEL OF EVIDENCE: IV.

Hamstring tendon autografts and allografts show comparable clinical outcomes and knee stability after anterior cruciate ligament reconstruction in patients over fifty years old with no signs of osteoarthritis progression.

PURPOSE: The aim of this study is to compare the functional outcomes and osteoarthritis (OA) progression after anterior cruciate ligament (ACL) reconstruction with either hamstring autografts or allografts in people over 50. METHODS: The clinical records of two consecutive cohorts of 61 cases in total over 50 years of age, undergoing ACL reconstruction, were included. The first cohort consisted of 29 allografts; the second cohort consisted of 32 autologous hamstring tendon grafts. The cases were evaluated pre- (T0) and post-operatively at six months (T1), 12 months (T2) and 24 months (T3). Clinical examination included the Lachman test, pivot shift test and objective (Objective IKDC [The International Knee Documentation Committee] score) and subjective clinical scores (Subjective IKDC score, Lysholm score and Tegner activity score). The degree of OA was evaluated using the Kellgren-Lawrence system at the time of the final follow-up, compared to the pre-operative condition. RESULTS: No pre-operative difference was found between the two groups (p > 0.05). No statistical difference was noted between the two groups at each follow-up (p > 0.05). At the final follow-up, both the groups significantly improved statistically in all the clinical and functional scores (p < 0.05). In both groups, one graft re-rupture was noted. No progression of OA was noted in both groups at final follow-up (p > 0.05). CONCLUSION: The graft choice does not influence the outcomes two years after ACL reconstruction in people over 50; thus, both treatments help in regaining knee stability with no signs of OA progression. REGISTRATION: Researchregistry7539- www.researchregistry.com .

Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1α.

Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducible factor HIF-1α in sarcopenia. To this end, we obtained skeletal muscle biopsies from elderly sarcopenic patients and compared them with those from young individuals. We found a decrease in the expression of HIF-1α and its target genes in sarcopenia, as well as of PAX7, the major stem cell marker of satellite cells, whereas the atrophy marker MURF1 was increased. We also isolated satellite cells from muscle biopsies and cultured them in vitro. We found that a pharmacological activation of HIF-1α and its target genes caused a reduction in skeletal muscle atrophy and activation of PAX7 gene expression. In conclusion, in this work we found that HIF-1α plays a role in sarcopenia and is involved in satellite cell homeostasis. These results support further studies to test whether pharmacological reactivation of HIF-1α could prevent and counteract sarcopenia.