Liposomes for intra-articular analgesic drug delivery in orthopedics: State-of-art and future perspectives. Insights from a systematic mini-review of the literature

Background and objectives: Liposomal structures are artificial vesicles composed of one or several lamellae of phospholipids which surround an inner aqueous core. Given the amphoteric nature of phospholipids, liposomes are promising systems for drug delivery. The present review provides an updated synthesis of the main techniques for the production of liposomes for orthopedic applications, focusing on the drawbacks of the conventional methods and on the advantages of high pressure techniques. Materials and Methods: Articles published in any language were systematically retrieved from two major electronic scholarly databases (PubMed/MEDLINE and Scopus) up to March 2020. Nine articles were retained based on the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines. Results: Liposome vesicles decrease the rate of inflammatory reactions after local injections, and significantly enhance the clinical effectiveness of anti-inflammatory agents providing controlled drug release, reducing toxic side effects. Conclusions: This review presents an update on the improvement in musculoskeletal ailments using liposome treatment

Outpatient Total Hip Arthroplasty: A Meta-Analysis

Introduction: Outpatient total hip arthroplasty (THA) is increasingly popular. This meta-analysis investigated the potential advantages of outpatient regimes for THA. Methods: This study followed the PRISMA guidelines. PubMed, Web of Science, Google Scholar, Embase, and Scopus databases were accessed in June 2021. All clinical studies investigating outpatient THA were considered. The outcomes of interest were pain, infection, mortality, revision, dislocation, readmission rates, and deep vein thrombosis (DVT). Results: Data from 102,839 patients were included. A total of 52% (153,168 of 102,839 patients) were women. The mean age of patients was 62.6 +/- 4.6 years, the mean BMI was 29.1 +/- 1.8 kg/m(2). Good comparability was found in age, BMI, and gender (p > 0.1). No difference was found in pain (p = 0.4), infections (p = 0.9), mortality (p = 0.9), rate of revision (p = 0.1), dislocation (p = 0.9), and readmission (p = 0.8). The outpatient group demonstrated a greater rate of DVT (OR 3.57; 95% CI 2.47 to 5.18; p < 0.0001). Conclusions: In selected patients, outpatient THA can be performed safely with optimal outcomes comparable with inpatient THA. Clear and comprehensive pre-operative planning should involve a multi-disciplinary group composed of orthopaedic surgeons, anaesthesia and rehabilitation specialists, and physiotherapists. Each centre performing outpatient THA should implement continuous homecoming welfare activity, to supervise physiotherapy and monitor anticoagulant therapy

Liposomes for Intra-Articular Analgesic Drug Delivery in Orthopedics: State-of-Art and Future Perspectives. Insights from a Systematic Mini-Review of the Literature.

Background and objectives: Liposomal structures are artificial vesicles composed of one or several lamellae of phospholipids which surround an inner aqueous core. Given the amphoteric nature of phospholipids, liposomes are promising systems for drug delivery. The present review provides an updated synthesis of the main techniques for the production of liposomes for orthopedic applications, focusing on the drawbacks of the conventional methods and on the advantages of high pressure techniques. Materials and Methods: Articles published in any language were systematically retrieved from two major electronic scholarly databases (PubMed/MEDLINE and Scopus) up to March 2020. Nine articles were retained based on the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines. Results: Liposome vesicles decrease the rate of inflammatory reactions after local injections, and significantly enhance the clinical effectiveness of anti-inflammatory agents providing controlled drug release, reducing toxic side effects. Conclusions: This review presents an update on the improvement in musculoskeletal ailments using liposome treatment

Impact of lysosomal storage disorders on biology of mesenchymal stem cells: Evidences from in vitro silencing of glucocerebrosidase (GBA) and alpha-galactosidase A (GLA) enzymes.

Lysosomal storage disorders (LDS) comprise a group of rare multisystemic diseases resulting from inherited gene mutations that impair lysosomal homeostasis. The most common LSDs, Gaucher disease (GD), and Fabry disease (FD) are caused by deficiencies in the lysosomal glucocerebrosidase (GBA) and alpha-galactosidase A (GLA) enzymes, respectively. Given the systemic nature of enzyme deficiency, we hypothesized that the stem cell compartment of GD and FD patients might be also affected. Among stem cells, mesenchymal stem cells (MSCs) are a commonly investigated population given their role in hematopoiesis and the homeostatic maintenance of many organs and tissues. Since the impairment of MSC functions could pose profound consequences on body physiology, we evaluated whether GBA and GLA silencing could affect the biology of MSCs isolated from bone marrow and amniotic fluid. Those cell populations were chosen given the former's key role in organ physiology and the latter's intriguing potential as an alternative stem cell model for human genetic disease. Our results revealed that GBA and GLA deficiencies prompted cell cycle arrest along with the impairment of autophagic flux and an increase of apoptotic and senescent cell percentages. Moreover, an increase in ataxia-telangiectasia-mutated staining 1 hr after oxidative stress induction and a return to basal level at 48 hr, along with persistent gamma-H2AX staining, indicated that MSCs properly activated DNA repair signaling, though some damages remained unrepaired. Our data therefore suggest that MSCs with reduced GBA or GLA activity are prone to apoptosis and senescence due to impaired autophagy and DNA repair capacity

Outpatient Total Knee Arthroplasty: A Meta-Analysis

Introduction: Outpatient total knee arthroplasty (TKA) is attracting growing interest. This meta-analysis compared patient reported outcome measures (PROMs), infection, readmission, revision, deep vein thrombosis (DVT), and mortality rates of outpatient versus inpatient TKA. Methods: This meta-analysis was conducted according to the 2020 PRISMA statement. In August 2021, the following databases were accessed: Pubmed, Web of Science, Google Scholar, Embase. All the clinical trials comparing outpatient versus inpatient (> 2 days) TKA were considered. Studies which reported data on revision settings were not considered, nor studies which included patients discharged between one and two days. Results: Data from 159,219 TKAs were retrieved. The mean follow-up was 5.8 & PLUSMN; 7.6 months. The mean age was 63.7 & PLUSMN; 5.0 years and the mean BMI 30.3 & PLUSMN; 1.8 kg/m(2). Comparability was found in age (p = 0.4), BMI (p = 0.3), and gender (p = 0.4). The outpatient group evidenced a greater Oxford knee score (p = 0.01). The inpatient group demonstrated a greater rate of revision (p = 0.03), mortality (p = 0.003), and DVT (p = 0.005). No difference was found in the rate of readmission (p = 0.3) and infection (p = 0.4). Conclusions: With regards to the endpoints evaluated in this meta-analysis, current evidence does not support outpatient TKA. However, given the limited data available for inclusion and the overall poor quality of the included articles, no reliable conclusion can be inferred. Further high quality clinical trials with clear eligibility criteria are required

Extensor Retinaculum Flap and Fibular Periosteum Ligamentoplasty After Failed Surgery for Chronic Lateral Ankle Instability

Background: The anterior talofibular ligament and the calcaneofibular ligament are 2 of the most frequently injured structures in sports, being damaged in 30% to 45% of all sports injuries. Most reconstructive procedures are successful but can deteriorate with time and can lead to low-grade radiographic degeneration. Methods: We operated on 26 consecutive patients from 2001 to 2008 who had failed previous surgical procedures for the lateral ligamentous complex of the ankle, with an average of 104 (range, 75-140) months. Results: The overall functional rating was excellent in 14 ankles, good in 10, fair in 1, and poor in 1. Twenty-four patients (92.3%) were satisfied with the procedure and 15 (57.7%) were able to return to their preinjury level of activity. Local complications were detected in 2 patients who presented with skin necrosis; 1 patient developed severe reflex sympathetic dystrophy. Conclusion: Revision surgery for the management of failure after surgical treatment of chronic lateral ankle instability is under debate, and the literature is devoid of clinical studies with long-term follow-up. The technique described offers a high rate of long-term excellent and good results, with a low rate of complications and a good rate of return to preinjury level. Level of Evidence: Level IV, retrospective case series