Joint health and pain in the changing hemophilia treatment landscape.

INTRODUCTION: Hemophilia is an inherited bleeding disorder. Bleeding, and in particular joint hemorrhage results in chronic arthropathy and disability. Acute and chronic pain are frequent and limit activity and participation and result in decreased health-related quality of life. Remarkable progress has been made in the diagnosis and treatment of hemophilia but bleeding continues to prove recalcitrant to currently available treatments and joint disease remains problematic. Physiotherapy and pain management are mainstays of current multidisciplinary integrated care of people with hemophilia (PWH). The focus of this review is on preservation of joint health in the era of new and innovative therapies. AREAS COVERED: A search of the PubMed Central was conducted on 1 February 2024 using the MeSH Major Topic terms identified as keywords for the manuscript. This review will highlight what is known and unknown about joint bleeding and arthropathy, including insights on pain as a related complication. EXPERT OPINION: Recent advances in therapeutic interventions aimed at promoting healthy joints in PWH will be discussed, including both the pharmacological treatment landscape and related strategies to promote joint health.

Ultrasound-guided joint procedures in hemophilia: technique, indications and tips.

INTRODUCTION: The therapeutic approach to pain in hemophilia should be multimodal. Intra-articular injections are a good option when joint lesions do not respond to hematological treatment or rehabilitation and orthopedic surgery is not yet indicated. Performing these procedures under ultrasound guidance has been shown to improve their accuracy and efficacy. AREAS COVERED: This article provides a practical overview of the most frequently employed ultrasound-guided intra-articular procedures on the joints of people with hemophilia. The article describes the key elements for performing the technique on the elbow, knee and ankle as the most affected joints. The particularities of the most frequent indications, arthrocentesis, synoviorthesis and analgesic injections with various products are detailed. EXPERT OPINION: Current hematological treatments have made it possible to incorporate new therapeutic tools for pain relief for people with hemophilia, including ultrasound-guided joint procedures, which offer excellent results.

[A quantitative study of mechanics in the treatment of atlantoaxial joint disorder by tendon relaxation manipulation].

OBJECTIVE: To explore dose-effect relationship of biomechanical parameters in treating atlantoaxial joint disorder by slimming manipulation. METHODS: From October 2022 to May 2023, 18 patients with atlantoaxial joint disorders were treated, including 10 males and 8 females;aged from 24 to 27 years old with an average of (25.50±1.10) years old;CT of cervical vertebra showed 16 patients with right side distortion and 2 patients with left side distortion. The mechanical parameters of treatment of atlantoaxial joint disorder by tendon relaxation manipulation were measured by wearing massage manipulation gloves. The magnitude, frequency and mechanical curve of force during tendon relaxation and starting force, pulling force, pulling time and mechanical curve during rehabilitation were quantified, the differences between the affected and contralateral manipulations were compared. RESULTS: The maximum force and frequency of Fengchi(GB20) on the affected side were (19.82±2.02) N and (116.83±14.49) times/min, and opposite side were (13.87±2.19) N and (188.89±16.03) times/min, respectively. There were statistically difference in the maximum force and frequency of both sides (P<0.05). The maximum force and frequency of Quepen (ST12) on the affected side were (14.44±3.27) N and (139.06±28.47) times/min, and those on the opposite side were (9.41±1.38) N and (142.50±28.47) times/min. There was difference in maximum force on both sides (P<0.05). The starting force, turning force and turning time of the affected side were (14.16±5.98) N, (11.56±6.63) N, (0.14±0.03) S, and the contralateral side were (8.94±3.39) N, (8.30±4.64) N, (0.18±0.04) S, respectively. The difference of starting force, turning force and turning time on both sides were statistically significant (P<0.05). CONCLUSION: By applying a light relaxation force on the affected side, the mechanical balance between cervical vertebrae could be restored, and recovery trend of atlantoaxial joint disorder could be strengthened. On this basis, the atlantoaxial odontoid process could be reversed by applying a light rotation force, which reflects the characteristics of high safety of the manipulation.

Arthrofibrosis of the knee in pediatric orthopedic surgery.

Arthrofibrosis is a challenging complication associated with knee injuries in both children and adults. While much is known about managing arthrofibrosis in adults, it is necessary to understand its unique aspects and management strategies in the pediatric population. This paper provides an overview of arthrofibrosis in pediatric orthopedic surgery, focusing on its causes, implications, classifications, and management. This paper is a comprehensive review of the literature and existing research on arthrofibrosis in pediatric patients. Arthrofibrosis is characterized by excessive collagen production and adhesions, leading to restricted joint motion and pain. It is associated with an immune response and fibrosis within and around the joint. Arthrofibrosis can result from various knee injuries in pediatric patients, including tibial spine fractures, ACL and PCL injuries, and extra-articular procedures. Technical factors at the time of surgery play a role in the development of motion loss and should be addressed to minimize complications. Preventing arthrofibrosis through early physical therapy is recommended. Non-operative management, including dynamic splinting and serial casting, has shown some benefits. New pharmacologic approaches to lysis of adhesions have shown promise. Surgical interventions, consisting of arthroscopic lysis of adhesions (LOA) and manipulation under anesthesia (MUA), can significantly improve motion and functional outcomes. Arthrofibrosis poses unique challenges in pediatric patients, demanding a nuanced approach that includes prevention, early intervention with non-operative means, and improvements in surgical techniques. Modern pharmacological interventions offer promise for the future. Customized interventions and research focused on pediatric patients are critical for optimal outcomes.

La artrofibrosis es una complicación difícil asociada con lesiones de rodilla tanto en niños como en adultos. Si bien se sabe mucho sobre el manejo de la artrofibrosis en adultos, es necesario comprender sus aspectos únicos y estrategias de manejo en la población pediátrica. Este documento proporciona una visión general de la artrofibrosis en la cirugía ortopédica pediátrica, centrándose en sus causas, implicaciones, clasificaciones y manejo. Este documento es una revisión completa de la literatura y la investigación existente sobre artrofibrosis en pacientes pediátricos. La artrofibrosis se caracteriza por una producción excesiva de colágeno y adherencias, lo que conduce a un movimiento articular restringido y dolor. Se asocia con una inmunorrespuesta y fibrosis dentro y alrededor de la articulación. La artrofibrosis puede ser el resultado de varias lesiones de rodilla en pacientes pediátricos, incluyendo fracturas de columna tibial, lesiones de LCA y LCP, y procedimientos extraarticulares. Los factores técnicos en el momento de la cirugía desempeñan un papel en el desarrollo de la pérdida de movimiento y deben abordarse para minimizar las complicaciones. Se recomienda prevenir la artrofibrosis a través de la fisioterapia temprana. La gestión no operativa, incluyendo el empalme dinámico y la fundición en serie, ha mostrado algunos beneficios. Los nuevos enfoques farmacológicos a la lisis de adherencias han demostrado ser prometedores. Las intervenciones quirúrgicas, consistentes en lisis artroscópica de adherencias (LOA) y manipulación bajo anestesia (MUA), pueden mejorar significativamente el movimiento y los resultados funcionales. La artrofibrosis plantea desafíos únicos en los pacientes pediátricos, exigiendo un enfoque matizado que incluye prevención, intervención temprana con medios no operatorios y mejoras en las técnicas quirúrgicas. Las intervenciones farmacológicas modernas ofrecen una promesa para el futuro. Las intervenciones e investigaciones personalizadas centradas en pacientes pediátricos son fundamentales para obtener resultados óptimos.

AAV mediated repression of Neat1 lncRNA combined with F8 gene augmentation mitigates pathological mediators of joint disease in haemophilia.

Haemophilic arthropathy (HA), a common comorbidity in haemophilic patients leads to joint pain, deformity and reduced quality of life. We have recently demonstrated that a long non-coding RNA, Neat1 as a primary regulator of matrix metalloproteinase (MMP) 3 and MMP13 activity, and its induction in the target joint has a deteriorating effect on articular cartilage. In the present study, we administered an Adeno-associated virus (AAV) 5 vector carrying an short hairpin (sh)RNA to Neat1 via intra-articular injection alone or in conjunction with systemic administration of a capsid-modified AAV8 (K31Q) vector carrying F8 gene (F8-BDD-V3) to study its impact on HA. AAV8K31Q-F8 vector administration at low dose, led to an increase in FVIII activity (16%-28%) in treated mice. We further observed a significant knockdown of Neat1 (~40 fold vs. untreated injured joint, p = 0.005) in joint tissue of treated mice and a downregulation of chondrodegenerative enzymes, MMP3, MMP13 and the inflammatory mediator- cPLA2, in mice receiving combination therapy. These data demonstrate that AAV mediated Neat1 knockdown in combination with F8 gene augmentation can potentially impact mediators of haemophilic joint disease.

A systematic review and meta-analysis of the efficacy of platelet-rich plasma products for treatment of equine joint disease.

BACKGROUND: Equine joint disease including septic arthritis (SA) and osteoarthritis (OA) is a critical cause of equine lameness. Platelet-rich plasma (PRP) is one of the most popular regenerative therapies to treat equine OA, even SA, but the evidence in support of the treatment is conflicting. OBJECTIVES: The aim of the study was to systematically review the current evidence on PRP products used for SA and OA, as well as the efficacy of PRP products as treatment for OA on the basis of a meta-analysis of the available literature. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic search of relevant databases (PubMed, Web of Science, Scopus) was performed to identify studies published from 2013 to 2023, in accordance with the PRISMA guidelines. Randomised controlled trials, non-randomised trials and controlled laboratory studies that used at least one type of PRP products were included. Dichotomous outcomes were presented using odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A total of 21 publications were identified in the systematic review and 5 of them in the meta-analysis. These publications involved various types of PRP products and reported different outcomes. Although most of the studies were associated with a high risk of bias, the overall estimated effect was consistent with a significant improvement in the PRP products treatment group compared with the control group (OR: 15.32; 95% CI: 3.00-78.15; p < 0.05). There was a significant improvement in clinical performance outcomes between the groups (OR: 36.64; 95% CI: 3.69-364.30; p < 0.05). CONCLUSION: PRP products as intra-articular treatment are likely efficacious for treatment of equine OA and have potential for treating SA. These conclusions might be affected by the limited number of randomised controlled studies and high variability of different types of PRP products. To better evaluate the efficacy of PRP, a widely recognised classification system and the utilisation of randomised, blinded, equivalency or non-inferiority trials are required.

Molecular portrait of chronic joint diseases: Defining endotypes toward personalized medicine.

Joint diseases affect hundreds of millions of people worldwide, and their prevalence is constantly increasing. To date, despite recent advances in the development of therapeutic options for most rheumatic conditions, a significant proportion of patients still lack efficient disease management, considerably impacting their quality of life. Through the spectrum of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA) as quintessential and common rheumatic diseases, this review first provides an overview of their epidemiological and clinical features before exploring how the better definition of clinical phenotypes has helped their clinical management. It then discusses the recent progress in understanding the diversity of endotypes underlying disease phenotypes. Finally, this review highlights the current challenges of implementing molecular endotypes towards the personalized management of RA, PsA and OA patients in the future.

Minimally invasive sacroiliac joint fusion using triangular titanium implants versus nonsurgical management for sacroiliac joint dysfunction: a systematic review and meta-analysis.

BACKGROUND: Minimally invasive sacroiliac joint (MISIJ) fusion is a surgical option to relieve SIJ pain. The aim of this systematic review and meta-analysis was to compare MISIJ fusion with triangular titanium implants (TTI) to nonoperative management of SIJ dysfunction. METHODS: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. We included prospective clinical trials that compared MISIJ fusion to nonoperative management in individuals with chronic low back pain attributed to SIJ dysfunction. We evaluated pain on visual analogue scale, Oswestry Disability Index (ODI) score, health-related quality of life (HRQoL) using the 36-Item Short Form Health Survey (SF-36) physical component (PCS) and mental component summary (MCS) scores, patient satisfaction, and adverse events. RESULTS: A total of 8 articles representing 3 trials that enrolled 423 participants were deemed eligible. There was a significant reduction in pain score with MISIJ fusion compared with nonoperative management (standardized mean difference [SMD] -1.71, 95% confidence interval [CI] -2.03 to -1.39). Similarly, ODI scores (SMD -1.03, 95% CI -1.24 to -0.81), SF-36 PCS scores (SMD 1.01, 95% CI 0.83 to 1.19), SF-36 MCS scores (SMD 0.72, 95% CI 0.54 to 0.9), and patient satisfaction (odds ratio 6.87, 95% CI 3.73 to 12.64) were significantly improved with MISIJ fusion. No significant difference was found between the 2 groups with respect to adverse events (SMD -0.03, 95% CI -0.28 to 0.23). CONCLUSION: Our analysis showed that MISIJ fusion with TTI shows a clinically important and statistically significant improvement in pain, disability score, HRQoL, and patient satisfaction with a similar adverse event profile to nonoperative management in patients with chronic low back pain attributed to SIJ dysfunction.

Arthrofibrosis After Total Knee Arthroplasty: A Critical Analysis Review.

¼ Arthrofibrosis after total knee arthroplasty (TKA) is the new formation of excessive scar tissue that results in limited ROM, pain, and functional deficits.¼ The diagnosis of arthrofibrosis is based on the patient's history, clinical examination, absence of alternative diagnoses from diagnostic testing, and operative findings. Imaging is helpful in ruling out specific causes of stiffness after TKA. A biopsy is not indicated, and no biomarkers of arthrofibrosis exist.¼ Arthrofibrosis pathophysiology is multifactorial and related to aberrant activation and proliferation of myofibroblasts that primarily deposit type I collagen in response to a proinflammatory environment. Transforming growth factor-beta signaling is the best established pathway involved in arthrofibrosis after TKA.¼ Management includes both nonoperative and operative modalities. Physical therapy is most used while revision arthroplasty is typically reserved as a last resort. Additional investigation into specific pathophysiologic mechanisms can better inform targeted therapeutics.

Arthrofibrosis - a myth or true joint disorder?

Authors, mostly specialists on rehabilitation and orthopedic surgery prove that arthrofibrosis is a commonly overlooked phenomenon, which may lead to serious limitation in the range of movement, leading to limitation in patients quality of functioning. The main goal of this article is to emphasize the importance of understanding a such complex condition. Non typical patomechanism, lack of biomarkers dedicated to this dysfunction and general lack of understanding in this pathology causes that risk factors and the most effective strategies remain vastly unknown. Pathophysiology of the arthrofibrosis in the joints is definitely multifactorial, but intense production of collagen seems to be the main factor. Most modern pharmacological methods concentrate on the regulation of collagen fiber production and reducing the inflammation. Inflammation from joint contractures stimulates the proliferation of activated cells that results in the production of extracellular matrix macromolecules to form fibrotic tissue that is deposited into the capsule, thereby resulting in fibrosis. Lack of unified classification scale is caused by relatively high variation of the functions fulfilled by particular joints and each treatment plan should be constructed individually. Quality of surgical treatment and physical therapy play a major role in both prevention and treatment of such complex condition as arthrofibrosis. Both iatrogenic mistakes and overly aggressive manual therapy are some of main factors increasing the risk of this pathological condition. Introducing properly conducted physical therapy treatment in the early stage is crucial to main the range of movement and preventing this significant problem.

Management of arthrofibrosis in neuromuscular disorders: a review.

Arthrofibrosis, or rigid contracture of major articular joints, is a significant morbidity of many neurodegenerative disorders. The pathogenesis depends on the mechanism and severity of the precipitating neuromuscular disorder. Most neuromuscular disorders, whether spastic or hypotonic, culminate in decreased joint range of motion. Limited range of motion precipitates a cascade of pathophysiological changes in the muscle-tendon unit, the joint capsule, and the articular cartilage. Resulting joint contractures limit functional mobility, posing both physical and psychosocial burdens to patients, economic burdens on the healthcare system, and lost productivity to society. This article reviews the pathophysiology of arthrofibrosis in the setting of neuromuscular disorders. We describe current non-surgical and surgical interventions for treating arthrofibrosis of commonly affected joints. In addition, we preview several promising modalities under development to ameliorate arthrofibrosis non-surgically and discuss limitations in the field of arthrofibrosis secondary to neuromuscular disorders.

Role of exosomes in bone and joint disease metabolism, diagnosis, and therapy.

Bone and joint diseases are prevalent and often fatal conditions in elderly individuals. Additionally, bone-derived cells may release exosomes that package and distribute a range of active substances, such as proteins, miRNAs, and numerous active factors, thereby facilitating material and information interchange between cells. Exososmes generated from bone may be utilized to manage bone production and resorption balance or even as biological or gene therapy carriers, depending on their properties and composition. In this review, we will discuss the composition, secretion, and uptake theory of exososmes, the role of exososmes in bone metabolism regulation, the pathogenesis and diagnosis of bone and joint diseases, and the application of exososmes in regenerative medicine. The findings will expand our understanding of the potential research and application space regarding exososmes.

Efficacy of non-operative treatment of patients with knee arthrofibrosis using high-intensity home mechanical therapy: a retrospective review of 11,000+ patients.

BACKGROUND: Recovery from knee surgery or injury can be hindered by knee arthrofibrosis, which can lead to motion limitations, pain and delayed recovery. Surgery or prolonged physical therapy are often treatment options for arthrofibrosis, but they can result in increased costs and decreased quality of life. A treatment option that can regain lost motion without surgery would help minimize risks and costs for the patient. The purpose of this study was to determine treatment efficacy of high-intensity home mechanical stretch therapy in patients with knee arthrofibrosis. METHODS: Records were reviewed for 11,000+ patients who were prescribed a high-intensity stretch device to regain knee flexion. Initial and last recorded knee flexion and days between measurements were available for 9842 patients (Dataset 1). Dataset 2 was a subset of 966 patients from Dataset 1. These 966 patients had separate more rigorous measurements available from physical therapy notes (Dataset 3) in addition to data from the internal database (Dataset 2). Within and between dataset statistics were calculated using t tests for comparison of means and Cohen's d for determination of effect size. RESULTS: All dataset showed significant gains in flexion (p < 0.01). Mean initial flexion, last recorded flexion and flexion gain were 79.5°, 108.4°, and 29.9°, respectively in Dataset 1. Differences between Datasets 2 and 3 had small effect sizes (Cohen's d < 0.17). The were no significant differences when comparing workers' compensation and non-workers' compensation patients. The average last recorded flexion for all datasets was above the level required to perform activities of daily living. Motion gains were recorded in under 60 days from device delivery. CONCLUSIONS: High-intensity home mechanical stretch therapy was effective in restoring knee flexion, generally in 2 months or less, and in avoiding additional surgery in severe motion loss patients regardless of sex, age, or workers' compensation status. We believe high-intensity stretching should be considered in any patient who is at risk for a secondary motion loss surgery, because in over 90% of these patients, the complications and costs associated with surgery can be avoided.

Advances in Engineered Three-Dimensional (3D) Body Articulation Unit Models.

Indeed, the body articulation units, commonly referred to as body joints, play significant roles in the musculoskeletal system, enabling body flexibility. Nevertheless, these articulation units suffer from several pathological conditions, such as osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, gout, and psoriatic arthritis. There exist several treatment modalities based on the utilization of anti-inflammatory and analgesic drugs, which can reduce or control the pathophysiological symptoms. Despite the success, these treatment modalities suffer from major shortcomings of enormous cost and poor recovery, limiting their applicability and requiring promising strategies. To address these limitations, several engineering strategies have been emerged as promising solutions in fabricating the body articulation as unit models towards local articulation repair for tissue regeneration and high-throughput screening for drug development. In this article, we present challenges related to the selection of biomaterials (natural and synthetic sources), construction of 3D articulation models (scaffold-free, scaffold-based, and organ-on-a-chip), architectural designs (microfluidics, bioprinting, electrospinning, and biomineralization), and the type of culture conditions (growth factors and active peptides). Then, we emphasize the applicability of these articulation units for emerging biomedical applications of drug screening and tissue repair/regeneration. In conclusion, we put forward the challenges and difficulties for the further clinical application of the in vitro 3D articulation unit models in terms of the long-term high activity of the models.

Native joint infections in Iceland 2003-2017: an increase in postarthroscopic infections.

OBJECTIVES: Nationwide study on the epidemiology, clinical characteristics and outcomes among patients with native joint infection (NJI) in Iceland, 2003-2017. METHODS: All positive synovial fluid culture results in Iceland were identified and medical records reviewed. RESULTS: A total of 299 NJI (40 children and 259 adults) were diagnosed in Iceland in 2003-2017, with a stable incidence of 6.3 cases/100 000/year, but marked gender difference among adults (33% women vs 67% men, p<0.001). The knee joint was most commonly affected, and Staphylococcus aureus was the most common isolate in both adults and children, followed by various streptococcal species in adults and Kingella kingae in children. NJI was iatrogenic in 34% of adults (88/259) but comprised 45% among 18-65 years and a stable incidence. Incidence of infections following arthroscopic procedures in adults increased significantly compared with the previous decade (9/100 000/year in 1990-2002 vs 25/100 000/year in 2003-2017, p<0.01) with no significant increase seen in risk per procedure. The proportion of postarthroscopic NJI was 0.17% overall but 0.24% for knee arthroscopy. Patients with postarthroscopic infection were more likely to undergo subsequent arthroplasty when compared with other patients with NJI (p=0.008). CONCLUSIONS: The incidence of NJI in Iceland has remained stable. The proportion of iatrogenic infections is high, especially among young adults, with an increase seen in postarthroscopic infections when compared with the previous decade. Although rare, NJI following arthroscopy can be a devastating complication, with significant morbidity and these results, therefore, emphasise the need for firm indications when arthroscopic treatment is considered.

The use of LED therapy to treat synovial joints disorders: scoping review.

The aim of this scoping review was to assess the extent of the literature on the use of LED therapy to treat synovial joint disorders. The JBI methodology for scoping reviews was followed. The databases used were PUBMED, EMBASE, Scopus, Web of Science, LILACS, PEDro, Cochrane Database, Google Scholar and ProQuest. To be included, studies should have used LED as therapy, and include at least one measure related to the structures of any synovial joint. The search strategy included all keywords and indexed terms identified in the articles. Studies in any language and in any year, whether published or not, were included. The analysis of the studies was carried out by two independent reviewers. Data were extracted from articles using a data extraction tool developed by the reviewers. After carrying out the definitive search and selection, 47 publications were included: 15 clinical trials, 8 clinical protocols, 12 animal studies, 4 in vitro studies and 8 reviews on the topic. Studies have shown great variability from the device and number of diodes used, to the parameters and dosimetry chosen. Some positive effects were observed: on cell proliferation (in vitro); on anti-inflammatory biomarkers (murine models) and on pain scale (clinical trials - TMD). Although, the cause of non-significant results in clinical trials was rarely discussed: depth of penetration, dosimetry, follow-up time? Thus, future studies should focus on answering more elementary aspects about the LED effect when used alone in different synovial joints.

Past and Future of Phage Therapy and Phage-Derived Proteins in Patients with Bone and Joint Infection.

Phage-derived therapies comprise phage therapy and the use of phage-derived proteins as anti-bacterial therapy. Bacteriophages are natural viruses that target specific bacteria. They were proposed to be used to treat bacterial infections in the 1920s, before the discovery and widespread over-commercialized use of antibiotics. Phage therapy was totally abandoned in Western countries, whereas it is still used in Poland, Georgia and Russia. We review here the history of phage therapy by focusing on bone and joint infection, and on the development of phage therapy in France in this indication. We discuss the rationale of its use in bacterial infection and show the feasibility of phage therapy in the 2020s, based on several patients with complex bone and joint infection who recently received phages as compassionate therapy. Although the status of phage therapy remains to be clarified by health care authorities, obtaining pharmaceutical-grade therapeutic phages (i.e., following good manufacturing practice guidelines or being "GMP-like") targeting bacterial species of concern is essential. Moreover, multidisciplinary clinical expertise has to determine what could be the relevant indications to perform clinical trials. Finally "phage therapy 2.0" has to integrate the following steps: (i) follow the status of phage therapy, that is not settled and defined; (ii) develop in each country a close relationship with the national health care authority; (iii) develop industrial-academic partnerships; (iv) create academic reference centers; (v) identify relevant clinical indications; (vi) use GMP/GMP-like phages with guaranteed quality bioproduction; (vii) start as salvage therapy; (vii) combine with antibiotics and adequate surgery; and (viii) perform clinical trials, to finally (ix) demonstrate in which clinical settings phage therapy provides benefit. Phage-derived proteins such as peptidoglycan hydrolases, polysaccharide depolymerases or lysins are enzymes that also have anti-biofilm activity. In contrast to phages, their development has to follow the classical process of medicinal products. Phage therapy and phage-derived products also have a huge potential to treat biofilm-associated bacterial diseases, and this is of crucial importance in the worldwide spread of antimicrobial resistance.

The Hip-Spine Challenge.

➤: The proper diagnosis and treatment of patients with concurrent hip and spine pathological processes can be challenging because of the substantial overlap in symptomatology. ➤: There is no consensus on which pathological condition should be addressed first. ➤: Factors such as advanced spinal degeneration, deformity, and prior fusion alter the biomechanics of the spinopelvic unit. Attention should be paid to recognizing these issues during the work-up for a total hip arthroplasty as they can result in an increased risk of dislocation. ➤: In patients with concurrent spine and hip degeneration, the surgeon must pay close attention to appropriate implant positioning and have consideration for implants with enhanced stability to minimize the risk of dislocation. ➤: A proper understanding of sagittal balance and restoration of this balance is integral to improving patient outcomes following spinal surgery. ➤: The advent of new imaging modalities, increased awareness of spinopelvic mobility, as well as a better understanding of sagittal alignment will hopefully improve our treatment of patients with hip-spine syndrome.

Iron homeostasis in arthropathies: From pathogenesis to therapeutic potential.

Iron is an essential element for proper functioning of cells within mammalian organ systems; in particular, iron homeostasis is critical for joint health. Excess iron can induce oxidative stress damage, associated with the pathogenesis of iron-storage and ageing-related diseases. Therefore, iron levels in body tissues and cells must be tightly regulated. In the past decades, excess iron content within joints has been found in some patients with joint diseases including hemophilic arthropathy, hemochromatosis arthropathy, and osteoarthritis (OA). Currently, increased evidence has shown that iron accumulation is closely associated with multiple pathological changes of these arthropathies. This review summarizes system-level and intracellular regulation of iron homeostasis, and emphasizes the role of iron in synovial alterations, cartilage degeneration, and subchondral bone of several arthropathies. Of note, we discuss the potential link between iron homeostasis and OA pathogenesis. Finally, we discuss the therapeutic potential of maintaining iron homeostasis in these arthropathies.