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.

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.

[Bilateral total hip arthroplasty in a 15-year-old patient with progressive pseudorheumatoid dysplasia. Case report and literature review]. / Artroplastía total de cadera bilateral en paciente de 15 años con displasia progresiva pseudorreumatoide. Reporte de caso y revisión bibliográfica.

Progressive pseudorheumatoid dysplasia (PPD) is an autosomal recessive hereditary disease of very low prevalence. It is characterized by the affection of multiple joints, generating arthrosis and progressive deformities from a very young age, which significantly affect the quality of life of patients. Its diagnosis is only confirmed by genetic testing, and no specific pharmacological treatment is still available. In the case of hip involvement, one treatment option is arthroplasty. In this case report, we present a 15-year-old boy with bilateral coxarthrosis secondary to PPD who underwent bilateral total hip arthroplasty in two stages. We highlight the characteristics of this rare entity, the intraoperative findings, the functional outcomes, and the impact on quality of life.

La displasia progresiva pseudorreumatoide (DPP) es una enfermedad hereditaria autosómica recesiva, de muy baja prevalencia. Se caracteriza por la afección de múltiples articulaciones, generando artrosis y deformidades progresivas desde muy temprana edad, que afectan considerablemente la calidad de vida de los pacientes. Su diagnóstico sólo se confirma por análisis genéticos y aún no se dispone de tratamiento farmacológico específico. Ante la afectación de la cadera, una opción de tratamiento está representada por la artroplastía. En este reporte de caso, presentamos un joven de 15 años, con coxartrosis bilateral secundaria a DPP, al cual se le realizó una artroplastía total de cadera bilateral, en dos tiempos. Destacamos las características propias de esta extraña entidad, los hallazgos intraoperatorios, sus resultados funcionales y el impacto en la calidad de vida.

Conventional Radiography Assessment of the Pediatric Knee: Pearls and Pitfalls.

Knee pain is one of the most common indications for radiography in the evaluation of musculoskeletal disorders in children and adolescents. According to international guidelines, knee radiographs should be obtained when there is the suspicion of an effusion, limited motion, pain to palpation, inability to bear weight, mechanical symptoms (such as "locking"), and persistent knee pain after therapy. When indicated, radiographs can provide crucial information for the clinical decision-making process. Because of the developmental changes occurring in the knee during growth, the assessment of knee radiographs can be challenging in children and adolescents. Radiologists unfamiliar with the appearance of the knee on radiographs during skeletal maturation risk overcalling or overlooking bone lesions. Image acquisition techniques and parameters should be adapted to children. This article describes the most common challenges in distinguishing pathology from the normal appearance of knee radiographs in the pediatric population, offering some pearls and pitfalls that can be useful in clinical practice.

[Research progress of ultrasound in diagnosis and treatment of shoulder joint diseases].

Objective: To review the research progress of ultrasound in the diagnosis and treatment of shoulder diseases, in order to provide a theoretical basis for the further development of ultrasound in shoulder surgery. Methods: The recent literature on the application of ultrasound in the shoulder joint was extensively reviewed. The application of ultrasound in the diagnosis and treatment of shoulder joint diseases, and the advantages and disadvantages of ultrasound were analysed, and the development trend of ultrasound technology in the shoulder joint area was prospected. Results: At present, the diagnosis of shoulder joint diseases mainly relies on MRI, however, with the development of ultrasound technology, ultrasound with the characteristics of convenient, reliable, and real-time dynamic evaluation is more and more recognized in the diagnosis process of shoulder joint diseases, combined with three-dimensional ultrasound, ultrasound intervention, and elastography can improve the accuracy, sensitivity, and specificity of the diagnosis, and is suitable for the diagnosis and treatment of various shoulder joint diseases, which is expected to carry out early prevention of shoulder joint diseases in the future and achieve more refined and minimally invasive treatment. Conclusion: Ultrasound technology has wide application prospect in shoulder joint diseases, but it is still in the developing stage, and the subjective dependence needs to be solved further.

Outcomes of Ulnar Shortening Osteotomy with an Intramedullary Bone Graft for Idiopathic Ulnar Impaction Syndrome.

Background: Although several techniques for the treatment of ulnar impaction syndrome (UIS) have been introduced, there have still been reports on various complications such as delayed union, nonunion, refracture, wrist pain, plate irritation, and chronic regional pain syndrome. This study aimed to compare the differences in radiological and clinical outcomes of patients in which intramedullary bone grafting was performed in addition to plate stabilization with those without additional bone grafting during ulnar shortening osteotomies (USOs). Methods: Between November 2014 and June 2021, 53 wrists of 50 patients with idiopathic UIS were retrospectively reviewed. Patients were divided into 2 groups according to whether intramedullary bone grafting was performed. Among the 53 wrists, USO with an intramedullary bone graft was performed in 21 wrists and USO without an intramedullary bone graft was performed in 32 wrists. Demographic data and factors potentially associated with bone union time were analyzed. Results: There was no significant difference between the 2 groups when comparing postoperative radioulnar distance, postoperative ulnar variance, amount of ulnar shortening, and postoperative Disabilities of the Arm, Shoulder and Hand score. Compared to the without-intramedullary bone graft group, bone union time of the osteotomy site was significantly shortened, from 8.8 ± 3.0 weeks to 6.7 ± 1.3 weeks in the with-intramedullary bone graft group. Moreover, there were no cases of nonunion or plate-induced symptoms. Both in univariable and multivariable analyses, intramedullary bone grafting was associated with shorter bone union time. Conclusions: USO with an intramedullary bone graft for idiopathic UIS has favorable radiological and clinical outcomes. The advantage of this technique is the significant shortening of bone union time.

[Tibiotalocalcaneal arthrodesis for end-stage ankle and hindfoot arthropathy: Short- and mid-term clinical outcomes].

OBJECTIVE: To analyze the clinical data of patients with end-stage ankle and hindfoot arthropathy who underwent tibiotalocalcaneal (TTC) arthrodesis by the same surgeon, explore the short- and mid-term clinical results, complications and functional improvement, and discuss the clinical prognosis and precautions of TTC arthrodesis. METHODS: Retrospective analysis was made on the clinical data of 40 patients who underwent TTC arthrodesis by the same surgeon from March 2011 to December 2020. In this study, 23 males and 17 females were included, with an average age of (49.1±16.0) years. All the patients underwent unilateral surgery. The clinical characteristics, imaging manifestations, main diagnosis and specific surgical techniques of the patients were recorded. The clinical outcomes were evaluated by comparison of the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) between pre-operation and at the last follow-up. The fusion healing time, symptom improvement (significant improvement, certain improvement, no improvement or deterioration) and postoperative complications were also recorded. RESULTS: The median follow-up time was 38.0 (26.3, 58.8) months. The preoperative VAS score was 6.0 (4.0, 7.0), and the AOFAS score was 33.0 (25.3, 47.3). At the last follow-up, the median VAS score was 0 (0, 3.0), and the AOFAS score was 80.0 (59.0, 84.0). All the significantly improved compared with their preoperative corresponding values (P < 0.05). There was no wound necrosis or infection in the patients. One patient suffered from subtalar joint nonunion, which was syphilitic Charcot arthropathy. The median bony healing time of other patients was 15.0 (12.0, 20.0) weeks. Among the included patients, there were 25 cases with significant improvement in symptom compared with that preoperative, 8 cases with certain improvement, 4 cases with no improvement, and 3 cases with worse symptoms than that before operation. CONCLUSION: TTC arthrodesis is a reliable method for the treatment of the end-stage ankle and hindfoot arthropathy. The function of most patients was improved postoperatively, with little impact on daily life. The causes of poor prognosis included toe stiffness, stress concentration in adjacent knee joints, nonunion and pain of unknown causes.

Minimial clinically important difference values in distal metaphyseal ulnar shortening for ulnar impaction syndrome and assessment of the relationship between level of the osteotomy and bone union time.

OBJECTIVE: We aimed to define minimal clinically important difference (MCID) values of patient-reported outcome measures (PROMs) for distal metaphyseal ulnar shortening and to assess the relationship between level of the osteotomy and time to bone union. METHODS: 20 patients who had distal metaphyseal ulnar shortening osteotomies due to ulnar impaction syndrome and had at least 6 months of follow-ups were included in this study. The mean follow-up period was 12.3 ± 7.01 months. The PROMs which consisted of patient-rated wrist evaluation (PRWE) and quick disabilities of arm, shoulder, and hand (QDASH) were recorded on the day before the surgery and at follow-up assessments. Grip strength and range of motion were recorded for operated and contralateral wrists at postoperative assessments. Postoperative radiological evaluations of distance of the osteotomy from the distal ulnar articular surface (osteotomy level), the union of osteotomy site; preoperative and postoperative evaluations of styloid-triquetral distance, and ulnar variance were performed using AP wrist x-rays. The MCID values for PRWE and QDASH were calculated using ROC curve analysis. RESULTS: Mean PRWE and QDASH scores decreased statistically significantly. The mean grip strength of contralateral wrists was higher. Mean ulnar variance decreased, whereas styloid-triquetral distance increased postoperatively. Patients with osteotomy levels of greater than 13.7 mm had a longer time from surgery to bone union. Furthermore, patients with time from surgery to bone union shorter than 7 weeks had an osteotomy closer to the ulnar articular surface. The MCID values for PRWE and QDASH were analyzed and calculated through the ROC curve as 22.25 and 20.45, respectively. CONCLUSION: This study has shown us that the osteotomy level affects the time to bone union and an osteotomy closer than 13.7 mm to the ulnar articular surface seems to result in shorter union time. Furthermore, MCID values were defined for PRWE and QDASH as 22.25 and 20.45, respectively. LEVEL OF EVIDENCE: Level IV, Therapeutic Study.

Prevalence of elbow dysplasia in 13 dog breeds in France: a retrospective radiographic study (2002-2022).

OBJECTIVE: To describe the prevalence of elbow dysplasia (ED) in 13 dog breeds in France. ANIMALS: A total of 18,870 elbow radiographs taken from 2002 to 2022 were evaluated by 2 independent examiners. METHODS: For each breed, the incidence of each of the 4 International Elbow Working Group scoring classes was extracted from the database. Breeds were excluded if fewer than 150 radiographs had been read for that breed. RESULTS: This study included 17,861 records for 13 dog breeds: American Akita, Alaskan Malamute, Old German Shepherd (Altdeutscher Schäferhund), American Staffordshire Terrier, Australian Shepherd, Belgian Shepherd, White Swiss Shepherd, Bernese Mountain Dog, Cane Corso, Czechoslovakian Wolfdog, Rhodesian Ridgeback, Rottweiler, and Dogue de Bordeaux. The overall prevalence of ED was 11.4%, ranging from 1.1% in the Czechoslovakian Wolfdog to 32.2% in the Dogue de Bordeaux. The Dogue de Bordeaux, Rottweiler, Bernese Mountain Dog, and Cane Corso breeds were most commonly affected by ED. The prevalence of ED was significantly higher in male dogs than in female dogs (17.5% vs 10.5%, P < .05). Joint incongruity and fragmented coronoid process were the 2 most common primary ED lesions identified. The prevalence of ED among the dogs evaluated decreased over the timeframe of the study. CLINICAL RELEVANCE: The results of this study help to clarify the prevalence of ED in different breeds in France. These data should be interpreted with caution as this study included a small percentage of the total number of dogs born for each breed in France over the study period.

Review of the clinical diagnosis of sacroiliac dysfunction in horses - Challenges and limitations.

Sacroiliac dysfunction (SID) is a condition seen in horses associated with poor performance that affects hind limb gait and impulsion. The condition comprises pain and dysfunction but there lacks clarity around the aetiopathogenesis and whether SID encompasses abnormal joint pathology, abnormal joint movement, abnormal regional biomechanical function, joint laxity and pain, or various combinations of these that may vary over time. Clinical assessment remains challenging for equine clinicians due to the deep location of the sacroiliac joint (SIJ) and surrounding structures which limits access for palpation, diagnostic imaging and joint-specific injection. There is no recognised single reference standard diagnostic test for SID. Clinical diagnosis has been based on ruling out other causes of hind limb lameness, along with combinations of ultrasonography, scintigraphy and periarticular anaesthesia of the SIJ. Recent studies have highlighted the lack of specificity of injections targeting the SIJ, with significant dispersal of injectate into surrounding structures including around the lumbosacral joint (LSJ). Advanced imaging modalities such as computed tomography offers promise for assessment of the structure and pathology of the SIJ and surrounding bony structures. However, there is a need to improve the understanding of the significance of anatomic variation of the sacroiliac region structures, with recent studies reporting detailed anatomic variation in groups of horses with and without SID. There are also limitations around functional assessment of the joint which is still largely reliant on a thorough clinical examination. This review aims to present an update on clinical approaches to the diagnosis of horses with SID, and to consider the challenges and limitations.

Multimorbidity healthcare expenditure in Belgium: a 4-year analysis (COMORB study).

BACKGROUND: The complex management of health needs in multimorbid patients, alongside limited cost data, presents challenges in developing cost-effective patient-care pathways. We estimated the costs of managing 171 dyads and 969 triads in Belgium, taking into account the influence of morbidity interactions on costs. METHODS: We followed a retrospective longitudinal study design, using the linked Belgian Health Interview Survey 2018 and the administrative claim database 2017-2020 hosted by the Intermutualistic Agency. We included people aged 15 and older, who had complete profiles (N = 9753). Applying a system costing perspective, the average annual direct cost per person per dyad/triad was presented in 2022 Euro and comprised mainly direct medical costs. We developed mixed models to analyse the impact of single chronic conditions, dyads and triads on healthcare costs, considering two-/three-way interactions within dyads/triads, key cost determinants and clustering at the household level. RESULTS: People with multimorbidity constituted nearly half of the study population and their total healthcare cost constituted around three quarters of the healthcare cost of the study population. The most common dyad, arthropathies + dorsopathies, with a 14% prevalence rate, accounted for 11% of the total national health expenditure. The most frequent triad, arthropathies + dorsopathies + hypertension, with a 5% prevalence rate, contributed 5%. The average annual direct costs per person with dyad and triad were €3515 (95% CI 3093-3937) and €4592 (95% CI 3920-5264), respectively. Dyads and triads associated with cancer, diabetes, chronic fatigue, and genitourinary problems incurred the highest costs. In most cases, the cost associated with multimorbidity was lower or not substantially different from the combined cost of the same conditions observed in separate patients. CONCLUSION: Prevalent morbidity combinations, rather than high-cost ones, made a greater contribution to total national health expenditure. Our study contributes to the sparse evidence on this topic globally and in Europe, with the aim of improving cost-effective care for patients with diverse needs.

The effect of cuff arthropathy stage on sleep disturbance and kinesiophobia in reverse shoulder arthroplasty patients.

BACKGROUND: The current study aimed to determine the changes in pre-and post-operative Pittsburg sleep quality index (PSQI) and Tampa scale of kinesiophobia (TSK) values ​​according to the Hamada classification in patients who underwent reverse shoulder arthroplasty (RSA) for rotator cuff tear arthropathy (RCTA). METHODS: One hundred and eight patients who underwent RSA for RCTA were reviewed retrospectively. The patients were divided into two groups with low grade (stages 1-2-3) (n = 49) and high grade (stages 4a-4b-5) (n = 59) according to the Hamada classification, which is the radiographic evaluation of RCTA. PSQI and TSK values ​​were calculated preoperatively, and post-operatively at the 6th week, 6th month, and 1st year. The change in PSQI and TSK values ​​between the evaluations and the effect of staging according to the Hamada classification on this change was examined. RESULTS: When compared in preoperative evaluations, PSQI and TSK scores were found to be lower in low-grade group 1 (7.39 ± 1.56, 51.88 ± 4.62, respectively) than in high-grade group 2 (10.47 ± 2.39, 57.05 ± 3.25, respectively) according to Hamada classification (both p < 0.001). In the postoperative evaluations, PSQI and TSK results decreased gradually compared to the preoperative evaluations, and there was a severe decrease in both parameters between the 6th-week and 6th-month evaluations (both p < 0.001). Preoperatively, 102 (95%) patients had sleep disturbance (PSQI ≥ 6), and 108 (100%) patients had high kinesiophobia (TSK > 37). In the 1st year follow-ups, sleep disturbance was observed in 5 (5%) patients and kinesiophobia in 1 (1%) patient. When the Hamada stages were compared, it was seen that there was a significant difference before the operation (both p < 0.001), but the statistically significant difference disappeared in the PSQI value in the 1st year (p = 0.092) and in the TSK value in the 6th month (p = 0.164) post-operatively. It was observed that Hamada staging caused significant differences in PSQI and TSK values ​​in the preoperative period but did not affect the clinical results after treatment. CONCLUSIONS: RSA performed based on RCTA improves sleep quality and reduces kinesiophobia. RCTA stage negatively affects PSQI and TSK before the operation but does not show any effect after the treatment.

Hypertrophied medial parapatellar plica: a case of a medial plica anatomical variation with insertion to the inter-meniscal ligament in an adolescent athlete treated arthroscopically.

PURPOSE: The present study aims to report the arthroscopic, radiological and clinical appearance of a rare anatomical variation of a hypertrophied medial parapatellar plica with its response to arthroscopic treatment. CASE PRESENTATION: A 14-year-old female handball athlete presented with a history of left knee injury during her participation in a handball training session and subsequent locked knee at 20º flexion. Tenderness was located at the medial joint line. Plain radiographs of the injured knee were normal. The magnetic resonance imaging revealed a hypertrophic medial parapatellar plica and a horizontal tear of the medial meniscus. A standard knee arthroscopy was performed. An extremely hypertrophied medial plica was identified, covering a great part of the medial femoral condyle extending up to the femoral trochlea. Distally, it was attached into the inter-meniscal ligament. The plica was excised and the medial meniscus tear was repaired. At 1-month post-operatively, the patient was completely asymptomatic and at 3-months she returned to her weekly training routine. CONCLUSIONS: This study presented a rare anatomical variation of a hypertrophied medial parapatellar plica with atypical course in the medial patellofemoral compartment and insertion into the inter-meniscal ligament. In combination with a medial meniscus tear led to a locked knee. Arthroscopic medial meniscus repair and plica excision resulted in complete resolution of symptoms.

A literature review of biomechanical studies on physiological and pathological sacroiliac joints: Articular surface structure, joint motion, dysfunction and treatments.

BACKGROUND: Sacroiliac joints are affected by mechanical environments; the joints are formed under mechanical stimulation, receive impact of walking between the upper and lower parts of the bodies and can be a cause of pain due to non-physiological loads. However, there are so far very few studies that reviewed biomechanics of physiological and pathological sacroiliac joints. This review article aims to describe the current sacroiliac joint biomechanics. METHODS: Previous original papers have been summarized based on three categories: articular surface structure, sacroiliac joint motion and sacroiliac joint dysfunction and treatments. FINDINGS: Although the articular surface morphologies vary greatly from individual to individual, many researchers have tried to classify the joints into several types. It has been suggested that the surface morphologies may not change regardless of joint dysfunction, however, the relationship between the joint structure and pain are still unclear. The range of sacroiliac joint motion is demonstrated to be less than 1 mm and there is no difference between physiological and pathological joints. The sacroiliac joint absorbs shock within the pelvis by the joint structures of pelvic morphology, ligaments and fat tissues. The morphology and motion of the sacroiliac joints may be optimized for upright bipedal walking. INTERPRETATION: There is no doubt that pelvic mechanical environments affect pain induction and treatment; however, no one has yet provided a concrete explanation. Future research could help develop treatments based on sacroiliac joint biomechanics to support joint function.