-
Annals of the Rheumatic Diseases Apr 2024Giant cell arteritis (GCA), the most common systemic vasculitis, is characterised by aberrant interactions between infiltrating and resident cells of the vessel wall.... (Review)
Review
Giant cell arteritis (GCA), the most common systemic vasculitis, is characterised by aberrant interactions between infiltrating and resident cells of the vessel wall. Ageing and breach of tolerance are prerequisites for GCA development, resulting in dendritic and T-cell dysfunction. Inflammatory cytokines polarise T-cells, activate resident macrophages and synergistically enhance vascular inflammation, providing a loop of autoreactivity. These events originate in the adventitia, commonly regarded as the biological epicentre of the vessel wall, with additional recruitment of cells that infiltrate and migrate towards the intima. Thus, GCA-vessels exhibit infiltrates across the vascular layers, with various cytokines and growth factors amplifying the pathogenic process. These events activate ineffective repair mechanisms, where dysfunctional vascular smooth muscle cells and fibroblasts phenotypically shift along their lineage and colonise the intima. While high-dose glucocorticoids broadly suppress these inflammatory events, they cause well known deleterious effects. Despite the emerging targeted therapeutics, disease relapse remains common, affecting >50% of patients. This may reflect a discrepancy between systemic and local mediators of inflammation. Indeed, temporal arteries and aortas of GCA-patients can show immune-mediated abnormalities, despite the treatment induced clinical remission. The mechanisms of persistence of vascular disease in GCA remain elusive. Studies in other chronic inflammatory diseases point to the fibroblasts (and their lineage cells including myofibroblasts) as possible orchestrators or even effectors of disease chronicity through interactions with immune cells. Here, we critically review the contribution of immune and stromal cells to GCA pathogenesis and analyse the molecular mechanisms by which these would underpin the persistence of vascular disease.
PubMed: 38684323
DOI: 10.1136/ard-2023-225270 -
Foot (Edinburgh, Scotland) Jun 2024The adult cavus foot represents a challenging clinical problem, with varied aetiology and complex, 3-dimensional deformities. Thus far, the cavus foot has eluded a... (Review)
Review
AIMS
The adult cavus foot represents a challenging clinical problem, with varied aetiology and complex, 3-dimensional deformities. Thus far, the cavus foot has eluded a unified classification. The aim of this paper was to appraise the literature to identify classification systems which guide the operative management of neurological cavus feet in adults.
METHODS
As the aim of this paper was broad, a scoping review was conducted. The review was conducted in line with published frameworks. Our principal research question was 'what classification systems that guide surgical management currently exist for neurological cavus feet in adults'. We searched CINAHL, Embase, OVID, Proquest, Pubmed, Scopus and Web of Science databases using MESH and non-MESH terms. Two authors independently reviewed abstracts / papers and a data extraction sheet was used to collect the relevant data.
RESULTS
A total of 1140 articles were initially screened, identifying 125 articles for which a full text review was performed. Only three articles met all our inclusion criteria. All these articles reported an anatomical classification with suggestions for treatment based on the classification. All were considered to comprise Level V evidence, and none reported outcomes of treatment based on the classification.
CONCLUSIONS
There is currently a paucity of robust classifications to guide treatment in neurological cavus feet in adults. The few classifications systems that exist are varied and do not as yet have sufficient evidence to support their widespread use. Further work is required, aimed at identifying specific features of cavus feet that would guide operative treatment.
Topics: Humans; Adult; Talipes Cavus
PubMed: 38678805
DOI: 10.1016/j.foot.2024.102098 -
Journal of Medical Case Reports Apr 2024Sprengel's deformity is a congenital abnormality of the shoulder girdle. Because scapular retraction, such as the Green procedure, is usually performed during childhood...
BACKGROUND
Sprengel's deformity is a congenital abnormality of the shoulder girdle. Because scapular retraction, such as the Green procedure, is usually performed during childhood to improve esthetics and shoulder function, Sprengel's deformity is rarely found in older patients.
CASE PRESENTATION
We presented a unique case of a Japanese female cadaver with Sprengel's deformity at the age of 80 years. Anatomical dissection and radiological imaging revealed musculoskeletal anomalies associated with Sprengel's deformity, including Klippel-Feil syndrome, presence of an omovertebral bone, and absence of the trapezius muscle. In addition, bilateral cervical ribs were in contact with the brachial plexus. These anomalies may lead to numbness, pain, and limited range of motion of the neck and upper girdle with aging.
CONCLUSIONS
Because most adult patients with Sprengel's deformity experience neck pain and limited movement of the shoulder, the presented case is a rare case of neglected Sprengel's deformity in an 80-year-old cadaver.
Topics: Humans; Female; Aged, 80 and over; Cadaver; Scapula; Klippel-Feil Syndrome; Congenital Abnormalities; Brachial Plexus; Shoulder Joint
PubMed: 38678290
DOI: 10.1186/s13256-024-04528-w -
Life (Basel, Switzerland) Apr 2024The AMTI VIVO™ six degree of freedom joint simulator allows reproducible preclinical testing of joint endoprostheses under specific kinematic and loading conditions....
The AMTI VIVO™ six degree of freedom joint simulator allows reproducible preclinical testing of joint endoprostheses under specific kinematic and loading conditions. When testing total knee endoprosthesis, the articulating femoral and tibial components are each mounted on an actuator with two and four degrees of freedom, respectively. To approximate realistic physiological conditions with respect to soft tissues, the joint simulator features an integrated virtual ligament model that calculates the restoring forces of the ligament apparatus to be applied by the actuators. During joint motion, the locations of the ligament insertion points are calculated depending on both actuators' coordinates. In the present study, we demonstrate that unintended elastic deformations of the actuators due to the specifically high contact forces in the artificial knee joint have a considerable impact on the calculated ligament forces. This study aims to investigate the effect of this structural compliance on experimental results. While the built-in algorithm for calculating the ligament forces cannot be altered by the user, a reduction of the ligament force deviations due to the elastic deformations could be achieved by preloading the articulating implant components in the reference configuration. As a proof of concept, a knee flexion motion with varying ligament conditions was simulated on the VIVO simulator and compared to data derived from a musculoskeletal multibody model of a total knee endoprosthesis.
PubMed: 38672801
DOI: 10.3390/life14040531 -
Biomolecules Apr 2024Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue... (Review)
Review
Ehlers-Danlos syndromes (EDSs) constitute a heterogeneous group of connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Asymptomatic EDSs, joint hypermobility without associated syndromes, EDSs, and hypermobility spectrum disorders are the commonest phenotypes associated with joint hypermobility. Joint hypermobility syndrome (JHS) is a connective tissue disorder characterized by extreme flexibility of the joints, along with pain and other symptoms. JHS can be a sign of a more serious underlying genetic condition, such as EDS, which affects the cartilage, bone, fat, and blood. The exact cause of JHS could be related to genetic changes in the proteins that add flexibility and strength to the joints, ligaments, and tendons, such as collagen. Membrane proteins are a class of proteins embedded in the cell membrane and play a crucial role in cell signaling, transport, and adhesion. Dysregulated membrane proteins have been implicated in a variety of diseases, including cancer, cardiovascular disease, and neurological disorders; recent studies have suggested that membrane proteins may also play a role in the pathogenesis of JHS. This article presents an exploration of the causative factors contributing to musculoskeletal pain in individuals with hypermobility, based on research findings. It aims to provide an understanding of JHS and its association with membrane proteins, addressing the clinical manifestations, pathogenesis, diagnosis, and management of JHS.
Topics: Humans; Ehlers-Danlos Syndrome; Joint Instability; Membrane Proteins
PubMed: 38672488
DOI: 10.3390/biom14040472 -
Science Advances Apr 2024We aimed to identify serum biomarkers that predict knee osteoarthritis (OA) before the appearance of radiographic abnormalities in a cohort of 200 women. As few as six...
We aimed to identify serum biomarkers that predict knee osteoarthritis (OA) before the appearance of radiographic abnormalities in a cohort of 200 women. As few as six serum peptides, corresponding to six proteins, reached AUC 77% probability to distinguish those who developed OA from age-matched individuals who did not develop OA up to 8 years later. Prediction based on these blood biomarkers was superior to traditional prediction based on age and BMI (AUC 51%) or knee pain (AUC 57%). These results identify a prolonged molecular derangement of joint tissue before the onset of radiographic OA abnormalities consistent with an unresolved acute phase response. Among all 24 protein biomarkers predicting incident knee OA, the majority (58%) also predicted knee OA progression, revealing the existence of a pathophysiological "OA continuum" based on considerable similarity in the molecular pathophysiology of the progression to incident OA and the progression of established OA.
Topics: Humans; Biomarkers; Female; Osteoarthritis, Knee; Middle Aged; Disease Progression; Aged
PubMed: 38669329
DOI: 10.1126/sciadv.adj6814 -
Journal of Orthopaedic Surgery and... Apr 2024patellar instability is a relatively frequent musculoskeletal disorder in children with Down syndrome (DS). However, such a condition has seldom been studied in the...
BACKGROUND
patellar instability is a relatively frequent musculoskeletal disorder in children with Down syndrome (DS). However, such a condition has seldom been studied in the literature, even less its surgical treatment. Different techniques have been offered for this condition; the evidence for surgical options is scarce and primarily based on case reports or case series with few patients and heterogeneous techniques. Given this background, we aimed to evaluate the outcomes of a uniform kind of surgical procedure for such a condition that combined lateral soft tissue release, medial patellofemoral ligament (MPFL) reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty (if needed).
MATERIALS AND METHODS
This retrospective study involved 11 skeletally immature patients (12 knees; 9 males and 2 females), 5.5 to 14.1 years of age, with DS who had patellofemoral instability (PFI) and were managed by this technique between October 2018 and March 2020. Preoperative radiography, CT scan, and MRI were performed to evaluate the physis status, lower limb alignment, patellar height, trochlear morphology, and any associated knee pathology. A functional knee assessment was done by using the Kujala score and the modified Lysholm score.
RESULTS
The mean time of follow-up (± SD) was 47.7 ± 5.8 months (range: 39-56). Pre-operatively, the Kujala score (± SD) was 52.6 ± 14.3 (range: (31-74), and at final follow-up, it was 92.2 ± 4.4 (range: (88-98), showing a significant improvement (P < 0.001). The preoperative modified Lysholm score (± SD) was 54.3 ± 8.1 (range: 39-62), and at final follow-up it was 92.4 ± 5.3 (range: 82-96), showing a significant improvement (P < 0.001). All patients had a stable patella without a recurrence of instability and regained full ROM. There was no incidence of a patellar fracture or femoral physis injury.
CONCLUSIONS
Our proposed technique of combined soft tissue procedures, including lateral soft tissue release, MPFL reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty, was an effective method for treating patellar instability in children with DS while avoiding physeal injury and patellar fracture. Functional scores and radiological outcomes were improved.
LEVEL OF EVIDENCE
IV; retrospective case series.
Topics: Humans; Down Syndrome; Male; Female; Child; Retrospective Studies; Joint Instability; Adolescent; Treatment Outcome; Child, Preschool; Patellofemoral Joint; Follow-Up Studies; Patellar Dislocation; Plastic Surgery Procedures; Orthopedic Procedures
PubMed: 38664709
DOI: 10.1186/s13018-024-04730-y -
Journal of Medical Genetics Jun 2024Clubfoot, presenting as a rigid inward and downward turning of the foot, is one of the most common congenital musculoskeletal anomalies. The aetiology of clubfoot is...
BACKGROUND
Clubfoot, presenting as a rigid inward and downward turning of the foot, is one of the most common congenital musculoskeletal anomalies. The aetiology of clubfoot is poorly understood and variants in known clubfoot disease genes account for only a small portion of the heritability.
METHODS
Exome sequence data were generated from 1190 non-syndromic clubfoot cases and their family members from multiple ethnicities. Ultra-rare variant burden analysis was performed comparing 857 unrelated clubfoot cases with European ancestry with two independent ethnicity-matched control groups (1043 in-house and 56 885 gnomAD controls). Additional variants in prioritised genes were identified in a larger cohort, including probands with non-European ancestry. Segregation analysis was performed in multiplex families when available.
RESULTS
Rare variants in 29 genes were enriched in clubfoot cases, including (a known clubfoot disease gene), , , and . In addition, rare variants in posterior genes () were enriched overall in clubfoot cases. In total, variants in these genes were present in 8.4% (100/1190) of clubfoot cases with both European and non-European ancestry. Among these, 3 are and 22 show variable penetrance, including 4 variants that segregate with clubfoot.
CONCLUSION
We report as a novel clubfoot disease gene and demonstrate a phenotypic expansion of known disease genes (myopathy gene , Ehlers-Danlos syndrome gene and nail-patella syndrome gene ) to include isolated clubfoot.
Topics: Humans; Clubfoot; Exome Sequencing; Homeodomain Proteins; Male; Female; Transcription Factors; Genetic Predisposition to Disease; Exome; Pedigree
PubMed: 38663984
DOI: 10.1136/jmg-2024-109846 -
Health Science Reports Apr 2024Scleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function....
Neurological, cardiac, musculoskeletal, and renal manifestations of scleroderma along with insights into its genetics, pathophysiology, diagnostic, and therapeutic updates.
BACKGROUND
Scleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function. Pathologically, it encompasses the persistent presence of inflammation, abnormal collagen buildup, and restructuring of blood vessels in various organs, resulting in a wide range of clinical symptoms. This review incorporates the most recent scientific literature on scleroderma, with a particular emphasis on its pathophysiology, clinical manifestations, diagnostic approaches, and treatment options.
METHODOLOGY
A comprehensive investigation was carried out on numerous databases, such as PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar, to collect pertinent studies covering diverse facets of scleroderma research.
RESULTS
Scleroderma presents with a range of systemic manifestations, such as interstitial lung disease, gastrointestinal dysmotility, Raynaud's phenomenon, pulmonary arterial hypertension, renal complications, neurological symptoms, and cardiac abnormalities. Serological markers, such as antinuclear antibodies, anti-centromere antibodies, and anti-topoisomerase antibodies, are important for classifying diseases and predicting their outcomes.
DISCUSSION
The precise identification of scleroderma is crucial for promptly and correctly implementing effective treatment plans. Treatment approaches aim to improve symptoms, reduce complications, and slow down the progression of the disease. An integrated approach that combines pharmacological agents, including immunosuppressants, endothelin receptor antagonists, and prostanoids, with nonpharmacological interventions such as physical and occupational therapy is essential for maximizing patient care.
CONCLUSION
Through the clarification of existing gaps in knowledge and identification of emerging trends, our goal is to improve the accuracy of diagnosis, enhance the effectiveness of therapeutic interventions, and ultimately enhance the overall quality of life for individuals suffering from scleroderma. Ongoing cooperation and creative research are necessary to advance the field and achieve improved patient outcomes and new therapeutic discoveries.
PubMed: 38660003
DOI: 10.1002/hsr2.2072 -
Acta Ortopedica Mexicana 2024Amniotic band syndrome (ABS) and clubfoot are distinct congenital musculoskeletal conditions that can occasionally co-occur, creating unique challenges in their... (Review)
Review
Amniotic band syndrome (ABS) and clubfoot are distinct congenital musculoskeletal conditions that can occasionally co-occur, creating unique challenges in their management. This paper summarizes the comprehensive discussion on the management of amniotic band syndrome (ABS) and clubfoot, emphasizing the critical role of the Ponseti method and the challenges faced in treatment, thereby providing a basis for further research and improved patient care.
Topics: Clubfoot; Humans; Amniotic Band Syndrome; Infant, Newborn; Infant; Casts, Surgical
PubMed: 38657150
DOI: No ID Found