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Children (Basel, Switzerland) Dec 2023A single congenital muscular torticollis (CMT) is a postural musculoskeletal deformity and is characterized by the shortening or stiffness of the sternocleidomastoid... (Review)
Review
A single congenital muscular torticollis (CMT) is a postural musculoskeletal deformity and is characterized by the shortening or stiffness of the sternocleidomastoid muscle. The reported incidence of CMT ranges from 0.2% to 2%. The objective is to evaluate the effect of physical therapy programs on CMT. For the search, PubMed, Scopus, Web of Science, PEDro and Cochrane databases were used. Randomized controlled trials published between 2018 and 2023 have been included. This study follows the PRISMA 2020 statement and has been registered in the PROSPERO database. Finally, six studies were included. The cervical range of motion (ROM) in rotation was the most analyzed variable, followed by the ultrasound evaluation; one of the studies included the analysis of children's motor development with the Alberta scale. All research found benefits associated with soft tissue mobilization, passive stretching techniques and manual therapy of the cervical spine. In conclusion, it is possible to recommend manual therapy and passive stretching techniques for the treatment of CMT, with significant results on the cervical ROM.
PubMed: 38275429
DOI: 10.3390/children11010008 -
Foot & Ankle Orthopaedics Jul 2023Ankle fractures are common musculoskeletal injuries that may result in tibiotalar joint dislocations. Ankle fracture-dislocations occur via similar mechanisms as ankle... (Review)
Review
Ankle fractures are common musculoskeletal injuries that may result in tibiotalar joint dislocations. Ankle fracture-dislocations occur via similar mechanisms as ankle fractures, although the persistence or magnitude of the deforming force is sufficient to disrupt any remaining bony or soft-tissue stability. Ankle fracture-dislocations likely represent distinct clinical entities, as the pathology, management, and patient outcomes following these injuries differ from those seen in more common ankle fractures without dislocation. Ankle fracture-dislocations have higher rates of concomitant injury including open fractures, chondral lesions, and intra-articular loose bodies. Long-term outcomes in ankle fracture-dislocations are worse than ankle fractures without dislocation. Higher rates of posttraumatic osteoarthritis and chronic pain have also been reported. In this review, we discuss the current literature regarding the history, management, and outcomes of ankle-fracture dislocations and highlight the need for future study.
PubMed: 37582190
DOI: 10.1177/24730114231195058 -
Frontiers in Pharmacology 2024Friedreich's ataxia (FRDA) is a rare childhood neurologic disorder, affecting 1 in 50,000 Caucasians. The disease is caused by the abnormal expansion of the GAA repeat... (Review)
Review
Friedreich's ataxia (FRDA) is a rare childhood neurologic disorder, affecting 1 in 50,000 Caucasians. The disease is caused by the abnormal expansion of the GAA repeat sequence in intron 1 of the gene, leading to the reduced expression of the mitochondrial protein frataxin. The disease is characterised by progressive neurodegeneration, hypertrophic cardiomyopathy, diabetes mellitus and musculoskeletal deformities. The reduced expression of frataxin has been suggested to result in the downregulation of endogenous antioxidant defence mechanisms and mitochondrial bioenergetics, and the increase in mitochondrial iron accumulation thereby leading to oxidative stress. The confirmation of oxidative stress as one of the pathological signatures of FRDA led to the search for antioxidants which can be used as therapeutic modality. Based on this observation, antioxidants with different mechanisms of action have been explored for FRDA therapy since the last two decades. In this review, we bring forth all antioxidants which have been investigated for FRDA therapy and have been signed off for clinical trials. We summarise their various target points in FRDA disease pathway, their performances during clinical trials and possible factors which might have accounted for their failure or otherwise during clinical trials. We also discuss the limitation of the studies completed and propose possible strategies for combinatorial therapy of antioxidants to generate synergistic effect in FRDA patients.
PubMed: 38379897
DOI: 10.3389/fphar.2024.1359618 -
JBMR Plus Jul 2023Mutations in the COL1A1 and COL1A2 genes, which encode type I collagen, are present in around 85%-90% of osteogenesis imperfecta (OI) patients. Because type I collagen...
Mutations in the COL1A1 and COL1A2 genes, which encode type I collagen, are present in around 85%-90% of osteogenesis imperfecta (OI) patients. Because type I collagen is the principal protein composition of bones, any changes in its gene sequences or synthesis can severely affect bone structure. As a result, skeletal deformity and bone frailty are defining characteristics of OI. Homozygous mice are utilized as models of severe progressive type III OI. Bone adapts to external forces by altering its mass and architecture. Previous attempts to leverage the relationship between muscle and bone involved using a soluble activin receptor type IIB-mFc (sActRIIB-mFc) fusion protein to lower circulating concentrations of activin A and myostatin. These two proteins are part of the TGF-β superfamily that regulate muscle and bone function. While this approach resulted in increased muscle masses and enhanced bone properties, adverse effects emerged due to ligand promiscuity, limiting clinical efficacy and obscuring the precise contributions of myostatin and activin A. In this study, we investigated the musculoskeletal and whole-body metabolism effect of treating 5-week-old wildtype (Wt) and / mice for 11 weeks with either control antibody (Ctrl-Ab) or monoclonal anti-activin A antibody (ActA-Ab), anti-myostatin antibody (Mstn-Ab), or a combination of ActA-Ab and Mstn-Ab (Combo). We demonstrated that ActA-Ab treatment minimally impacts muscle mass in / mice, whereas Mstn-Ab and Combo treatments substantially increased muscle mass and overall lean mass regardless of genotype and sex. Further, while no improvements in cortical bone microarchitecture were observed with all treatments, minimal improvements in trabecular bone microarchitecture were observed with the Combo treatment in / mice. Our findings suggest that individual or combinatorial inhibition of myostatin and activin A alone is insufficient to robustly improve femoral biomechanical and microarchitectural properties in severely affected OI mice. © 2023 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 37457877
DOI: 10.1002/jbm4.10753 -
Clinical Therapeutics Sep 2023Psoriatic arthritis (PsA) is a chronic autoimmune disease that causes a variety of musculoskeletal abnormalities. Musculoskeletal ultrasound in PsA is becoming... (Review)
Review
PURPOSE
Psoriatic arthritis (PsA) is a chronic autoimmune disease that causes a variety of musculoskeletal abnormalities. Musculoskeletal ultrasound in PsA is becoming increasingly popular, both in clinical practice and research. This narrative reviews recent literature on the utility of ultrasound in PsA.
METHODS
A search of PubMed was used to identify publications written in English, with titles containing the term psoriatic arthritis and either ultrasound, ultrasonography, or sonographic. A total of 178 publications were identified; those that were not relevant (n = 59), were not original research (n = 45), or that had small (<30) sample sizes (n = 34) were excluded, leaving 40 studies for review of the use of ultrasound in various aspects of PsA. Publications with similar findings were grouped into seven domains: (1) the use of ultrasound findings compared to clinical assessment; (2) the use of ultrasound in the assessment of enthesitis; (3) the use of ultrasound in the assessment of nails; (4) the use of ultrasound as a screening tool in patients with psoriasis at risk for PsA; (5) the use of ultrasound in differentiating PsA from other similar conditions; (6) the use of ultrasound as a measure of disease activity; and (7) the use of ultrasound compared to MRI.
FINDINGS
In recent studies, ultrasound measures of inflammation tended to agree with objective clinical findings of disease, such as swollen joint counts, while being less influenced by subjective measures, such as pain. Ultrasound has utility in the assessment of enthesitis and psoriatic nail disease in PsA, and as an overall measure of disease activity. Ultrasound-based outcomes measures have been used in observational studies and in clinical trials involving PsA, and may have utility as a measure of treatment response. The findings from recent studies suggest that ultrasound may have utility in improving the accuracy and precision of screening programs designed to identify subclinical PsA in cohorts of patients with psoriasis; however, cost-efficacy remains to be determined. Beyond screening, ultrasound may have utility in the diagnosis of PsA in patients with suspected inflammatory arthritis, and ultrasound measures of inflammation agree with MRI measures of inflammation, meaning that incorporating ultrasound into clinical practice might help to overcome the barriers associated with MRI.
IMPLICATIONS
As ultrasound technology continues to advance, and associated costs decrease, it is likely that ultrasound will become more integrated into the clinical journeys of patients with PsA.
Topics: Humans; Arthritis, Psoriatic; Severity of Illness Index; Ultrasonography; Psoriasis; Enthesopathy; Inflammation
PubMed: 37563062
DOI: 10.1016/j.clinthera.2023.07.017 -
Primary Care Diabetes Dec 2023The current study ushers in a comprehensive review in clinical research to demonstrate the prevalence of musculoskeletal (MSK) complications in diabetes mellitus and the... (Review)
Review
The current study ushers in a comprehensive review in clinical research to demonstrate the prevalence of musculoskeletal (MSK) complications in diabetes mellitus and the most relevant clinical aspects. In particular, revealing the early symptoms of the disorders, the pathology lurking behind the complications and their optimal management. In diabetes mellitus, MSK complications are common and are largely due to similar pathogenetic factors responsible for the internal organ complications associated with diabetes leading to chronic low-intensity inflammatory processes. MSK disorders develop by vasculopathy, neuropathy, arthropathy or combinations of the above, which are not specific to diabetes. However, their prevalence is significantly increased in diabetes and contributes to the disability impairing patients' quality of life. Locomotor disease affects approximately 34.4-83.5 % of patients suffering from type-2 diabetes mellitus. Several musculoskeletal abnormalities (cheiroarthropathy, Dupuytren's contracture, trigger finger, ect.) can be diagnosed upon physical examination, although certain symptoms (frozen shoulder, neurogenic arthropathy, septic arthritis, etc.) require differential diagnostic considerations. Early identification regarding characteristic symptoms in the treatment reducing inflammation and pain, followed with increasingly strenuous exercise therapy, aligned with optimal management of carbohydrate metabolism, proves essential in alleviating MSK complications.
Topics: Humans; Quality of Life; Musculoskeletal Diseases; Joint Diseases; Dupuytren Contracture; Diabetes Mellitus, Type 2
PubMed: 37643934
DOI: 10.1016/j.pcd.2023.08.003 -
Journal of Medical Genetics Feb 2024The Ehlers-Danlos syndromes (EDS) are heritable disorders of connective tissue (HDCT), reclassified in the 2017 nosology into 13 subtypes. The genetic basis for...
BACKGROUND
The Ehlers-Danlos syndromes (EDS) are heritable disorders of connective tissue (HDCT), reclassified in the 2017 nosology into 13 subtypes. The genetic basis for hypermobile Ehlers-Danlos syndrome (hEDS) remains unknown.
METHODS
Whole exome sequencing (WES) was undertaken on 174 EDS patients recruited from a national diagnostic service for complex EDS and a specialist clinic for hEDS. Patients had already undergone expert phenotyping, laboratory investigation and gene sequencing, but were without a genetic diagnosis. Filtered WES data were reviewed for genes underlying Mendelian disorders and loci reported in EDS linkage, transcriptome and genome-wide association studies (GWAS). A genetic burden analysis (Minor Allele Frequency (MAF) <0.05) incorporating 248 Avon Longitudinal Study of Parents and Children (ALSPAC) controls sequenced as part of the UK10K study was undertaken using TASER methodology.
RESULTS
Heterozygous pathogenic (P) or likely pathogenic (LP) variants were identified in known EDS and Loeys-Dietz (LDS) genes. Multiple variants of uncertain significance where segregation and functional analysis may enable reclassification were found in genes associated with EDS, LDS, heritable thoracic aortic disease (HTAD), Mendelian disorders with EDS symptomatology and syndromes with EDS-like features. Genetic burden analysis revealed a number of novel loci, although none reached the threshold for genome-wide significance. Variants with biological plausibility were found in genes and pathways not currently associated with EDS or HTAD.
CONCLUSIONS
We demonstrate the clinical utility of large panel-based sequencing and WES for patients with complex EDS in distinguishing rare EDS subtypes, LDS and related syndromes. Although many of the P and LP variants reported in this cohort would be identified with current panel testing, they were not at the time of this study, highlighting the use of extended panels and WES as a clinical tool for complex EDS. Our results are consistent with the complex genetic architecture of EDS and suggest a number of novel hEDS and HTAD candidate genes and pathways.
Topics: Child; Humans; Genome-Wide Association Study; Longitudinal Studies; Ehlers-Danlos Syndrome; Connective Tissue Diseases
PubMed: 37813462
DOI: 10.1136/jmg-2023-109329