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Biochimica Et Biophysica Acta Apr 2015The term hereditary inclusion-body myopathies (HIBMs) defines a group of rare muscle disorders with autosomal recessive or dominant inheritance and presence of muscle... (Review)
Review
The term hereditary inclusion-body myopathies (HIBMs) defines a group of rare muscle disorders with autosomal recessive or dominant inheritance and presence of muscle fibers with rimmed vacuoles and collection of cytoplasmic or nuclear 15-21 nm diameter tubulofilaments as revealed by muscle biopsy. The most common form of HIBM is due to mutations of the GNE gene that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. This results in abnormal sialylation of glycoproteins that possibly leads to muscle fiber degeneration. Mutations of the valosin containing protein are instead responsible for hereditary inclusion-body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD), with these three phenotypic features having a variable penetrance. IBMPFD probably represents a disorder of abnormal cellular trafficking of proteins and maturation of the autophagosome. HIBM with congenital joint contractures and external ophthalmoplegia is due to mutations of the Myosin Heavy Chain IIa gene that exerts a pathogenic effect through interference with filament assembly or functional defects in ATPase activity. This review illustrates the clinical and pathologic characteristics of HIBMs and the main clues available to date concerning the possible pathogenic mechanisms and therapeutic perspectives of these disorders. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
Topics: Animals; Contracture; Frontotemporal Dementia; Humans; Muscle Fibers, Skeletal; Muscular Dystrophies, Limb-Girdle; Mutation; Myosin Heavy Chains; Myositis, Inclusion Body; N-Acetylneuraminic Acid; Ophthalmoplegia; Osteitis Deformans; Protein Processing, Post-Translational
PubMed: 25149037
DOI: 10.1016/j.bbadis.2014.08.007 -
Acta Orthopaedica Apr 2019Background and purpose - Up to 20% of patients are dissatisfied after total knee arthroplasty (TKA), mainly because of pain and restricted physical function. We...
Background and purpose - Up to 20% of patients are dissatisfied after total knee arthroplasty (TKA), mainly because of pain and restricted physical function. We developed a prediction model for 6-month knee range of motion, knee pain, and walking limitations in patients undergoing TKA surgery. Patients and methods - We performed a prospective cohort study of 4,026 patients who underwent elective, primary TKA between July 2013 and July 2017. Candidate predictors included demographic, clinical, psychosocial, and preoperative outcome measures. The outcomes of interest were (i) knee extension and flexion range of motion, (ii) knee pain rated on a 5-point ordinal scale, and (iii) self-reported maximum walk time at 6 months post TKA. For each outcome, we fitted a multivariable proportional odds regression model with bootstrap internal validation. Results - At 6 months post TKA, around 5% to 20% of patients had a flexion contracture ³ 10°, range of motion < 90°, moderate to severe knee pain, or a maximum walk time £ 15 minutes. The model c-indices (the probabilities to correctly discriminate between 2 patients with different levels of follow-up TKA outcomes) when evaluating these patients were 0.71, 0.79, 0.65, and 0.76, respectively. Each postoperative outcome was strongly influenced by the same outcome measure obtained preoperatively (all p-values < 0.001). Additional statistically significant predictors were age, sex, race, education level, diabetes mellitus, preoperative use of gait aids, contralateral knee pain, and psychological distress (all p-values < 0.001). Interpretation - We have developed models to predict, for individual patients, their likely post-TKA levels of knee extension and flexion range of motion, knee pain, and walking limitations. After external validation, they can potentially be used preoperatively to identify at-risk patients and to help patients set more realistic expectations about surgical outcomes.
Topics: Aged; Arthralgia; Arthroplasty, Replacement, Knee; Female; Humans; Knee Joint; Male; Middle Aged; Mobility Limitation; Osteoarthritis, Knee; Outcome Assessment, Health Care; Perioperative Period; Postoperative Complications; Prognosis; Range of Motion, Articular; Risk Assessment; Taiwan
PubMed: 30973090
DOI: 10.1080/17453674.2018.1560647 -
Lakartidningen May 2019
Topics: Algorithms; Diagnosis, Differential; Dupuytren Contracture; Ganglion Cysts; Humans; Sick Leave; Trigger Finger Disorder; Wrist Joint
PubMed: 31192400
DOI: No ID Found -
Hand (New York, N.Y.) Jun 2023Revision procedures for recurrent Dupuytren disease (DD) can be difficult and carry a high risk of complications. Our goal was to describe surgical strategies used for... (Review)
Review
BACKGROUND
Revision procedures for recurrent Dupuytren disease (DD) can be difficult and carry a high risk of complications. Our goal was to describe surgical strategies used for cases of recurrence and report on their outcomes.
METHODS
We reviewed 1 surgeon's operative cases for recurrent DD performed at 1 institution. Prior procedures included collagenase injection, percutaneous needle fasciotomy, or open surgical fasciectomy in the same digit or area of the hand.
RESULTS
From January 1981 to December 2020, 54 procedures were performed on 33 patients for recurrent DD. Most patients were men (82%), had bilateral involvement (64%) and family history (52%), and some had ectopic disease in their feet (24%). The small finger was involved in 76% of the cases, and the proximal interphalangeal (PIP) joint was involved in 83% of these digits. The procedures included 38 partial fasciectomies (72%), 12 dermofasciectomies (23%), 3 radical fasciectomies (6%), 1 of each needle fasciotomy, ray amputation, and PIP joint arthrodesis (2%). Twenty-three patients (43%) required full thickness skin grafts with an average area of 7.1 cm (range: 1-20 cm).
CONCLUSIONS
This study highlights the complexity of recurrent DD case management and found the treatment required for 95% of patients in this series was open partial fasciectomy with or without demofasciectomy. Full thickness skin grafting was necessary in nearly half of the cases.
Topics: Male; Humans; Female; Dupuytren Contracture; Collagenases; Hand; Fasciotomy; Injections
PubMed: 34963318
DOI: 10.1177/15589447211060447 -
BMC Musculoskeletal Disorders Jul 2022Arthrofibrosis, or rigid contracture of major articular joints, is a significant morbidity of many neurodegenerative disorders. The pathogenesis depends on the mechanism... (Review)
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.
Topics: Contracture; Fibrosis; Humans; Joint Capsule; Joint Diseases; Joints; Knee Joint; Range of Motion, Articular
PubMed: 35906570
DOI: 10.1186/s12891-022-05677-z -
Journal of Applied Physiology... May 2019Skeletal muscle contractures represent the permanent shortening of a muscle-tendon unit, resulting in loss of elasticity and, in extreme cases, joint deformation. They... (Review)
Review
Skeletal muscle contractures represent the permanent shortening of a muscle-tendon unit, resulting in loss of elasticity and, in extreme cases, joint deformation. They may result from cerebral palsy, spinal cord injury, stroke, muscular dystrophy, and other neuromuscular disorders. Contractures are the prototypic and most severe clinical presentation of increased passive mechanical muscle force in humans, often requiring surgical correction. Intraoperative experiments demonstrate that high muscle passive force is associated with sarcomeres that are abnormally stretched, although otherwise normal, with fewer sarcomeres in series. Furthermore, changes in the amount and arrangement of collagen in the extracellular matrix also increase muscle stiffness. Structural light and electron microscopy studies demonstrate that large bundles of collagen, referred to as perimysial cables, may be responsible for this increased stiffness and are regulated by interaction of a number of cell types within the extracellular matrix. Loss of muscle satellite cells may be related to changes in both sarcomeres and extracellular matrix. Future studies are required to determine the underlying mechanism for changes in muscle satellite cells and their relationship (if any) to contracture. A more complete understanding of this mechanism may lead to effective nonsurgical treatments to relieve and even prevent muscle contractures.
Topics: Animals; Cerebral Palsy; Contracture; Extracellular Matrix; Humans; Muscle Contraction; Muscle, Skeletal; Tendons
PubMed: 30571285
DOI: 10.1152/japplphysiol.00278.2018 -
Stem Cells (Dayton, Ohio) Mar 2020The aim of this study was to explore the therapeutic effects of fat grafting on radiation-induced hind limb contracture. Radiation therapy (RT) is used to palliate...
The aim of this study was to explore the therapeutic effects of fat grafting on radiation-induced hind limb contracture. Radiation therapy (RT) is used to palliate and/or cure a range of malignancies but causes inevitable and progressive fibrosis of surrounding soft tissue. Pathological fibrosis may lead to painful contractures which limit movement and negatively impact quality of life. Fat grafting is able to reduce and/or reverse radiation-induced soft tissue fibrosis. We explored whether fat grafting could improve extensibility in irradiated and contracted hind limbs of mice. Right hind limbs of female 60-day-old CD-1 nude mice were irradiated. Chronic skin fibrosis and limb contracture developed. After 4 weeks, irradiated hind limbs were then injected with (a) fat enriched with stromal vascular cells (SVCs), (b) fat only, (c) saline, or (d) nothing (n = 10/group). Limb extension was measured at baseline and every 2 weeks for 12 weeks. Hind limb skin then underwent histological analysis and biomechanical strength testing. Irradiation significantly reduced limb extension but was progressively rescued by fat grafting. Fat grafting also reduced skin stiffness and reversed the radiation-induced histological changes in the skin. The greatest benefits were found in mice injected with fat enriched with SVCs. Hind limb radiation induces contracture in our mouse model which can be improved with fat grafting. Enriching fat with SVCs enhances these beneficial effects. These results underscore an attractive approach to address challenging soft tissue fibrosis in patients following RT.
Topics: Adipose Tissue; Animals; Contracture; Female; Hindlimb; Humans; Mice; Mice, Nude; Radiation Injuries, Experimental
PubMed: 31793745
DOI: 10.1002/stem.3115 -
Communications Biology Nov 2023Dupuytren's contracture, a superficial dermal fibrosis, causes flexion contracture of the affected finger, impairing hand function. Specific single-nucleotide...
Dupuytren's contracture, a superficial dermal fibrosis, causes flexion contracture of the affected finger, impairing hand function. Specific single-nucleotide polymorphisms within genes in the Wnt signalling pathway are associated with the disease. However, the precise role of Wnt signalling dysregulation in the onset and progression of Dupuytren's contracture remains unclear. Here, using a fibrosis mouse model and clinical samples of human Dupuytren's contractures, we demonstrate that the activation of Wnt/β-catenin signalling in Tppp3-positive cells in the dermis of the paw is associated with the development of fibrosis. Fibrosis development and progression via Wnt/β-catenin signalling are closely related to stromal cell-macrophage interactions, and Wnt/β-catenin signalling activation in Tppp3-positive stromal cells causes M2 macrophage infiltration via chemokine Cxcl14, resulting in the formation of a TGF-β-expressing fibrotic niche. Inhibition of Cxcl14 mitigates fibrosis by decreasing macrophage infiltration. These findings suggest that Cxcl14-mediated stromal cell-macrophage interaction is a promising therapeutic target for Wnt/β-catenin-induced fibrosis.
Topics: Animals; Mice; Humans; Dupuytren Contracture; beta Catenin; Ligands; Wnt Signaling Pathway; Fibrosis
PubMed: 37980373
DOI: 10.1038/s42003-023-05558-8 -
Annals of Physical and Rehabilitation... Nov 2019Joint contractures and acquired deforming hypertonia are frequent in dependent older people. The consequences of these conditions can be significant for activities of... (Review)
Review
Joint contractures and acquired deforming hypertonia are frequent in dependent older people. The consequences of these conditions can be significant for activities of daily living as well as comfort and quality of life. They can also negatively affect the burden of care and care costs. However, etiological factors and pathophysiologic mechanisms remain only partly understood. As a result, preventive interventions and treatments focus entirely on controlling symptoms rather than the causes. Moreover, the effectiveness of these interventions remains to be validated. The purpose of this position paper is to present current data on etiological factors contributing to the development of joint contractures and acquired deforming hypertonia in older people. The pathophysiologic mechanisms of joint contractures in animal models are also presented.
Topics: Aged; Aged, 80 and over; Aging; Animals; Contracture; Female; Humans; Male; Muscle Hypertonia; Risk Factors
PubMed: 30537536
DOI: 10.1016/j.rehab.2018.10.005 -
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