OBJECTIVES: The phase 3 ProDERM study demonstrated intravenous immunoglobulin (IVIg) was safe and effective in patients with dermatomyositis (DM). This analysis assessed clinical and serological predictors of IVIg response in DM patients from ProDERM. METHODS: ProDERM was a prospective, randomized, placebo-controlled study of DM patients. For weeks 0-16, patients received 2.0 g/kg IVIg (Octagam, 10%) or placebo every 4 weeks. Eligible patients entered the open-label extension phase, where all received IVIg to week 40. Univariate and multivariate analyses examined associations between baseline variables and total improvement score (TIS), including myositis disease activity assessment tool (MDAAT; assessing different organ involvement), and myositis-specific and myositis-associated autoantibodies. RESULTS: Ninety-five patients were enrolled. Univariate analyses found no significant association between TIS at week 16 or 40 and age; sex; ethnicity; disease duration/activity; cutaneous, skeletal, gastrointestinal or muscle disease activity; or previous failed or concomitant medications. Multivariate analysis found patients with higher MDAAT cutaneous scores had a better chance of at least minimal TIS improvement. Higher MDAAT pulmonary scores were associated with a lower, but still considerable, chance of improvement. Patients with TIF1-γ antibodies had a better TIS response; however, after controlling for cutaneous disease activity, there was no significant association between antibody classification (including anti-TIF1-γ) and efficacy outcome. CONCLUSION: IVIg was effective in treating DM patients regardless of demographic features and autoantibody status (for most autoantibodies). Patients with higher cutaneous disease activity and/or anti-TIF1-γ responded best to IVIg, while pulmonary disease activity predicted a lower, but still effective, IVIg response, warranting further investigation. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02728752.
- Klíčová slova
- anti-TIF1-γ, autoantibody, autoimmune, cutaneous, dermatomyositis, intravenous immunoglobulin, myositis-associated antibodies, myositis-specific antibodies,
- MeSH
- autoprotilátky krev imunologie MeSH
- dermatomyozitida * farmakoterapie imunologie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- imunologické faktory * terapeutické užití MeSH
- intravenózní imunoglobuliny * terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- autoprotilátky MeSH
- imunologické faktory * MeSH
- intravenózní imunoglobuliny * MeSH
OBJECTIVE: Idiopathic inflammatory myopathies (IIMs, myositis) are rare systemic autoimmune disorders that lead to muscle inflammation, weakness, and extramuscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis data set to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes. METHODS: We performed association analyses on 14,903 individuals (3,206 patients and 11,697 controls) with genotypes and imputed data from the Trans-Omics for Precision Medicine reference panel. Fine-mapping and expression quantitative trait locus colocalization analyses in myositis-relevant tissues indicated potential causal variants. Functional annotation and network analyses using the random walk with restart (RWR) algorithm explored underlying genetic networks and drug repurposing opportunities. RESULTS: Our analyses identified novel risk loci and susceptibility genes, such as FCRLA, NFKB1, IRF4, DCAKD, and ATXN2 in overall IIMs; NEMP2 in polymyositis; ACBC11 in dermatomyositis; and PSD3 in myositis with anti-histidyl-transfer RNA synthetase autoantibodies (anti-Jo-1). We also characterized effects of HLA region variants and the role of C4. Colocalization analyses suggested putative causal variants in DCAKD in skin and muscle, HCP5 in lung, and IRF4 in Epstein-Barr virus (EBV)-transformed lymphocytes, lung, and whole blood. RWR further prioritized additional candidate genes, including APP, CD74, CIITA, NR1H4, and TXNIP, for future investigation. CONCLUSION: Our study uncovers novel genetic regions contributing to IIMs, advancing our understanding of myositis pathogenesis and offering new insights for future research.
The RFC4 gene has recently been linked to a multisystemic disorder Morimoto-Ryu-Malicdan neuromuscular syndrome, with myopathy being one of the key symptoms described in nine patients. We report the case of two brothers with a rapidly progressive congenital myopathy characterized by severe hypotonia and axial muscle weakness associated with previously unpublished biallelic variants in the RFC4 gene. Whole exome sequencing revealed biallelic variants NM_002916.5:c.1019_1020insCAAA and NM_002916.5:c.982_983insACT, corresponding to the protein-level changes p.(Gly341Lysfs*4) and p.(Thr328delinsAsnSer) in both brothers. This case expands the phenotypic spectrum of Morimoto-Ryu-Malicdan neuromuscular syndrome, highlighting severe early-onset axial muscle weakness, severe hypotonia, and preserved intellectual development. We also provide novel insights into the clinical progression and potential multidisciplinary interventions for patients with Morimoto-Ryu-Malicdan neuromuscular syndrome. Our findings highlight the importance of advanced genetic diagnostics and international collaboration in identifying rare neuromuscular diseases and improving the clinical management of affected patients.
- Klíčová slova
- Cerebellar atrophy, Hearing loss, Morimoto-Ryu-Malicdan neuromuscular syndrome, Multisystemic disorders, Myopathy, RFC4,
- MeSH
- dítě MeSH
- fenotyp MeSH
- lidé MeSH
- myotonia congenita * genetika patofyziologie MeSH
- předškolní dítě MeSH
- progrese nemoci MeSH
- sourozenci MeSH
- svalová hypotonie * genetika patofyziologie MeSH
- svalová slabost * genetika patofyziologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Spasticity often results in significant disability, which complicates rehabilitation and daily activities. This review explores the role of botulinum toxin type A (BoNT-A) in the treatment of spasticity, focusing on its effects on muscle structure and activity, function, cortical reorganization, and pain. Our findings indicate that BoNT-A injections improve motor function and gait, particularly in stroke patients, by reducing abnormal muscle activity and enhancing postural control. However, BoNT-A may also induce unwanted biomechanical changes, such as muscle atrophy and alterations in contractile elements, which could impact long-term muscle function. Regarding pain management in spasticity, BoNT-A has shown promise by reducing both peripheral and central sensitization mechanisms. Additionally, BoNT-A influences the central nervous system (CNS) by inducing cortical reorganization, which may further contribute to clinical improvements. Lastly, BoNT-A treatment requires careful consideration of individual patient characteristics to optimize outcomes and minimize side effects. A multidisciplinary approach that combines BoNT-A with physical therapy is essential to maximize functional recovery and improve the quality of life in patients with spasticity.
- Klíčová slova
- Botulinum toxin, Cortical reorganization, Muscle, Pain, Spasticity,
- MeSH
- bolest * farmakoterapie MeSH
- botulotoxiny typu A * terapeutické užití farmakologie MeSH
- kosterní svaly * účinky léků MeSH
- lidé MeSH
- management bolesti MeSH
- nervosvalové látky * terapeutické užití farmakologie MeSH
- svalová spasticita * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- botulotoxiny typu A * MeSH
- nervosvalové látky * MeSH
Metastases of the articular process, temporomandibular joint (TMJ), are rare findings. Their frequency is around 5% of patients with metastatic involvement of the mandible. The most common primary tumor is adenocarcinoma of the lung in women and adenocarcinoma of the prostate in men. The authors present 3 patients with TMJ metastasis. These were metastasis of breast adenocarcinoma, prostate adenocarcinoma, and lung adenocarcinoma. TMJ metastases are rare but complicated to diagnose because their presence may be accompanied by symptoms typical of other TMJ diseases (discopathy, arthritis, osteoarthritis). However, the authors recommend the unequivocal exclusion of a metastatic process in cases where the patient has a positive cancer history and their complaints do not respond to usual therapy.
- Klíčová slova
- Adenocarcinoma, TMJ metastasis, limited jaw mobility,
- MeSH
- adenokarcinom * sekundární patologie MeSH
- diferenciální diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- nádory mandibuly * sekundární MeSH
- nádory plic * patologie MeSH
- nádory prostaty * patologie MeSH
- nádory prsu * patologie MeSH
- nemoci temporomandibulárního kloubu MeSH
- počítačová rentgenová tomografie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Temporomandibular disorders (TMDs) are conditions with multifactorial etiology and complex treatment. Among the non-invasive therapeutic possibilities for these conditions is the Front Plateau, a partial anterior plate made from colourless self-curing acrylic resin. It is a simple procedure that can be carried out in a single clinical section promoting muscle relaxation to reduce symptoms associated with TMDs. This study aims to report a prospective, consecutive, single-centric case series to evaluate the Front Plateau's effectiveness in patients with temporomandibular disorders. A questionnaire adapted from the Research Diagnostic Criteria for TMDs was used and 4 patients were treated with the Front Plateau plaque. Patients were monitored after 5 and 9 months, respectively, after starting to use the Front Plateau. Of the 4 cases listed, 2 showed significant improvement in initial signs and symptoms. Front Plateau may be a favourable treatment option for patients with TMD, if the guidelines are followed. Clinical trials on this modality should seek to minimize possible biases and limitations associated with the design of this type of research.
- Klíčová slova
- Conservative treatment, Occlusal splints, Temporomandibular joint, Temporomandibular joint disc, Temporomandibular joint disorders,
- MeSH
- akrylové pryskyřice * MeSH
- lidé MeSH
- nemoci temporomandibulárního kloubu * terapie MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- přehledy MeSH
- Názvy látek
- akrylové pryskyřice * MeSH
PURPOSE: The authors evaluated a cohort of 12 patients with histologically verified pigmented villonodular synovitis of the TMJ between 2018 and 2023. METHODS: The authors evaluated 12 patients (12 women). Only unilateral involvement was present in all patients. The mean age of the patients was 49.5 years. The authors focused on the evaluation of clinical symptoms, imaging findings, and arthroscopic findings. They also evaluated the effect of therapy, including the incidence of recurrence. The evaluation of therapy was performed at a minimum of 12 months after therapy and a maximum of 4.5 years after therapy. RESULTS: Pain was the predominant clinical symptom (12 patients, 100%). Therapy consisted of arthroscopy and open surgery. Radiographs were taken in all patients. In 5 patients (42%) the joint structures were without obvious pathological changes, in 7 patients (58%) there was a finding of irregularities on the joint head. Magnetic resonance imaging was performed in all patients, and in 10 cases (83%) there was a finding of joint space enlargement, effusion. Therapy consisted of TMJ arthroscopy with removal of pathological tissue. If the joint was completely filled with pathological tissue, after histological verification, open surgery with complete removal of joint structures and subsequent reconstruction of the TMJ was indicated. Recurrence of PVNS was not reported in the cohort. CONCLUSION: PVNS is an uncommon benign lesion affecting the TMJ. In the authors' study, pain was the predominant symptom and effusion was the predominant finding on magnetic resonance imaging. Long-term follow-up is appropriate in patients with proven PVNS. This is due to the risk of recurrence, which is also associated with the difficulty of complete repair of the lesion in the anatomically limited space of the TMJ. The authors recommend 1,3,6 months after surgery, and annually for the first 5 years after surgery. One, two, and five years after surgery, they recommend a follow-up MRI. The results of the study support the view that MRI should always be indicated in patients with pain of arthrogenic origin lasting more than 3 months, and if effusion is found, arthroscopy should always be the next step. This procedure will ensure early detection of PVNS.
- Klíčová slova
- Diffuse tenosynovial giant cell tumor, Pigmented villonodular synovitis, TMJ,
- MeSH
- artroskopie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- nemoci temporomandibulárního kloubu * chirurgie diagnostické zobrazování patologie MeSH
- recidiva MeSH
- retrospektivní studie MeSH
- synovitida pigmentová vilonodulární * chirurgie diagnostické zobrazování patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: This study aimed to assess the mid-term effects of focused extracorporeal shockwave therapy (ESWT) on clinical symptoms and tendon structure in patellar tendinopathy. Ultrasound (US) evaluation and an innovative in vivo analysis of intra-tendinous morphology using validated spatial frequency analysis (SFA) software were employed to quantify the organization and density of collagen fascicles. METHODS: This prospective cohort study included 21 recreational athletes (mean age 29.9 ± 9.3 years) with chronic unilateral symptomatic patellar tendinopathy. ESWT was applied as monotherapy over four weekly sessions. Pain was assessed using the Numeric Rating Scale (NRS) and disease severity with the Victorian Institute of Sports Assessment - Patella (VISA-P) questionnaire. Morphological parameters, such as tendon diameter (TD), were assessed with US and analyzed using SFA software. The asymptomatic tendons served as controls. Follow-up assessments were conducted at the end of the treatment period and 3 months posttreatment. RESULTS: Baseline evaluations revealed increased TD in proximal part of the tendon ( P = 0.001) and decreased organization of collagen fascicles ( P = 0.013) in symptomatic tendons compared to asymptomatic controls. At the 3-month follow-up, symptomatic tendons showed significant reductions in TD ( P < 0.001) and improvements in both organization and density of collagen fascicles throughout various parameters - peak spatial frequency radius (PSFR) ( P = 0.024), P6 ( P = 0.05), Q6 ( P = 0.016), PPP ( P = 0.003). No significant morphological changes were observed in asymptomatic tendons. Clinical evaluations demonstrated significant reductions in NRS ( P < 0.001) and increases in Victorian Institute of Sports Assessment - Patella (VISA-P) scores ( P < 0.001) at all time points. CONCLUSION: The study suggests that ESWT may have the potential to induce positive structural changes in patellar tendinopathy, including improved organization and density of collagen fascicles. These findings indicate that ESWT could be a promising noninvasive approach to managing patellar tendinopathy, with observed improvements in clinical symptoms and tendon structure. However, further high-quality research is needed to confirm these results and establish their long-term efficacy.
- Klíčová slova
- extracorporeal shockwave therapy, jumper’s knee, patellar tendinopathy, spatial frequency analysis, ultrasound,
- MeSH
- dospělí MeSH
- léčba mimotělní rázovou vlnou * metody MeSH
- lidé MeSH
- ligamentum patellae * diagnostické zobrazování patologie MeSH
- mladý dospělý MeSH
- prospektivní studie MeSH
- tendinopatie * terapie diagnostické zobrazování patologie MeSH
- ultrasonografie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Duchenne muscular dystrophy (DMD) patients are monitored periodically for cardiac involvement, including cardiac MRI with gadolinium-based contrast agents (GBCA). Texture analysis (TA) offers an alternative approach to assess late gadolinium enhancement (LGE) without relying on GBCA administration, impacting DMD patients' care. The study aimed to evaluate the prognostic value of selected TA features in the LGE assessment of DMD patients. RESULTS: We developed a pipeline to extract TA features of native T1 parametric mapping and evaluated their prognostic value in assessing LGE in DMD patients. For this evaluation, five independent TA features were selected using Boruta to identify relevant features based on their importance, least absolute shrinkage and selection operator (LASSO) to reduce the number of features, and hierarchical clustering to target multicollinearity and identify independent features. Afterward, logistic regression was used to determine the features with better discrimination ability. The independent feature inverse difference moment normalized (IDMN), which measures the pixel values homogeneity in the myocardium, achieved the highest accuracy in classifying LGE (0.857 (0.572-0.982)) and also was significantly associated with changes in the likelihood of LGE in a subgroup of patients with three yearly examinations (estimate: 23.35 (8.7), p-value = 0.008). Data are presented as mean (SD) or median (IQR) for normally and non-normally distributed continuous variables and numbers (percentages) for categorical ones. Variables were compared with the Welch t-test, Wilcoxon rank-sum, and Chi-square tests. A P-value < 0.05 was considered statistically significant. CONCLUSION: IDMN leverages the information native T1 parametric mapping provides, as it can detect changes in the pixel values of LGE images of DMD patients that may reflect myocardial alterations, serving as a supporting tool to reduce GBCA use in their cardiac MRI examinations.
- Klíčová slova
- Cardiac MRI, Duchenne muscular dystrophy, Radiomics, Texture analysis,
- MeSH
- dítě MeSH
- Duchennova muskulární dystrofie * diagnostické zobrazování MeSH
- gadolinium MeSH
- kontrastní látky MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- mladiství MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- gadolinium MeSH
- kontrastní látky MeSH
BACKGROUND: Low levels of vitamin D have been associated with several autoimmune diseases. A growing body of evidence supports the association of vitamin D with skeletal muscle damage, regeneration, and energy and lipid metabolism. The aim was to analyse vitamin D and its receptor (VDR) in the muscle tissue of patients with idiopathic inflammatory myopathies (IIM) and to relate them to clinical parameters and muscle lipid and energy metabolism. METHODS: Forty-six patients with IIM and 67 healthy controls (HC) were included in the study. 27 IIM patients participated in a 24-week exercise intervention. Muscle biopsies were obtained from 7 IIM patients before/after training, 13 non-exercising IIM controls, and 21 HC. Circulating concentrations of 25(OH)D and 1,25(OH)D were measured. Gene expression of VDR and CYP27B1, the enzyme converting 25(OH)D to hormonally active 1,25(OH)D, was determined by qPCR in muscle tissue and primary muscle cells. Lipid oxidative metabolism was assessed in muscle tissue (mRNA, qPCR) and primary muscle cells (radioactive assays). RESULTS: Lower levels of active 1,25(OH)D were observed in IIM patients compared with HC (mean ± SD: 125.0 ± 45.4 vs. 164.7 ± 49.2 pmol/L; p < 0.0001). 25(OH)D was associated with CRP (r = -0.316, p = 0.037), MITAX (r = -0.311, p = 0.040) and HAQ (r = -0.390, p = 0.009) in IIM. After 24 weeks of training, active 1,25(OH)D was associated with MMT8 (r = 0.866, p < 0.0001), FI-2 (r = 0.608, p = 0.013) and HAQ (r = -0.537, p = 0.032). Gene expression of both VDR and CYP27B1 in primary muscle cells decreased after training (p = 0.031 and p = 0.078, respectively). Associations of VDR mRNA in muscle tissue with MMT-8 (IIM: r = -0.559, p = 0.013), serum CK (HC: r = 0.484, p = 0.031), myoglobin (IIM: r = 0.510, p = 0.026) and myostatin (IIM: r = -0.519, p = 0.023) were observed. The expression of VDR in differentiated muscle cells correlated negatively with the complete oxidation of palmitic acid (r = -0.532, p = 0.028). Muscle mRNA of carnitine palmitoyl transferase 1 (CPT1) (downregulated in IIM, p = 0.001) correlated positively with serum 1,25(OH) vitamin D (r = 0.410, p = 0.042). CONCLUSION: Reduced biologically active vitamin D in circulation suggests its impaired metabolism in IIM. Serum vitamin D levels and gene expression of its receptor and activating enzyme in muscle tissue were modified by regular exercise and associated with disease manifestations, physical fitness, and muscle lipid metabolism of IIM patients.
- Klíčová slova
- Lipid metabolism, Mitochondria, Muscle, Myositis, Physical activity, Vitamin D,
- MeSH
- 1-alfa-hydroxylasa 25-hydroxyvitaminu D3 MeSH
- cvičení fyziologie MeSH
- dospělí MeSH
- kosterní svaly * metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolismus lipidů * fyziologie MeSH
- myozitida * metabolismus MeSH
- receptory kalcitriolu * metabolismus genetika MeSH
- senioři MeSH
- tělesná výkonnost * fyziologie MeSH
- vitamin D * metabolismus krev analogy a deriváty MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 1-alfa-hydroxylasa 25-hydroxyvitaminu D3 MeSH
- CYP27B1 protein, human MeSH Prohlížeč
- receptory kalcitriolu * MeSH
- VDR protein, human MeSH Prohlížeč
- vitamin D * MeSH
