Muscle Symptoms Research Articles

Clinical features of mitochrondrial diseases: A retrospective study in adult patients with muscle symptoms

Clinical features of mitochrondrial diseases: A retrospective study in adult patients with muscle symptoms

No benefit of vitamin D supplementation on muscle function and health-related quality of life in primary cardiovascular prevention patients with statin-associated muscle symptoms: A randomized controlled trial

Statins are the leading lipid-lowering drugs, reducing blood cholesterol by controlling its synthesis. Side effects are linked to the use of statins, in particular statin-associated muscle symptoms (SAMS). Some data suggest that vitamin D supplementation could reduce SAMS. The purpose of this study was to evaluate the potential benefits of vitamin D supplementation in a randomized controlled trial. Men (n = 23) and women (n = 15) (50.5 ± 7.7 years [mean ± SD]) in primary cardiovascular prevention, self-reporting or not SAMS, were recruited. Following 2 months of statin withdrawal, patients were randomized to supplementation (vitamin D or placebo). After 1 month of supplementation, statins were reintroduced. Before and 2 months after drug reintroduction, muscle damage (creatine kinase and myoglobin) was measured. Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (FHG) were also measured with isokinetic and handheld dynamometers, respectively. The Short Form 36 Health Survey (SF-36) questionnaire and a visual analog scale (VAS) were administrated to assess participants' self-reported health-related quality of life and SAMS intensity, respectively. Repeated-measures analysis was used to investigate the effects of time, supplementation, and their interaction, according to the presence of SAMS. Despite no change for objective measures, subjective measures worsened after reintroduction of statins, independent of supplementation (VAS, SF-36 mental component score, all p < 0.05). However, no interaction between time and supplementation according to the presence of SAMS was observed for any variables. Vitamin D supplementation does not appear to mitigate SAMS.

Hallazgos clínicos, de laboratorio y evolución en pacientes con síndrome autoinmune/autoinflamatorio inducido por adyuvantes (ASIA)

Introduction and objectiveAutoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) suggests that contact with different adjuvants such as silicones or aluminium used as excipient in some vaccines can cause the appearance of different symptomatology. Materials and methodsA retrospective analysis of the clinical manifestations, laboratory parameters, treatment, and evolution of a case series of 13 patients with ASIA syndrome related to silicone implants and vaccines was performed. ResultsIn 10 (77%) of the patients there was a history of silicone implants, in the rest of the patients there was a history of vaccination. The most frequent symptom in patients with silicone prostheses was Raynaud's phenomenon (72%), while in patients with a history of vaccination, arthralgias and myalgias were the most frequent symptoms. One patient met the criteria for primary Sjögren's syndrome while another patient had limited systemic sclerosis and associated Sjögren's syndrome. Most of the patients had elevated acute phase reactants (61%), while in the group of patients with a history of silicone prosthesis 60% presented positivity for antinuclear antibodies. ConclusionRaynaud's phenomenon and skeletal muscle symptoms were the most common manifestations in patients with breast prosthesis and vaccination history, respectively.

Effect of adding hip exercises to general rehabilitation treatment of knee osteoarthritis on patients’ physical functions: a randomized clinical trial

BackgroundHip adductor and abductor strength were both reduced in KOA patients. But to date, most of the researches have only focused on quadriceps combined with hip abductor strengthening versus quadriceps strengthening.ObjectiveThe aim of the study is to evaluate the effect of adding hip abductor and adductor strengthening to quadriceps strengthening on lower limb strength, knee pain and physical function in patients with medial compartmental knee osteoarthritis.MethodsIn this study, 42 participants, were randomly divided into two groups: the general treatment group (GT group) and the added-hip-exercise group (AH group). All participants were given a general rehabilitation treatment. The AH group performed hip abductor and adductor strengthening in addition to the general rehabilitation treatment. Knee and hip muscle strength, Five Times Sit-to-Stand Test (FTSST), the Timed Up and Go Test (TUGT), Numerical Rating Scale (NRS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were assessed at baseline and 6 weeks. A two-sided 2-sample unpaired t test was performed to compare the difference in mean change scores between AH and GT groups.ResultsFinally, 36 participants completed the study: both groups consist of 18 participants. In the per-protocol analysis, the AH group had a greater improvement in knee extension strength (mean changes, 7.84 versus 36.48; P < 0.001) and hip abduction strength (mean changes, 5.05 versus 26.62; P = 0.001) than the control group. Similarly, the AH group had a greater improvement in the FTSST time (mean changes, 0.40 s versus 3.57 s; P < 0.001) and the TUFT time (mean changes, 0.18 s versus 1.67 s; P = 0.002) than the GH group. No statistical difference was found in the change of WOMAC pain scores and NRS between the 2 groups.ConclusionsOlder adults with knee OA in the AH group had superior muscle strength, symptoms and daily activity performance at the 6th week than those in the GT group. And adding hip exercises could expedite improvement of pain at the 2th week, but not at the 6th week.Trial registrationClinical trial registration numbers and date of registration: ChiCTR-IOR-16009124, Registered 30 August 2016.

Potential role of geranylgeraniol in managing statin-associated muscle symptoms: a COVID-19 related perspective.

Myopathy is the most common side effect of statins, but it has not been addressed effectively. In anticipation of its wider use as a small molecule to complement the current COVID-19 management, a pharmacological solution to statin-associated muscle symptoms (SAMS) is warranted. Statins act by suppressing the mevalonate pathway, which in turn affects the downstream synthesis of isoprenoids required for normal physiological functions. CoQ10 and geranylgeraniol (GG) syntheses are reduced by statin use. However, CoQ10 supplementation has not been shown to reverse SAMS. GG is an obligatory substrate for CoQ10 synthesis, an endogenous nutrient critical for skeletal muscle protein synthesis. Multiple studies showed GG supplementation is effective in reversing SAMS. This opinion paper proposes employing GG to prevent SAMS in pleiotropic statin use, including usage in the post-COVID-19 pandemic era.

Cardiovascular phenotype of the duchenne muscular dystrophy carrier female rat

Abstract Background Duchenne muscular dystrophy (DMD) is a lethal, severely progressive muscle-wasting disease. It is an X-linked recessive disease caused by mutations in the DMD gene encoding dystrophin protein and consequently the absence of dystrophin protein synthesis. Besides the skeletal muscle abnormalities, DMD patients are often suffering cardiovascular symptoms include cardiac fibrosis, dilated cardiomyopathy, arrhythmia, and congestive heart failure. Heterozygous female DMD carriers rarely acquire skeletal muscle symptoms, however the cardiac abnormalities are often underrepresented. There are few studies to date characterizing cardiovascular abnormalities in female DMD carriers and the mechanisms underlying the cardiac manifestations are still not fully known. Aims and Methods: Therefore, the aim of this study was to investigate the cardiovascular phenotype of 9 months old female DMD carrier rats and compare with age-matched wildtype rats. Objectives included assessment of cardiac function via transthoracic echocardiography, vascular function using wire myography, cardiac fibrosis and dystrophin via histology, mRNA expression of inflammatory markers via RT-qPCR, measurements of ACE1 and ACE2 activity, as well as expression of dystrophin, SERCA, sarcolipin, BAG3, and Connexin43 (Cx43) using western blotting. The cardiac function, vascular endothelial function, ACE1 and ACE2 activity, and collagen deposition in cardiac tissue were similar between the female DMD carrier and wildtype rats. The echocardiography data revealed thinning of the left-ventricular posterior wall indicating trend towards cardiac atrophy and dysfunction (p&amp;lt;0.05). Wire myography data showed trends of impaired endothelium-independent relaxation and hypercontractility, suggesting the potential vascular abnormalities. Histological analysis showed thickening of intima-media layer in coronary arteries, addition to reduced dystrophin staining, further affirming dystrophin loss impairs smooth muscle cell function (p&amp;lt;0.05, respectively). Protein expression of dystrophin, SERCA2, and BAG3 was decreased in female DMD carrier rats in the myocardium. We also found decreased levels of Cx43 at the intercalated discs, with a concomitant increase in the phosphorylation of Serine368 on Cx43 that very often precedes ubiquitination and degradation of Cx43 channels. In agreement, higher levels of the ubiquitin ligase Nedd4 were observed in hearts of female DMD carrier rats, implicating Cx43 degradation in cardiac dysfunction observed in these animals. Conclusions These findings indicate that female DMD carrier rats do not develop severe cardiac systolic dysfunction nor dilated cardiomyopathy at the age of 9 months unlike male DMD rats as previously described(1). However, the female DMD carrier rats begin to manifest tendencies towards cardiac and vascular dysfunction in association with a changes of calcium handling protein and Cx 43 expression in the heart.

Physical status, symptoms and health-related quality of life during a severe exacerbation of COPD: Recovery and discriminative capacity for future events

ObjectiveSevere acute exacerbations of chronic obstructive pulmonary disease (AECOPD) can have a negative impact on functional capacity, symptoms and health-related quality of life (HRQOL). This study aimed to i) investigate the recovery of muscle strength, functional capacity, symptoms, and HRQOL in patients after a severe AECOPD; ii) compare with matched patients with stable COPD (SCOPD); and iii) assess whether these assessments at hospital discharge could discriminate patients’ risk for future events. MethodsThis observational study assessed patients with AECOPD during hospital discharge (T1) and one month after discharge (T2). Patients with SCOPD were assessed once. Quadriceps force, handgrip strength, short physical performance battery (SPPB), 6-min walk distance (6 MWD), COPD assessment test (CAT), London chest activity of daily living (LCADL), modified medical research council, checklist individual strength-fatigue, patient health questionnaire, and physical activity (Actigraph) were measured. Exacerbation-related readmission and mortality within six months and 1-year were collected. ResultsForty-four patients with AECOPD were matched with 44 patients with SCOPD. At T2, a significant improvement was found for the SPPB total score, 6 MWD, CAT score, and LCADL score. Compared to patients with SCOPD, a worse LCADL score was found at T2 in patients with AECOPD. Patients with AECOPD that were readmitted or died had a worse SPPB classification and five-repetition sit-to-stand test at T1. ConclusionPatients after severe AECOPD improved in functional capacity and HRQOL one month after hospital discharge, but ADL performance was still worse compared to SCOPD. Patients who were readmitted or died had significantly worse scores on functional tests at hospital discharge.

4 Resting State Functional Connectivity Impairments Implicate CNS Mechanisms Underlying Chronic Pain and Depression in Gulf War Veterans’ Illness

Objective:Around 200,000 veterans (up to 32% of those deployed) of the 1991 Gulf War (GW) suffer from GW veterans’ illness (GWVI). GWVI is a poorly understood chronic medical condition, characterized by symptoms indicative of brain function deficits in multiple domains. Among the symptoms of brain impairment GWVI-related chronic headaches and body muscle and joint pain conditions (GWVI-HAP) are the most debilitating, affecting around 64% of the GWVI veterans. Further, depression carries a very high co-morbid rate (&gt;50%) in patients with chronic pain, including GWVI-HAP. In this preliminary study, we examined the integrity of brain function networks in a group of GWI-HAP veterans, with resting state fMRI (rsfMRI).Participants and Methods:Data from the first twenty-two GWVI-HAP veterans from two ongoing parallel clinical trials was examined. Of these 14 subjects (GWVI-HAP-DM) had mild depression (Hamilton Rating Scale for Depression (HSRD &lt; 13); and 8 subjects (GWVI-HAP-DS) had moderate to severe depression (HSRD &gt; 14). Written informed consent was obtained from all participants in the protocol approved by the local Institutional Review Board. RsfMRI data was acquired on a Siemens 3T Prisma-Fit MRI scanner using a 10-minute whole-brain high resolution simultaneous multi-slice (SMS) gradient echo echo-planar imaging (EPI) sequence: TR/TE/FA = 2.2 sec/ 27 msec/80°, and analyzed with well-established image processing pipelines. Functional connectivity (FC) to different regions implicated in depression and chronic pain was assessed with seed-based correlation analysis. Between group differences in FC were obtained with 2-sample t-tests.Results:GWVI-HAP-DS group exhibited significantly (p &lt; 0.05) reduced FC compared to GWVI-HAP-DM between frontal lobe (medial (mPFC), and dorsolateral (dlPFC) prefrontal cortex) and the striatum. This indicates that malfunction of fronto-striatal circuits could be a source of the increased chronic pain and depression seen in veterans with GWVI- HAP-DS. Dysregulation of fronto-striatal networks has been implicated in major depressive disorder as well as many chronic pain conditions. In addition, FC between mPFC, and salience network (SN; anterior insula and dorsal anterior cingulate) and limbic (subgenual and ventral anterior cingulate) regions were also reduced in GWVI-HAP-DS. Similarly, mPFC and SN also exhibited reduced FC to pain processing regions (posterior insula, centromedian thalamus and cerebellum). These FC impairments could reflect greater deficits in regulation of and salience attribution to emotions and nociception in the GWVI-HAP-DS group. Finally, GWVI-HAP-DS also exhibited reduced FC between nodes of the default mode network. DMN impairments also have been observed in many depressive and chronic pain conditions.Conclusions:The results of this preliminary analysis implicate impairments in cognitive control of emotion and nociception as a mechanism underlying the enhanced chronic pain and depression observed in GWVI-HAP veterans, especially those with moderate to severe depression. A fuller picture of deficits in FC in brain function networks is expected to emerge as more GWI-HAP subjects of both groups along with age matched healthy controls are examined in this ongoing project. Better understanding of impairments in these networks in GWI-HAP will benefit the rehabilitation of veterans with GWI-HAP.

Effect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH.

In clinical trials, burosumab ameliorates symptoms of pain, fatigue, and stiffness and improves performance on certain muscle function studies in patients with X-linked hypophosphatemia (XLH). This work aimed to determine if burosumab increases adenosine triphosphate (ATP) synthesis in skeletal muscle of treatment-naive adults with XLH, and if so, whether that correlates with improved muscle function. Ten untreated, symptomatic adults with XLH had ATP synthesis rates measured in the right calf using the 31P magnetic resonance spectroscopy saturation transfer technique. Baseline muscle function tests and symptoms of pain, fatigue, stiffness, and lower-extremity joint pain were quantified. All participants were treated with burosumab, 1 mg/kg every 4 weeks for 12 weeks. ATP synthesis rates and muscle function tests were repeated 2 weeks ("peak") and 4 weeks ("trough") after the third dose of burosumab. All symptoms improved with treatment. Performance on the 6-Minute Walk Test (6MWT) and Sit to Stand (STS) tests also improved. Muscle strength and ATP synthesis rates did not change over the 3 months of the study. When individuals whose performances on the 6MWT and STS test were at or better than the median outcome for those tests were compared to those whose outcomes were below the median, no difference was observed in the rate of change in ATP synthesis. Intracellular muscle concentrations of phosphate were normal. The improvement in the 6MWT and STS test without changes in muscle strength or ATP synthesis rates suggests that reductions in pain, fatigue, and stiffness may partly explain the improved performance. Intracellular phosphate in skeletal muscle is insulated from hypophosphatemia in XLH.

The role of muscle degeneration and spinal balance in the pathophysiology of lumbar spinal stenosis: Study protocol of a translational approach combining in vivo biomechanical experiments with clinical and radiological parameters.

To describe a study protocol for investigating the functional association between posture, spinal balance, ambulatory biomechanics, paraspinal muscle fatigue, paraspinal muscle quality and symptoms in patients with symptomatic lumbar spinal stenosis (sLSS) before and 1-year after elective surgical intervention. Single-centre prospective, experimental, multimodal (clinical, biomechanical, radiological) study with three instances of data collection: baseline (study visit 1), 6-month follow-up (remote) and 1-year follow-up (study visit 2). Both study visits include an in vivo experiment aiming to elicit paraspinal muscle fatigue for postural assessment in a non-fatigued and fatigued state. At baseline and 1-year follow-up, 122 patients with sLSS will be assessed clinically, perform the back-performance scale assessment and complete several patient-reported outcome measure (PROMs) questionnaires regarding overall health, disease-related symptoms and kinesiophobia. Posture and biomechanical parameters (joint kinematics, kinetics, surface electromyography, back curvature) will be recorded using an optoelectronic system and retroreflective markers during different tasks including overground walking and movement assessments before and after a modified Biering-Sørensen test, used to elicit paraspinal muscle fatigue. Measurements of muscle size and quality and the severity of spinal stenosis will be obtained using magnetic resonance imaging (MRI) and sagittal postural alignment data from EOS radiographies. After each study visit, physical activity level will be assessed during 9 days using a wrist-worn activity monitor. In addition, physical activity level and PROMs will be assessed remotely at 6-month follow-up. The multimodal set of data obtained using the study protocol described in this paper will help to expand our current knowledge on the pathophysiology, biomechanics, and treatment outcome of degenerative sLSS. The results of this study may contribute to defining and/or altering patient treatment norms, surgery indication criteria and post-surgery rehabilitation schedules. The protocol was approved by the regional ethics committee and has been registered at clinicaltrials.gov (NCT05523388).

Prescribing statin therapy in physically (in)active individuals vs prescribing physical activity in statin-treated patients: A four-scenario practical approach

Statins are among the most commonly prescribed medications worldwide. Statin-associated muscle symptoms (SAMS) represent a frequent statin-related adverse effect associated with statin discontinuation and increased cardiovascular disease (CVD) events. Emerging evidence indicate that the majority of SAMS might not be actually caused by statins, and the nocebo/drucebo effect (i.e. adverse effects caused by negative expectations) might also explain SAMS. Physical activity (PA) is a cornerstone in the management of CVD risk. However, evidence of increased creatine-kinase levels in statin-treated athletes exposed to a marathon has been generalized, at least to some extent, to the general population and other types of PA. This generalization is likely inappropriate and might induce fear around PA in statin users. In addition, the guidelines for lipid management focus on aerobic PA while the potential of reducing sedentary behavior and undertaking resistance training have been overlooked. The aim of this report is to provide a novel proposal for the concurrent prescription of statin therapy and PA addressing the most common and clinically relevant scenarios by simultaneously considering the different stages of statin therapy and the history of PA. These scenarios include i) statin therapy initiation in physically inactive patients, ii) PA/exercise initiation in statin-treated patients, iii) statin therapy initiation in physically active patients, and iv) statin therapy in athletes and very active individuals performing SAMS-risky activities.

Muscle dysmorphia symptomatology is prospectively associated with suicidal thoughts, suicidal behaviors, and non-suicidal self-injury among a sample of Canadian adolescents and young adults.

Limited, primarily cross-sectional research has identified associations between muscle dysmorphia and suicidal thoughts suicidal behaviors, and non-suicidal self-injury (NSSI). This study aimed to investigate the associations between muscle dysmorphia and suicidal thoughts, suicidal behaviors, and NSSI prospectively over a 1-year period among a large, diverse sample of Canadian adolescents and young adults. Data from wave one (2021) and wave two (2022) of the Canadian Study of Adolescent Health Behaviors were analyzed (N = 912). Multiple modified Poisson regression analyses were used to determine the associations between muscle dysmorphia symptomatology at wave one and three items of suicidal thoughts and behaviors and one item of NSSI at wave two. Unadjusted models and adjusted models were estimated. Total muscle dysmorphia symptomatology and symptoms of Appearance Intolerance were prospectively associated with suicidal ideation and suicide planning at 12-month follow-up. These findings were significant across unadjusted and adjusted models. Findings from this study expand prior research and underscore the clinical complexity of muscle dysmorphia. Future research should investigate mechanisms explaining the association between muscle dysmorphia and suicide and develop interventions to prevent suicide among people with muscle dysmorphia.

Genetic polymorphisms in ABCB1 are correlated with the increased risk of atorvastatin-induced muscle side effects: a cross-sectional study

Genetic factors are recognized as risk factors for statin-associated muscle symptoms (SAMS), which are the most common cause of statin intolerance. The aim of this study was to determine whether there is an association between polymorphisms 1236C > T, 2677G > T/A, and 3435C > T in the ABCB1 gene, encoding the efflux transporter of statins, and SAMS, as results on this topic are still controversial. A cross-sectional study was conducted on patients with or without SAMS using atorvastatin. The influence of non-genetic variables on SAMS was also evaluated. Our results show that patients with TT genotype in 1236C > T, 2677G > T/A, and 3435C > T polymorphisms had higher risk of developing SAMS, compared to wild type and heterozygous carriers together (OR 4.292 p = 0.0093, OR 5.897 p = 0.0023 and OR 3.547 p = 0.0122, respectively). Furthermore, TTT/TTT diplotype was also associated with a higher risk of SAMS, OR 9.234 (p = 0.0028). Only family history of cardiovascular disease was found to be a risk factor for SAMS, in addition to the known non-genetic variables. We believe that ABCB1 genotyping has great potential to be incorporated into clinical practice to identify high-risk patients in a timely manner.

Correlation between B-cell epitope profile and clinical features of anti-MDA5 antibody-positive dermatomyositis.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) dermatomyositis patients exhibit a variety of clinical features. We therefore investigated whether patterns of B-cell epitope recognition are linked to the clinical course of MDA5+ dermatomyositis. Our cross-sectional study used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 24 MDA5+ myositis patients. Correlations between clinical features and standardized anti-MDA5 subfragment antibody titres were assessed via Spearman's rank correlation coefficients. Twenty-four MDA5+ patients submitted serum samples within a median of 0 (interquartile range, 0-74) days from the initial clinic visit. In addition to typical dermatomyositis rashes, these patients exhibited muscle symptoms (n = 11), vascular dysfunction (n = 9) and interstitial lung disease (ILD) (n = 16). Female patients exhibited higher titres of antibodies recognizing fragment H (aa 905-1026) compared with male patients. Muscle involvement was associated with higher levels of anti-fragment F (aa 646-801) antibody. Conversely, patients with vascular abnormalities had higher anti-fragment B (aa 130-284) and E (aa 517-671) antibody titres than those without vascular dysfunction. Four patients died due to ILD progression and showed higher anti-fragment A (aa 1-155) antibody titres than the other 20 patients. Differences in the ratio of anti-fragment to anti-full-length MDA5 antibody titres were found for sex (H: anti-MDA5) and vascular dysfunction (anti-fragment B, E: anti-MDA5). Various clinical features of MDA5+ dermatomyositis correlated with levels of antibodies targeting selected subfragments of this autoantigen, providing a link between fragment-specific immune responses and disease course.

Development and application of pharmacological statin-associated muscle symptoms phenotyping algorithms using structured and unstructured electronic health records data.

Statins are widely prescribed cholesterol-lowering medications in the United States, but their clinical benefits can be diminished by statin-associated muscle symptoms (SAMS), leading to discontinuation. In this study, we aimed to develop and validate a pharmacological SAMS clinical phenotyping algorithm using electronic health records (EHRs) data from Minnesota Fairview. We retrieved structured and unstructured EHR data of statin users and manually ascertained a gold standard set of SAMS cases and controls using the published SAMS-Clinical Index tool from clinical notes in 200 patients. We developed machine learning algorithms and rule-based algorithms that incorporated various criteria, including ICD codes, statin allergy, creatine kinase elevation, and keyword mentions in clinical notes. We applied the best-performing algorithm to the statin cohort to identify SAMS. We identified 16 889 patients who started statins in the Fairview EHR system from 2010 to 2020. The combined rule-based (CRB) algorithm, which utilized both clinical notes and structured data criteria, achieved similar performance compared to machine learning algorithms with a precision of 0.85, recall of 0.71, and F1 score of 0.77 against the gold standard set. Applying the CRB algorithm to the statin cohort, we identified the pharmacological SAMS prevalence to be 1.9% and selective risk factors which included female gender, coronary artery disease, hypothyroidism, and use of immunosuppressants or fibrates. Our study developed and validated a simple pharmacological SAMS phenotyping algorithm that can be used to create SAMS case/control cohort to enable further analysis which can lead to the development of a SAMS risk prediction model.

Msi2 enhances muscle dysfunction in a myotonic dystrophy type 1 mouse model

BackgroundMyotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by a CTG repeat expansion in the 3′ untranslated region of the DM1 protein kinase gene. Characteristic degenerative muscle symptoms include myotonia, atrophy, and weakness. We previously proposed an Musashi homolog 2 (MSI2)>miR-7>autophagy axis whereby MSI2 overexpression repressed miR-7 biogenesis that subsequently de-repressed muscle catabolism through excessive autophagy. Because the DM1 HSALR mouse model expressing expanded CUG repeats shows weak muscle-wasting phenotypes, we hypothesized that MSI2 overexpression was sufficient to promote muscle dysfunction in vivo. MethodsBy means of recombinant AAV murine MSI2 was overexpressed in neonates HSALR mice skeletal muscle to induce DM1-like phenotypes. ResultsSustained overexpression of the murine MSI2 protein in HSALR neonates induced autophagic flux and expression of critical autophagy proteins, increased central nuclei and reduced myofibers area, and weakened muscle strength. Importantly, these changes were independent of MBNL1, MBNL2, and Celf1 protein levels, which remained unchanged upon Msi2 overexpression. ConclusionsGlobally, molecular, histological, and functional data from these experiments in the HSALR mouse model confirms the pathological role of MSI2 expression levels as an atrophy-associated component that impacts the characteristic muscle dysfunction symptoms in DM1 patients.

P133 Influence of X-chromosome activation pattern in muscles on symptoms and progression of cardiac and muscle symptoms signs in women with pathogenic dystrophin gene variants: a 6-year follow-up of 53 patients

P133 Influence of X-chromosome activation pattern in muscles on symptoms and progression of cardiac and muscle symptoms signs in women with pathogenic dystrophin gene variants: a 6-year follow-up of 53 patients

PCSK9 Inhibitor Therapy as an Alternative for Statin Intolerance

Scientific relevance. The main cause of cardiovascular pathologies is atherosclerosis, which is secondary to lipid metabolism disorders, in particular, the accumulation of low-density lipoprotein (LDL) cholesterol. Dyslipidaemia treatment with the largest evidence base predominantly includes statins in combination therapy, but their use is limited by into lerance in some patients. Alternatively, the treatment may include proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.Aim. The study aimed to analyse the applicability of PCSK9 inhibitors in patients with statin intolerance.Discussion. According to the literature analysis, the most common presentation of statin intolerance is statin-associated muscle symptoms. The pathogenesis of statin-associated adverse events is mainly mediated by HMGCoA reductase inhibition, treatment effects on cellular and subcellular processes and skeletal muscles, and patients’ genetic makeup. The mechanism of action of PCSK9 inhibitors is entirely different and involves binding and inactivation of the PCSK9 protein, which lowers blood LDL cholesterol levels. PCSK9 inhibitors have been associated with some adverse drug reactions, most notably immunogenicity; however, PCSK9 inhibitors effectively reduce LDL levels even if patients develop antibodies.Conclusions. Therefore, PCSK9 inhibitors are a safe, well-tolerated, and effec tive therapeutic strategy for hyperlipidaemia in patients with statin intolerance.

Statin-Induced Myopathy

Scientific relevance. Being the main class of medicinal products for dyslipidaemia treatment, statins are widely used in clinical practice in various patient populations. However, statins can cause statin-associated muscle symptoms (SAMS), which are the most frequent and, in some cases, even life-threatening adverse reactions associated with these medicinal products.Aim. The study aimed to perform a systematic review of the epidemiology, classification, and physiological pathogenesis of SAMS, risk factors for this complication, and clinical guidelines for primary care physicians regarding the identification and treatment of patients with SAMS.Discussion. SAMS is an umbrella term that covers various forms of myopathies associated with satin therapy. According to the published literature, the prevalence of SAMS varies considerably and may depend on the study design, inclusion criteria, and the medicinal product used. SAMS has multiple putative pathogenic pathways that include genetically determined processes, abnormalities in mitochondrial function, defects in intracellular signalling and metabolic pathways, and immune-mediated reactions. The main known risk factors for developing SAMS include high-dose statins, drug–drug interactions, genetic polymorphisms, female sex, older age, Asian race, history of kidney, liver, and muscle disease, and strenuous physical activity. Given the lack of universally recognised algorithms for diagnosing SAMS, clinicians should consider the clinical presentation and the temporal relationship between statin therapy and symptoms. Other factors to consider include changes in muscle-specific enzyme levels and, in some cases, the results of blood tests for antibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase.Conclusions. To ensure the safety of statin therapy, it is essential to raise clinicians’ awareness of the risk factors for SAMS, indicative clinical and laboratory findings, and the need for dynamic patient monitoring, including the involvement of clinical pharmacologists.

Food insecurity is associated with muscle dysmorphia symptomatology among a sample of Canadian adolescents and young adults

Prior research has documented the association between food insecurity and eating disorders, disordered eating behaviors, and body dissatisfaction. No known research has investigated whether food insecurity is associated with muscle dysmorphia symptomatology, which was the aim of this study. Data from 912 adolescents and young adults in Canada were analyzed. Linear regression analyses were used to determine the association between experiencing past year food insecurity and current muscle dysmorphia symptomatology. Among the sample, 15.7% reported experiencing any food insecurity. In regression analyses, food insecurity was significantly associated with greater overall muscle dysmorphia symptomatology and symptoms of Functional Impairment and Appearance Intolerance. Nearly one in five (18.5%) participants who reported food insecurity were at clinical risk for muscle-dysmorphia. Findings add to the growing literature on the adverse correlates of food insecurity and underscore the need for more research and intervention efforts to address the relationship between food insecurity and muscle dysmorphia symptomatology.