Muscle Symptoms Research Articles

Decoding the Intricacies of Statin-Associated Muscle Symptoms.

Hyperlipidemia is the major cardiovascular morbidity and mortality risk factor. Statins are the first-line treatment for hyperlipidemia. Statin-associated muscle symptoms (SAMS) are the main reason for the discontinuation of statins among patients. The purpose of this review is to guide clinicians to recognize the difference between self-limited and autoimmune statin myopathy in addition to the factors that potentiate them. Finally, treatment strategies will be discussed. This review mostly focuses on new data in the past 3 years. Recent findings suggest that SAMS is a complex and multifactorial condition that involves mitochondrial dysfunction, oxidative stress, and immune-mediated mechanisms. Effective management of SAMS requires a thorough evaluation of the patient's symptoms, risk factors, and medication history, as well as consideration of alternative treatment options. While statins are effective in reducing the risk of cardiovascular events, their use is associated with a range of adverse effects, including SAMS.

Lipid-lowering approaches to manage statin-intolerant patients.

Statins have improved the potential to prevent cardiovascular disease events and to prolong the lives of patients. Statins, among the most widely used drugs worldwide, reduce the levels of low-density lipoprotein cholesterol (LDL-C) by an average of 30-50%. However, non-adherence to statin therapy, due to statin intolerance, might be as high as 60% after 24 months of treatment and is associated with a 70% increase in the risk of cardiovascular disease events. Statin intolerance can be classified as a complete inability to tolerate any dose of a statin or a partial intolerance with the inability to tolerate the dose necessary to achieve the patient-specific therapeutic objective. Reasons for discontinuation are many, with statin-associated muscle symptoms being cited as the most frequent reason for stopping therapy and the incidence of muscle symptoms increasing with treatment intensity. Considering the causal effect of LDL-C in the atherosclerotic process, clinicians should consider that regardless of the lipid-lowering drugs patients are willing to take, any reduction in LDL-C they achieve will afford them some benefit in reducing cardiovascular risk. Besides statins, the current therapeutic armamentarium offers different strategies to reach LDL-C targets in statin-intolerant patients (i.e. a fixed combination between a lower dose of statin plus ezetimibe, bempedoic acid, or proprotein convertase subtilisin/kexin type 9 inhibition).

Quantitative ultrasonography reveals skeletal muscle abnormalities in carriers of DMD pathogenic variants.

Carriers of DMD pathogenic variants may become symptomatic and develop muscle-related manifestations. Despite that, few studies have attempted to characterize changes in the muscles of these carriers using imaging tools, particularly muscle ultrasound (MUS). The aim of this study was to compare lower limb MUS findings in carriers of DMD pathogenic variants (cDMD) vs healthy controls. Twenty-eight women (15 cDMD and 13 controls) underwent clinical evaluation and MUS. We collected information about muscle-related symptoms and assessed muscle strength. MUS was performed by a single physician (blind to the genetic status of subjects). The following muscles were assessed: rectus femoris, sartorius, tibialis anterior, and medial gastrocnemius. For each site, we computed data on muscle thickness, cross-sectional area, sound attenuation index, and elastography. Between-group comparisons were assessed using nonparametric tests and p-values <.05 were deemed significant. None of the subjects had objective muscle weakness, but exercise intolerance/fatigue was reported by four cDMDs and only one control. Regarding MUS, sound attenuation indices were significantly higher among carriers for all muscles tested. Longitudinal and axial deep echo intensities for the rectus femoris and tibialis anterior were also higher in the cDMD group compared with controls. No significant between-group differences were noted for elastography values, muscle area, or mean echo intensities. cDMD have skeletal muscle abnormalities that can be detected using quantitative MUS. Further studies are needed to determine whether such abnormalities are related to muscle symptoms in these patients.

Development and Validation of the Pharmacological Statin-Associated Muscle Symptoms Risk Stratification Score Using Electronic Health Record Data.

Statin-associated muscle symptoms (SAMS) can lead to statin nonadherence. This paper aims to develop a pharmacological SAMS risk stratification (PSAMS-RS) score using a previously developed PSAMS phenotyping algorithm that distinguishes objective vs. nocebo SAMS using electronic health record (EHR) data. Using our PSAMS phenotyping algorithm, SAMS cases and controls were identified from Minnesota Fairview EHR, with the statin user cohort divided into derivation (January 1, 2010, to December 31, 2018) and validation (January 1, 2019, to December 31, 2020) cohorts. A Least Absolute Shrinkage and Selection Operator regression model was applied to identify significant features for PSAMS. PSAMS-RS scores were calculated and the clinical utility of stratifying PSAMS risk was assessed by comparing hazard ratios (HRs) between fourth vs. first score quartiles. PSAMS cases were identified in 1.9% (310/16,128) of the derivation and 1.5% (64/4,182) of the validation cohorts. Sixteen out of 38 clinical features were determined to be significant predictors for PSAMS risk. Patients within the fourth quartile of the PSAMS scores had an over sevenfold (HR: 7.1, 95% confidence interval (CI): 4.03-12.45, derivation cohort) or sixfold (HR: 6.1, 95% CI: 2.15-17.45, validation cohort) higher hazard of developing PSAMS vs. those in their respective first quartile. The PSAMS-RS score is a simple tool to stratify patients' risk of developing PSAMS after statin initiation which could inform clinician-guided pre-emptive measures to prevent PSAMS-related statin nonadherence.

Clinical characteristics and symptom progression of dermatomyositis subtypes: A retrospective analysis of a prospective database

BackgroundDisease characteristics of classic dermatomyositis (DM) and clinically amyopathic DM (CADM) are well-established, but there exists limited knowledge on disease progression of these subtypes. ObjectiveTo longitudinally track and characterize classic DM and CADM patients that experience changes in disease presentation. MethodsWe conducted a retrospective review of prospectively collected data on 269 DM patients of a longitudinal database. ResultsA total of 51% had classic DM and 49% had CADM. Forty percent of the classic DM patients became post-myopathic (PmDM). Median CDASI-A score was lower in PmDM patients than classic DM patients (13.0 vs 16.0), but 45% of the PmDM patients had CDASI-A scores >14. Five percent of the CADM patients developed muscle involvement. Compared to CADM patients, those that developed muscle symptoms had milder skin disease before subtype conversion (median CDASI-A 12.0 vs 16.0) and at subtype conversion (median CDASI-A 9.0 vs 16.0). LimitationsRetrospective study conducted at a single tertiary-care dermatology clinic. Conclusion40% of classic DM patients became PmDM. The majority continue with muscle disease, and many continue to have moderate/severe skin disease. CADM has a low risk of progressing to muscle disease, with extent of skin disease as a potential predictive factor.

Caregiver Burden with Duchenne and Becker Muscular Dystrophy in Japan: A Clinical Observation Study.

Objective Skeletal muscle weakness and cardiomyopathy can be seen in carriers of dystrophinopathy. Therefore, the health management of caregivers of Duchenne/Becker muscular dystrophy (DMD/BMD) patients who are themselves carriers is an important issue. However, few studies have focused on caregivers who have dystrophin mutations. Methods In this cross-sectional study conducted at five hospitals, the daily living, situation medical treatment status, genetic testing, physical assessment, care burden, and quality of life of caregivers of DMD/BMD patients were surveyed. Results The subjects were 36 main caregivers (mean age 55.7±8.4 years old), of whom 52.8% were diagnosed as carriers, 8.3% were noncarriers, and 38.9% were not confirmed. In addition, half of the caregivers were not examined regularly at medical institutions. Of all caregivers, 54.3% had muscle or cardiac symptoms, and 75% had elevated serum creatine kinase levels. The mean Zarit Caregiver Burden Interview (ZBI) total score of current caregivers was 20.9±13.1. The frequency of a ZBI total score ≥25 was significantly higher in caregivers diagnosed as carriers than in caregivers unexamined as carriers (p=0.04). The health-related quality of life score (Short Form 36; SF-36) in caregivers was slightly lower than the Japanese standard scores in the sections of physical functioning, role limitations-physical, bodily pain, and social functioning. Conclusion Some caregivers of DMD/BMD patients can themselves have muscular or cardiac symptoms and a heavy care burden. It is therefore necessary for carrier caregivers, especially women, to undergo regular health checkups and receive appropriate health management.

Skeletal muscle mitochondrial capacity in patients with statin-associated muscle symptoms (SAMS)

ObjectiveThe objective of this article is to evaluate near-infrared spectroscopy (NIRS), a non-invasive technique to assess tissue oxygenation and mitochondrial function, as a diagnostic tool for statin-associated muscle symptoms (SAMS).MethodsWe...

Statin Associated Muscular Adverse Effects.

Statins are widely used in the treatment of hyperlipidemia and in the prevention of cardiovascular diseases. However, they may induce muscular adverse effects that range from asymptomatic elevation of creatine kinase to life threatening rhabdomyolysis. The aim of the study was to describe epidemiological and clinical characteristics of patients with muscular adverse effects. We conducted a retrospective and descriptive study over a ten-year period from January 2010 to December 2019. We included all cases of statin associated muscular adverse effects notified to the Tunisian National Centre of Pharmacovigilance during this period. The study involved 22 muscular adverse effects related to statins (28% of all adverse events reported with statins during this period). Patient's mean age was 58.7 years and the sex ratio was 1.6. There were 12 cases of isolated creatine kinase elevation, 5 cases of myalgia, 3 cases of myopathy, one case of myositis and one case of rhabdomyolysis. Muscular adverse effects occurred 7 days to 15 years after starting this drug. In all cases, the statin was withdrawn after muscular adverse effects and resolution of symptoms was observed within 10 days to 18 months. In seven cases, creatine kinase persisted elevated for 18 months. Involved statins were atorvastatin, simvastatin, rosuvastatin and fluvastatin. Early recognition of muscle symptoms is required to prevent rhabdomyolysis. Further researchare needed to completely elucidate the pathophysiology of statin-induced muscular adverse effects.

Fatigue as hallmark of Fabry disease: role of bioenergetic alterations.

Fabry disease (FD) is a lysosomal storage disorder due to the impaired activity of the α-galactosidase A (GLA) enzyme which induces Gb3 deposition and multiorgan dysfunction. Exercise intolerance and fatigue are frequent and early findings in FD patients, representing a self-standing clinical phenotype with a significant impact on the patient's quality of life. Several determinants can trigger fatigability in Fabry patients, including psychological factors, cardiopulmonary dysfunctions, and primary alterations of skeletal muscle. The "metabolic hypothesis" to explain skeletal muscle symptoms and fatigability in Fabry patients is growing acknowledged. In this report, we will focus on the primary alterations of the motor system emphasizing the role of skeletal muscle metabolic disarrangement in determining the altered exercise tolerance in Fabry patients. We will discuss the most recent findings about the metabolic profile associated with Fabry disease offering new insights for diagnosis, management, and therapy.

The use of statins and inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK 9) in patients with dyslipidemia

Scientific relevance. According to the WHO data, cardiovascular diseases rank first as the cause of human death. In 2022, 18,601,923 people died from cardiovascular diseases, which amounted to 33 % of the total mortality in the world. Malignant neoplasms rank second with 9,958,133 deaths, representing 17.6 % of total mortality. Among cardiovascular diseases, ischemic heart disease (IHD), the pathogenesis of which is associated with impaired cholesterol and lipoprotein metabolism, is leading. The use of statin drugs is recommended as a first-line lipid-lowering therapy. As an alternative to HMG-CoA reductase inhibitors (statins), proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9) were discovered in 2003, however, they are less popular due to insuf ficient data on these drugs and their costliness. Purpose of the work: to study the safety of using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with dyslipidemia and compare the advantages and disadvantages in relation to the ef fects of HMG-CoA reductase (statins). Discussion: The analysis of literature data has shown that the most frequent manifestations of intolerance to statins are muscle symptoms. The main mechanisms of statin-associated complications are mediated by inhibition of HMG-CoA reductase, as well as by the effect of drugs on cellular and subcellular processes, skeletal muscles and genetic features of patients. PCSK9 inhibitors have a fundamentally different mechanism of action — they bind and inactivate PCSK9, which leads to a decrease of low-density lipoprotein cholesterol in the blood level. A small number of undesirable reactions have been identified for drugs of this group, the most important of which is immunogenicity. However, even if patients have antibodies to PCSK9 inhibitor, the efficacy of the drug in reducing the level of low-density lipoproteins remains high.Conclusion. In medical studies, PCSK9 inhibitors have been shown to perform better compared to HMG-CoA reductase inhibitors; meanwhile, patients continue to use statins as lipid-lowering medications.

The atorvastatin metabolite pattern in muscle tissue and blood plasma is associated with statin muscle side effects in patients with coronary heart disease; An exploratory case-control study

Background and aimsStatin-associated muscle symptoms (SAMS) is a prevalent cause of statin discontinuation. It is challenging and time-consuming for clinicians to assess whether symptoms are caused by the statin or not, and diagnostic biomarkers are requested. Atorvastatin metabolites have been associated with SAMS. We aimed to compare atorvastatin pharmacokinetics between coronary heart disease (CHD) patients with and without clinically statin intolerance and statin-dependent histopathological alterations in muscle tissue. Secondarily we aimed to assess genetic variants relevant for the observed pharmacokinetic variables. MethodsTwenty-eight patients with CHD and subjective SAMS were included in the exploratory MUSE biomarker study in 2020. Participants received atorvastatin 40 mg/day for seven weeks followed by no statins for eight weeks. Muscle biopsies and blood were collected at the end of each period. Four patients were categorized as clinically intolerant to ≥3 statins prior to study start whereas four patients had signs of muscle cell damage during treatment. ResultsWe found significantly lower levels of atorvastatin acids, and higher lactone/acid ratios in the statin intolerant, both in muscle and plasma. With optimal cut-off, the combination of 2-OH-atorvastatin acid and the 2-OH-atorvastatin lactone/acid ratio provided sensitivity, specificity, and predictive values of 100 %. Patients with variants in UGT1A1 and UGT1A3 had higher lactone metabolite levels than those with wild type, both in muscle and plasma. ConclusionAtorvastatin metabolites appear promising as biomarkers for the identification of clinical statin intolerance in patients with self-perceived SAMS, but the findings have to be confirmed in larger studies.

Statins Ticagrelor and Rhabdomyolysis: A Coincidence or a Drug Interaction?

Statins play a key role in the management of atherosclerotic cardiovascular disease for both primary and secondary prevention. However, their increasing usage has correspondingly led to a higher incidence of adverse effects, with muscle symptoms being the most common. An intriguing drug interaction exists between ticagrelor and high-intensity statins, which may exacerbate the adverse effects of statin-induced rhabdomyolysis, leading to significant consequences. This study was conducted to examine the profile of patients who have experienced statin-induced rhabdomyolysis while undergoing percutaneous transluminal coronary angioplasty (PTCA). This was an observational study that included 1,862 patients who underwent PTCA at our institute over the course of 1 year. Over a 1-year period, we encountered four patients who were being treated with high-intensity statin therapy following acute coronary syndrome. These patients presented with muscle weakness and kidney injury. A notable commonality among all patients was the co-prescription of ticagrelor. Two patients died, while the other 2 were successfully managed through hydration, electrolyte balance, dialysis, and alternative lipid management drugs. The concomitant use of ticagrelor and high-intensity statins should be carefully considered due to the additional risk of rhabdomyolysis and kidney injury. Future pharmacokinetic studies are needed to establish a causal relationship and predict potential drug interactions, which, if not avoided, could be fatal.

An Observational Study on the Clinical Characteristics and Prognosis of Patients With Interstitial Lung Disease Secondary to Dermatomyositis and Antisynthetase Syndrome.

Objective: Identify the clinical characteristics and prognostic factors in patients with idiopathic inflammatory myopathy (IIM) combined with interstitial lung disease (ILD). Methods: IIM-ILD patients who were hospitalized at Guangxi Medical University from January 2017 to December 2022 were retrospectively analyzed and classified as having dermatomyositis (DM)-ILD or -ILD. Clinical and laboratory results were analyzed. Results: There were 39 males and 111 females, the mean age of disease onset was 50.4 ± 12.3 years, and the median disease duration was 3 months (range: 1-6). Ninety-seven patients had DM-ILD, and 53 had ASS-ILD. The DM-ILD group had 72% positivity for the anti-MDA5 antibody and 5.2% positivity for the anti-Mi-2 antibody; the ASS-ILD group had 67.9% positivity for the anti-Jo-1 antibody and 17% positivity for the anti-EJ antibody. Muscle symptoms, skin ulcers, rash, rapidly progressing interstitial lung disease (RP-ILD), and elevated levels of serum carcinoembryonic antigen were more common in DM-ILD patients (all p < 0.05). However, pericardial effusion and pleural effusion, elevated creatinine kinase, and elevated C-reactive protein were more common in ASS-ILD patients. After a median follow-up of 15.5 months, there were more deaths in the DM-ILD group (42.3% vs. 13.2%, p < 0.001). Multivariate Cox regression analysis showed that RP-ILD, dyspnea, and the usual interstitial pneumonia type of ILD had negative associations with overall survival (OS), and arthralgia had a positive association with OS (all p < 0.05). Conclusion: DM-ILD patients were more prone to secondary RP-ILD and skin ulcers, had milder symptoms of myositis and less severe serositis, and had lower survival rates than the ASS-ILD patients. RP-ILD, dyspnea, and the usual interstitial pneumonia type of ILD had adverse effects on prognosis, but arthralgia was a protective factor.

Gender and age-related features of anxiety and depressive symptoms in patients in the acute phase of COVID-19.

Aim: To investigate the gender and age characteristics of psychopathological symptoms in patients in the acute phase of respiratory infection SARS-CoV-2. Materials and Methods: A total of 66 patients aged 8 to 92 years, sick with COVID-19 during inpatient treatment with lung damage from 30 to 70%, confirmed radiologically, in the period up to 20 days from the onset of the disease, were examined. To assess the mental status of patients with COVID-19, we used a clinical, clinical-psychopathological, psychometric method, which included the following questionnaires as part of psychiatric screening for studying psychopathological symptoms upon admission to the hospital. The Patient Health Questionnaire - PHQ-9, The Generalised Anxiety Disorder - GAD-7, Hamilton Test were used. The research data collection period is from 2020 to 2022. Results: Acute respiratory infection СОVID-19 affects the psycho-emotional state. During inpatient treatment, 60.6% of patients have symptoms of depression, 66.1% have anxiety symptoms. Most women with COVID-19 are characterized by moderate depression according to PHQ-9, mild anxiety according to GAD-7, and moderate anxiety according to Hamilton. Mild depression characterizes most men according to PHQ-9, absence of anxiety according to GAD-7, and mild anxiety according to Hamilton. Anxiety symptoms were less pronounced among men with COVID-19, with insomnia and respiratory symptoms being the most significant. Among women, anxiety (p≤0.001), tension, depression (p≤0.001), somatic muscle (p≤0.001) and respiratory symptoms (p≤0.001) predominate in the structure of anxiety during the active phase of COVID-19. Conclusions: The data obtained will be useful in the development of psychoprophylactic measures in patients with COVID-19.

Machine learning-based prediction model for the efficacy and safety of statins.

The appropriate use of statins plays a vital role in reducing the risk of atherosclerotic cardiovascular disease (ASCVD). However, due to changes in diet and lifestyle, there has been a significant increase in the number of individuals with high cholesterol levels. Therefore, it is crucial to ensure the rational use of statins. Adverse reactions associated with statins, including liver enzyme abnormalities and statin-associated muscle symptoms (SAMS), have impacted their widespread utilization. In this study, we aimed to develop a predictive model for statin efficacy and safety based on real-world clinical data using machine learning techniques. We employed various data preprocessing techniques, such as improved random forest imputation and Borderline SMOTE oversampling, to handle the dataset. Boruta method was utilized for feature selection, and the dataset was divided into training and testing sets in a 7:3 ratio. Five algorithms, including logistic regression, naive Bayes, decision tree, random forest, and gradient boosting decision tree, were used to construct the predictive models. Ten-fold cross-validation and bootstrapping sampling were performed for internal and external validation. Additionally, SHAP (SHapley Additive exPlanations) was employed for feature interpretability. Ultimately, an accessible web-based platform for predicting statin efficacy and safety was established based on the optimal predictive model. The random forest algorithm exhibited the best performance among the five algorithms. The predictive models for LDL-C target attainment (AUC = 0.883, Accuracy = 0.868, Precision = 0.858, Recall = 0.863, F1 = 0.860, AUPRC = 0.906, MCC = 0.761), liver enzyme abnormalities (AUC = 0.964, Accuracy = 0.964, Precision = 0.967, Recall = 0.963, F1 = 0.965, AUPRC = 0.978, MCC = 0.938), and muscle pain/Creatine kinase (CK) abnormalities (AUC = 0.981, Accuracy = 0.980, Precision = 0.987, Recall = 0.975, F1 = 0.981, AUPRC = 0.987, MCC = 0.965) demonstrated favorable performance. The most important features of LDL-C target attainment prediction model was cerebral infarction, TG, PLT and HDL. The most important features of liver enzyme abnormalities model was CRP, CK and number of oral medications. Similarly, AST, ALT, PLT and number of oral medications were found to be important features for muscle pain/CK abnormalities. Based on the best-performing predictive model, a user-friendly web application was designed and implemented. This study presented a machine learning-based predictive model for statin efficacy and safety. The platform developed can assist in guiding statin therapy decisions and optimizing treatment strategies. Further research and application of the model are warranted to improve the utilization of statin therapy.

Statin-associated muscle symptoms : performance and quality of life

Statins use is linked to side effects, notably muscular ones, known as Statin-Associated Muscle Symptoms (SAMS). These can include a pain, an increased sensitivity to palpation, aches, and cramps. SAMS are a real problem in the clinical management of patients, as it is difficult to causally link these complaints with drug use, and they may lead to a reduction in statin intake, or even to the patient -discontinuing their use. The absence of objective markers and the -variety of possible clinical manifestations of these muscular -complaints impede a full understanding of the objective and -subjective impacts of these symptoms on the everyday life of sympto-matic patients. This article assess the current state of knowledge on the impact of SAMS on performance and health--related quality of life.

DERMATOMYOSITIS UNMASKING HIDDEN BREAST CARCINOMA: A CASE REPORT

Dermatomyositis is a rare autoimmune disorder characterized by muscle weakness and skin abnormalities. It is associated with malignancy in 15 to 30% of cases. We present the case of a 73-year-old female patient who initially presented with itchy purplish skin lesions, photosensitivity and oral ulcers. The patient also complained of difficulty in standing, joint pain of the shoulders, knees and ankles, but no joint swelling or morning stiffness. Relevant investigations revealed a surprising discovery of underlying left breast carcinoma, which was asymptomatic. This case highlights the importance of recognizing dermatomyositis as a paraneoplastic syndrome and its potential to unmask hidden malignancies. Dermatomyositis has long been recognized as a paraneoplastic syndrome, meaning that it can precede the clinical manifestation of an underlying malignancy. In this case, the patients initial presentation with dermatomyositis-related skin and muscle symptoms served as a sentinel sign, alerting clinicians to investigate further. The patient responded positively to treatment with intravenous methylprednisolone and was subsequently referred for further management of the breast carcinoma.

Statins adherence and associated muscle symptoms in elderly coronary heart disease patients

Statins adherence and associated muscle symptoms in elderly coronary heart disease patients

Comparing the remote effects of dry needling and ischemic pressure on pain intensity and threshold of the myofascial trigger points in women: A Single Blinded Randomized Clinical Trial

ObjectiveThe current study aimed to investigate the remote effects of upper trapezius (UT) Dry needling (DN) and ischemic pressure (IP) on the pain intensity and threshold of the MTrPs in the extensor carpi radialis longus (ECRL) and the first dorsal interosseous (FDI) muscles. MethodsTwenty-eight subjects were allocated into two groups in a randomized clinical trial study undergoing DN and IP interventions on the MTrPs of the UT muscle for 3 sessions. Pressure pain intensity was assessed by visual analog scale (VAS) and pressure pain threshold (PPT) before and after interventions. Upper limb functions were evaluated by the disabilities of the arm, shoulder, and hand (DASH) questionnaire. ResultsThere were significant interactions between muscle, group, and time for PPT, muscle and group, group and time, and muscle and time for VAS (P < 0.05). In DN group, PPTs and VAS of the ECRL and FDI were changed after treatment in all sessions (P < 0.05). In ECRL and FDI muscles, the DN was more effective than IP (P < 0.05). Comparing the pain intensity and threshold of the ECRL, FDI, and UT muscles it was revealed that the improvement in symptoms of the ECRL muscle was the most in the DN group (P < 0.05). There was a significant interaction between group and time for DASH (P < 0.05). In both groups, the DASH score was reduced (P < 0.001). ConclusionsUT muscle DN demonstrated significantly better remote effects in alleviating symptoms of the ipsilateral distal muscles than IP. Both interventions were effective in improving the upper limb function in myofascial pain syndrome patients. Implications for practice•This study evaluated the remote effects of most common treatments on myofascial trigger points.•Dry needling showed therapeutic effects on pain alleviation in terms of both immediate and short term in the extensor carpi radialis longus muscle.•First dorsal interosseous pain threshold and intensity improved following dry needling of the upper trapezius while it is not connected to the upper trapezius muscle myofascially.

Effect of statin treatment on metabolites, lipids and prostanoids in patients with Statin Associated Muscle Symptoms (SAMS).

Between 5-10% of patients discontinue statin therapy due to statin-associated adverse reactions, primarily statin associated muscle symptoms (SAMS). The absence of a clear clinical phenotype or of biomarkers poses a challenge for diagnosis and management of SAMS. Similarly, our incomplete understanding of the pathogenesis of SAMS hinders the identification of treatments for SAMS. Metabolomics, the profiling of metabolites in biofluids, cells and tissues is an important tool for biomarker discovery and provides important insight into the origins of symptomatology. In order to better understand the pathophysiology of this common disorder and to identify biomarkers, we undertook comprehensive metabolomic and lipidomic profiling of plasma samples from patients with SAMS who were undergoing statin rechallenge as part of their clinical care. We report our findings in 67 patients, 28 with SAMS (cases) and 39 statin-tolerant controls. SAMS patients were studied during statin rechallenge and statin tolerant controls were studied while on statin. Plasma samples were analyzed using untargeted LC-MS metabolomics and lipidomics to detect differences between cases and controls. Differences in lipid species in plasma were observed between cases and controls. These included higher levels of linoleic acid containing phospholipids and lower ether lipids and sphingolipids. Reduced levels of acylcarnitines and altered amino acid profile (tryptophan, tyrosine, proline, arginine, and taurine) were observed in cases relative to controls. Pathway analysis identified significant increase of urea cycle metabolites and arginine and proline metabolites among cases along with downregulation of pathways mediating oxidation of branched chain fatty acids, carnitine synthesis, and transfer of acetyl groups into mitochondria. The plasma metabolome of patients with SAMS exhibited reduced content of long chain fatty acids and increased levels of linoleic acid (18:2) in phospholipids, altered energy production pathways (β-oxidation, citric acid cycle and urea cycles) as well as reduced levels of carnitine, an essential mediator of mitochondrial energy production. Our findings support the hypothesis that alterations in pro-inflammatory lipids (arachidonic acid pathway) and impaired mitochondrial energy metabolism underlie the muscle symptoms of patients with statin associated muscle symptoms (SAMS).