Search Results (358)

Background: Myofascial temporomandibular disorders (TMDs) are associated with pain and trigger points in the masticatory muscles. Dry needling (DN) is used for myofascial pain, but evidence regarding immediate effects remains limited. Objective: This participant- and outcome-assessor-blinded randomized controlled trial evaluated immediate clinical and electromyographic effects of a single DN session targeting the masseter and anterior temporalis muscles in patients with myofascial TMD. Methods: Forty-four participants diagnosed according to the Research Diagnostic Criteria for Temporomandibular Disorders were randomly allocated to a DN group or a sham needling group. Pain intensity was assessed using a visual analog scale, and surface electromyographic activity of the masseter and anterior temporalis muscles was recorded at rest and during maximal clenching. Measurements were obtained before treatment and 10 min after the intervention. Adverse events were recorded throughout the observation period. Results: Forty participants completed the study, with 20 in each group. Pain intensity decreased significantly in the DN group compared with the sham group (p < 0.001). An uncorrected analysis indicated reduced resting activity of the left anterior temporalis muscle; however, no electromyographic variable remained significant after correction for multiple comparisons. No serious adverse events occurred. Minor transient bleeding and mild post-needling soreness were reported in a small number of participants receiving DN. Conclusions: A single DN session produced a significant immediate reduction in pain intensity in patients with myofascial TMD, without consistent immediate changes in surface electromyographic activity. Longer follow-up and repeated-session studies are needed to determine the durability and clinical relevance of these effects. Full article

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, and lowering low-density lipoprotein cholesterol (LDL-C) remains a cornerstone of cardiovascular prevention. Statins are among the most extensively studied and widely prescribed medications and have demonstrated substantial benefits in reducing major adverse cardiovascular events in both primary and secondary prevention settings. Nevertheless, the effectiveness of statin therapy in routine clinical practice is frequently compromised by poor adherence, treatment discontinuation, concerns regarding adverse effects, and persistent residual cardiovascular risk. This narrative review synthesises contemporary evidence relating to the mechanisms of action of statins, their role in primary and secondary prevention, determinants of medication adherence, statin-associated muscle symptoms (SAMSs), and emerging developments in precision cardiovascular medicine. Current evidence indicates that although statins remain highly effective in reducing cardiovascular risk, long-term treatment success is strongly influenced by behavioural, psychological, social, and healthcare system factors. Increasing attention has also been directed towards the multifactorial nature of SAMSs and the contribution of nocebo effects to perceived statin intolerance. Emerging approaches involving pharmacogenomics, artificial intelligence, digital health technologies, and multidimensional risk assessment offer opportunities for more individualised prevention strategies, although important limitations relating to cost, accessibility, and external validity remain. Overall, contemporary cardiovascular prevention requires a patient-centred approach that integrates biological, behavioural, and social determinants of health to optimise treatment adherence and improve long-term cardiovascular outcomes. Full article

Background/Objectives: Passive postural change from the supine position to sitting requires rapid circulatory and autonomic adjustment. This small-scale exploratory study examined whether prior verbal notice is associated with changes in cerebral and peripheral haemoglobin dynamics and heart rate variability during passive postural change in healthy middle-aged and older men. Methods: Ten healthy men completed both experimental conditions in randomized order: passive postural change with prior verbal notice and passive postural change without prior verbal notice. Each condition consisted of 10 min of supine rest, 10 min of sitting with feet on the floor, and 10 min in the supine position after return. Near-infrared spectroscopy was used to assess haemoglobin changes in the left frontal region and right gastrocnemius muscle, and heart rate variability was used to estimate autonomic modulation. Results: In both conditions, frontal total haemoglobin and oxygenated haemoglobin decreased shortly after sitting and subsequently tended to recover by approximately 5 min after postural change. The low-frequency/high-frequency (LF/HF) ratio increased earlier in the prior-notice condition, and no adverse events occurred. Because the sample was small, these findings should be interpreted as preliminary within-sample patterns rather than as confirmatory evidence. Conclusions: Prior verbal notice may be associated with earlier autonomic adjustment during passive postural change. The findings do not establish clinical benefit or causality. Larger crossover studies that include women, frail older adults, and clinical populations are needed before firm clinical recommendations can be made. Full article

Long non-coding RNAs (lncRNAs) constitute an important group of regulatory RNA molecules involved in the control of gene expression at the epigenetic, transcriptional, and post-transcriptional levels. In recent years, their crucial role in the pathophysiology of cardiovascular diseases, particularly coronary heart disease, has become increasingly evident. The aim of this review is to present current knowledge regarding the mechanisms of lncRNA action in the cardiovascular system, their involvement in the molecular processes associated with myocardial ischaemia, and their potential diagnostic and therapeutic applications. We discuss the molecular mechanisms responsible for the regulation of cardiomyocyte apoptosis, oxidative stress, mitochondrial dysfunction, angiogenesis, coronary vessel remodelling, and cardiac fibrosis. Particular attention is paid to selected lncRNAs involved in coronary heart disease, including MIAT, MALAT1, ANRIL, and H19, which influence inflammatory processes, vascular smooth muscle cell proliferation, responses to hypoxia, and cardiac fibrosis. The potential of lncRNAs as diagnostic and prognostic biomarkers in coronary artery disease is also discussed. Current evidence suggests that molecules such as MALAT1, MIAT, LIPCAR, and HCG11 may have considerable diagnostic and prognostic value, including for predicting major adverse cardiovascular events and the no-reflow phenomenon following percutaneous coronary intervention. Furthermore, contemporary therapeutic strategies targeting lncRNAs are presented, including antisense oligonucleotides, siRNAs, and CRISPR/Cas9 genome-editing technologies. Despite promising preclinical findings, the clinical application of lncRNA-based therapies remains limited by challenges related to safety, delivery of therapeutic molecules, and translation of experimental findings into clinical practice. Nevertheless, lncRNAs represent a promising avenue for the development of precision medicine and may play an important role in the future diagnosis and treatment of cardiovascular diseases. Full article

Botulinum neurotoxin (BoNT) injection into the masseter muscle is used in selected conditions associated with excessive or painful masseter activity, including oromandibular dystonia, masseter-related myalgia, and bruxism-associated masticatory muscle pain. However, clinical outcomes and adverse-event profiles vary widely, partly because injection technique, dose, dilution, injection depth, anatomical targeting, patient selection, and injector experience have not been consistently standardized. This review examines the anatomical and pharmacological rationale for motor endplate zone (MEZ)-targeted BoNT injection into the masseter muscle. MEZ-targeted injection is not presented as an established clinical guideline or as a proven superior technique but as a hypothesis-generating framework for future controlled studies. Anatomical and electrophysiological studies indicate that neuromuscular junctions in the masseter muscle are concentrated within relatively restricted MEZs. From a pharmacological perspective, delivery of BoNT close to these zones may allow more efficient neuromuscular blockade with lower doses, although direct clinical evidence demonstrating superiority over conventional techniques remains insufficient. Reported adverse events may be influenced by excessive dosing, inaccurate injection depth, diffusion into adjacent structures, or repeated high-dose injections. Future studies should evaluate anatomically informed, dose-minimized injection strategies using clearly defined clinical populations, standardized diagnostic criteria, detailed reporting of injection technique, objective functional outcomes, and systematic adverse-event assessment. Full article

Intra-articular platelet-rich plasma (PRP) injections represent a promising biological treatment for early-stage knee osteoarthritis (KOA). As cord blood-derived PRP (CB-PRP) contains higher levels of bioactive mediators, this prospective study aimed to compare the efficacy and safety of CB-PRP versus homologous donor PRP (HD-PRP) in patients with early KOA and to evaluate whether CB-PRP results in greater clinical improvement. Fifty-one patients aged 46–70 years with Kellgren–Lawrence grade 1–2 were randomized to receive either CB-PRP or HD-PRP. Each underwent three intra-articular injections at four-week intervals. Outcomes included pain-related overall health perception assessed by the EuroQol Visual Analogue Scale (EQ-VAS), function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS), and quadriceps muscle strength evaluated by dynamometry. Assessments were performed at baseline and at 1, 2, 3, 6, and 12 months. Both groups showed improvements in pain and function over 12 months, with no statistically significant between-group differences (p = 0.46). EQ-VAS increased from 59 ± 19 to 83 ± 9 in the CB-PRP group and from 59 ± 18 to 77 ± 18 in the HD-PRP group. KOOS improved from 50 ± 25 to 68 ± 23 and from 38 ± 28 to 59 ± 24, respectively. Quadriceps strength showed no intergroup differences. Adverse events were mild and self-limiting. Both treatments demonstrated comparable clinical benefits and favorable safety profiles. Full article

Background/Objectives: Intensified training in adolescent soccer players increases oxidative stress, muscle damage, inflammation, and immune suppression, but direct comparisons of nutritional countermeasures are lacking. This randomised, double-blind, placebo-controlled trial compared the effects of 14-day coenzyme Q10 (CoQ10) versus taurine supplementation on haematological, oxidative, muscle damage, inflammatory, hormonal, and immune biomarkers in under-19 soccer players undergoing three repeated 90 min Soccer Match Simulation (SMS) sessions. Methods: Twenty-four male players (age 17.9 ± 0.7 years) received placebo (n = 8), CoQ10 (300 mg/day, n = 8), or taurine (4 g/day plus 4 g pre-session, n = 8). Blood was collected at baseline (T0), post-first session (T1), post-third session (T2), and 24 h post-third session (T3). Biomarkers included creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), total antioxidant capacity (TAC), interleukins (IL-6, IL-10, TNF-α), cortisol, testosterone, CD4/CD8 ratio, immunoglobulins (IgA, IgG), and plasma volume (Dill–Costill). Data were analysed by two-way repeated-measures ANOVA. Results: CoQ10 was superior in reducing MDA (T2: 0.83 ± 0.02 vs. 1.24 ± 0.03 μmol/L, p < 0.001), LDH (434 ± 9 vs. 684 ± 12 U/L, p < 0.001), and cortisol (20.2 ± 0.6 vs. 30.4 ± 0.8 μg/dL, p < 0.001), and preserved the testosterone:cortisol ratio (24.5 ± 1.1 vs. 13.6 ± 1.0 × 10⁻³, p < 0.001). CoQ10 was more effective than taurine in lowering IL-6 at T2 (3.5 ± 0.2 vs. 3.9 ± 0.2 pg/mL, p = 0.03), whereas taurine was more effective in increasing IL-10 (7.5 ± 0.2 vs. 5.7 ± 0.2 pg/mL, p = 0.005). Both supplements preserved CD4 counts (CoQ10: 790 ± 13, taurine: 795 ± 14 vs. placebo: 680 ± 15 cells/μL, p < 0.01) and the CD4/CD8 ratio, as well as IgA and IgG levels, with no between-supplement differences for immune outcomes (p > 0.05). No adverse events occurred. Conclusions: For adolescent soccer players undergoing intensified training, CoQ10 may be preferred when the goal is reducing oxidative stress, muscle damage, and catabolic load; taurine may be preferred for targeted anti-inflammatory support (IL-10 elevation). Either supplement effectively attenuated changes in circulating immune biomarkers. These preliminary findings provide evidence-based guidance for targeted sports nutrition, pending confirmation in larger trials. Full article

Background: Heller myotomy (HM) is the standard surgical treatment for achalasia. Complete muscular division while preserving mucosal integrity is essential for optimal outcomes. Indocyanine green fluorescence (ICG) imaging has recently emerged as a potential intraoperative adjunct during minimally invasive HM, although evidence remains limited and heterogeneous. Methods: A scoping review was conducted according to PRISMA-ScR recommendations. PubMed, Scopus, and Web of Science were systematically searched to identify clinical studies reporting intraoperative ICG use during laparoscopic or robotic HM. Data regarding surgical approach, fluorescence technique, intraoperative applications, and outcomes were extracted and descriptively synthesized. Results: Four clinical studies published between 2022 and 2024 were included, involving 58 patients overall, of whom 41 underwent minimally invasive HM with intraoperative ICG fluorescence assessment. Two main fluorescence strategies were identified. Intravenous ICG administration was exclusively evaluated during robotic Heller myotomy, whereas all laparoscopic studies employed intraluminal ICG instillation through a nasogastric tube. Fluorescence imaging was used to assess myotomy completeness, identify residual muscle fibers, and detect mucosal perforation. Intraluminal ICG enabled direct visualization of the mucosal tube and facilitated leak detection, whereas intravenous administration enhanced tissue contrast and identification of residual muscular bundles. No ICG-related adverse events were reported. However, the available evidence was limited to small observational series with heterogeneous protocols and inconsistent outcome reporting. Conclusions: ICG fluorescence appears technically feasible during minimally invasive HM and may support intraoperative assessment of myotomy completeness and mucosal integrity. Although early clinical experience is encouraging, the available evidence remains insufficient to support routine implementation of ICG-guided assessment during Heller myotomy, highlighting the need for standardized prospective comparative studies. Full article

Background/Objectives: Orofacial myofascial pain (MFP) is one of the leading causes of chronic orofacial pain, often resulting in functional limitations and a compromised quality of life. Intramuscular injection therapies appear to be a promising alternative for patients resistant to conservative treatment. The objective of this rapid review was to synthesize evidence from randomized controlled trials evaluating intramuscular injectable therapies for orofacial myofascial pain. Specifically, the review aimed to compare the clinical effects of different injectable agents on pain intensity, mandibular function, and patient-reported outcomes, and to identify methodological limitations and research gaps within the current evidence base. Methods: A comprehensive search across five databases (ACM, BASE, Cochrane, PubMed, and Scopus) was conducted on March 15, 2026. Randomized controlled trials (RCTs) published between 2022 and 2026 that investigated the use of active injectable agents into the masticatory muscles for clinically diagnosed myofascial pain syndrome were included. Data regarding post-interventional pain intensity, masticatory function, mandibular range of motion, and safety were extracted to compare therapeutic efficacy across interventions. Results: A total of five RCTs met the inclusion criteria. Eligible studies evaluated intramuscular injections of botulinum toxin A, platelet-rich plasma (PRP), magnesium sulfate, and lidocaine, with sample sizes ranging from 30 to 180 participants. Across all interventions, consistent reductions in pain intensity and enhancements in masticatory function were observed. Furthermore, no major adverse events were reported. Conclusions: Intramuscular injectable therapies represent an emerging approach for reducing orofacial myofascial pain, particularly as a treatment for patients with persistent symptoms. Full article

Background and Objectives: GLP-1 receptor agonists (GLP-1 RAs) are effective weight-loss therapies, but data on body composition changes in pediatric obesity remain scarce. The primary objective was to evaluate the effects of GLP-1 RAs on body composition in children with obesity. Materials and Methods: We conducted a retrospective study of children with obesity evaluated at the National Institute for Mother and Child Health “Alessandrescu-Rusescu”, Bucharest, Romania, who initiated weekly injectable GLP-1 RA therapy (semaglutide) between January and December 2025. Patients were assessed at baseline and after a median follow-up of 5 months. Eight of ten participants with complete paired data were included in the final analysis; two were excluded because one was a non-responder with weight gain and suspected non-compliance, while one responder could not maintain the standing position for bioimpedance measurement. Bioimpedance analysis and anthropometry were performed at both visits. Paired data were analyzed using Wilcoxon signed-rank tests. Results: Eight children (4 boys, 4 girls; mean age 14.9 ± 1.8 years) completed the study. Significant Body Mass Index (BMI) Z-score improvements were observed (CDC: −0.14, p = 0.012; WHO: −0.37, p = 0.012), with a median weight reduction of 4.75 kg (p = 0.036). While absolute muscle mass showed non-significant change (−1.3 kg, p = 0.362), predicted muscle mass percentage increased significantly (+1.9%, p = 0.012), suggesting selective fat loss. Fat-free mass percentage increased (+2.0%, p = 0.012) with reciprocal fat mass reduction (absolute: −3.85 kg, p = 0.017; percentage: −2.0%, p = 0.012). Fat-free mass index remained stable (−0.67 kg/m², p = 0.161). No serious adverse events occurred. Sensitivity analysis (n = 10) confirmed the robustness of the results, with improvements in BMI Z-scores remaining significant. Conclusions: In this preliminary pilot study, GLP-1 RA therapy in children with obesity was associated with significant improvements in BMI Z-scores and favorable shifts in body composition, consistent with selective fat loss and relative preservation of lean mass. These exploratory findings are hypothesis-generating and support the conduct of larger prospective controlled studies with body composition as a primary endpoint. Full article

Cervical dystonia and spasticity are debilitating neuromuscular disorders that substantially impair quality of life. Botulinum toxin type A (BoNT-A) is a cornerstone therapy; however, heterogeneity in dosing, muscle selection, and guidance techniques can limit outcomes, and Mexico-specific practical guidance is limited. We convened a multidisciplinary panel of Mexican rehabilitation and neurology specialists with extensive experience in BoNT-A injection; recommendations were developed through a three-phase process: a targeted literature search, a structured online survey of Mexican rehabilitation and neurology specialists, and an in-person meeting (21 February 2025) where clinicians reviewed aggregated survey results and refined practical recommendations through structured deliberation. The manuscript provides pragmatic guidance on evaluation and goal setting, muscle selection, working dilutions, dosing ranges, and reinjection intervals, emphasizing ultrasound (US) and/or electromyography (EMG) for deep or high-risk targets. It also summarizes key adverse events and proposes a stepwise approach to inadequate response, prioritizing reassessment of diagnosis, goals, targeting, and techniques before considering immunogenicity testing, product switching, or alternative interventions. These recommendations aim to improve standardization, safety, and goal attainment in routine Mexican practice. Full article

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely recommended for the treatment of acute (low) back pain, despite modest effectiveness and well-known safety concerns, particularly in older patients. Pridinol is a centrally acting antispasmodic with a mechanism-oriented approach targeting muscle spasm, a key component of acute back pain. While a previous real-world analysis demonstrated a significantly better tolerability and effectiveness of pridinol compared with NSAIDs, age-dependent effects have not yet been systematically evaluated. Objective: To assess the age dependency of effectiveness, safety, and tolerability of pridinol versus NSAIDs in patients with acute (low) back pain under real-world conditions, based on already available data. Methods: This secondary analysis used propensity score-matched real-world data from the German Pain e-Registry (PROVIDENCE study; EUPAS identifier: 49718). A total of 934 patients with acute (low) back pain treated for four weeks with either pridinol (n = 467) or NSAIDs (n = 467) were stratified by age (<65 vs. ≥65 years). Outcomes included the incidence of adverse drug reactions (ADRs), ADR-related treatment discontinuations, time to ADR occurrence, and clinically meaningful improvement in pain-related disability (≥50% reduction in modified Pain Disability Index). Analyses were performed within and between age strata. Results: Overall, ADRs were reported by 9.0% of pridinol-treated patients and 20.8% of NSAID-treated patients (p < 0.001). In the pridinol cohort, ADR rates were virtually identical in patients <65 and ≥65 years (8.9% vs. 9.2%; p = 0.940). In contrast, NSAID-treated patients showed a pronounced age-related increase in ADR incidence (17.3% vs. 32.1%; p < 0.001). ADR-related treatment discontinuation rates under NSAIDs increased markedly with age (5.9% vs. 21.1%; p < 0.001), whereas rates under pridinol remained low and age independent (3.1% vs. 4.6%; p = 0.447). Gastrointestinal and cardiovascular ADRs were the main contributors to the age-related risk increase under NSAIDs, while corresponding events under pridinol were rare across age groups. Clinically meaningful improvement in pain-related disability was achieved with pridinol/NSAIDs in 91.9/48.0% (<65 years) and 88.1/47.7% (≥65 years; p < 0.001 for both). Conclusions: Age is a major modifier of NSAID-related risk but not of pridinol tolerability in acute (low) back pain. While NSAID-associated ADRs and treatment discontinuations increase substantially in patients aged 65 years or older, pridinol demonstrates a stable, age-independent safety profile combined with significantly better functional outcomes. These findings suggest that, particularly in older patients, mechanism-oriented alternatives such as pridinol may offer a more favorable benefit–risk profile than NSAIDs. Full article

Chronic coronary syndromes (CCSs) are increasingly recognized as complex immunometabolic vascular disorders in which coronary microvascular dysfunction (CMD), persistent low-grade inflammation, oxidative stress, and maladaptive cellular remodeling contribute to ischemic symptoms and adverse outcomes beyond epicardial stenosis. CMD represents a heterogeneous condition comprising both functional and structural endotypes and constitutes a major determinant of myocardial ischemia, heart failure progression, and adverse cardiovascular outcomes, even in the absence of obstructive coronary artery disease. Emerging evidence indicates that immunometabolic reprogramming of endothelial cells, vascular smooth muscle cells, and immune cells sustains microvascular dysfunction in CCSs. Metabolic shifts toward glycolysis, mitochondrial dysfunction, redox imbalance, and dysregulated lipid metabolism promote chronic inflammatory activation within the coronary microenvironment. Convergent mitochondrial stress (including NAD⁺ decline) and redox injury promote endothelial senescence and increase susceptibility to regulated cell death, progressively limiting vasodilatory reserve and predisposing to microvascular rarefaction. Pyroptosis and ferroptosis-like lipid peroxidation further exacerbate endothelial barrier disruption and inflammatory amplification. In parallel, inflammasome activation, iron-dependent lipid peroxidation, impaired autophagy, and endoplasmic reticulum stress form interconnected molecular networks that amplify vascular injury through self-reinforcing mechanisms. This narrative review integrates mechanistic and translational evidence linking immunometabolic dysregulation, mitochondrial stress, thromboinflammatory signaling, endothelial senescence, and regulated cell death to distinct CMD endotypes. We propose a systems-level framework in which coronary microvascular dysfunction is conceptualized as an immunometabolic vascular network disorder, with reduced coronary flow reserve (CFR)—often termed myocardial flow reserve (MFR) in PET studies—emerging as the integrative functional endpoint of these interacting molecular perturbations and a robust predictor of major cardiovascular events. Full article

Pulmonary hypertension (PH) is a progressive, multifactorial syndrome characterized by elevated pulmonary arterial pressure and right heart dysfunction, associated with significant morbidity, impaired quality of life, and poor prognosis. Advances in classification, hemodynamic definitions, and targeted pharmacotherapies have improved understanding and management, yet therapeutic challenges persist across the five World Health Organization groups of PH. Historically, exercise was discouraged due to concerns about adverse hemodynamic effects, but growing evidence has suggested that structured, supervised training is safe and beneficial. Randomized trials and meta-analyses show improvements in six-minute walk distance, peak oxygen uptake, right ventricular function, ventilatory efficiency, and health-related quality of life, with a low incidence of adverse events. Physiological adaptations include favorable cardiac remodeling, enhanced endothelial function, improved skeletal and respiratory muscle performance, and improved neurohormonal activity. Despite this evidence, barriers such as patient fears, limited clinical expertise, and restricted access to specialized rehabilitation programs hinder widespread implementation. Current guidelines recommend supervised exercise as part of pulmonary rehabilitation for patients with stable PH, supporting its role as an adjunct to pharmacotherapy. This descriptive review briefly summarizes the pathophysiology of PH, phenotype-related differences and current therapeutic approaches, and the beneficial adaptations to exercise training, with the aim of informing exercise specialists and supporting safer, more effective integration of exercise-based rehabilitation into patient care. Full article

Intravenous (IV) iron is used to replenish iron stores in patients with iron-deficiency anemia (IDA) who do not benefit from oral iron supplementation. Hypophosphatemia is an increasingly recognized adverse event associated with certain IV iron formulations. Mild/moderate hypophosphatemia may be asymptomatic or present with symptoms similar to those seen in patients with IDA, including fatigue, malaise, and muscle weakness. Persistent hypophosphatemia can cause osteomalacia due to reduced bone mineralization, leading to bone pain and pseudofractures. Ferric carboxymaltose (FCM) can impact phosphate homeostasis through an increase in fibroblast growth factor 23, leading to increased urinary phosphate excretion and hypophosphatemia. In clinical trials, rates of hypophosphatemia were significantly higher in patients receiving FCM compared with other IV iron formulations, such as ferric derisomaltose and ferumoxytol. Treatment guidelines recommend monitoring serum phosphate levels in patients receiving FCM who are at risk for low phosphate or who require repeat infusions, and alternative iron formulations should be considered in at-risk patients. This narrative review summarizes current evidence regarding IV iron-induced hypophosphatemia in individuals with IDA and examines the underlying pathophysiology and clinical evidence for IV iron-induced hypophosphatemia, particularly with FCM, the populations most at risk, and the clinical consequences of persistent hypophosphatemia. Full article