Search Results (1,454)

Pompe disease (PD) is a rare, autosomal recessive neuromuscular disorder caused by mutations in the gene encoding acid alpha-glucosidase (GAA). The resulting deficiency in GAA, a lysosomal enzyme, leads to the pathological accumulation of glycogen, primarily in cardiac and skeletal muscles. PD presents as a clinical continuum spanning two major phenotypes: infantile-onset Pompe disease (IOPD), the most severe form, typically characterized by onset before 12 months of age, rapid hypertrophic cardiomyopathy, and severe hypotonia; and late-onset Pompe disease (LOPD), which manifests between 12 months of age and adulthood, and is characterized by progressive axial and proximal muscle weakness and respiratory insufficiency. Enzyme replacement therapy (ERT), available since 2006, has improved survival, particularly in IOPD, but is limited by variable efficacy and limited penetration of the blood–brain barrier, necessitating new approaches. In this comprehensive review, we focus on advances in the understanding and management of PD. First, we explore recent diagnostic advances and the characterization of multisystem involvement in PD. Next, we critically discuss the advantages and limitations of current ERT approaches, and advances achieved with next-generation ERT (avalglucosidase alfa, cipaglucosidase alfa + miglustat). Finally, we summarize cutting-edge, potentially curative strategies, including substrate reduction therapy and novel experimental therapies (e.g., gene therapy) that seek to circumvent the limitations of ERT, provide durable effects, and potentially penetrate the central nervous system. Full article

Approximately 30% of patients with tremor-dominant Parkinson’s disease (PD) have rest tremor that persists despite optimal dopaminergic therapy. When deep brain stimulation and focused ultrasound are unavailable or declined, the therapeutic options narrow. Botulinum toxin (BoNT) offers a targeted, titratable, reversible approach, but whether a peripheral neuromuscular blocking agent makes sense for a centrally generated tremor is a legitimate question that deserves a direct answer. This narrative critical review appraises what is currently known across PD and non-PD tremor conditions, defines the technical requirements for safe and effective injection, and provides a practical framework for patient selection and clinical management. The PD-specific literature rests on a single positive double-blind randomized controlled trial of 30 patients; all remaining data are open-label or extrapolated from other tremor conditions, and this narrative synthesis combines heterogeneous conditions, outcome scales, and toxin protocols. A recurring technical observation is that, in the available trials, individualized, EMG-guided injection has been associated with substantially lower rates of hand weakness than fixed-dose injection (reported reductions from roughly 30–70% to below 15%) while maintaining tremor reduction, although the degree of benefit and weakness risk vary with the tremor syndrome, injected muscles, baseline impairment, dose, and guidance method. The careful patient selection this approach requires helps the individual clinician and patient achieve tremor relief, but it departs from the unselected real-world PD population and introduces selection bias that makes a large, statistically representative cohort difficult to assemble. In well-selected patients at centers with the appropriate expertise, BoNT may be a clinically useful option, but routine adoption is not yet supported. Full article

Background: Oculopharyngodistal myopathy (OPDM) is a rare disorder with progressive ptosis, ophthalmoplegia, and oral incompetence, which pose challenges to management. While surgical interventions for blepharoptosis have been reported, addressing concurrent facial muscle weakness remains a significant challenge in comprehensive disease management. Case: A 59-year-old woman with OPDM exhibited severe ptosis and oral incompetence. Despite undergoing prior cosmetic interventions, these symptoms had progressively worsened over 10 years. Preoperative evaluation revealed complete ptosis with a margin reflex distance 1 (MRD-1) of 0 mm and preserved Bell’s phenomenon. A two-stage reconstruction using fascia lata grafting corrected ptosis with a frontalis sling and restored oral competence with U-shaped grafts anchored to the zygomatic arches. Results: At 3 years and 6 months postoperatively, eyelid elevation had improved without corneal exposure, and oral competence was restored, resolving drooling. Conclusions: Semi-dynamic reconstruction using fascia lata grafting effectively addresses ptosis and oral incompetence in OPDM, improving visual and swallowing functions and enhancing quality of life. Full article

Background: Physical activity is a key modifiable factor influencing healthy aging, yet data on activity patterns and their physiological correlates in older adults from Central Asia remain limited. Understanding these relationships is essential for informing region-specific health promotion strategies. Objectives: This study assessed physical activity levels among urban-dwelling older adults in Astana, Kazakhstan, and examined associations between activity level, body composition, visceral fat accumulation, metabolic indicators, and muscle strength. Methods: A cross-sectional study was conducted among 608 adults aged ≥60 years (median age: 68 years; 82.1% women). Physical activity was measured using the validated Physical Activity Scale for the Elderly (PASE). Anthropometric and body composition indicators, including BMI, total and visceral fat, skeletal muscle mass, and handgrip strength, were evaluated. Spearman correlation and linear regression analyses were applied. The analyses were exploratory and did not include adjustment for potential confounders such as sex, chronic disease burden, or socioeconomic status; therefore, the observed associations should be interpreted with caution. Results: The median PASE score was 55.55, with 61.8% of participants demonstrating moderate activity levels, primarily through walking and household tasks. In analyses without adjustment for potential confounding factors, PASE scores showed weak inverse associations with visceral fat (ρ = −0.214; p < 0.001) and waist-to-hip ratio (ρ = −0.154; p < 0.001), as well as weak positive associations with handgrip strength. Across the reported significant associations, correlation coefficients ranged from |ρ| = 0.103 to 0.235, and the explanatory capacity of the regression models was low, with R² values ranging from 0.6% to 8.2%. Conclusions: Higher habitual physical activity may be linked to selected bioelectrical impedance parameters, WHR, and handgrip strength among urban older adults. Given the cross-sectional design, causal interpretation should be approached with caution. These findings provide meaningful regional baseline evidence for future longitudinal and intervention studies on physical activity and healthy aging in Central Asia. Full article

Background/Objectives: Functional vulnerability may identify older adults hospitalized with Crohn’s disease flares who are at increased risk for adverse outcomes, but its prognostic significance in this setting remains incompletely defined. We evaluated the association between administratively defined functional vulnerability, identified using administrative diagnostic codes, and short-term clinical outcomes among adults aged ≥65 years hospitalized with Crohn’s disease flares. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Research Network through February 2026. Functional vulnerability was identified using ICD-10-CM codes for frailty, sarcopenia, cachexia, abnormal weight loss, muscle weakness, gait/mobility abnormalities, or reduced mobility within 12 months before or during the index hospitalization. Patients coded only for nonspecific weakness or fatigue were excluded from the functional vulnerability cohort. Patients underwent 1:1 propensity score matching using demographic, comorbidity, Crohn’s disease-related, medication, nutritional, and laboratory variables. The primary outcome was 30-day all-cause mortality. Results: Among 18,420 eligible patients, 2846 met criteria for functional vulnerability, and 15,574 did not. After matching, 2720 patients remained in each cohort. Functional vulnerability was associated with higher 30-day mortality (RR 1.61, 95% CI 1.21–2.14), 90-day mortality (RR 1.40, 95% CI 1.14–1.72), bowel surgery (RR 1.29, 95% CI 1.07–1.56), sepsis (RR 1.41, 95% CI 1.18–1.68), acute kidney injury (RR 1.26, 95% CI 1.10–1.44), ICU admission (RR 1.32, 95% CI 1.13–1.55), TPN use (RR 1.47, 95% CI 1.20–1.79), and 90-day readmission (RR 1.17, 95% CI 1.07–1.29). Functionally vulnerable patients also had longer hospital stays (8.9 vs. 6.7 days; mean difference 2.2 days, 95% CI 1.9–2.5). Conclusions: Administratively defined functional vulnerability identified through diagnostic coding was associated with worse short-term outcomes among older adults hospitalized with Crohn’s disease flares. Although functional vulnerability is a recognized predictor of adverse outcomes across hospitalized populations broadly, these findings quantify its prognostic significance specifically in Crohn’s disease flare hospitalizations and suggest that functional vulnerability may identify a high-risk geriatric IBD phenotype that could benefit from early multidisciplinary assessment, nutritional optimization, rehabilitation planning, and post-discharge care coordination. Full article

Fatigue and muscle wasting are common clinical manifestations of inherited and acquired neuromuscular disorders, including peripheral neuropathies, neuromuscular junction disorders, and myopathies. These conditions encompass a wide disease spectrum with variable prognoses, making accurate diagnosis essential for appropriate management. Congenital myasthenic syndromes (CMSs) are rare, inherited disorders characterized by impaired neuromuscular transmission. Although symptoms often begin in infancy or early childhood, later onset during adolescence or adulthood is increasingly recognized. Clinical phenotypes vary according to the underlying molecular defect, but fatigable weakness predominantly affecting axial and proximal limb muscles is a hallmark feature. We report an adolescent male who developed progressive proximal muscle weakness and wasting over several years, resulting in significant functional impairment. Initial evaluation suggested limb–girdle muscular dystrophy. However, comprehensive investigations, including whole-exome sequencing, identified a heterozygous CHRNB1 mutation consistent with postsynaptic CMS. Targeted pharmacological therapy led to clinical improvement. This case highlights the importance of considering CMS in patients presenting with limb–girdle weakness and underscores the value of genetic testing in establishing an accurate diagnosis and guiding treatment. Full article

Background and Objectives: Assessing knee extensor (KE) strength is important for detecting muscle weakness in older adults, yet dynamometry is often impractical in community settings. This study examined whether smartphone-derived kinematics during the Five Times Sit-to-Stand Test (FTSST) could predict seated isometric KE strength. Materials and Methods: A cross-sectional study included 105 community-dwelling older adults (68.19 ± 5.85 years). A smartphone application extracted rising time, vertical velocity, and smartphone-estimated relative vertical power during the FTSST. KE strength was measured as maximum voluntary isometric contraction (MVIC) using fixed-frame dynamometry with a Lafayette dynamometer head. Bioelectrical impedance-derived body composition variables were reported descriptively but excluded from the primary prediction models to maintain a transparent movement-based model independent of device-specific body-composition estimates. Hierarchical regression models used smartphone-derived variables and transparent non-BIA covariates. Agreement was examined using Bland–Altman analysis. Results: Smartphone-estimated relative vertical power showed the strongest correlation with MVIC (r = 0.787, p < 0.001). The combined model including sex, age, femur length, and smartphone-estimated relative vertical power explained 71.6% of MVIC variance (adjusted R² = 0.716, SEE = 3.276 kg), outperforming vertical velocity, rising time, and total FTSST time models. Internal validation using repeated 10-fold cross-validation showed CV-R² = 0.701, CV-adjusted R² = 0.689, CV-RMSE = 3.343 kg, and CV-MAE = 2.739 kg. Bland–Altman analysis showed minimal mean bias (0.00 kg), 95% limits of agreement from −6.296 to 6.296 kg, and significant proportional bias (slope = −0.172, p = 0.002), indicating overestimation in weaker individuals and underestimation in stronger individuals. Conclusions: Consistent with our hypothesis, smartphone-estimated relative vertical power was the strongest kinematic predictor of seated isometric KE strength among the evaluated FTSST-derived variables. This approach may support community screening and monitoring, but it should not replace standardized dynamometry for precise individual-level strength quantification. Full article

Free amino acids (FAAs) are important low-molecular-weight metabolites involved in osmotic regulation, acid–base balance, and nitrogen metabolism in fish exposed to saline–alkaline environments. To characterize tissue-specific FAA responses in mandarin fish (Siniperca chuatsi), 10 cm juveniles were exposed for 96 h to freshwater control (FW), salinity stress (S, salinity 8), alkalinity stress (A, alkalinity 20 mmol/L), or combined saline–alkaline stress (SA, salinity 8 + alkalinity 20 mmol/L). The contents of 19 FAAs were compared among plasma, muscle, liver, brain, and kidney. FAA profiles showed clear tissue specificity. Total FAA (17) decreased in plasma under all stress treatments, increased in muscle under S and SA but decreased under A, increased in liver and kidney, and decreased under single stress but increased under combined stress in brain. Distinct tissue distribution patterns were observed for functional FAA groups. Under salinity stress, osmoregulation-related FAAs, particularly Ala and Pro, showed higher contents mainly in muscle, liver, and kidney. Under alkalinity stress, kidney showed concurrent increases in multiple FAAs, including Ala, Pro, Glu, Gln, Val, Ile, and Leu, whereas brain was characterized by a high Gln content. Under combined saline–alkaline stress, liver was the main tissue in which multiple functional FAA groups increased simultaneously, kidney maintained elevated levels of several FAAs, and brain showed treatment-specific high levels of Gln and Tau. Redundancy analysis (RDA) indicated weak constrained explanatory power of salinity and alkalinity for the overall FAA profile, whereas tissue-specific differentiation was evident. Glu, Gln, and Pro showed directional consistency with the salinity vector, whereas Val and Leu tended to align with the alkalinity-related ordination direction. Overall, acute saline–alkaline exposure induced a functional and tissue-specific distribution pattern of FAAs rather than a uniform whole-body shift in mandarin fish. 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

Renal tubular disorders are often overlooked causes of acquired or inherited bone hypomineralization and fragility fractures in adults. The proximal tubule reabsorbs glucose, phosphate, low-molecular-weight proteins, amino acids, bicarbonate, and much of the sodium, potassium, chloride, and calcium. The distal nephron—the thick ascending limb of the loop of Henle, the distal convoluted tubule, and the collecting duct—regulates urine concentration and dilution, maintains acid-base balance via urinary proton secretion, and controls electrolytes, including sodium, potassium, magnesium, and calcium. Tubular defects may cause hyperphosphaturia (high urinary phosphate), hypercalciuria (high urinary calcium), or chronic metabolic acidosis (renal tubular acidosis, RTA). These changes weaken bone mineralization, disrupt bone turnover, and raise the risk of muscle weakness and fractures. This review summarizes acquired and genetic tubulopathies linked to hyperphosphaturia, hypercalciuria, and RTA and outlines a practical diagnostic approach for outpatients with bone fragility and suspected renal tubulopathy. Full article

Background/Objectives: Andersen–Tawil Syndrome (ATS) is an ultra-rare autosomal dominant condition secondary to deleterious variants in KCNJ2 or KCNJ5 in the majority of patients. It is variably characterized by a triad of Long QT Syndrome (LQTS)/ventricular arrhythmias with a prominent U-wave, episodic flaccid muscle weakness/paralysis and skeletal abnormalities. Other clinical features include distinctive facial dysmorphisms, dental anomalies, and mild learning difficulties. Limited data are available regarding the initial presenting sign or symptoms of ATS. Methods: In this study, we include data from 18 patients across eight families. In our cohort, the main clues that led probands to genetic testing were syncope (three families), which was associated with dysmorphic features in one case; LQTS (one family); asymptomatic premature ventricular contractions (PVCs) (three families); and a case incidentally identified during routine cardiac evaluations and due to short stature (one family). Results: Following thorough investigations, a prolonged QT interval was detected in five individuals and prominent U-waves were observed in the majority of the court. Distinctive facial features were consistently present (100%) and can be suggested as a clinical tool for accelerated diagnosis. Skeletal manifestations ranged from 37.5% to 93.7% including short stature, scoliosis and finger defects. Only two patients showed periodic paralysis (PP). Conclusions: Regarding the clinical management of ATS, we underline the importance of the multidisciplinary, personalized, and longitudinal approach, where arrhythmia may not be the leading sign but remains the most potentially critical prognostic factor. Full article

Background/Objectives: Injury occurrence in physically active young adults is considered a multifactorial phenomenon influenced by body composition and training-related characteristics. This study aimed to investigate the multidimensional relationships between body composition, training context variables, and injury phenotypes in physically active university students using exploratory multivariate approaches. Methods: The study included 418 physically active university students. Participants completed questionnaires regarding injury history, physical activity, and sport participation and underwent standardized anthropometric and body composition assessments. Analyses included Kendall’s Tau correlations, multiple correspondence analysis (MCA), hierarchical clustering, heatmap phenotyping, tanglegram-based clustering analysis, and distance-based redundancy analysis (dbRDA). The tanglegram analyses were intended as exploratory structure-matching procedures designed to evaluate similarities in hierarchical organization between domains rather than direct biological associations, causal relationships, or predictive effects. Results: Weak but significant associations were observed between selected body composition variables and injury outcomes, particularly for skeletal-muscle-related indicators and lower limb injuries. MCA and clustering analyses identified partially differentiated sport-training profiles and exploratory injury-burden phenotypes. Topology-based cross-domain matching analyses suggested partial structural correspondence between body composition, training context, and injury phenotypes; however, the most anatomically coherent patterns were observed for local body composition variables. Nevertheless, overall cross-domain concordance remained weak-to-moderate. dbRDA demonstrated statistically significant but weak associations for body composition (adjusted R² = 0.027, p = 0.001) and the combined explanatory model (adjusted R² = 0.022, p = 0.023), whereas the training context model was not significant (adjusted R² = 0.002, p = 0.304). Conclusions: Injury occurrence was weakly associated with body composition and training context characteristics within a multidimensional exploratory framework. The findings are consistent with the interpretation of injury occurrence as a heterogeneous and predominantly multifactorial phenomenon and highlight the utility of multidimensional exploratory approaches for investigating complex injury-related patterns. Full article

Background: Severe knee trauma and chronic cruciate ligament insufficiency are commonly accompanied by marked quadriceps femoris (QF) atrophy and weakness. High-load strengthening is often poorly tolerated by patients with compromised joint stability; therefore, low-load blood flow restriction resistance training (LL-BFRT) may serve as an effective alternative. Case presentation: A 38-year-old male presented 27 months after motorcycle-related polytrauma with right knee pain, instability, complete anterior and posterior cruciate ligament ruptures, and partial QF denervation after femoral nerve injury. Before surgery, he completed a supervised 5-week LL-BFRT prehabilitation program (13 sessions). Results: Lean thigh circumference increased by 5.9% proximally and 17.7% distally. Voluntary activation increased from 87.2% to 92.5%, and maximal QF EMG median frequency decreased by 7.4%. Knee extensor isometric and concentric (60°/s) peak torque increased by 52.4% and 36.9%, respectively. QF isometric endurance time increased from 48.5 to 61.8 s. Stair-climbing time decreased from 18.9 to 10.6 s, repetitions in the step-down test increased from 10 to 17, and the Y-balance test composite score increased from 77.7% to 99.4%. Conclusions: Substantial physiological and clinical improvements in QF voluntary activation, maximal strength, endurance, and lower limb function were observed following a short-term LL-BFRT program in a patient with multiple ligament injuries. Changes in lean thigh circumference were consistent with possible improvements in muscle size; however, muscle hypertrophy was not directly assessed. Full article

Background: 5q spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by progressive muscle weakness. Nusinersen, the first disease-modifying therapy for SMA, has demonstrated efficacy in both clinical trials and real-world studies. However, the precise timing of therapeutic onset following Nusinersen administration remains unclear. Methods: This retrospective study analyzed clinical data from patients with genetically confirmed 5q SMA who received Nusinersen treatment for at least six months at Peking University First Hospital. Motor function was assessed using standardized scales prior to each dose. Results: In total, 74 patients were screened, of whom 62 were enrolled, including 14 with type 1, 29 with type 2, and 19 with type 3 SMA. Thirty-two patients completed motor function assessments. After six months of treatment, 62.5% achieved a primary clinically meaningful response (an increase of ≥4 points in CHOP-INTEND or ≥3 points in HFMSE). Seven patients (21.9%) attained or regained motor milestones. Median improvements were 6 points in CHOP-INTEND (p = 0.001), 4 points in HFMSE (p = 0.003), and 1.5 points in RULM (p = 0.045). Further analysis indicated that the available median time to treatment response was approximately 2 months. In patients with severe scoliosis or prior spinal surgery, ultrasound-guided lumbar puncture demonstrated a high success rate (94.9%). Regarding safety, intrathecal injection-related adverse events occurred in eight patients (12.9%), and no adverse events led to treatment discontinuation. Conclusions: During the loading phase, Nusinersen provides clinical benefit for the majority of patients, with a median time to therapeutic response for monitoring of approximately 2 months. Ultrasound-guided intrathecal administration is the preferred approach for individuals with complicated spinal conditions. These findings may help guide clinical expectations for physicians, patients, and caregivers. Full article

Background/Objectives: Pulmonary complications and respiratory muscle weakness are common in individuals with type 2 diabetes mellitus (Type 2 DM). Physical inactivity may further contribute to impaired respiratory muscle performance and reduced cough effectiveness in this population. The aim of this study was to examine the relationship between physical activity level, respiratory muscle strength, and cough strength in individuals with Type 2 DM. This study was an observational cross-sectional study. Methods: Thirty individuals with Type 2 DM and thirty age- and sex-matched healthy controls were included. Their physical activity level was assessed using the International Physical Activity Questionnaire (IPAQ), and respiratory muscle strength was evaluated using maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), whereas cough strength was assessed using a peak expiratory flow meter. Group comparisons were performed using the Mann–Whitney U test, and associations were analyzed using Spearman’s correlation coefficients. Additional multivariable regression analyses were conducted after adjustment for body mass index (BMI) and waist circumference. Results: Physical activity level, respiratory muscle strength, and cough strength were significantly lower in individuals with Type 2 DM than in healthy controls (p < 0.05). Within the Type 2 DM group, IPAQ scores were positively correlated with MIP (r = 0.438, p = 0.016), MEP (r = 0.581, p = 0.001), and cough strength (r = 0.619, p < 0.001), and diabetes duration was negatively correlated with MIP (r = −0.412, p = 0.024). After adjustment for BMI and waist circumference, Type 2 DM status remained independently associated with lower MIP (B = −15.69, 95% CI: −26.58 to −4.80, p = 0.006) and lower cough strength (B = −90.51, 95% CI: −161.52 to −19.50, p = 0.013). Conclusions: Individuals with Type 2 DM demonstrated lower physical activity levels, respiratory muscle strength, and cough strength than healthy controls. Higher physical activity levels were associated with better respiratory muscle strength and cough strength, whereas longer diabetes duration was associated with lower inspiratory muscle strength. These findings suggest that respiratory muscle function and cough performance may be adversely affected in individuals with Type 2 DM, warranting further investigation in larger longitudinal studies. Full article