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Keywords = orthopedics

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21 pages, 3544 KB  
Article
Biomechanical Analysis and Mid-Term Clinical Outcomes of the Dynamic-Transitional Optima Hybrid Lumbar Device
by Shih-Hao Chen, Shang-Chih Lin, Chi-Ruei Li, Zheng-Cheng Zhong, Chih-Ming Kao, Mao-Shih Lin and Hsi-Kai Tsou
J. Clin. Med. 2025, 14(22), 8087; https://doi.org/10.3390/jcm14228087 - 14 Nov 2025
Abstract
Background/Objectives: Spinal fusion with static fixation—surgically joining two or more vertebrae to eliminate motion—is commonly employed to treat degenerative spinal disease. However, the rigidity imposed by static constructs and the increased load on the adjacent segments frequently result in complications such as [...] Read more.
Background/Objectives: Spinal fusion with static fixation—surgically joining two or more vertebrae to eliminate motion—is commonly employed to treat degenerative spinal disease. However, the rigidity imposed by static constructs and the increased load on the adjacent segments frequently result in complications such as disc or facet degeneration, spinal stenosis (SS), and segmental instability. This study investigates the effectiveness of pedicle-based dynamic stabilization using the Dynesys system, particularly in a dynamic-transitional optima (DTO) hybrid configuration, in mitigating adjacent segment disease (ASD) and improving clinical outcomes. In this work, we analyzed the mechanical performance and intermediate-term clinical effects of the DTO hybrid lumbar device, focusing on how the load-sharing properties of the Dynesys cord–spacer stabilizers may contribute to junctional complications in individuals with diverse grades of intervertebral disc degeneration. Study Design/Setting: We designed a combined biomechanical finite element (FE) and experimental analysis to predict the clinical outcomes. Patient Sample: Among 115 patients with lumbar SS enrolled for analysis, 31 patients (mean age: 68.5 ± 7.5 years), with or without grade I spondylolisthesis (18/13), underwent a two-level DTO hybrid procedure—L4–L5 static fixation and L3–L4 dynamic stabilization—with minimal decompression to preserve the posterior tension band. Post-surgical follow-ups were conducted for over 48 months (range: 49–82). Outcome Measures: Radiological assessments were performed by two neurosurgeons, one orthopedic surgeon, and one neuroradiologist. The posterior disc height, listhesis distance, and dynamic angular changes were measured pre- and postoperatively to evaluate ASD progression. Methods: Dynamic instrumentation was assigned to the L3–L4 motion segment with lesser disc deterioration, in contrast to the L4–L5 segment, where static fixation was applied due to its greater degree of degeneration. FE analysis was performed under displacement-controlled conditions. Intersegmental motion analysis was conducted under load-controlled conditions in a synthetic model. Results: The DTO hybrid devices reduced stress and motion at the transition segment. However, compensatory biomechanical effects were more pronounced at the adjacent cephalad than the caudal segments. In the biomechanical trade-off zone—where balance between motion preservation and stabilization is critical—the flexible Dynesys cord significantly mitigated stiffness-related issues during flexion. At the L3–L4 transition level, the cord–spacer configuration enhanced dynamic function, increasing motion by 2.7% (rotation) and 12.7% (flexion), reducing disc stress by 4.1% (flexion) and 12.9% (extension), and decreasing the facet contact forces by 4.9% (rotation) and 15.6% (extension). The optimal cord stiffness (50–200 N/mm) aligned with the demands of mild disc degeneration, whereas stiffer cords were more effective for segments with higher degeneration. The pedicle screw motion in dynamic Dynesys systems—primarily caused by axial translation rather than vertical displacement—contributed to screw–vertebra interface stress, influenced by the underlying disc or bone degeneration. Conclusions: Modulating the cord pretension in DTO instrumentation effectively lessened the interface stress occurring at the screw–vertebra junction and adjacent facet joints, contributing to a reduced incidence of pedicle screw loosening, ASD, and revision rates. The modified DTO system, incorporating minimal decompression and preserving the posterior complex at the dynamic level, may be biomechanically favourable and clinically effective for managing transitional degeneration over the mid-term. Full article
21 pages, 4616 KB  
Article
Topology Optimization of a Patient-Specific Femoral Component for Total Knee Endoprosthesis
by Mohad Tanveer, Salman Khalid, Jun Young Kim, Jinwoo Song and Heung Soo Kim
Appl. Sci. 2025, 15(22), 12099; https://doi.org/10.3390/app152212099 - 14 Nov 2025
Abstract
This study presents a computational framework for the topology optimization of a patient-specific femoral component used in the total knee endoprosthesis. The motivation stems from the growing need to enhance implant longevity and biomechanical compatibility by optimizing internal structural design according to physiological [...] Read more.
This study presents a computational framework for the topology optimization of a patient-specific femoral component used in the total knee endoprosthesis. The motivation stems from the growing need to enhance implant longevity and biomechanical compatibility by optimizing internal structural design according to physiological loading conditions. A finite element–based density optimization method was employed to determine the optimal material distribution within the femoral component while maintaining anatomical geometry and functional constraints. The model was developed using realistic boundary conditions derived from knee joint mechanics, and the resulting design was compared with a conventional reference geometry. The optimized configuration exhibited more uniform stress distribution, reduced peak von Mises stresses, and improved mass efficiency without compromising mechanical stiffness. These findings demonstrate that the proposed method can significantly improve the structural performance and reliability of knee prostheses. The study concludes that integrating patient-specific modeling with topology optimization offers a promising pathway for developing advanced, individualized orthopedic implants and supports future experimental validation through 3D printing and biomechanical testing. Full article
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20 pages, 3217 KB  
Article
Avocado–Soybean Unsaponifiables Enhance Tendon Healing via Anti-Inflammatory and Antioxidant Mechanisms in a Rat Achilles Injury Model
by Mustafa Dinç, Ömer Cevdet Soydemir, Hünkar Çağdaş Bayrak, Recep Karasu, Bilal Aykaç and Mehmet Emre Topcu
Medicina 2025, 61(11), 2035; https://doi.org/10.3390/medicina61112035 - 14 Nov 2025
Abstract
Background and Objectives: Tendon healing is a multifactorial process influenced by inflammation and oxidative stress. Avocado–soybean unsaponifiables (ASU), recognized for their anti-inflammatory and antioxidant properties in osteoarthritis, have not yet been evaluated in tendon repair. This study aimed to investigate the effects of [...] Read more.
Background and Objectives: Tendon healing is a multifactorial process influenced by inflammation and oxidative stress. Avocado–soybean unsaponifiables (ASU), recognized for their anti-inflammatory and antioxidant properties in osteoarthritis, have not yet been evaluated in tendon repair. This study aimed to investigate the effects of systemic ASU administration on histological, biomechanical, and biochemical parameters of tendon healing in a rat Achilles tendon injury model. Materials and Methods: Twenty male Wistar rats underwent bilateral Achilles tendon transection and repair. The ASU group received intraperitoneal ASU (300 mg/kg/day) for four weeks; controls received saline. Right tendons were analyzed histologically using a semiquantitative scoring system adapted from Curtis–DeLee, Bonar, and Modified Soslowsky criteria. Left tendons were tested biomechanically for maximum force, displacement, stress, stiffness, and energy parameters. Serum interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were measured by ELISA. Results: ASU markedly improved histological healing with better collagen alignment, reduced inflammation, and normalized tenocyte morphology (p < 0.001). Biomechanical strength increased, with higher maximum force (p = 0.002), displacement (p = 0.004), stress (p = 0.001), and total energy to failure (p = 0.001). Serum IL-1β, IL-6, and TNF-α levels were lower (p < 0.001), while TAS increased and TOS/OSI decreased (p < 0.001). Conclusions: Systemic ASU administration enhances tendon healing by improving tissue organization, increasing mechanical strength, and modulating systemic inflammation and oxidative stress. These findings suggest that ASU may serve as a safe, clinically relevant adjunct therapy to promote tendon regeneration. Full article
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10 pages, 924 KB  
Article
CBCT Evaluation of Cortical Bone Thickness in the Nasal Floor and Lateral Wall: Considerations for Implant Anchorage—A Retrospective Multicentre Study
by Fodor Romulus Calin, Bartosz Dalewski, Stefan Ihde, Marta Czuczwał, Vitomir S. Konstantinovic, Vivek Gaur, Jacek Kotuła and Łukasz Pałka
Dent. J. 2025, 13(11), 539; https://doi.org/10.3390/dj13110539 - 14 Nov 2025
Abstract
Background/Objectives: Primary implant stability depends on cortical bone thickness. While alveolar cortices are well studied, little is known about the nasal floor and lateral wall, which may provide alternative anchorage in atrophic maxillae. Methods: This retrospective, multicenter study analyzed 149 anonymized CBCT scans [...] Read more.
Background/Objectives: Primary implant stability depends on cortical bone thickness. While alveolar cortices are well studied, little is known about the nasal floor and lateral wall, which may provide alternative anchorage in atrophic maxillae. Methods: This retrospective, multicenter study analyzed 149 anonymized CBCT scans (83 women, 66 men; mean age 52.6 ± 13.5 years). Cortical thickness was measured at six reproducible anatomical points (A–F) defined by chosen landmarks. Measurements were taken on coronal planes aligned with implant anchorage point of interest (POI) using gray-value thresholding. Intra- and inter-observer reliability was excellent (ICC = 0.89 and 0.84). Post hoc power analysis confirmed >80% power to detect 0.15 mm differences. Non-parametric tests and mixed-effects models assessed variability and risk factors. Results: Thickness varied significantly by site (p < 0.001). The thickest cortices were at point A (median 1.36 mm, IQR 1.10–1.61) and point F (1.35 mm, 1.14–1.57), the thinnest at point B (1.15 mm, 0.96–1.32). Cortical thickness was slightly lower in men (p = 0.048) and decreased with age (−0.005 mm/year, p = 0.010). No significant associations were detected with smoking, diabetes, or thyroid disease. Conclusions: The anterior nasal spine and lateral wall near the sinus junction provide the greatest cortical thickness, supporting their use as potential implant anchorage sites in atrophic maxillae. Full article
(This article belongs to the Special Issue Dentistry in the 21st Century: Challenges and Opportunities)
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23 pages, 4665 KB  
Article
Preclinical Mechanistic Evaluation of Hyaluronan/Niacinamide (Vitamin B3) Hydrogels: Toward an Enhanced Viscosupplement System with Ancillary Anti-Arthritic Attributes
by Farid Hadjab, Stivens Antoine, Béatrice Hamel, Mohamed Benderdour, Hassan Fahmi, Alexandre Porcello, Virginie Philippe, Robin Martin, Cíntia Marques, Kelly Lourenço, Corinne Scaletta, Nathalie Hirt-Burri, Philippe Abdel-Sayed, Lee Ann Applegate and Alexis E. Laurent
Bioengineering 2025, 12(11), 1246; https://doi.org/10.3390/bioengineering12111246 - 14 Nov 2025
Abstract
Osteoarthritis (OA), a degenerative joint disease primarily affecting the hips and knees, is characterized by multifactorial dysregulation of chondrocyte homeostasis and currently lacks curative treatment options. Intra-articular hyaluronic acid (HA) injections have clinically provided symptomatic relief for three decades; however, HA’s rapid in [...] Read more.
Osteoarthritis (OA), a degenerative joint disease primarily affecting the hips and knees, is characterized by multifactorial dysregulation of chondrocyte homeostasis and currently lacks curative treatment options. Intra-articular hyaluronic acid (HA) injections have clinically provided symptomatic relief for three decades; however, HA’s rapid in vivo degradation by free radicals and hyaluronidases limits its efficacy. We hypothesized that adding niacinamide (vitamin B3) to linear HA hydrogels would provide ancillary anti-inflammatory and anti-catabolic properties, thereby improving HA-based viscosupplementation therapy. This preliminary preclinical mechanistic study investigated the functional effects of incorporating niacinamide into linear HA-based hydrogels using in vitro cellular models. Initially, Raw 264.7 macrophages and C28/I2 or SW1353 human chondrocytes were pre-treated with varying concentrations of HA/B3, with or without lipopolysaccharide (LPS) or interleukin-1β (IL-1β), respectively. Subsequently, pro-inflammatory and pro-catabolic markers were quantified biochemically. Results demonstrated that HA/B3 hydrogels exhibited enhanced functional stability compared to HA alone and possessed significant anti-inflammatory and anti-catabolic properties, without inducing cytotoxicity in either cell line. In Raw 264.7 macrophages, HA/B3 inhibited LPS-induced tumor necrosis factor-α (TNF-α) release and suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression. In vitro, HA/B3 hydrogels reduced IL-1β-induced IL-6 production in primary chondrocytes by 16% and suppressed PGE2 concentration in both macrophages and chondrocytes by 60%, effects superior to HA alone. Finally, a rat primary articular chondrocyte model suggested slight anti-hypertrophic effects of HA/B3 in vitro. Collectively, these findings suggest that HA/B3 hydrogels possess anti-arthritic potential, highlighting a novel strategy for next-generation viscosupplement systems. Full article
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18 pages, 8857 KB  
Article
Biomimetic Porous Coatings on a Biocompatible Ti-15Mo Alloy as a Platform for Local Delivery of Anticancer Drugs to Patient Tissues
by Svetlana Gatina, Ruzil Farrakhov, Alfiz Gareev, Azat Sabitov, Nariman A. Enikeev, Natalia Anisimova and Mikhail Kiselevskiy
Biomedicines 2025, 13(11), 2779; https://doi.org/10.3390/biomedicines13112779 - 14 Nov 2025
Abstract
Background and Objectives: Currently, the development of local drug delivery systems for the treatment of cancer patients is a pressing issue. Such systems allow for the targeted delivery of anticancer drugs directly to the tumor site, ensuring prolonged drug release or reducing the [...] Read more.
Background and Objectives: Currently, the development of local drug delivery systems for the treatment of cancer patients is a pressing issue. Such systems allow for the targeted delivery of anticancer drugs directly to the tumor site, ensuring prolonged drug release or reducing the risk of recurrence after tumor removal, minimizing the impact on healthy tissues and thereby reducing the overall toxic load on the body. This work is devoted to evaluating the prospects of using scaffolds based on low-modulus titanium Ti-15Mo alloy with a biomimetic coating as a platform for the local administration of the cytostatic drug cisplatin into the patient’s body. Methods: Porous coatings were obtained by plasma electrolytic oxidation in an aqueous solution of sodium phosphate and calcium acetate with the addition of various components. The influence of coating parameters on the corrosion resistance of samples and on the antiproliferative effect of cisplatin-loaded scaffolds was evaluated. Human K562 hemoblastosis, HT116 intestinal cancer, and SKOV3 ovarian cancer cell lines were used as cell models. Results: It was shown that the addition of sodium phosphate (the PS type electrolyte) provides the formation of a coating with a developed system of interconnected pores characterized by an attractive combination of parameters: high porosity (17%), high pore size (3.9 μm), and considerable thickness (17.4 μm). This coating demonstrated the best corrosion resistance in a Ringer solution as compared to the other tested states. In addition, the PS coating loaded with cisplatin exhibited a pronounced cytotoxic effect on cancer cells. This effect was attributed to its ability to fix cisplatin on the surface, which slows down its release into the extracellular environment, increasing the time of its action, thereby contributing to a more effective (by more than 3 times) suppression of tumor cell proliferation compared to the action of the standard form of the drug in the form of a solution when changing the growth medium and subsequent incubation for 48 h. Conclusions: PS scaffolds made of low-modulus titanium alloy Ti-15Mo with a biomimetic surface in an electrolyte based on an aqueous solution of sodium phosphate and calcium acetate with the addition of sodium silicate can be used as an advanced platform for the local delivery of the cytostatic drug cisplatin, which makes them promising for application in orthopedic oncology. Full article
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21 pages, 3884 KB  
Article
CpG ODN Activates TLR9 and Upregulates TLR3 via the p38 MAPK-ATF3 Signaling Axis to Synergistically Enhance Dendritic Cell Vaccine Efficacy
by Lv Zhou, Zhuowei Lei, Qian Jiang, Linpeng Xu, Quanji Wang, Yimin Huang and Ting Lei
Cells 2025, 14(22), 1785; https://doi.org/10.3390/cells14221785 - 13 Nov 2025
Abstract
Toll-like receptor 9 (TLR9) and Toll-like receptor 3 (TLR3), which are widely expressed in dendritic cells (DCs), function as key pattern recognition receptors (PRRs) in the immune system. Their primary roles involve specifically detecting pathogen-associated molecular patterns (PAMPs): TLR9 recognizes unmethylated CpG motifs [...] Read more.
Toll-like receptor 9 (TLR9) and Toll-like receptor 3 (TLR3), which are widely expressed in dendritic cells (DCs), function as key pattern recognition receptors (PRRs) in the immune system. Their primary roles involve specifically detecting pathogen-associated molecular patterns (PAMPs): TLR9 recognizes unmethylated CpG motifs predominantly found in bacterial and viral DNA, while TLR3 identifies viral double-stranded RNA (dsRNA), a molecular signature associated with viral replication. Their specific agonists [CpG ODN (a TLR9 agonist) and poly(I:C) (a TLR3 agonist)] can effectively activate DCs and enhance the expression of immune activation-related molecules. In this study, by establishing a mouse primary dendritic cell model and a glioma-bearing mouse model, and employing techniques such as transcriptome sequencing, we found that combined stimulation with CpG ODN and poly(I:C) significantly enhanced the anti-tumor function of DCs: in vitro, DCs subjected to combined stimulation showed upregulation of anti-tumor-related surface markers, enhanced migratory capacity, and a more effective activation of CD8+ T cells; in vivo, a DC vaccine loaded with tumor lysate antigen and stimulated with this combined regimen significantly delayed the progression of glioma in tumor-bearing mice. Further investigation revealed that the underlying mechanism for this enhanced effect may involve TLR9 activation promoting TLR3 upregulation through the p38 MAPK-ATF3 signaling axis. Consequently, we designed a sequential stimulation protocol (first CpG ODN then poly(I:C)), which demonstrated a stronger anti-glioma effect compared to simple combined stimulation. This study provides a new strategy for enhancing the immune efficacy of DC vaccines and has potential significance for promoting the clinical translation of DC vaccines. Full article
(This article belongs to the Topic Advances in Glioblastoma: From Biology to Therapeutics)
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16 pages, 5717 KB  
Article
Targeting the Galectin Axis in Osteoarthritis: Chondroprotective Effects of Dietary and Pharmacological Phytochemicals
by Katharina M. Pichler, Selina Kottinger, Bettina Rodriguez Molina, Jürgen Alphonsus, Sebastian Schmidt, Reinhard Windhager, Herbert Kaltner, Mario Rothbauer and Stefan Toegel
Molecules 2025, 30(22), 4391; https://doi.org/10.3390/molecules30224391 - 13 Nov 2025
Abstract
Background/Objectives: Galectins contribute to the pathogenesis of osteoarthritis (OA) by amplifying inflammatory and catabolic signaling, yet targeted therapeutic approaches remain limited. Three Dimensional (3D) models offer a promising platform to study human OA pathophysiology and evaluate novel interventions. Methods: We established 3D pellet [...] Read more.
Background/Objectives: Galectins contribute to the pathogenesis of osteoarthritis (OA) by amplifying inflammatory and catabolic signaling, yet targeted therapeutic approaches remain limited. Three Dimensional (3D) models offer a promising platform to study human OA pathophysiology and evaluate novel interventions. Methods: We established 3D pellet cultures derived from human OA chondrocytes to investigate galectin-induced extracellular matrix (ECM) remodeling and the chondroprotective potential of phytochemicals. OA pellets were stimulated with individual galectins (Gal-1, -3, -4, -8) or a Gal-1/-3/-8 mixture, followed by co-treatment with Brazilin, Diacerein, Quercetin, Resveratrol, or Avocado-Soybean Unsaponifiables (ASU). Morphological, histological, biochemical, and gene expression analyses were performed to assess tissue integrity and molecular responses. Results: Galectin treatment induced pronounced pellet shrinkage, matrix depletion, and upregulation of matrix-degrading enzymes (MMP-1, MMP-3, MMP-13, ADAMTS-4), while suppressing matrix synthesis markers (COL2A1, COL1A1), highlighting their cooperative catabolic effects. Co-treatment with phytochemicals conferred differential protection: Brazilin and Diacerein most consistently preserved pellet size, reduced matrix-degrading gene expression, and attenuated pro-MMP-13 secretion. Resveratrol restored histological matrix density but failed to suppress pro-MMP-13 secretion. Notably, no phytochemical fully restored COL2A1 expression under galectin-induced stress. Conclusions: Our study identifies Brazilin, Diacerein, and Resveratrol as promising modulators of galectin-driven cartilage degeneration and demonstrates the translational potential of patient-derived chondrogenic pellets as a human-relevant platform for preclinical drug evaluation in OA. The 3D culture effectively recapitulates key aspects of OA pathophysiology and offers a robust system to advance therapeutic discovery targeting ECM remodeling. Full article
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11 pages, 633 KB  
Article
Eight-Year Cohort Study Examining Bicycling-Related Maxillofacial Fractures and Factors Contributing to Injury
by Luis Miguel Gonzalez-Perez, Johan Wideberg and Carlos Alvarez-Delgado
Osteology 2025, 5(4), 34; https://doi.org/10.3390/osteology5040034 - 13 Nov 2025
Abstract
Objectives: The aim of this study was to determine the epidemiological characteristics of bicycling-related maxillofacial fractures in a defined population and to identify factors contributing to these injuries. Methods: An 8-year cohort study was carried out, including all patients presenting with bicycling-related maxillofacial [...] Read more.
Objectives: The aim of this study was to determine the epidemiological characteristics of bicycling-related maxillofacial fractures in a defined population and to identify factors contributing to these injuries. Methods: An 8-year cohort study was carried out, including all patients presenting with bicycling-related maxillofacial fractures at a tertiary care center from 2017 through 2024. Data recorded for each patient included age, gender, date and cause of injury, contributing factors, type of facial fractures, other injuries, hospital stay, and helmet use. Statistical analysis was performed. Continuous variables were assessed for normality (Shapiro–Wilk test) and compared using the Mann–Whitney test. Categorical variables were analyzed with chi-square tests. A p-value ≤ 0.05 was considered statistically significant. Results: Out of 899 cycling accident patients seeking medical treatment, 122 (13%) sustained facial fractures, accounting for 4% of all facial fracture cases in our department during the study period. In our cohort, the male–female ratio was 2.6:1, and the mean age was 29.5 years (SD 12.8, range 13–77). Collision with another object/vehicle was the most common cause (64%), followed by isolated falls (36%). A total of 135 facial fractures were recorded (some patients had multiple fractures). Mandibular fractures were most frequent (49% of patients), followed by zygomatic (32%), orbital (13%), nasal (7%), maxillary (2%) and frontal (2%) fractures. Among mandibular injuries, condylar fractures were the most common subtype (63%). Dental injuries were found in 27% of patients. The most common dental trauma was tooth fracture (43% of those with dental injuries), followed by tooth luxation (32%) and tooth avulsion (25%). In 80% of cases involving dental injuries, the upper anterior teeth were involved. Concomitant injuries were present in 20% of patients, most often orthopedic limb injuries. Only 27% of patients reported always wearing a helmet, whereas 43% reported never having worn one. Conclusions: Bicycling-related facial injuries are a noteworthy subset of facial trauma. Missed or delayed diagnosis can lead to lasting deformities and functional issues. Preventive strategies—especially promoting helmet use and improving helmet design—along with broader safety measures are important to reduce the incidence and severity of these injuries. Full article
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12 pages, 374 KB  
Article
Biomarkers Linked to Malnutrition Identified According to GLIM Criteria Among Older Community-Dwelling Adults: Results from the ilSIRENTE Study
by Hélio José Coelho-Júnior, Riccardo Calvani, Anna Picca, Matteo Tosato, Andrea Russo, Francesco Landi and Emanuele Marzetti
Nutrients 2025, 17(22), 3543; https://doi.org/10.3390/nu17223543 - 13 Nov 2025
Abstract
Objective: This study aimed to examine the associations between malnutrition and circulating blood markers in older adults. Methods: We conducted a prospective cohort study on octogenarians residing in the mountain community of the Sirente geographic area in Central Italy. Data collection [...] Read more.
Objective: This study aimed to examine the associations between malnutrition and circulating blood markers in older adults. Methods: We conducted a prospective cohort study on octogenarians residing in the mountain community of the Sirente geographic area in Central Italy. Data collection was conducted from December 2023 to September 2024. Malnutrition was defined based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. A panel of blood markers was examined, and principal component analysis (PCA) was used to identify clusters of related molecules. Both unadjusted and adjusted binary logistic regression models were applied to investigate the associations between malnutrition and these molecular clusters. Results: Data from 196 older adults (mean age: 86.2 years) were analyzed. Malnutrition was positively associated with PC 2 (i.e., urea, c-terminal agrin fragment, and potassium) (odds ratio [OR] = 1.647, p-value: 0.039) and negatively associated with PC 3 (i.e., hemoglobin, hematocrit, and red blood cell count) (OR = 0.567, p-value: 0.022) and PC 4 (i.e., calcium, albumin, total protein levels, and HDL cholesterol) (OR = 0.607, p-value: 0.035). Conclusions: Findings of the present study suggest that different clusters of blood markers are associated with malnutrition in older adults. Specifically, malnutrition is associated with clusters related to kidney function, anemia, neuromuscular function, and nutrient availability. These associations likely reflect the underlying biological mechanisms contributing to the development of malnutrition in this population. Full article
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15 pages, 1080 KB  
Systematic Review
Association of FLAIR Positivity and Worse Outcomes After Intravenous Thrombolysis in Known-Onset Strokes: A Systematic Review and Meta-Analysis
by Esra Zhubi, Azamat Bissenov, Anna Sára Lengyel, Réka Tóth, András Attila Horváth, Szabolcs Kéri, Marie Anne Engh, Péter Hegyi and Bence Gunda
J. Clin. Med. 2025, 14(22), 8031; https://doi.org/10.3390/jcm14228031 - 12 Nov 2025
Abstract
Background/Objectives: MRI FLAIR signal serves as a time surrogate in unknown onset strokes; however, its prognostic value in early known-onset strokes treated with intravenous thrombolysis (IVT) remains unclear. We aim to evaluate whether FLAIR positivity predicts hemorrhagic transformation and less favorable functional [...] Read more.
Background/Objectives: MRI FLAIR signal serves as a time surrogate in unknown onset strokes; however, its prognostic value in early known-onset strokes treated with intravenous thrombolysis (IVT) remains unclear. We aim to evaluate whether FLAIR positivity predicts hemorrhagic transformation and less favorable functional outcome following IVT within 4.5 h of symptom onset. Methods: A systematic search of Embase, PubMed, and Cochrane Library was conducted. We included studies reporting 90-day functional outcome and hemorrhagic transformation after intravenous thrombolysis within 4.5 h of symptom onset in relation to the FLAIR signal on pre-treatment MRI. Two reviewers independently extracted data and assessed bias using QUIPS. A random-effects model was used for meta-analysis. The study protocol was registered in PROSPERO (CRD42023486781). Results: Six studies comprising 951 patients were included in the final analysis. Patients with FLAIR-positive lesions (25.86%) had non-significantly higher odds of hemorrhagic transformation (OR, 3.47; 95% CI, 0.51–23.57; p = 0.131) and significantly higher odds of unfavorable 90-day outcome (OR, 2.14; 95% CI, 1.01–4.55; p = 0.049). The pooled sensitivity and specificity of FLAIR status for predicting hemorrhagic transformation were 41.2% and 82.1%. The pooled sensitivity and specificity of FLAIR status for predicting less favorable outcome were 40.9% and 78.1%, respectively. Conclusions: FLAIR positivity is significantly associated with less favorable 90-day functional outcome and a trend toward a higher rate of hemorrhagic transformation following IVT within 4.5 h of symptom onset. It may aid risk stratification but should not preclude treatment in eligible patients. Full article
(This article belongs to the Section Clinical Neurology)
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15 pages, 1219 KB  
Article
Association Between Lower-Limb Fractures and Carpal Tunnel Syndrome: A Nationwide Population-Based Cohort Study
by Chun-Hui Chang, Hao-Yu Tseng, Wen-Tien Wu, Ru-Ping Lee, Jen-Hung Wang and Kuang-Ting Yeh
Healthcare 2025, 13(22), 2879; https://doi.org/10.3390/healthcare13222879 - 12 Nov 2025
Abstract
Background: Lower-limb fractures often require prolonged use of assistive devices, which may increase mechanical stress on the upper extremities. However, the association between lower-limb fractures and subsequent carpal tunnel syndrome (CTS) remains unclear. Methods: This nationwide population-based cohort study used Taiwan’s National Health [...] Read more.
Background: Lower-limb fractures often require prolonged use of assistive devices, which may increase mechanical stress on the upper extremities. However, the association between lower-limb fractures and subsequent carpal tunnel syndrome (CTS) remains unclear. Methods: This nationwide population-based cohort study used Taiwan’s National Health Insurance Research Database (2011–2019) to identify 10,140 patients with lower-limb fractures and 10,140 propensity score-matched controls. Cox regression analysis estimated CTS risk after adjusting for demographics and comorbidities. Results: Patients with lower-limb fractures demonstrated increased CTS risk compared to controls (adjusted hazard ratio [HR] = 1.12, 95% confidence interval [CI]: 1.003–1.26; p = 0.044), with stronger associations in males (HR = 1.28, 95% CI: 1.05–1.55) and younger adults aged 20–65 years (HR = 1.19, 95% CI: 1.03–1.38). Conclusions: Lower-limb fractures are associated with modestly increased CTS risk, particularly in males and younger patients. Though biologically plausible, this observational study cannot establish causality. Heightened clinical awareness may be warranted, though prospective validation is needed. Full article
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20 pages, 1878 KB  
Article
Circulating microRNA Profiles in Acute Spinal Cord Injury: Evidence for Distinct Plasma Signatures Compared with Polytrauma Patients
by Jason-Alexander Hörauf, Miriam Saenger, Philipp Störmann, André El Saman, Ingo Marzi, Dirk Henrich, Liudmila Leppik and Cora Rebecca Schindler
Int. J. Mol. Sci. 2025, 26(22), 10954; https://doi.org/10.3390/ijms262210954 - 12 Nov 2025
Abstract
Traumatic spinal cord injury (SCI) is a devastating complication of trauma, causing long-term disability and significant socioeconomic burden. Beyond the primary mechanical insult, secondary injury cascades involving apoptosis, oxidative stress, and inflammation amplify tissue damage. MicroRNAs (miRNAs) regulate these processes at the post-transcriptional [...] Read more.
Traumatic spinal cord injury (SCI) is a devastating complication of trauma, causing long-term disability and significant socioeconomic burden. Beyond the primary mechanical insult, secondary injury cascades involving apoptosis, oxidative stress, and inflammation amplify tissue damage. MicroRNAs (miRNAs) regulate these processes at the post-transcriptional level, yet data on circulating miRNAs in human SCI remain scarce. This study aimed to characterize acute plasma miRNA expression patterns in isolated traumatic SCI that may indicate SCI-specific signatures. Plasma was collected from five SCI patients at admission and 48 h post-injury and five healthy controls (HCs), and next-generation sequencing (NGS) was performed on plasma RNAs. Differentially expressed miRNAs were identified, and selected candidate miRNAs were validated by droplet digital PCR (ddPCR) in an expanded cohort of SCI patients, polytrauma patients without neurotrauma (PT), and HC (each n = 8). Pathway enrichment and validated target analysis were performed to assess biological relevance of candidate miRNAs. At emergency room admission, 46 miRNAs were differentially expressed in SCI plasma (18 upregulated, 28 downregulated). By 48 h, a global downregulation was observed, with 47 miRNAs significantly decreased compared with HC. ddPCR validation revealed markedly stronger suppression of miR-182-5p, miR-190a-5p, miR-144-5p, and miR-30c-5p expression levels in SCI compared with PT. Pathway analysis indicated enrichment of mitochondrial oxidative phosphorylation pathways, and target prediction suggested that the identified miRNAs may be linked to neuroprotective and regenerative functions. Our findings demonstrate early and profound alterations in circulating miRNAs after acute SCI. The downregulation of the identified miRNAs may reflect maladaptive changes that promote neuroinflammation and hinder axonal regeneration, although the exact functional consequences remain to be clarified. These data suggest that circulating miRNAs could hold promise as diagnostic and prognostic biomarkers and, potentially, as therapeutic targets to influence secondary injury processes. However, given the exploratory nature and limited sample size of this study, the findings should be validated in larger, sufficiently powered cohorts to robustly delineate differences between patient groups. Full article
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11 pages, 1327 KB  
Article
Effectiveness of Mobile Exergaming with Sensor-Based Visual Feedback as an Adjunct Therapy for Home-Based Quadriceps Exercise Training in Knee Osteoarthritis: A Prospective Randomized Controlled Trial
by Chavarat Jarungvittayakon, Paphon Sa-ngasoongsong, Danai Chockchaisakul, Jaturong Bamrungchaowkasem and Siwadol Wongsak
Life 2025, 15(11), 1738; https://doi.org/10.3390/life15111738 - 12 Nov 2025
Abstract
Background: Exergame applications were introduced recently for orthopedic rehabilitation. This study aimed to evaluate the effectiveness of a 6-week home-based quadriceps exercise with mobile exergaming for treatment of primary knee osteoarthritis (KOA). Methods: A prospective randomized controlled trial was conducted in 56 primary [...] Read more.
Background: Exergame applications were introduced recently for orthopedic rehabilitation. This study aimed to evaluate the effectiveness of a 6-week home-based quadriceps exercise with mobile exergaming for treatment of primary knee osteoarthritis (KOA). Methods: A prospective randomized controlled trial was conducted in 56 primary KOA patients. All patients were allocated into two groups (n = 28 each group). Intervention group received the 6-week mobile exergaming program using a smartphone exercise game with a wearable wireless motion sensor. Control group received a standard 6-week exercise program. Outcomes were active knee arc of motion, quadriceps muscle power, visual analog scale score, timed “Up and Go” (TUG) test, and Knee Injury and Osteoarthritis Outcome Score (KOOS) at a 6-week follow-up. Results: At 6-week post-exercise, the intervention group significantly improved quadriceps power, arc of motion, VAS score at rest and on motion, TUG test, and KOOS-symptom domain compared to the control group (p < 0.05 all). No device- or exercise-related complications were found. Conclusions: Mobile exergaming with visual feedback control using a wearable wireless sensor significantly improves KOA outcomes compared to standard home-based exercise as early as 6 weeks post-application. Full article
(This article belongs to the Special Issue Advances in Knee Biomechanics)
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17 pages, 2492 KB  
Article
Effects of a History of Adductor-Related Groin Pain on Kicking Biomechanics and HAGOS Subscales in Male Soccer Players: A Comprehensive Analysis Using 1D-SPM
by Tomonari Sugano, Ryo Kuboshita, Seigaku Hayashi, Yasutaka Kobayashi and Masahito Hitosugi
Appl. Sci. 2025, 15(22), 12003; https://doi.org/10.3390/app152212003 - 12 Nov 2025
Abstract
Adductor-related groin pain (AGP) is a prevalent and frequently recurrent chronic injury among soccer players. This study investigated the impact of AGP history on kicking kinematics, kinetics, and patient-reported outcomes in regional-league soccer players using one-dimensional statistical parametric mapping (1D-SPM). Twenty male athletes [...] Read more.
Adductor-related groin pain (AGP) is a prevalent and frequently recurrent chronic injury among soccer players. This study investigated the impact of AGP history on kicking kinematics, kinetics, and patient-reported outcomes in regional-league soccer players using one-dimensional statistical parametric mapping (1D-SPM). Twenty male athletes were allocated to a group with prior AGP (GP group: n = 8) or without AGP (non-GP group, n = 12), and evaluated during maximal instep and inside-foot kicks using three-dimensional motion analysis and the Copenhagen Hip and Groin Outcome Score (HAGOS). The GP group reported significantly lower HAGOS for pain and quality of life. The 1D-SPM analysis revealed that the GP group employed a compensatory kinetic chain strategy, characterized by impaired trunk–pelvis rotation, increased reliance on the stance leg (SL) for stability, and altered kicking leg (KL) mechanics with reduced hip flexion power. These findings reveal that the underlying deficit in AGP is not isolated muscle weakness but a ‘lack of adaptability in motor control’, resulting in inefficient load distribution and contributing to the high recurrence rates in the adductors and SL. Rehabilitation should adopt a kinetic chain-oriented approach that also addresses stance limb function to mitigate recurrence and optimize performance. Full article
(This article belongs to the Special Issue Advances in Sports Science and Biomechanics)
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