Medicine and Pharmacology

Abstract: Background: Laminins, a family of heterotrimeric glycoproteins, are fundamental components of the basement membrane and play critical roles in tissue architecture, cell adhesion, migration, differentiation, and hemostasis. Methods: This comprehensive integrative review synthesizes the current state of knowledge on the expression, administration, and modulation of laminin-derived bioactive peptides and isoforms. Results: Laminin peptides and isoforms exhibit diverse, context-dependent effects across physiological and pathological processes, including cancer progression, neurodegeneration, inflammation, tissue regeneration, and exercise-induced adaptations. In cancer, laminins modulate tumor growth, metastasis, and angiogenesis through complex signaling pathways involving PI3K/Akt, MAPK/ERK, and STAT3. In the nervous system, neuronal survival, axonal guidance, and regeneration, offering therapeutic potential for the treatment of neurodegenerative diseases and nerve injury. In inflammation and tissue repair, laminins regulate immune cell trafficking, cytokine production, and wound healing. Furthermore, laminins are integral to exercise-induced muscle adaptation, influencing satellite cell activation, myogenesis, and angiogenesis. Additionally, polylaminin, a biomimetic polymer of laminin assembled under acidic conditions, has emerged as a powerful tool for nerve regeneration, spinal cord repair, and stem cell expansion. Conclusions: The multifaceted nature of laminins underscores their significance as promising targets for novel therapeutic strategies across a broad spectrum of human diseases.

Abstract: Background: Tumor Treating Fields (TTFields) are being investigated for pelvic malignancies, while total hip arthroplasty (THA) is increasingly common. This study evaluated whether THA prosthetic materials influence TTFields distribution and target dosimetry in ovarian tumors. Methods: Patient-specific finite element models were generated from computed tomography datasets of four patients with ovarian carcinoma. Three-dimensional simulations assigned cortical bone or Ti6Al4V titanium alloy, Co28Cr6Mo cobalt-chromium alloy, or tantalum to both femurs. Electric field (E), specific absorption rate (SAR), and current density (CD) were quantified in the clinical target volume (CTV), femur, and skin using 95%, 50%, and 5% volume-based metrics. Results: Metallic implant properties produced minor CTV dosimetric changes, with mean and median percent differences generally within ±3.4% across metrics. Tantalum most closely approximated cortical bone, typically within ±1%. Implants substantially reduced femoral distributions of E and SAR, while increasing CD. Skin exposure decreased modestly across 95% and 50% volumes, with slight increases in localized hotspots. Conclusions: THA materials alter femoral distributions of TTFields while largely preserving clinically relevant CTV dosimetry, of which tantalum closely approximated cortical bone. Tantalum also reduced exposure across skin volumes. Implant composition alone will unlikely alter TTFields treatment planning for patients with ovarian malignancies undergoing THA.

Abstract: Background: Osteoporosis, is characterized by a compromise in bone strength, which is defined by a combination of bone mineral density (BMD) and bone quality. It is a common disease in the older people and undergo asymptomatic progression for years. One of the most severe complications of osteoporosis is fracture, which is not only diminishes the life quality of patients but also imposes a substantial burden on both families and health care systems. The survey of risk factors in this cohort shown that some factors truly contribute to the progress of osteoporosis, such as gender, body mass index (BMI) or the history of fractures. The results can prompt clinicians to conduct early screening and patient care and facilitate targeted interventions for older adults, who frequently present with multiple underlying comorbidities. Objectives: This study aimed to determine the prevalence of osteoporosis and identify associated risk factors among elderly patients. Methods: A cross-sectional descriptive study enrolled 400 ambulatory patients aged 60 years or older. BMD was measured at two anatomical sites: the femoral neck and the lumbar spine. Exclusion criteria comprised patients currently undergoing oncological therapy, as well as those with a history of or current treatment for osteoporosis. Results: Several risk factors that increase the likelihood of osteoporosis in the elderly include female sex, low body BMI < 23 kg/m² and a history of post-traumatic fractures. Female sex and low BMI were significantly associated with a higher prevalence of osteoporosis at both anatomy sites, whereas physical activity level showed no statistically significant effect. The duration postmenopause was significantly associated with an increased prevalence of osteoporosis at both the lumbar spine and femoral neck, exhibiting a progressive rise over time that peaked at age 30 years postmenopause. A history of fracture was significantly associated with osteoporosis status at both the lumbar spine and femoral neck, with a higher proportion of past fractures observed among participants with osteoporosis. (p < 0.05). Conclusions: This study emphasizes that female sex, low BMI, prolonged postmenopausal duration (age 30 years), and a prior history of fractures are significant clinical indicators of osteoporosis in the elderly. These findings highlight the critical need for targeted, early BMD screening programs prioritizing these high-risk groups to prevent severe osteoporotic complications and improve patient care.

Abstract: Background: Nanotechnological surface modifications on titanium implants aim to optimize bone-tissue interaction, accelerate osseointegration, and prevent the release of toxic wear debris. This study evaluated the tissue response and biomechanical stability of advanced carbon- and metal-oxide-based nanocoatings in an in vivo model. Methods: Grade IV titanium implants were evaluated under four conditions using a split-body design in the distal femurs of 12 adult male New Zealand white rabbits: uncoated (control), coated with Graphene Diamond-like Carbon (DLC), Niobium via Chemical Vapor Deposition (CVD), and Niobium via Sol-Gel technique. Follow-up periods were set at 30 and 60 days. Analysis included a Reverse Torque Test (RTQ) for biomechanical stability and histopathological evaluation (H&amp;E and Picrosirius Red under polarized light) to assess bone organization, osteoclastic proliferation, collagen matrix maturation, and coating delamination. Results: RTQ values significantly increased from 30 to 60 days across all groups (p &lt; 0.05), with Graphene-DLC and uncoated titanium achieving the highest biomechanical anchorage. Graphene-DLC maintained excellent interfacial stability, accelerated bone mineralization (low osteoid volumes), and promoted intensive, physiologically normal bone coupling and lamellar remodeling at 60 days. Conversely, Niobium-CVD and Niobium-Gel coatings exhibited severe late-stage delamination, which released particulate debris, triggered chronic foreign body reactions, increased osteoclastic bone resorption, and compromised biomechanical interlocking. Conclusions: Graphene-DLC coatings successfully preserve structural integrity and effectively enhance functional osseointegration, matching or exceeding the biomechanical performance of conventional titanium. However, interface optimization is mandatory for Niobium-based coatings to prevent mechanical failure and debris-induced osteolysis.

Abstract: Background: Musculoskeletal disorders such as osteoarthritis, chronic low back pain, radicular syndromes and osteoporosis produce major clinical burdens, and noninvasive therapies capable of reaching deep anatomical structures are increasingly needed. Nuclear magnetic resonance therapy (molecular biophysical stimulation therapy; NMRT MBST) applies resonance-based magnetic fields to deliver uniform biophysical stimulation independent of tissue depth. This review synthesizes clinical and mechanistic evidence to evaluate the therapeutic potential of NMRT MBST and contextualize it within emerging deep-tissue biophysical treatment strategies. Methods: A systematic search of PubMed, Ovid Embase and peer-reviewed, published reviews identified 15 studies, including randomized trials, imaging investigations, observational cohorts, long-term follow-ups and blinded veterinary work. Experimental literature examining cellular, metabolic and molecular responses to NMRT MBST was reviewed to align biological effects with clinical outcomes. Results: NMRT MBST is consistently reported as safe, with no treatment-emergent adverse events. Clinical findings indicate improvements in pain, function and, in selected studies, imaging or densitometric parameters across osteoarthritis, spine-related pain, radicular syndromes and osteoporosis. Placebo-controlled effects were demonstrated in finger-joint osteoarthritis and radicular pain. Mechanistic studies have shown anti-inflammatory, mitochondrial, redox, anabolic, neurotrophic, epigenetic and circadian effects that closely parallel near-infrared photobiomodulation, supporting the concept of NMRT MBST as a deep-penetrating analogue capable of reaching tissues inaccessible to light. Conventional pulsed electromagnetic field therapy is physically the closest comparator but shows a narrower mechanistic overlap. This positions NMRT MBST within a broader therapeutic framework in which biophysical stimulation may modulate metabolic–inflammatory–regenerative axes in deep musculoskeletal and central nervous system (CNS) structures. Conclusions: NMRT/MBST appears to be a safe and biologically coherent deep-tissue biophysical therapy with promising clinical effects. Larger trials, optimized dosing, mechanistic biomarkers and head-to-head comparisons with established modalities are needed to define its therapeutic role and to clarify how deep-acting biophysical interventions may be integrated into future musculoskeletal and CNS care.

Abstract: Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents for bone regeneration due to their ability to modulate osteogenesis, angiogenesis, and immune responses. This review summarizes current knowledge on EV biology, including their classification, biogenesis, and molecular cargo, with a particular focus on their role in bone healing. EVs derived from mesenchymal stromal cells and other cell sources promote osteoblast differentiation, inhibit osteoclast activity, enhance vascularization, and modulate inflammation through the transfer of bioactive proteins and non-coding RNAs. Recent advances in EV engineering, biomaterial-assisted delivery, and isolation techniques are discussed, together with their translational potential for the treatment of critical bone defects and avascular osteonecrosis. Although preclinical evidence is highly encouraging, clinical translation remains limited by challenges in standardization, scalable manufacturing, and regulatory approval. Overall, EV-based therapies represent a promising future strategy for regenerative orthopedics and bone tissue engineering.

Abstract: The Wikidata Knee Replacement Ecosphere is a structured knowledge graph dataset of knee replacement surgery. It was built and curated on Wikidata by a single board certified orthopedic surgeon between January 17, 2026 and August 16, 2026. The dataset organizes into four domain clusters: surgical techniques; instruments and enabling technology; patient education and advocacy organizations; and surgeon to surgeon education and collaboration platforms. The core of the dataset is a three axis taxonomy of knee arthroplasty techniques. The axes cover alignment, approach, and guidance. The literature layer links 206 distinct peer reviewed scholarly articles to the taxonomy through 358 main subject statements. The counts were frozen on August 17, 2026. All external identifiers were verified against their live source databases under a documented identifier verification protocol, the Reference Verification Convention v2.0. The live data are public on Wikidata under the CC0 1.0 public domain dedication and are queryable through the Wikidata SPARQL endpoints. A version 1.2 snapshot is deposited on Zenodo at DOI 10.5281/zenodo.21969159. The deposit contains a documentation PDF and two machine readable CSV catalog files. Appendix A lists the 34 items created for the dataset. Appendix B catalogs the scholarly works created for the dataset and contains a total of 148 rows. This article describes the data model, the construction and verification methodology, and the SPARQL queries that reproduce the reported counts.

Abstract: Continuous, objective records of spinal motion during ordinary life have not been available; assessment relies on intermittent questionnaires and brief supervised motion capture. A dual inertial-sensor garment applies the Zero-Cycle method, which treats the spine’s recurrent return to a consistent configuration once per gait cycle—present although no segment is ever stationary—as a body-intrinsic reference, emitting one fixed-dimensional feature vector per cycle. Resetting heading at each return bounds drift from linear growth to \( O(\sqrt{N}) \) and supplies the correction a magnetometer would otherwise provide, so no magnetic fusion is required; the per-cycle local frame removes subject-specific calibration. In a four-patient pilot conducted unsupervised at home, 88,027 cycles were analysed over 13 to 16 days each. The stream was stable over weeks and showed intervention-associated change, reported as Cliff’s delta with the cycle as the unit of analysis: sustained reduction in structural responders and none in a non-structural comparison case. The instrument was built to measure Dubousset’s cone of economy; the recording also contained a quantity that was not sought—the precision of the spine’s return to neutral, corresponding to Panjabi’s neutral zone, a complementary description of spinal control. The contribution is a substrate for machine learning rather than a more accurate sensor.

Abstract: Background/Objectives: Minimal invasive temporary spanning plate (SP) fixation has been established as a valuable treatment for complex distal radius fractures; while short-term outcomes are promising, long-term data remains limited. This study conducts a long-term outcome analysis of patients treated with SP fixation to address this gap within the current literature. Methods: We conducted a retrospective single-center study of patients treated with a spanning plate for distal radius fractures at a level I trauma center between 2018 and 2025. Indications for spanning plate fixation included distal radius fractures with severe metaphyseal comminution, radiocarpal fracture dislocations and very distal intra-articular fractures where standard osteosynthesis was not feasible. The inclusion criteria required a minimum follow-up of one year. Hospital records were screened for healing data and adverse events. Included patients were contacted for assessment of functional scores using the Patient-Rated Wrist Evaluation (PRWE) and a Visual Analogue Scale (VAS) for pain, as well as a 5-point Likert scale for satisfaction. Results: A total of 35 patients (mean age 57; 89% AO type C) were included. The SP was removed on average 3.8 months postoperatively. Radiological union was achieved at a mean of 8.6 weeks, with one non-union requiring reoperation. Complications included one implant failure and two Extensor Pollicis Longus (EPL) ruptures. Three other reoperations occurred: two for DRUJ instability and one wrist denervation due to osteoarthritis. Twenty-six patients responded to functional questionnaires at a mean follow-up of 58.3 months. They reported a mean satisfaction score of 4.1, mean resting VAS pain of 1.7, and a mean PRWE score of 16.7. Conclusions: Radiological, functional, and patient-rated outcomes demonstrate that excellent short-term results are successfully maintained over a 4.5-year period. The spanning plate technique proves to be a reliable and durable treatment option for complex distal radius fractures with a low long-term complication rate.

Abstract: Background/Objectives: Ultrasound-guided percutaneous lavage (UGPL) is an established minimally invasive treatment for symptomatic calcific tendinitis of the shoulder after failure of conservative management. However, treatment outcomes are variable, and the prognostic significance of symptom duration and radiographic characteristics of calcific deposits remains uncertain. This study evaluated the clinical and radiographic outcomes of UGPL and identified predictors of treatment failure. Methods: A retrospective analysis of prospectively collected data was performed on 65 patients who underwent UGPL for rotator cuff calcific tendinitis between 2018 and 2022. Patients were stratified into an acute group (symptom duration < 7 days, severe pain, Gärtner type III deposits) and a chronic group (symptom duration >15 days, moderate pain, Gärtner type I–II deposits). Clinical outcomes included pain assessed with the visual analog scale (VAS), shoulder range of motion, and Rotator Cuff Quality of Life (RC-QOL) scores. Radiographic and ultrasound examinations evaluated calcification morphology, size, and resorption before treatment and at 3 months. Treatment failure was defined as persistent pain (VAS >5 at 6 months) and/or the need for arthroscopic surgery. Results: Patients in the acute group demonstrated significantly greater improvements in pain, shoulder mobility, and RC-QOL scores at all follow-up evaluations compared with the chronic group (all p < 0.001). Complete radiographic resorption of calcifications occurred in 77% of acute cases, whereas 68% of chronic cases showed no radiographic change. Calcification size decreased significantly more in the acute group (p < 0.001). Arthroscopic surgery was required in 15% of acute patients compared with 41% of chronic patients (p = 0.017). Chronic symptom duration, dense Gärtner type I–II calcifications, and smaller baseline deposits were associated with an increased risk of treatment failure. Conclusions: UGPL provides excellent clinical and radiographic outcomes in patients with acute, resorptive-phase calcific tendinitis. Chronic symptoms and dense calcific deposits are associated with reduced treatment success and higher rates of surgical intervention. Combining symptom duration with radiographic morphology may improve patient selection and optimize outcomes following UGPL.

Abstract: Background and Objectives: Post-traumatic elbow stiffness is a disabling condition often resulting from a combination of capsular contracture, osseous impingement, and residual instability, rendering it exceptionally challenging to treat. The aim of this study was to evaluate the outcomes of a comprehensive surgical approach for the treatment of post-traumatic elbow stiffness. Materials and Methods: A retrospective case series of 20 consecutive patients treated between 2018 and 2025 was conducted. Etiologies included distal humeral fractures (n = 9), terrible triad injuries (n = 4), elbow dislocations (n = 3), olecranon fractures (n = 2), and neglected radial head fractures (n = 2). All patients underwent anterior and posterior arthrolysis with triceps tenolysis. Additional procedures included ligament reconstruction, radial head arthroplasty, an-terior capsule repair, tricepsplasty, and ulnar nerve transposition when indicated. El-bow range of motion was assessed preoperatively and during follow-up at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year postoperatively. Results: Mean flexion im-proved from 81.0° to 125.3°, while the extension deficit improved from 66.5° to 16.5°. Mean supination increased from 54.8° to 82.8°, and mean pronation from 67.0° to 84.5°. The mean flexion-extension arc improved from 14.5° to 108.8°, representing a mean gain of 94.3°. One transient sensory ulnar neuropathy, one case of postoperative triceps insufficiency requiring revision surgery were observed and one patient devel-oped postoperative skin blistering following a posterior approach. Conclusions: Com-prehensive, pathology-oriented surgical treatment resulted in substantial improve-ment in elbow motion and restoration of a functional range of movement.

Abstract: Epitalon is a synthetic tetrapeptide derived from the amino acid composition of Epithalamin, a polypeptide extract derived from the bovine pineal gland. Current preclinical evidence suggests that Epitalon may activate telomerase by upregulating human telomerase reverse transcriptase (hTERT). In aged primates, Epitalon has also been associated with restoring evening melatonin synthesis and circadian cortisol rhythms. It has also been shown to enhance endogenous antioxidant defenses, including the activity of superoxide dismutase (SOD) and glutathione peroxidase. These mechanisms may be relevant to the future of regenerative medicine, as dysregulation of these pathways has been independently implicated in common musculoskeletal conditions, including osteoarthritis, disc degeneration, osteoporosis, and impaired tissue repair. In female mice, although Epitalon did not affect mean lifespan, the maximum lifespan increased by 12.3%. Evidence suggests that it may preserve retinal integrity in hereditary retinitis pigmentosa without reported adverse effects.[1] No human randomized controlled trials, pharmacokinetic studies, or registered trials of Epitalon have been reported at the time of this publication. The related polypeptide preparation Epithalamin, however, does have limited human studies in elderly patients. Epithalamin treatment was associated with a reduced incidence of cardiovascular and musculoskeletal disease, as well as decreased mortality over 6-8 years of follow-up.[2] This review synthesizes the available evidence on Epitalon in the context of regenerative medicine.

Abstract: Knee osteoarthritis (OA) is increasingly recognized as a whole-joint disorder involving periarticular soft tissues in addition to intra-articular structures. A recently published technical report described an ultrasound-guided posteromedial knee injection targeting a fascial–periarticular convergence region operationally termed the popliteal fascial retinaculum. In the present study, we evaluated preliminary longitudinal clinical outcomes after this procedure in patients with mild-to-moderate knee OA. Background/Objectives: Knee OA is a common cause of chronic pain, stiffness, and disability. In the present study, we evaluated preliminary 12-month WOMAC outcomes after a three-session ultrasound-guided posteromedial fascial–periarticular injection in patients with Kellgren–Lawrence grade 1–3 knee OA. Methods: This retrospective analysis of a prospectively maintained single-center clinical registry included 10 patients treated between October 2023 and October 2025. Each patient received three monthly ultrasound-guided posteromedial injections using 30 mL of 5% dextrose with 0.1% lidocaine (lignocaine). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was recorded at baseline and at 1, 3, 6, and 12 months after the final injection. Data are mean ± SD, median (IQR), and 95% CI. In exploratory inferential analyses, we used Friedman tests and Wilcoxon signed-rank tests with Bonferroni correction. Results: The mean WOMAC total score improved from 59.5 ± 4.33 at baseline to 38.6 ± 4.50 at 1 month, 34.3 ± 4.45 at 3 months, 30.6 ± 3.06 at 6 months, and 28.5 ± 2.51 at 12 months after the final injection, corresponding to a mean 12-month within-patient change of −31.0 points (95% CI −32.58 to −29.42; −52.1%). Mean pain improved from 12.6 ± 1.35 to 5.6 ± 0.70, stiffness from 4.7 ± 0.48 to 2.1 ± 0.32, and physical function from 42.2 ± 2.62 to 20.8 ± 2.15. All 10 patients had lower WOMAC total scores at 12 months than at baseline. Friedman tests were significant for all four WOMAC domains (all p ≤ 5.05 × 10−7); Wilcoxon signed-rank tests versus baseline reached the theoretical minimum p at n = 10 (Bonferroni-adjusted p = 7.81 × 10−3) at every follow-up timepoint. No serious adverse events were documented; mild transient post-procedural soreness occurred in three patients. Conclusions: In this small retrospective pilot cohort, ultrasound-guided posteromedial fascial–periarticular injection was associated with sustained improvement in WOMAC pain, stiffness, physical function, and total scores over 12 months. These findings are preliminary and hypothesis-generating; non-specific effects including placebo, regression to the mean, and natural symptomatic fluctuation cannot be excluded. Prospective controlled trials are required to establish safety, reproducibility, mechanism, and comparative effectiveness.

Abstract: Background/Objectives: One-stage revision has become an increasingly accepted strategy for the treatment of chronic periprosthetic joint infection (PJI) of the knee in carefully selected patients. The use of a resorbable defensive antibacterial coating (DAC® hydrogel) represents an attractive adjunct to reduce bacterial adhesion and biofilm formation on revision implants. However, evidence regarding its long-term performance remains limited. Methods: We retrospectively reviewed 52 consecutive patients undergoing one-stage revision for knee PJI or infected spacer between 2014 and 2023 using a standardized surgical and antimicrobial protocol including local application of DAC hydrogel loaded with vancomycin alone or vancomycin plus meropenem. Clinical, microbiological and radiographic outcomes were evaluated. Infection-free survival was assessed using Kaplan–Meier analysis. Results: Forty-eight patients underwent revision for PJI and four for septic spacers. Four patients were unavailable for final evaluation. At mean follow-up of 7.0 ± 2.7 years (range 3–11 years), no infection recurrence was obtained in 47 of 48 clinically evaluable patients, corresponding to an infection-free survivorship of 97.9% at final follow-up. Mean Knee Society Score improved from 47.7 to 84.4 points, while functional KSS improved from 41.9 to 82.9 points. Pain at rest decreased from 6.9 to 0.7 and pain during movement from 8.1 to 1.6 on the visual analogue scale. Conclusions: This series represents, to our knowledge, the longest reported follow-up of one-stage knee revision using DAC antibacterial hydrogel. The favorable results obtained using hybrid fixation, with cemented epiphyseal fixation combined with uncemented stems coated with antibiotic-loaded DAC hydrogel, further expand the potential indications for this strategy. Larger comparative multicenter studies are warranted to confirm these findings.

Abstract: Background/Objectives: Humeral head osteonecrosis is a recognised complication following locked plate fixation of complex proximal humeral fractures, yet the clinical relevance of necrotic lesion extent remains poorly characterised. This study aimed to quantify MRI-defined osteonecrosis extent and examine its associations with radiographic severity, shoulder motion, and functional outcomes. Methods: Twenty-five patients with Neer three- or four-part proximal humeral fractures treated by locked plate fixation between 2010 and 2022 were retrospectively reviewed. Active shoulder range of motion, Constant score, American Shoulder and Elbow Surgeons (ASES) score, and visual analogue scale (VAS) pain were assessed at final follow-up. Osteonecrosis severity was graded using the Cruess classification. MRI necrotic extent was quantified with a modified angle-based method on coronal and axial images; associations with outcomes were assessed by linear regression. Results: At a mean follow-up of 85.4 ± 34.1 months, osteonecrosis was identified in 12 of 25 patients (48%). Patients with osteonecrosis demonstrated significantly lower shoulder abduction (96.7 ± 27.1° vs. 121.8 ± 29.2°; p = 0.031), internal rotation (48.3 ± 15.9° vs. 66.4 ± 15.5°; p = 0.014), and external rotation (36.7 ± 16.7° vs. 51.8 ± 26.4°; p = 0.041) than those without. Functional outcome scores did not differ significantly between groups. Greater total necrotic angle was associated with higher radiographic Cruess stage and reduced shoulder abduction (β = −0.141; 95% CI −0.259 to −0.024; p = 0.020). Conclusions: MRI-defined osteonecrosis extent correlates with radiographic severity and reduced shoulder motion after locked plate fixation of proximal humeral fractures. Larger necrotic lesions are associated with decreased shoulder abduction, whereas no clear relationship was identified between necrotic extent and global functional outcome scores. Quantitative MRI assessment may provide additional clinically relevant information on the structural severity of post-traumatic humeral head osteonecrosis.

Abstract: Background: Posterior spinal fusion (PSF) provides reliable deformity correction for adolescent idiopathic scoliosis (AIS); however, it reduces lumbar mobility because of the fusion of motion segments. Hybrid fixation, which combines thoracic PSF with thoracolumbar/lumbar vertebral body tethering (VBT), aims to preserve lumbar function while maintaining satisfactory deformity correction. Methods: This retrospective comparative cohort study included 66 adolescents with double-major AIS treated with hybrid fixation (n = 30) or posterior long fusion (n = 36). Radiographic outcomes, lumbar flexibility, sagittal range of motion (ROM), lumbar core muscle strength (LCMS), SRS-22r Function scores, complications, and revision surgery were assessed after a minimum follow-up of 24 months. Multivariable regression analyses were used to identify independent predictors of postoperative functional outcomes. Results: Both procedures achieved excellent correction of the main thoracic curve and satisfactory global spinal alignment. Posterior long fusion provided greater thoracolumbar/lumbar curve correction (p < 0.001), whereas hybrid fixation resulted in significantly better lumbar flexibility, sagittal ROM, and LCMS (all p ≤ 0.006). Revision surgery was more frequent after hybrid fixation (20.0% vs. 0%, p = 0.007), primarily because of tether-related complications. Conclusions: Hybrid fixation better preserves objective lumbar function than posterior long fusion while maintaining satisfactory deformity correction in adolescents with double-major AIS. These functional benefits should be balanced against the higher revision burden, supporting individualized treatment selection and shared decision-making when considering motion-preserving surgical strategies.

Abstract: Background and Objectives: Melatonin is traditionally recognized as a central regulator of circadian rhythms, but it is also a pleiotropic molecule with antioxidant, anti-inflammatory, mitochondrial-protective and immunomodulatory properties. These mechanisms are biologically relevant to degenerative, inflammatory and traumatic disorders of the musculoskeletal system. Materials and Methods: This narrative review summarizes evidence from PubMed/MEDLINE, Scopus and Web of Science regarding the role of melatonin in bone metabolism, cartilage homeostasis, osteoarthritis, muscle injury, tendon and ligament healing, spine disorders, sports medicine and musculoskeletal rehabilitation. Preclinical studies, translational investigations, clinical trials, systematic reviews and relevant mechanistic papers were considered. Results: Experimental evidence suggests that melatonin promotes osteoblast differentiation, limits osteoclastogenesis, protects chondrocytes from oxidative stress and apoptosis, modulates nuclear factor kappa B and nuclear factor erythroid 2-related factor 2 signaling, supports mitochondrial homeostasis and may influence autophagy, mitophagy and ferroptosis. These effects have potential implications for osteoporosis, fracture healing, osteoarthritis, tendinopathy, intervertebral disc degeneration and recovery after strenuous exercise. Clinical evidence remains promising but insufficient to define standardized orthopedic indications. Conclusions: Melatonin is a biologically plausible adjunct in musculoskeletal medicine, particularly where oxidative stress, low-grade inflammation and mitochondrial dysfunction contribute to disease progression. Well-designed randomized controlled trials are required to determine indications, timing, dose, route of administration and clinically meaningful outcomes.

Abstract: Background: Artificial intelligence (AI) has expanded rapidly across orthopaedic practice, yet routine clinical adoption remains limited despite strong technical performance. This narrative review examines why a persistent gap separates technical maturity from clinical maturity across the orthopaedic patient care pathway. Methods: We performed a structured qualitative evidence synthesis of contemporary high-level evidence (systematic reviews, diagnostic test accuracy meta-analyses, and structured narrative reviews) retrieved from PubMed/MEDLINE and reference screening, covering January 2022 to June 2026. Twenty-one evidence syntheses were analysed thematically across six predefined domains and organised according to the orthopaedic patient pathway. Reporting followed the SANRA (Scale for the Assessment of Narrative Review Articles) criteria. Results: Musculoskeletal imaging and fracture detection represented the most mature domains, with several applications reaching early clinical adoption. Applications in arthroplasty planning, shoulder surgery, perioperative prediction, multimodal AI, and clinical decision support remained at developing or emerging stages. Recurrent barriers included limited external validation, dataset heterogeneity, poor workflow interoperability, limited explainability, regulatory and ethical uncertainty, and scarce patient-centred outcome evidence. Conclusion: The principal challenge facing orthopaedic AI is no longer algorithm development but clinical translation. We propose the ORION Clinical Readiness Framework, an evidence-informed model describing the transition from Technical Performance to Clinical Validation, Workflow Integration, Patient Benefit, and Routine Clinical Adoption, to guide implementation and future research.

Abstract: 1) Background/Objectives: Sarcopenia is common in older surgical candidates and may affect perioperative risk and recovery after total hip arthroplasty (THA). Quantifying its burden and severity gradient in THA pathways can inform surgeon-led optimization. 2) Methods: A cross-sectional analysis of baseline preoperative data at a tertiary center (October 2019 to December 2022) was conducted. Consecutive adults with hip osteoarthritis undergoing primary THA were screened. Sarcopenia was staged per EWGSOP2: probable (low handgrip), confirmed (probable and low skeletal muscle index by whole-body DXA), and severe (confirmed and low gait speed). 3) Results: Of 312 screened patients, 203 completed baseline assessment (95 men, 108 women). According to the EWGSOP2 algorithm, 57 patients had low handgrip strength, 30 fulfilled criteria for confirmed sarcopenia, and 21 had severe sarcopenia. No significant association was observed for sex. Sarcopenia diagnosis was associated with older age, lower body mass index (BMI), higher comorbidity burden, lower functional independence, greater cognitive impairment, poorer mental health, and worse hip-related function (all p < 0.05). In multivariable analysis, older age (OR 1.104 per year; 95% CI 1.031-1.183), lower BMI (OR 0.877 per kg/m2; 95% CI 0.785-0.978), and lower functional independence (Barthel Index: OR 0.940 per point; 95% CI 0.895-0.988) were independently associated with confirmed sarcopenia. Increasing sarcopenia severity was associated with higher pain intensity, lower hemoglobin levels, poorer proximal femoral morphology, and worse hip-related quality of life (all p < 0.05). 4) Conclusions: In THA candidates, sarcopenia is prevalent and is related to older age, lower BMI and lower functional independence. Integrating EWGSOP2-based sarcopenia screening may identify patients with poorer baseline reserve who could benefit from targeted nutritional and functional optimization strategies before surgery.

Abstract: Background: Myelodysplastic clubfoot is rigid, recurrent, and may limit ambulation in children with myelomeningocele. This study evaluated early functional mobility after modified Turco posteromedial release. Methods: Thirty-nine children (55 feet) with myelodysplastic clubfoot who underwent modified Turco posteromedial release after failed conservative treatment were retrospectively reviewed. Functional outcomes were assessed preoperatively and at final follow-up using the Gross Motor Function Classification System (GMFCS) and Functional Mobility Scale (FMS) at distances of 5, 50, and 500 meters. Deformity severity, quadriceps function, complications, recurrence, and reintervention were also recorded. Results: Mean age at surgery was 4.2 ± 2.4 years; mean follow-up was 3.7 years. Median preoperative GMFCS was III, and median preoperative FMS total score was 7. The FMS total score improved across the Dimeglio severity groups: 10–13 (moderate), 7–10 (severe), and 4–7 (very severe). Gains were most consistent at 50 m, reflecting school-level mobility. Children with low lumbar involvement improved across all FMS distances; those with thoracic-level involvement showed limited gains. Children with sacral involvement reached higher postoperative FMS scores. Preserved quadriceps function was associated with better functional outcomes. Recurrence occurred in 14 feet (25.4%) and early wound problems in 12 feet (21.8%). Conclusions: Modified Turco posteromedial release was associated with improved distance-specific mobility, particularly in children with low lumbar or sacral neurological levels and preserved quadriceps function. The GMFCS remained largely stable, with limited changes compared to FMS gains.