Medicine and Pharmacology

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.

Abstract: Purpose: To characterize the documented spectrum of degenerative lumbar spine disease across 500 consecutive magnetic resonance imaging (MRI) radiology reports using a transparent, reproducible text-extraction pipeline, to quantify which descriptors distinguish reports retained for degenerative analysis from those excluded, and to develop a reproducible image-based assessment pipeline that derives per-disc imaging features for benchmarking against radiologist Pfirrmann grading. Methods: We analyzed 500 lumbar MRI reports (386 unique patients; December 2018 to November 2025). Reports were screened against degenerative-disease eligibility criteria. From each report we extracted morphological and severity keywords, explicit segmental level mentions (L1–L2 to L5–S1), Modic-change mentions, and an ordinal degeneration severity (0–3) derived by a published rule set. Field completeness was quantified. Differences in keyword prevalence between included and excluded reports were tested with the Fisher exact test, with Benjamini–Hochberg control of the false discovery rate (FDR). A complementary MATLAB image-processing pipeline was executed across 316 studies to derive per-disc imaging features (predicted Pfirrmann grade, normalized disc height, T2 signal index, severity and quality control) for benchmarking against radiologist Pfirrmann grading. Results: 385 of 500 reports (77.0%) met inclusion criteria; exclusions were predominantly trauma/fracture (58/115) and prior surgery (38/115). Narrative fields were complete, but the structured morphological-keyword field was missing in 49.4% of records. Disc bulge was the dominant descriptor (53.8%), followed by mild (27.5%), stenosis (18.7%) and severe (16.4%). The lower segments L4–L5 (27.0%) and L5–S1 (28.4%) dominated level mentions. After FDR correction, bulge, mild, dehydration and central were significantly enriched among included reports (all q < 0.05). Derived severity was broadly balanced (report-level: 28.0% none, 30.2% mild, 19.8% moderate, 22.0% severe). Conclusions: Free-text lumbar MRI reports encode a recognizable but heterogeneous degenerative vocabulary that is sufficient for cohort construction yet inconsistent for quantitative grading. The text-derived severity is reasonable but should be regarded as a noisy proxy; we therefore developed and executed a reproducible image-based assessment pipeline, deriving per-disc features and quality control across 316 studies; benchmarking these outputs against an adjudicated Pfirrmann gold standard is the immediate next step toward clinically defensible, image-based phenotyping.

Abstract: Background/Objectives: Rotator cuff tears are a leading cause of shoulder disability. While multi-sequence MRI is standard, the optimal deep learning integration of het-erogeneous image series and clinical metadata remains unresolved. This study evalu-ated a hierarchical, sequence-aware multimodal framework for patient-level binary rotator cuff tear classification. Methods: A single-center cohort of 199 patients (100 tears, 99 controls) was analyzed across four MRI sequences (T1 coronal, T2 fat-suppressed sagittal, and proton density [PD] fat-suppressed coronal and trans-verse/axial) and nine demographic features. Under a patient-level stratified three-fold cross-validation scheme preventing data leakage, we evaluated ResNet50 and Vision Transformer baselines (Study 0), full-protocol fusion topologies (Study 1), and system-atically mapped sequence-subset combinations with or without metadata (Study 2). Results: In Study 0, the PD coronal ResNet50 model was the top baseline (AUC = 0.9834, F1 = 0.9515). In Study 1, late decision fusion yielded the highest AUC (0.9909), while feature concatenation optimized threshold balance (F1 = 0.9502). In Study 2, a streamlined three-sequence subset with metadata (C14M: T2 + PDc + PDt) achieved peak performance (AUC = 0.9961, 95% CI: 0.9806–0.9986, F1 = 0.9618, MCC = 0.9238), outperforming the full protocol (AUC = 0.9909, F1 = 0.9355). Metadata utility was con-figuration-dependent, assisting only fluid-sensitive combinations. Conclusions: Rather than indiscriminately aggregating entire clinical protocols, multimodal fusion is opti-mized by selecting complementary imaging series. For binary classification, excluding non-fat-suppressed T1 images in favor of a streamlined T2 and PD set stabilized by clinical demographics maximizes diagnostic capacity.

Abstract: Degenerative musculoskeletal diseases represent a major cause of chronic pain and disability worldwide and are increasingly associated with dysregulated oxidative stress and impaired redox signaling. Conventional therapeutic strategies are often limited to symptomatic management, prompting interest in adjunctive approaches that target underlying biological mechanisms. Among these, medical ozone therapy has been proposed as a redox-modulating intervention in various musculoskeletal conditions. Methods: A narrative clinical-mechanistic review of the literature was conducted using PubMed/MEDLINE, Scopus, and Google Scholar to identify experimental and clinical studies examining oxidative stress, redox signaling, and the application of medical ozone therapy in degenerative musculoskeletal disorders. Preclinical models published between 2000 and 2025 and randomized clinical trials published between 2020 and 2025 were critically evaluated and synthesized qualitatively, with attention to biological plausibility, clinical outcomes, and methodological limitations. Results: Evidence from experimental studies supports a role for controlled oxidative stimuli in activating adaptive cellular defense pathways, including redox-sensitive signaling mechanisms involved in inflammation and tissue homeostasis. Clinical studies across conditions such as intervertebral disc disease, knee osteoarthritis, and other degenerative or overuse-related disorders report short- to mid-term improvements in pain and function following ozone therapy. However, substantial heterogeneity in study design, treatment protocols, and outcome measures limits comparability and precludes definitive conclusions regarding efficacy. Conclusion: Current evidence suggests that ozone therapy may exert biologically plausible effects through hormetic redox modulation and may provide symptomatic benefit in selected patients with degenerative musculoskeletal diseases. Nonetheless, the lack of standardized protocols and high-quality long-term data warrants cautious interpretation. Further rigorous clinical trials integrating mechanistic biomarkers and standardized methodologies are needed to clarify the therapeutic role and safety profile of ozone therapy in musculoskeletal medicine.

Abstract: Biomechanical theory and coaching heuristics suggest contact depth meaningfully constrains swing mechanics and batted ball outcomes. Our purpose was to examine the relationship between contact depth and key hitting metrics during live collegiate competition. Markerless motion capture and ball tracking data were collected during live NCAA Division I games from 2,779 batted balls from 239 hitters. Outcomes included contact depth, exit velocity, maximum swing speed, swing speed at contact, and vertical and horizontal attack angles. Regressions assessed relationships with velocity and swing speed variables, while partial least squares regression evaluated attack angles. Mean contact depth was 20.1±7.2 inches in front of the hitter’s center of mass. Contact depth weakly explained exit velocity (r²=0.04,p< 0.001) but significantly predicted maximum swing speed (r²=0.20 p< 0.001). No meaningful relationship was observed with swing speed at ball contact (r²=0.01,p>0.01). Contact depth showed a strong association with the combined structure of vertical and horizontal attack angles, with the primary PLS component explaining 80.0% of contact depth variance. Contact depth influences swing mechanics and attack angles and is associated with peak, but not contact, bat speed. These findings highlight contact depth as a critical covariate for interpreting swing metrics and designing biomechanical assessments, analytic models, and on-field interventions.

Abstract: Thumb pain is involved in multiple conditions—de Quervain’s tenosynovitis, carpometacarpal (CMC) osteoarthritis, carpal tunnel syndrome, intersection syndrome, and myofascial pain syndrome—that frequently coexist, yet they are traditionally managed as separate entities. These conditions may share a common pathological substrate: fascial densification characterized by hyaluronic acid aggregation and impaired fascial gliding. This narrative review synthesizes anatomical, biomolecular, and clinical evidence supporting a unified fascial basis for five converging thumb pain conditions. We describe a representative 15-point ultrasound-guided fascia hydrorelease (FHR) protocol targeting the shared fascial substrate of the thumb–wrist–forearm complex, with each treatment point mapped to specific anatomical stress concentration sites. Ultrasound examination consistently reveals “stacking fascia”—densified fascial layers visualized as hyperechoic band-like lesions with reduced gliding—across multiple anatomical sites in patients regardless of primary diagnosis. A four-direction screening test assessing thumb flexion, extension, abduction, and adduction in three modes (active contraction, resistance loading, and passive stretch), combined with nine validated clinical tests (Finkelstein, Eichhoff, WHAT, Phalen, Tinel-wrist, Grind, Lever, Durkan, and Tinel-dorsal/Wartenberg), enables systematic identification of the affected fascial structures. The 15-point FHR protocol addresses dorsal and volar fascial pathology, including periarterial release for potential vascular improvement in CMC osteoarthritis. We propose Thumb Pain Syndrome (TPS) as a unifying clinical framework recognizing the shared fascial substrate underlying five common thumb pain conditions. The 15-point FHR protocol offers a systematic, minimally invasive treatment approach that may serve as a non-surgical alternative for refractory cases where conventional pharmacological or surgical interventions have reached their limits. Further controlled studies are needed to validate this integrated fascial perspective.

Abstract: Background and objectives: Gold-based therapies are increasingly being studied for their potential to alleviate osteoarthritic (OA) symptoms, although their overall evidence remains inconclusive. Methods: We conducted a systematic search (January 20, 2026) across five databases. We included both human and animal cohort studies and randomized controlled trials that reported on the effects of metallic gold nanoparticles (AuNP), microparticles (µGold), and bead implants (GBI) on osteoarthritic symptoms. The risk of bias was assessed using the Cochrane, CAMARADES, and ROBINS-I tools. Results: A total of 18 studies met the inclusion criteria. We analyzed 7 studies on AuNP, 1 on µGold, and 10 on GBI, grouping them by study type. In the analysis of five randomized studies on BMI in human and animal OA, a significant difference between the intervention and the control was found in one human and one animal study. The seven randomized studies examining AuNP for animal OA reported significant differences between the intervention and control groups. The cohort studies assessing the success of BMI in animals demonstrate different 95% CI’s, with a total success of 668/782. One human cohort study of µGold demonstrates a wide 95% CI of success. Conclusions: Although the evidence is of low quality and shows moderate heterogeneity, the results support the use of AuNP, µGold, and GBI for OA treatment. Notably, µGold may provide superior localized delivery via a single intra-articular administration and potentially enable greater gold-ion release than GBI and AuNP do.

Abstract: Plyometric training is proposed as a method to improve neuromuscular performance in climbing. However, its specific effects on upper-body explosive capacity and rate of force development (RFD) in advanced boulder climbers remain unclear. The objective was to determine the effect of 10-week plyometric training on neuromuscular performance in advanced boulder climbers. Eighteen male climbers were assigned to: intervention group (n=9, 29.7±4.5yr) or control group (n=9, 31.3±5.6yr). Finger flexor strength and RFD (20-mm grip, 0–200ms, 20–80%), isometric pull-up strength and RFD (load cell), upper-body power (plyometric push-up, Power Slap), and lower-body power (CMJ) were assessed. The intervention comprised two plyometric sessions/week for 10 weeks. Significant differences were observed in pull-ups (Δ difference = +3.89 repetitions; 95% CI:0.30, 7.48; p=0.036; η²p=0.248), push-up power (Δ difference = +174.25 W; 95% CI: 5.05, 343.46; p=0.044; η²p=0.128), isometric pull-up RFD at 200ms (Δ difference = +107.85 kg/s; 95% CI: 27.54, 188.16; p=0.012; η²p=0.336), and the 20–80% range (Δ difference = +261.78 kg/s; 95% CI: 23.09, 500.47; p=0.034; η²p=0.253). No significant differences were observed in finger flexor strength, finger RFD, maximal isometric pull-up strength, Power Slap, or CMJ. The plyometric program produced specific neuromuscular adaptations in advanced boulder climbers, confirming trained movement pattern.

Abstract: Dorsal metacarpal disease (DMD) is a common musculoskeletal injury in young racehorses, and effective non-invasive treatments remain of clinical interest. This study aimed to evaluate whether high-intensity laser therapy (HILT), applied as the sole intervention, reduces clinical signs of DMD compared with untreated horses withdrawn from training. During the 2023–2024 racing seasons, 15 Arabian racehorses diagnosed with DMD were enrolled; 9 received HILT and 6 served as controls without laser therapy. The treatment protocol consisted of five daily HILT sessions followed by five sessions administered every other day. Thermographic, orthopedic, and radiographic examinations of the third metacarpal bones were performed before and after the treatment period in both groups, with additional thermographic and clinical assessments conducted throughout therapy. The results showed that horses treated with HILT did not exhibit a significant reduction in pain and lameness accompanied by thermographic changes consistent with decreased inflammation. These findings indicate that HILT did not alleviate clinical signs associated with DMD in the affected horses; however, further controlled studies are required to determine its effect on tissue healing processes and to optimize treatment duration.

Abstract: Background/Objectives: The anticoagulant used for blood collection is a fundamental but underexplored variable in platelet-rich plasma (PRP) preparation. Ethylenediaminetetraacetic acid (EDTA) and sodium citrate act on platelets through distinct calcium chelation mechanisms with potentially different consequences for PRP quality. Our group has previously demonstrated that biological and demographic variables independently modulate platelet composition in PRP; the present study extends this analysis to the pre-analytical anticoagulant variable. No prospective paired clinical study has systematically compared the effects of EDTA and sodium citrate on platelet morphological parameters in a real clinical setting. This study aimed to characterise these differences and evaluate their implications for orthobiologic therapy. Methods: A prospective within-subject paired-sample study was conducted at Instituto Cugat – Quirónsalud Barcelona (November 2025–April 2026). Twenty-six consecutive adult patients undergoing routine blood extraction prior to orthopaedic procedures had blood drawn simultaneously into K₂-EDTA and sodium citrate (3.2%) tubes. Full haematological analysis was performed on a Sysmex XN automated analyser within 30 minutes. Primary outcomes were mean platelet volume (MPV), platelet distribution width (PDW), large platelet ratio (P-LCR), large platelet cell count (P-LCC), and plateletcrit (PCT). Statistical comparisons used the paired t-test or Wilcoxon signed-rank test; effect sizes were quantified as Cohen's d. Results: Seven of eight platelet-related parameters differed significantly between anticoagulants (all p<0.001). Compared to sodium citrate, EDTA produced systematically higher MPV (+10.1%, d=2.81), P-LCR (+25.8%, d=2.41), P-LCC (+24.3%, d=1.70), PDW (+13.5%, d=1.33), PCT (+7.3%, d=0.78), RDW-CV (+2.0%, d=0.83), and RDW-SD (+2.6%, d=0.80). MPV was higher with EDTA in all 26/26 paired samples without exception. Total platelet count did not differ significantly (p=0.135). Effect sizes for all morphological parameters were large (d≥0.78). Conclusions: EDTA induces large, reproducible, and universal platelet morphological changes consistent with calcium chelation-induced swelling, not genuine platelet hypertrophy. These artefactual changes systematically overestimate platelet size and large platelet indices by up to 26%, with direct implications for PRP quality assessment in orthobiologic medicine. Sodium citrate should remain the anticoagulant of choice for PRP preparation. Clinicians using EDTA must recognise that morphological parameters do not reflect functional platelet capacity.

Abstract: Thymosin beta-4 (TB4) and the related compound commonly referred to as TB-500 are widely discussed in tissue healing and musculoskeletal medicine, but the scope and nature of the supporting literature remain unclear. We conducted a scoping review to map the evidence on TB4 and TB-500 in tissue healing, regeneration, and musculoskeletal repair. PubMed, Europe PMC, and ClinicalTrials.gov were searched through March 2026. English-language in vitro, animal, human, and registered clinical trial sources directly evaluating TB4, TB-500, or included derivatives in repair-related contexts were eligible. Of 1772 records identified, 80 studies were included. The evidence base was weighted toward mixed and in vitro designs, and most studies evaluated TB4 rather than TB-500. The most common tissue categories were wound/skin/soft tissue, vascular/endothelial, ocular/cornea, and bone. Direct musculoskeletal tissue categories such as tendon, ligament, muscle, cartilage, and spine/intervertebral disc were comparatively sparse. Human evidence was concentrated in ocular/cornea and wound/skin/soft tissue settings, whereas direct TB-500 evidence was limited to a single included study. Overall, the mapped literature supports the popular interest in several repair-related pathways but remains unevenly distributed and largely preclinical, with limited human evidence directly relevant to musculoskeletal applications.

Abstract: Background and Objectives: Acetabular fracture surgery is associated with substantial perioperative blood loss and prolonged operative time. Routine preoperative pelvic computed tomography (CT) carries information about body composition that is not currently exploited for risk stratification. We tested whether (i) CT-defined pelvic sarcopenia is associated with lower preoperative haemoglobin and a greater perioperative haemoglobin drop, and (ii) preoperative subcutaneous fat cross-sectional area (CSA) independently predicts operative time, after adjustment for surgical approach, age, fracture complexity and sarcopenia status. Materials and Methods: In this single-centre retrospective cohort study, 48 adults (37 men, 11 women; mean age 40.2 ± 16.5 years) who underwent open reduction and internal fixation (ORIF) for unilateral acetabular fractures between 2016 and 2024 were included. Pelvic muscle and subcutaneous fat CSAs were measured on the contralateral side of preoperative CT images using ImageJ. Sarcopenia was defined a priori as a sex-specific bottom tertile of psoas CSA. Group comparisons used Welch's t-test or Mann–Whitney U; correlations used Pearson's r; the multivariable model used ordinary least squares regression. A sensitivity power analysis was performed for all primary tests. Results: Sarcopenic patients (n = 17) had significantly lower preoperative haemoglobin (12.63 ± 1.24 vs. 14.00 ± 1.53 g/dL; mean difference −1.37 g/dL, 95% CI −2.20 to −0.55; p = 0.002; Cohen's d = 0.96) and a greater perioperative haemoglobin drop (ΔHb 1.64 ± 0.91 vs. 2.46 ± 1.87 g/dL; p = 0.046; d = 0.52) compared with non-sarcopenic patients (n = 31). Psoas, iliacus, gluteus medius–minimus and total muscle CSAs all correlated positively with preoperative haemoglobin (r = 0.42 to 0.49; all p ≤ 0.003). In the multivariable model (overall F[6, 41] = 3.71, p = 0.005; adjusted R² = 0.26), subcutaneous fat CSA (B = +0.25 min/cm², 95% CI +0.09 to +0.41, p = 0.004) and the modified Stoppa approach (vs. Kocher–Langenbeck; +65 min, p = 0.001) independently predicted operative time, while age, fracture complexity and sarcopenia did not. Conclusions: Routine preoperative pelvic CT in acetabular fracture patients can be repurposed as a one-stop opportunistic screen for two clinically actionable phenotypes: pelvic sarcopenia, which flags lower haematopoietic reserve and a greater perioperative haemoglobin drop, and elevated subcutaneous adiposity, which independently predicts longer operative time. Both findings can be obtained at zero marginal cost or radiation burden and could inform preoperative blood-product preparation, prehabilitation triage, and operating-room scheduling.

Abstract: As the population ages, the incidence and prevalence of musculoskeletal degeneration, such as osteoarthritis increases. While the currently accepted treatment options provide symptomatic and functional improvement, they do not halt the progression of osteoarthritis. This results in eventual need for surgery for many patients with advanced osteoarthritis. Due to seemingly inevitable progression of OA, many clinicians and researchers have shifted their focus to regenerative therapies. Orthobiologics, a specific type of regenerative therapy designed to treat orthopedic conditions, have been gaining traction in recent years due to utilization of autologous biological substances and synthetic peptides in healing in musculoskeletal injuries and degenerative conditions. Orthobiologics can be distinguished into one of four classes: cell-based, biologic fluids-based, matrix-based and molecular-based, and based on its composition. In this review, key examples of each class, mechanism of action, and current clinical data for each agent are examined. Limitations of current orthobiologics involve lack of standardization in preparation and administration each agent as well as uniformity in assessment end points across different clinical studies. Lastly, we will discuss future directions of orthobiologics as a therapy for treatment in osteoarthritis.

Abstract: In the present study, data were compiled to compare trunk extension strength between healthy female and male participants. Participants (124 females, 115 males) performed isometric maximal voluntary contraction (MVC) tests in an upright standing position. In addition, upper body weight was determined. Outcome parameters included maximal force values, expressed as torque, as well as upper body weight (also in torque values). Furthermore, the ratio between MVC and upper body weight was calculated. Highly significant differences were observed for MVC (men: 241 Nm, women: 162 Nm, p< 0.0001) and for upper body torque (men: 115 Nm, women: 80 Nm, p< 0.0001). After normalization to upper body torque, no relevant differences between sexes were detectable (men: 2.16, women: 2.00, p=0.0055, Effect size: 0.364). Despite substantial sex-related differences in absolute force capacity, relative strength—when adjusted for upper body weight—does not differ meaningfully between men and women. Both sexes are characterized by a physiological strength reserve of approximately 100% of their upper body weight.

Abstract: Metabolic disorders, including obesity, type 2 diabetes mellitus (T2DM), dyslipidemia, and metabolic dysfunction–associated fatty liver disease (MAFLD), represent a major and escalating global health burden. These conditions are now recognized as systemic disorders arising from dysregulated inter-organ communication among metabolically active tissues. Central mechanisms include insulin resistance, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and neuroendocrine dysregulation. Exercise is increasingly recognized as a potent multisystem therapeutic intervention. Beyond energy expenditure, it induces coordinated molecular adaptations across tissues, including improved mitochondrial function, reduced inflammation, and enhanced metabolic flexibility. Exercise-induced signaling molecules (exerkines) and gut microbiota remodeling further mediate systemic metabolic benefits. This review synthesizes current evidence on exercise as an integrative therapy for metabolic disorders, with emphasis on molecular mechanisms, organ-specific adaptations, and clinical applications. Emerging roles of membrane microdomains such as caveolae are discussed as potential regulators of metabolic signaling, although their role in exercise adaptation remains incompletely defined.

Abstract: Background: Mitochondrial bioenergetic dysregulation disrupts immune-metabolic homeostasis and promotes pro-inflammatory microenvironments in osteoarthritis (OA) synovitis. Nevertheless, the mechanistic contributions of mitochondrial energy metabolism to synovitis pathogenesis in OA remain poorly defined. Methods: We analyzed mitochondrial energy metabolism-related genes (MEMRGs) in OA synovitis by integrating transcriptomic data from OA synovial tissues (GSE55235, GSE55457). LASSO regression and maximal clique centrality (MCC) algorithms were applied to identify hub genes, and single-cell RNA sequencing (GSE152805) was used to examine cell-type-specific expression patterns. Functional validation was performed in IRS2-knockdown THP-1 macrophages. Results: We identified 22 mitochondrial energy metabolism-related differentially expressed genes (MEMR-DEGs), which were enriched in AMPK signaling, glucagon signaling, and insulin signaling pathways. Four hub genes (FOXO3, FASN, PTGS2, IRS2) were identified and negatively correlated with synovial macrophage infiltration. Single-cell RNA sequencing revealed IRS2 was specifically upregulated in a synovial macrophage cluster. Functional studies in IRS2-knockdown THP-1 macrophages demonstrated that IRS2 deficiency impaired IL-4-induced M2 macrophage polarization and reduced mitochondrial membrane potential, mediated by suppression of AKT/FOXO1 signaling. Conclusions: Our study reveals the role of MEMRGs in OA synovium, and highlights the molecular mechanism by which IRS2 potentially coordinates mitochondrial energy metabolism via the AKT/FOXO1 signaling pathways to maintain synovial macrophage M2 polarization homeostasis. These findings provide novel molecular targets for targeting immune-metabolic pathways in OA therapy.

Abstract: Background/Objectives: Large language models (LLMs) are increasingly applied to medical image interpretation; however, their diagnostic accuracy and reliability in musculoskeletal radiology remain uncertain. This study evaluates the diagnostic performance and confidence calibration of LLMs in detecting and classifying bone tumors on radiographs. Methods: This retrospective observational study analyzed a dataset of 257 radiographs with confirmed diagnoses obtained from Radiopaedia, including normal studies and a spectrum of benign and malignant bone tumors. Cases were selected to ensure representation across multiple tumor types. Three LLMs (ChatGPT 5.3, X-ray Interpreter GPT-4.1, and X-ray Interpreter Gemini) evaluated each image using a standardized prompt assessing abnormality detection, tumor detection, classification, and confidence. Outcomes included diagnostic accuracy, false positive abnormality rates, false negative rates, tumor hallucination rates, and confidence calibration. Results: Abnormality detection was high across models, with Gemini demonstrating the highest sensitivity (up to 100%). Tumor detection was strongest in lesions with characteristic features, including osteosarcoma and osteochondroma. False negative rates varied substantially, with GPT-4.1 demonstrating the highest rate (29.9%), followed by ChatGPT (24.8%) and Gemini (6.6%). Primary diagnostic accuracy was highest for osteosarcoma in GPT-4.1 (80%), while ChatGPT 5.3 performed best in benign lesions, including osteochondroma (84.6%) and non-ossifying fibroma (76.9%). Tumor subtype classification remained limited across all models and was poorest for Ewing sarcoma (0% in ChatGPT and GPT-4.1; 10.3% in Gemini). False positive abnormality rates were highest in GPT-4.1 (40.7%), followed by Gemini (25.9%) and ChatGPT (13.5%). Tumor hallucination occurred only in Gemini (12.3%). All models demonstrated confidence miscalibration, with higher confidence observed in incorrect predictions and in tumor-negative cases. Conclusions: LLMs demonstrate strong performance in detecting radiographic abnormalities but remain limited in tumor subtype classification, particularly for diagnostically challenging lesions such as Ewing sarcoma. Elevated false positive and false negative rates, along with systematic overconfidence—especially in GPT-4.1—highlight important limitations for clinical use. These findings support the role of LLMs as adjunctive tools rather than independent diagnostic systems.