Medicine and Pharmacology

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.

Abstract: (1) Background: Femoroacetabular impingement syndrome (FAIS) is a common cause of hip pain and functional limitation in young and physically active individuals. Although hip arthroscopy is an established treatment when conservative management fails, objective data on early postoperative changes in active hip range of motion (ROM) remain limited. This study aimed to evaluate changes in active hip ROM three months after arthroscopic treatment for FAIS using inertial measurement units (IMUs) and to investigate their relationship with patient-reported outcomes. (2) Methods: A prospective cohort of patients undergoing hip arthroscopy for FAIS was assessed preoperatively and at a three-month follow-up. Active hip ROM—including flexion, internal rotation, external rotation, and total rotation—was measured using IMU sensors, while subjective outcomes were evaluated using the Hip disability and Osteoarthritis Outcome Score (HOOS). (3) Results: Significant improvements were observed across all HOOS subscales at follow-up. Active hip ROM increased significantly in internal rotation, external rotation, and total rotation of the operated hip, whereas changes in hip flexion were minimal and no meaningful changes were observed in the non-operated hip. (4) Conclusions: Hip arthroscopy for FAIS leads to early improvements in both patient-reported outcomes and active hip mobility, particularly in rotational movements, although the relationship between ROM and subjective outcomes appears weak.

Abstract: Background: Adolescent idiopathic scoliosis (AIS) may influence pelvic orientation and lower limb alignment, but data after completion of spinal correction are limited . Methods: In this retrospective study, 70 consecutive AIS patients (61 females, 9 males; mean age 17.0 ± 3.2 years, range 13–30 years) treated surgically (n = 52) or with brace therapy (n = 18) between 2010 and 2020 were analyzed. Patients were grouped by main curve location as thoracic (n = 28), lumbar (n = 21) or thoracolumbar (n = 21). Pre treatment standing full spine radiographs were used to measure Cobb angles, coronal balance and pelvic coronal obliquity angle (PCOA). After completion of spinal correction, full length weight bearing lower limb radiographs were obtained to assess femoral and tibial lengths, mechanical axis deviation (MAD), femoral neck–shaft angle (NSA), and distal/proximal femoral mechanical and anatomical angles. Results: Mean PCOA for the whole cohort was 2.3 ± 1.9°, and mean MAD was −0.41 ± 10.2 mm on the right and −0.7 ± 8.0 mm on the left. PCOA, coronal balance, MAD, right anatomical lateral distal femoral angle (aLDFA) and right mechanical lateral distal femoral angle (mLDFA) differed significantly among the three groups (p<0.05). Thoracolumbar versus thoracic curves showed higher PCOA and greater coronal imbalance (p = 0.011 and p = 0.004). The lumbar group demonstrated bilateral valgus alignment with more negative MAD values than the thoracic group (right MAD −5.88 ± 8.8 mm, left MAD −3.5 ± 7.5 mm; p = 0.004 and p = 0.005). The thoracic group had higher right aLDFA and mLDFA than lumbar and thoracolumbar groups (all p<0.05). No between group differences were found in femoral or tibial lengths or NSA (p>0.05) Conclusions: After spinal correction, AIS patients show subtle but measurable differences in coronal lower limb alignment according to curve location. Pelvic obliquity and MAD are more pronounced in lumbar and thoracolumbar curves, whereas limb lengths and NSA remain comparable among groups. These small deviations may influence long term load distribution and should be considered in the clinical assessment of AIS, particularly in patients with distal curve patterns.

Abstract: Background: Sacroiliac joint (SIJ) disruption alters posterior pelvic ring stability and may result in abnormal sacral stress redistribution. The biomechanical effects of different fixation strategies on sacral load transfer remain controversial. This study aimed to compare sacral stress patterns under unilateral and bilateral SIJ instability using three fixation techniques in a three-dimensional finite element model. Methods: A three-dimensional lumbosacral–pelvic finite element model was reconstructed from computed tomography data of a healthy adult and validated against previously published pelvic biomechanical data. SIJ instability was simulated by reducing the friction coefficient to represent ligamentous failure. Three fixation constructs were analyzed: anterior plate with posterior screw fixation, spinopelvic fixation, and hybrid fixation. A 750 N axial compressive load was applied to simulate static standing conditions; dynamic loading scenarios such as walking or sitting were not included. Peak sacral von Mises stress and stress amplification factors were calculated and compared with the intact model. Results: Anterior plate combined with posterior screw fixation produced the highest sacral stress amplification (SAF = 3.46 under unilateral instability; peak stress 265.40 MPa), exceeding three times the intact value, particularly under unilateral left instability (SAF = 3.46). Spinopelvic fixation significantly reduced peak sacral stress (125.66 MPa under bilateral instability; SAF = 1.64) but remained above physiological levels. Hybrid fixation demonstrated sacral stress values closest to the intact condition (81.64 MPa; SAF = 1.06), with minimal amplification and near-symmetrical load distribution. Conclusions: Fixation strategy significantly influences sacral load redistribution following SIJ disruption. Hybrid fixation most effectively restored near-physiological sacral stress patterns, whereas anterior plate with posterior screw fixation resulted in excessive stress concentration. Hybrid stabilization may provide a biomechanically balanced approach for unstable posterior pelvic injuries.

Abstract:

Background: Evidence on the role of synthetic biomimetic bone substitutes in the surgical management of proximal humerus fractures remains limited. This study aimed to evaluate the clinical, radiographic, and safety outcomes of a porous hydroxyapatite bone substitute used as an adjunct to locking-plate fixation in proximal humerus fractures with metaphyseal bone loss. Methods: We performed a retrospective cohort study including 45 patients treated between January 2022 and January 2025 with open reduction and internal fixation using a locking plate and a preformed porous hydroxyapatite scaffold (ENGIpore SH). Patients were evaluated clinically and radiographically at 1, 3, 6, and 12 months after surgery. Functional outcome was assessed with the Constant-Murley Score (CMS), and pain was assessed using the Visual Analogue Scale (VAS). Longitudinal changes over time were analyzed using mixed-effects models for repeated measures. Results: CMS improved progressively over follow-up, whereas VAS pain scores decreased significantly over time. No cases of device migration or radiographic resorption were observed during follow-up. Adverse events were recorded, but no complication was considered directly attributable to the implanted biomaterial. Conclusions: In this retrospective series, graft augmentation with a porous hydroxyapatite scaffold during locking-plate fixation of proximal humerus fractures with bone void was associated with progressive functional improvement and pain reduction, without evident device-related safety concerns. Owing to the observational design and lack of a control group, these findings should be interpreted as supportive of feasibility and short- to mid-term safety rather than proof of biomaterial efficacy.

Abstract: Background/Objectives: Diagnosing periprosthetic joint infection (PJI) after megaprosthetic reconstruction may be difficult due to altered inflammatory responses, extensive prior surgery, and the limited performance of conventional criteria such as the 2018 ICM score. Synovial calprotectin is a rapid neutrophil-derived biomarker that may improve diagnostic accuracy in this challenging setting. The primary aim of this study was to evaluate the diagnostic performance of synovial calprotectin in detecting periprosthetic infection in patients treated with tumor megaprostheses; secondary aims included comparison with ICM classification, assessment in infection classification-inconclusive cases, and exploratory performance in patients with low CRP. Methods: This prospective study included 20 consecutive megaprosthesis patients evaluated for suspected PJI at ATTIKON University Hospital, Athens, with a minimum follow-up of 1 year after biomarker testing. Synovial calprotectin was measured using a lateral-flow assay (positive ≥ 50 mg/L) and compared with a predefined infection reference standard. ICM final status (0 = aseptic, 1 = inconclusive, 2 = infected) was recorded for all cases. Other synovial biomarkers (α-defensin, leukocyte esterase, synovial D-dimer) were not routinely available. The cohort had a mean age of 52.9 ± 22.5 years, 70% were male, and reconstructions involved the knee (80%), hip (15%), and humerus (5%). Preoperative cultures were positive in 40%, systemic WBC was elevated in 55%, and the median time from last surgery to testing was 1.0 years (IQR 0.46–2.0). Among infected cases, the most common microorganisms were coagulase-negative staphylococci (61.5%) and Staphylococcus aureus (23.1%), with 30.8% demonstrating polymicrobial infection. Results: Thirteen of 20 patients (65%) were classified as infected. Using the ≥ 50 mg/L threshold, synovial calprotectin demonstrated high diagnostic accuracy, and no false positives, yielding a sensitivity of 92.3%, specificity of 100%, PPV of 100%, NPV of 87.5%, LR+ = ∞, and LR− = 0.08. The AUC for continuous values was 1.00. Agreement with the Parvizi final classification was substantial (κ = 0.76), with no directional discordance (McNemar p = 1.00). Among the three ICM-inconclusive cases, calprotectin correctly reclassified two (66.7%). In patients with low CRP (< 10 mg/L), a clinically difficult subgroup, calprotectin maintained strong performance (sensitivity 75%, specificity 100%, NPV 85.7%). Conclusion: Synovial calprotectin demonstrated excellent diagnostic accuracy for PJI in megaprosthesis patients, with high sensitivity, perfect specificity, and substantial agreement with the 2018 ICM criteria. It successfully clarified most ICM-inconclusive cases and remained reliable even in patients with low CRP. These findings support calprotectin as a valuable adjunctive biomarker in the complex diagnostic environment of megaprosthetic reconstruction and justify further validation in larger cohorts.

Abstract: Schatzker type V and VI tibial plateau fractures are complex, high-energy injuries involving significant articular and soft tissue damage. Management remains controversial, with open reduction and internal fixation (ORIF) and Ilizarov external fixation (EF) being primary strategies. This narrative review synthesizes evidence on functional recovery, radiological outcomes, complications, cost-effectiveness, and feasibility in low-resource environments such as rural Pakistan. Multiple studies report comparable long-term functional outcomes for both methods. EF offers advantages in early rehabilitation, reduced rates of deep infection, and cost-effectiveness. Hybrid techniques, combining minimal internal fixation with Ilizarov frames, enhance articular stability while preserving soft tissue integrity. Choice of fixation should consider fracture complexity, soft tissue condition, surgeon experience, and institutional resources. EF emerges as a practical and effective option in low-resource settings, ensuring safe and efficient fracture management.

Abstract: Background/Objectives: Total knee arthroplasty (TKA) is one of the most common surgeries among people over 60. Joint line restoration plays an important role in knee biomechanics, with joint line elevation or depression after TKA being associated with poorer postoperative outcomes, although there is no consensus regarding the threshold at which these variations become clinically relevant. The objectives of this study were to evaluate whether a joint line variation greater than 4 mm after primary TKA affects postoperative outcomes, and to assess the concordance between different radiographic methods used to measure joint line height. Methods: A retrospective study was conducted including patients over 60 who underwent primary TKA for knee osteoarthritis. Joint line height variations were evaluated preoperatively and postoperatively using three radiographic measurements: lateral femoral epicondyle-fibular head (LEFH) distance, adductor tubercle-joint line (ATJL) distance, Blackburne-Peel index. Quality of life was assessed using the Short Form-12 (SF-12) questionnaire, and functionality using the Knee Society Score (KSS). Statistical analysis was carried out using R software. Results: Seventy-nine patients were included. No statistically significant associations were found between joint line displacement and functional outcomes (KSS), quality of life (SF-12), or postoperative complications. Concordance analysis between radiographic methods showed a significant but weak correlation between the LEFH and ATJL measurements (ρ = 0.39; p &lt; 0.001). Conclusions: Joint line displacement after primary TKA was not associated with poorer postoperative outcomes in this cohort. The weak concordance observed between radiographic measurement methods highlights the need for standardized criteria.

Abstract: A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: describe briefly the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article, it must not contain results which are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Abstract: Background/Objectives: Lower-limb total joint arthroplasty (TJA) has been associated with neuroprotective effects, including reduced incidence of dementia and Parkinson disease. Whether these effects are mediated by restored ambulation (specific to lower-limb surgery) or by the systemic anti-inflammatory consequences of arthroplasty (shared by all joint replacement procedures) remains undetermined. We used total shoulder replacement (TSR) as a negative control comparator to interrogate this mechanistic question. Methods: Using the TriNetX US Collaborative Network (114 million patients), we constructed propensity score-matched cohorts comparing TSR patients to total knee arthroplasty (TKA) patients (66,038 per group) following a 730-day lag period. Five pre-specified outcomes were tracked: incident dementia, sarcopenia, Parkinson disease, cataract (active positive control), and elevated C-reactive protein (CRP). Matching balanced 18 demographic and comorbidity covariates. Kaplan–Meier survival analysis with log-rank testing and Cox proportional hazards regression were performed. Results: After propensity matching, TSR and TKA groups were balanced on all covariates (standardized mean differences < 0.10 for all 18 variables). Compared to TKA, TSR patients showed no significant reduction in incident dementia (HR = 1.63, 95% CI: 0.75–3.55, p = 0.217) or sarcopenia (HR = 1.32, 95% CI: 0.72–2.45, p = 0.369). Notably, TSR patients had significantly higher rates of incident Parkinson disease (HR = 1.24, 95% CI: 1.08–1.41, p = 0.002) and more frequent CRP elevation (HR = 1.13, 95% CI: 1.06–1.21, p < 0.001) than TKA patients. The cataract control outcome did not differ between groups (HR = 0.98, 95% CI: 0.89–1.08, p = 0.698). Conclusions: TSR does not replicate the neuroprotective effects associated with lower-limb TJA, and is associated with greater inflammatory burden and higher Parkinson disease incidence than TKA after careful propensity matching. These findings support the hypothesis that restored ambulation—rather than surgical anti-inflammatory effects alone—is the primary mediator of neuroprotection following lower-limb arthroplasty, with important implications for understanding the biology of exercise-dependent neuroprotection.

Abstract: Background/Objectives: Pes planovalgus is one of the most common misalignments in children. In this study the established biomechanical foot orthoses (BMFO) are being compared with a more recent treatment: sensorimotor foot orthoses (SMFO). SMFO are a more recent treatment and aim to correct malalignment by specifically modulating muscle activity rather than relying solely on passive mechanical support, as is the case with BMFO. Methods: Thirty-two children and adolescents aged six to six-teen participated in this study. After randomized group allocation, the rearfoot angle was analyzed by two-dimensional gait analysis in the SMFO-group (n=18) and the BMFO group (n=14) under three conditions: without foot orthoses (baseline), with foot orthoses (immediate) and after four weeks of use. Results: (1) SMFO and BMFO significantly improved the rearfoot angle immediately after application, (2) the achieved correction was maintained over four weeks in both groups, and (3) despite baseline differences, the superior rate of improvement in the SMFO-group resulted in comparable rearfoot alignment between SMFO and BMFO at the four-week follow-up. Conclusions: Based on the results, it can be concluded that SMFO and BMFO are comparable methods for treating pes planovalgus in children and adolescents.

Abstract: Background: Knee osteoarthritis (OA) is traditionally framed as a mechanical “wear-and-tear” disorder. Contemporary evidence supports OA as a whole-joint, immunometabolic and neurosensory disease in which low-grade inflammation modulates tissue homeostasis and pain. In midlife women, the menopause transition coincides with abrupt endocrine changes that plausibly amplify inflammatory tone, alter neuromuscular function, and increase pain sensitisation—often with symptoms disproportionate to imaging. Objective: To synthesise the biological rationale and clinical evidence linking menopausal hormonal decline with OA-relevant inflammatory and neuromuscular mechanisms, and to propose a collaborative orthopaedic model integrating menopause health expertise. Methods: Narrative synthesis of mechanistic, epidemiologic, and clinical trial data on OA inflammation, menopause-related musculoskeletal symptoms, and hormone therapy effects on pain/function and musculoskeletal resilience. Evidence is interpreted with attention to outcome type (symptoms vs structural progression), confounding in observational studies, and timing/continuity considerations. Key Findings: (1) OA pain and disability correlate imperfectly with radiographic severity, consistent with synovitis, adipose-derived mediators, subchondral remodelling, and peripheral/central sensitisation. (2) Perimenopause is associated with increased prevalence of musculoskeletal pain, suggesting a biological inflection period rather than linear age-related decline. (3) Oestrogen decline plausibly shifts immune signalling toward pro-inflammatory pathways (e.g., IL-6/TNF-α/NF-κB), while progesterone and androgen changes may influence sleep quality, recovery capacity, muscle strength, and neuromuscular control—factors strongly linked to knee OA outcomes. (4) Menopausal hormone therapy (when appropriately indicated and supervised) may reduce joint pain in some women and may improve musculoskeletal resilience; however, evidence for disease-modifying structural effects on OA remains limited and confounded. Clinical Implications: Orthopaedic care for midlife women with knee OA should include endocrine-aware phenotyping, screening for menopause-transition symptom clusters, and structured referral pathways to women’s hormonal health specialists. Optimising the systemic biological environment may enhance the durability of rehabilitation, regenerative strategies, and surgical outcomes. Conclusion: Menopause transition biology is a clinically relevant modifier of OA symptom expression and functional decline. Integrating hormonal health expertise into orthopaedic pathways is not scope expansion—it is precision care aligned with modern OA biology.

Abstract:

Proper planning of athletes’ workload during training, especially in preparation for championships or other important competitions, is crucial to avoid serious health complications. Athletes are exposed to significant physical, emotional and psychological stress during training and competitions. The assessment of athletes’ physiological parameters before and after training is important not only for their athletic performance but also for their general health, both during active participation in sport and later in life. The aim of this study was to determine anthropometric characteristics and changes in the retinal vessel diameters, arterial blood pressure, heart rate, cerebrospinal fluid pressure and blood oxygenation in all handball players before and after competitive training and to relate these parameters to the most important modifiable cardiovascular risk factors. Methods. The study took place as part of training sessions in training centers. The test subjects were instructed to abstain from sport and alcohol for 24 hours, not to consume any caffeinated or carbonated drinks for 6 hours and not to eat for at least 2 hours before the measurements. Baseline measurements were carried out on all handball players. The experiments began at 18:00. On arrival, physical activity was assessed, and anthropometric measurements were taken. Participants were then asked to rest in a seated position. After a 10-minute rest, arterial blood pressure, heart ratio and blood oxygenation were measured. The retinal fundus of professional handball players was imaged immediately before and after a competitive match using a non-mydriatic fundus camera. Results. 13 handball players took part in the study. After training, the average weight of the subjects decreased by 0.515 (0.41) kg, systolic blood pressure by 3.85 (15.15) mmHg, diastolic by 4.85 (9.045) mmHg, MAP by 4.565 (7.87) mmHg, CSFP by 0.79 (1.44) mmHg, SpO2by 1.15 (1.625) %. After training, only the average heart rate increased by 38.23 (36.33) bmp. Mean retinal arterial diameter decreased slightly in both eyes, whereas mean venous diameter increased. Conclusions. We found a significant increase in mean heart rate after training, but a slight decrease in the other parameters analyzed: systolic blood pressure, diastolic blood pressure, MAP, CSFP, SpO2 and weight. We would attribute the decrease in these indicators to insufficient recovery of fluid balance. Venous measurements exhibited greater inter-individual variability that arterial measurements, with a non-significant trend toward post-exercise arterial narrowing and venous widening.

Abstract: Background/Objectives: Chronic low back pain (CLBP) affects approximately 20% of the global population. While cannabis-based therapies have shown short-term analgesic potential, long-term evidence remains scarce. This study assessed the four-year efficacy of inhaled cannabis therapy on pain and disability outcomes, while exploring BioWell gas discharge visualization (GDV) parameters as non-invasive biomarkers. Methods: In this prospective observational study (IRB 0634-25-RMC and 807-21-RMC), 241 adults with CLBP (mean age 49.3 ± 14.9 years; 62.2% male) who had failed ≥1 year of conventional therapy initiated inhaled cannabis (predominantly smoking, 91%). Cannabis contained THC (4–22%) and CBD (2–22%), with dosing titrated from 21.5 g/month (Year 1) to 56.7 g/month (Year 4). Primary outcomes—NRS, ODI, BPI severity and interference—and secondary BioWell stress and vitality were assessed annually. Analyses included repeated-measures ANOVA, mixed-effects models, ROC analysis, network analysis, K-means clustering, and survival analysis. Results: Of 241 enrolled patients, 229 (95.0%) completed Year 4 follow-up. NRS decreased from 8.08 ± 1.61 to 2.71 ± 1.46 (p < 0.001), ODI from 55.05 ± 15.90 to 36.82 ± 8.47 (p < 0.001), BPI severity from 7.94 ± 1.71 to 1.11 ± 0.53 (p < 0.001), and BPI interference from 5.84 ± 2.02 to 2.20 ± 1.69 (p < 0.001). BioWell stress discriminated moderate-to-severe pain (NRS > 4) with AUC 0.71 (95% CI 0.65–0.77). Fibromyalgia at baseline predicted discontinuation (HR 1.59, 95% CI 1.18–2.14, p = 0.003). Conclusions: Inhaled cannabis therapy was associated with sustained reductions in pain and disability over four years. BioWell stress showed modest discriminative ability as a biomarker. These findings are associative and require confirmation in controlled trials.

Abstract: Background: Supported standing is commonly prescribed for children and adolescents with cerebral palsy (CP) to support musculoskeletal health and participation. However, objective data on plantar loading under different positioning conditions are limited, particularly in individuals with severe motor impairment (GMFCS IV–V). This study quantified plantar loading as an operational measure of foot weight-bearing during supported standing across combinations of verticalization angle and hip/knee flexion. Methods: Twenty-six children and adolescents with CP (GMFCS IV–V; 6–17 years) were assessed using a standardized back-supported standing system. Plantar loading was measured with two calibrated force plates at six verticalization angles (0°, 30°, 45°, 60°, 75°, 90°) combined with four hip/knee flexion angles (0°, 15°, 30°, 45°). Loading was expressed as percentage of body weight (% BW). Effects were analyzed using repeated-measures analysis of variance. Results: Plantar loading increased progressively with increasing verticalization angles across all hip/knee flexion conditions. Clinically relevant loading levels (>70% BW) were achieved at a verticalization angle of 60° in most flexion conditions. Maximum plantar loading was observed at 90° verticalization combined with 30° hip/knee flexion (96.4% BW). At 90° verticalization, plantar loading remained substantial even with 45° hip/knee flexion (81.4% BW). Increasing hip/knee flexion did not result in a linear reduction in plantar loading; a significant decrease was observed only at 45° flexion. Conclusion: Verticalization angle is the primary determinant of plantar loading during supported standing in children and adolescents with severe CP. Clinically meaningful plantar loading – and thus effective foot weight-bearing – can be achieved at moderate verticalization angles despite hip and knee flexion, supporting flexible positioning strategies.