Search Results (831)

The choroid plexus (CP) has traditionally been regarded as a cerebrospinal fluid-producing structure; however, increasing evidence indicates that it functions as a dynamic regulatory interface involved in immune surveillance, metabolic homeostasis, and brain clearance. Neuroimaging studies consistently report CP enlargement across aging and diverse neurological and neuropsychiatric disorders, yet the underlying cellular mechanisms remain poorly integrated. In this review, we synthesize morphological, molecular, and imaging evidence to propose a sequential degenerative model of the CP epithelium. This model comprises: (1) regulated epithelial cell loss via apical extrusion, (2) compensatory hypertrophy of residual cells, (3) mitochondrial remodeling with oncocytic-like change, and (4) progressive blood–cerebrospinal fluid barrier dysfunction. At the molecular level, alterations in epithelial adhesion systems—particularly SPINT1-mediated protease regulation and E-cadherin–based adherens junction stability—may initiate epithelial instability. Hypertrophic epithelial cells exhibit increased mitochondrial burden, reflected by Tom20 expression, which may initially support metabolic adaptation but ultimately contribute to oxidative stress and functional decline. At the macroscopic level, the cumulative effects of cell loss, hypertrophy, and mitochondrial remodeling likely underlie CP enlargement detectable by magnetic resonance imaging. This framework positions CP enlargement as an imaging-visible manifestation of epithelial stress and provides a structural–molecular basis for interpreting CP alterations in brain aging and neurodegenerative disorders. Full article

Major orthopedic limb surgery is often accompanied by external coaptation; the combined effect of these interventions can lead to muscle atrophy and functional impairment. Large animal models, including goats, are commonly used to study orthopedic interventions, yet longitudinal data on muscle changes after such interventions are limited. This study quantified gastrocnemius muscle adaptations in adult Boer-cross goats undergoing a clinically representative unilateral tibial segmental ostectomy and external coaptation protocol. Muscles on the operated side exhibited statistically significant decreases in mass, length, optimal fiber length, and CSA, and increases in nucleus density compared to muscles on the contralateral, non-operated side (p < 0.05). Although muscle properties showed partial recovery over time, mass and CSA remained 20–30% lower on the operated side than on the non-operated side at 12 months post-surgery despite cast removal at about 2 months post-surgery. Muscle CSA was positively correlated with bone mineral density and peak vertical ground reaction forces measured during the in vivo study. The extent of muscle recovery in the goat model was less than that observed for other mammalian models of hindlimb remobilization. More research is needed to understand the complex interaction between surgery, external coaptation, and muscle properties in the goat model. Full article

Lumbar intervertebral disc herniation is a common cause of low back and radicular leg pain, traditionally managed with a combination of conservative therapies and, when indicated, surgical discectomy. An intriguing phenomenon observed in many patients is the spontaneous resorption of herniated disc material over time, often correlating with significant symptom improvement. This article is presented as a narrative review synthesizing experimental, imaging, and clinical literature relevant to spontaneous disc resorption and its implications for clinical decision-making. This paper provides a comprehensive overview of spontaneous disc herniation resorption, exploring the underlying pathophysiological mechanisms and the factors that predict which herniations are likely to regress without surgery. Key mechanisms include inflammatory-mediated degradation of disc fragments, neovascularization with macrophage infiltration and phagocytosis of extruded nucleus pulposus tissue, and biological processes such as enzymatic matrix breakdown and cellular apoptosis that collectively lead to shrinkage of the herniated mass. Patient and disc characteristics that favour spontaneous resorption are identified, such as younger age, extruded or sequestered fragment type, larger initial herniation size, and robust inflammatory response on imaging, whereas certain chronic degenerative changes may reduce this likelihood. We also review current clinical guidelines and expert recommendations on when surgical intervention is warranted versus when conservative management and observation are appropriate. Understanding the probability of natural disc fragment resolution is critical in guiding treatment decisions. In the absence of severe neurological deficits or intractable pain, a period of non-operative management can often be pursued safely, given that the majority of patients experience substantial relief within a few months as discs regress. Conversely, timely surgery is advised for those with neurological compromise or refractory symptoms. By synthesizing the latest evidence on spontaneous disc herniation resorption and its predictors, this review aims to assist neurosurgeons and spine specialists in optimizing patient selection for conservative care and identifying the proper timing for surgical intervention to achieve the best clinical outcomes. Given the narrative design, conclusions are based on synthesis of heterogeneous evidence rather than formal comparative analysis. Full article

Background and Objectives: Intertrochanteric hip fractures (ITFs) are common in older adults and frequently coexist with knee osteoarthritis (KOA). Although both conditions share key biomechanical risk factors, the specific relationship between KOA severity and ITF stability has not been well defined. Recent evidence suggests that degenerative knee changes may alter lower-limb load distribution and increase susceptibility to unstable fracture patterns. This study evaluated whether KOA severity, graded using the Kellgren–Lawrence (KL) system, is associated with ITF stability according to the 2018 AO/OTA classification. Materials and Methods: A retrospective observational study was conducted on 138 patients with IHFs treated between 2018 and 2023. KOA severity was assessed using KL grades I–IV on non-weight-bearing anteroposterior knee radiographs. Lateral wall thickness (LWT) was measured using the Hsu method, with <20.5 mm indicating fracture instability. Statistical analyses included correlation, linear regression, logistic regression, and receiver operating characteristic (ROC) curve analysis to examine the association between KL grade and fracture stability. Results: Among 138 patients, 98 (71.0%) had unstable ITFs. Advanced KOA was significantly more common in the unstable group (KL III 45.9%, KL IV 48.0%; p < 0.001). KL grade showed a significant inverse correlation with LWT (Pearson’s r = −0.394, p < 0.001). Each one-grade increase in KL severity was associated with a 3.8 mm reduction in LWT (p < 0.001). In multivariable logistic regression, KL grade remained an independent predictor of fracture instability (adjusted OR = 4.9, 95% CI: 2.8–8.8, p < 0.001), whereas age and comorbidities were not significant. ROC analysis demonstrated good discriminatory power (AUC = 0.79). A KL ≥ III threshold achieved 95% sensitivity and 56% specificity for predicting instability. Conclusions: Higher KOA severity is strongly associated with unstable ITF patterns. KL grade independently predicts instability and may serve as a simple, accessible radiographic indicator of biomechanical vulnerability and fracture risk in older adults. Incorporating KOA severity into the preoperative evaluation may enhance risk stratification, guide selection of fixation strategy, and support individualized rehabilitation planning. Full article

Background/Objectives: Atlantoaxial posterior fusion has unique characteristics, and it is anticipated that adjacent segment degenerative changes following fusion surgery may present distinctive findings. This study aims to analyze the risk factors for degenerative changes in subaxial levels following the increasingly common atlantoaxial posterior fusion procedure. Methods: A total of 58 patients (19 males, 39 females) who had neutral, flexion, and extension plain lateral radiographs taken and a follow-up record of approximately two years post-surgery were included in the final study cohort. The study analyzed surgical methods, patient demographics, hospitalization-related factors, visual analog scale (VAS) for neck pain, and radiologic parameters. Patients were classified into the radiologic subaxial pathology (RSP) group (n = 34) and the non-RSP group (n = 24) using several radiologic indicators of spinal instability or arthritic changes, and the risk factors for RSP were analyzed. Results: The RSP group showed a significantly higher proportion of females and prevalence of rheumatoid arthritis (RA). At 3 months postoperatively, the C1-7 sagittal vertical axis (SVA) was significantly lower in the RSP group. Multivariate regression analysis using significant variables (p < 0.05) such as sex, RA and 3-month C1-7 SVA showed that RA and 3-month C1-7 SVA were significantly associated with RSP. Among radiologic parameters related to surgery, multivariate analysis identified 3-month C1-7 SVA as the sole risk factor for RSP. To explore its correlation with other radiologic parameters at 3 months postoperatively, linear logistic regression analysis was conducted. Significant positive correlations were observed with the C1-2 Cobb angle. Conclusions: This study identified RA and C1-7 SVA as the most significant risk factors for RSP in atlantoaixal posterior fusion. Full article

Background and Objectives: The biological state of anterior cruciate ligament (ACL) remnant tissue may influence postoperative healing, yet the molecular changes associated with injury chronicity remain poorly defined. This study evaluated MMP-13 and TGF-β1 expression in human ACL remnants to characterize their regenerative or fibrotic potential. Materials and Methods: ACL remnants from acute (<3 months) and chronic (>6 months) injuries were analyzed using histology, immunohistochemistry, and QuPath-based digital quantification. Clinical outcomes were correlated with marker expression. Protein–protein interaction and KEGG enrichment analyses were performed to identify extracellular matrix (ECM)-related pathways associated with MMP-13 and TGF-β1. Results: Chronic ACL remnants exhibited disorganized ECM structure with significantly higher MMP-13 and TGF-β1 expression across all digital metrics, including DAB-positive area, cell density, optical density, and H-score (p < 0.01). Higher expression of both markers correlated with lower IKDC and Lysholm scores and greater residual pivot-shift positivity. Bioinformatic analysis identified 39 shared proteins enriched in ECM-receptor interaction, TGF-β signaling, and fibrosis-related pathways, aligning with the degenerative phenotype observed in chronic tissue. Conclusions: ACL remnant biology evolves from a reparative profile in acute injuries to a fibrotic, matrix-degradative state in chronic injuries. MMP-13 and TGF-β1 serve as indicators of remnant quality and may help guide timing of surgery and future biologic strategies aimed at improving ACL reconstruction outcomes. Full article

Background: Children’s behavior and lifestyle are changing rapidly, potentially exceeding the capacity of physiological adaptation. Contemporary lifestyles may negatively affect spinal development and contribute to dysfunction and premature degeneration. Despite the increasing prevalence of postural changes, cervical spine disorders in adolescents remain under-researched. Methods: This narrative review is based on a comprehensive search of PubMed/MEDLINE and Scopus. The search strategy included a broad review of anatomical and biomechanical literature from the past 25 years and a focused review of studies from the last 15 years to reflect recent generational changes. Results: The immature spine has distinct structural and biomechanical characteristics that increase susceptibility to maladaptive responses to unbalanced forces. High screen time is associated with sedentary behavior and increased consumption of ultra-processed foods, which may affect metabolic health and musculoskeletal development. Childhood and adolescent obesity are increasingly prevalent and may influence spinal development, including through myosteatosis. Data on the consequences of cervical and lumbar lordosis loss in adolescents remain limited. Although degenerative spinal disorders are well recognized in adults, their identification in younger populations may be inadequate. Conclusions: Modern lifestyle factors pose a growing risk to children’s spinal health through complex interactions among behavioral, metabolic, and biomechanical mechanisms. The developing spine’s vulnerability and the coexistence of multiple, interrelated risk factors support the need for integrated preventive strategies rather than single-factor interventions. Future studies should focus on models capturing these interactions and their long-term consequences. Full article

Osteoarthritis is the most common musculoskeletal disorder. It primarily affects people in their mid-40s and older. As the disease progresses, degenerative changes occur in the synovial membrane, subchondral bone, and cartilage. Ultimately, the entire joint and its surrounding tissues become structurally and functionally impaired. Several sets of biochemical markers have been proposed to enable timely diagnosis and anticipate disease progression. However, only a few of these markers are routinely used to evaluate disease activity in subgroups. We conducted a cross-sectional, single-center cohort study of 72 patients with knee osteoarthritis. Diagnoses were established based on clinical data and radiological findings. We examined two Wnt/β-catenin signaling inhibitors, serum DKK-1 and sclerostin, and two bone/cartilage metabolic regulatory factors, RANKL and OPG, correlating these with disease activity and pain scores (WOMAC, VAS, and KOFUS), radiographic stage, inflammatory molecules and indices, and bone mineral density. DKK-1 levels were higher in the intensive pain group (VAS > 5) and positively correlated with the KOFUS throughout the study. This correlation was stronger in individuals with a BMI < 30. Serum DKK-1 levels were higher in patients with lower bone mineral density. No significant modifications in SOST, RANKL, or OPG levels were found in any of the above settings. In our patient cohort with mild-to-moderate knee osteoarthritis (OA), sclerostin, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were not related to pain or disease activity. In contrast, DKK-1 was an indicator of pain and low-grade flare-ups. Furthermore, DKK-1 was associated with the KOFUS and impaired bone turnover in non-obese subgroups. Confirming these relationships in larger groups of patients would contribute to more efficient use of DKK-1 in disease stratification algorithms. Full article

Background and Objectives: Understanding the structural differences in the sacroiliac joint (SIJ) is essential for distinguishing inflammatory from degenerative disorders. This study aimed to evaluate disease-related morphological patterns and morphometric characteristics of the sacroiliac joint. Additionally, machine learning models were applied to classify inflammatory, degenerative, and control groups based on the morphological and morphometric characteristics of the sacroiliac joint. Materials and Methods: This retrospective study included Magnetic Resonance Imaging (MRI) images of 209 individuals (a total of 418 sacroiliac joints) between the ages of 18 and 75. Participants’ age, sex, disease-related sacroiliac joint morphological features (joint surface type), erosion, sclerosis and inflammation in the joint were determined. Right/left joint space and right/left joint length were measured. According to these anatomical features, machine learning models and a deep neural network were used to classify joints as control, inflammatory, or degenerative. Stratified 5-fold cross-validation was used. Results were reported as mean ± SD with macro averaged precision, recall, and F1-score. Results: The degenerative group was significantly higher than the other groups in terms of mean age (p = 0.001). Both right and left sacroiliac joint spaces were significantly narrower in the inflammatory and degenerative groups than in controls (right SIJ space: p = 0.002; left SIJ space: p = 0.001). Erosion was significantly more frequent in pathological groups (p = 0.001). Although the iliosacral complex was the most common joint type in all groups, no significant difference was observed between the disease groups (right, p = 0.852; left, p = 0.935). In classification, SVM (RBF) and XGBoost achieved the highest accuracy (both: 0.9518 ± 0.0380 and 0.9518 ± 0.0436, respectively) and macro-F1 (0.9509 ± 0.0387 and 0.9506 ± 0.0443). Conclusions: Disease-related morphological and morphometric changes in the sacroiliac joint can be reliably assessed with MRI. These features can then be used in machine learning models to differentiate between inflammatory and degenerative joint disorders. Carefully examining these anatomical features plays a key role in reaching an accurate diagnosis. Machine learning supports this process by helping to interpret the findings in a more consistent and objective way. Full article

Background: The aim of this study was to comprehensively investigate the potential degenerative effects of periodontitis severity on retinal and choroidal structures in patients with different types of diabetic retinopathy (DR). Materials and Methods: The study’s Clinical Trials Registration Number is NCT07137013. A total of 100 participants (56 females and 44 males), each group consisting of 20 individuals, were allocated into five groups: systemically healthy controls (G1), diabetic patients without DR (G2: DM+ DR−), non-proliferative DR without diabetic macular edema (G3: NPDR DME−), non-proliferative DR with diabetic macular edema (G4: NPDR DME+), and proliferative DR (G5: PDR). Ocular examinations were performed using optical coherence tomography (OCT) and OCT angiography (OCTA). Retinal layer thicknesses, choroid-sclera interface (CSI), ganglion cell layer (GCL), retinal nerve fiber layer (RNFL), and peripapillary CSI were assessed by OCT, whereas superficial and deep retinal vessel densities and the foveal avascular zone (FAZ) were evaluated by OCTA. Clinical periodontal status was assessed using plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL). Results: In the G3 and G5 groups, the presence of stage III–IV periodontitis was associated with a marked increase in retinal layer thickness. GCL + Inner Plexiform Layer (GCL+) thickness was significantly reduced in individuals with stage III–IV periodontitis in almost all regions of the G5 group, except for the 3 mm nasal and inferior areas. Peripapillary CSI values showed a significant decrease with increasing periodontitis severity. RNFL thickness was significantly reduced in individuals with stage III–IV periodontitis, particularly in the G5 group. OCTA analyses demonstrated significant reductions in superficial and deep retinal vessel densities in several regions in the presence of stage III–IV periodontitis. Moreover, FAZ areas were significantly enlarged in individuals with stage III–IV periodontitis in the G2 and G5 groups. Conclusions: Periodontal inflammation, particularly in advanced periodontitis (stage III–IV), induces degenerative changes in the retinal microvasculature and neural tissues. Increasing periodontitis severity may represent a potential provoking factor in the pathogenesis of DR. Full article

Aging is a progressive degenerative process characterized by the depletion of tissue stem cell reserves, organ atrophy, sarcopenia, and an impaired capacity to respond to physiological stress and injury. These changes lead to a reduction in both overall life expectancy and disease-free lifespan. Since aging represents a major risk factor for numerous diseases, including neurodegenerative, cardiovascular, and metabolic disorders, recent research has increasingly focused on identifying effective intervention strategies to promote “healthy aging” by slowing down the aging process as much as possible. At the molecular level, multiple factors contribute to cellular aging and, consequently, to the onset of senescence. These include mitochondrial dysfunction, defective DNA repair mechanisms, epigenetic reprogramming, and chronic low-grade inflammation. Among the mechanisms driving cellular senescence, oxidative stress is recognized as a key contributor to the loss of replicative capacity. When reactive oxygen species (ROS) levels exceed a critical threshold, they can damage essential macromolecules, including DNA. Therefore, ROS and oxidative stress represent crucial therapeutic targets to be considered in strategies aimed at counteracting cellular senescence. Based on these causal factors, several strategies have been identified that target modifiable lifestyle determinants, with a primary focus on nutrition and nutraceutical interventions. In this context, the present review aims to critically analyze scientific evidence regarding nutritional approaches designed to slow down the aging process, including their effects at the molecular level. Specifically, these strategies aim to reduce inflammation, preserve mitochondrial function to modulate ROS production, and protect macromolecules from oxidative stress. Full article

This study presents a finite element (FE) investigation of intervertebral disc (IVD) degeneration in the human lumbar spine (L1–L3 segment). The model, based on CT-derived geometry and isotropic hyperelastic representation of disc tissues, incorporates controlled simplifications, detailed in the limitations section. Degenerative changes were parametrically simulated across healthy, mild, moderate, and severe stages by reducing disc height (up to 60%), nucleus pulposus volume (up to 70%), and adjusting tissue stiffness to reflect dehydration and fibrosis. Displacement-controlled compressive loading was applied to assess von Mises stress distributions, reaction forces, and load transfer mechanisms. Results indicate significant load redistribution: annulus fibrosus stresses increased by up to 175% in severe degeneration, while nucleus pulposus stresses decreased by ~70%, indicating a diminished compressive load-bearing contribution of the nucleus. Model predictions were validated against cadaveric and in vivo data, confirming trends in intradiscal pressure (IDP) reductions (40–70%) and stress elevations. The parametric framework elucidates interactions between geometric and material changes, providing clinicians with insights into degeneration progression and guiding biomedical engineers in implant design and interventions. Full article

Spinal fusion remains a common surgical treatment for degenerative cervical spine pathology. By eliminating segmental motion, fusion alters spinal biomechanics and redistributes mechanical loads to adjacent levels. These changes contribute to adjacent segment degeneration (ASD). Motion-preserving spinal implants have been developed to address these limitations. Cervical disc arthroplasty (CDA) is the most widely used example. Such devices aim to maintain physiologic kinematics while preserving segmental stability. Their biomechanical behavior varies with implant design, material properties, and constraint characteristics. Previous research does not holistically compare fusion with motion-preserving treatments on the spine, resulting in an incomplete understanding of when motion-preserving devices should be considered in treatment over fusion constructs and which specific motion-preserving implants are most appropriate. This narrative review synthesizes experimental, computational, and clinical studies comparing rigid fusion constructs to motion-preserving technologies in the cervical spine. Emphasis is placed on segmental range of motion, load transmission, intradiscal pressure, facet joint forces, and adjacent-segment mechanics. By comparing effectiveness across motion-preserving treatments, alongside their effectiveness to fusion constructs, we found that CDA more closely preserves near-physiologic motion compared to fusion. Taken together, this review underscores the importance of biomechanics-informed implant design for guiding future innovation in spinal implant technologies. Full article

Background: Anterior Cruciate Ligament (ACL) tears are increasingly frequent among adolescents and are often accompanied by meniscal and chondral injuries that may compromise long-term outcomes. While risk factors are well documented in adults, they remain less well defined in younger patients, who present unique anatomical and activity-related characteristics. Understanding these associations is essential for optimizing surgical timing and outcomes in this age group. The purpose of this study was to determine the rate of concomitant intra-articular injuries in adolescents undergoing ACL reconstruction and to identify associated risk factors. Methods: We retrospectively reviewed 186 adolescents (12–18 years) who underwent primary ACL reconstruction using a bone–patellar tendon–bone (BPTB) autograft between 1999 and 2020. Demographic, anthropometric, and intraoperative findings on meniscal and chondral lesions were collected. Multivariable logistic regression models were used to identify factors associated with concomitant injuries. Results: Concomitant intra-articular lesions were found in 108 of 186 patients (58.1%). Meniscal tears were the most common finding, involving the lateral meniscus in 27.4%, the medial meniscus in 18.8%, and both menisci in 11.9%. The posterior horn was the most common tear location, and longitudinal and bucket handle patterns predominated. Older age was associated with any concomitant lesion (p = 0.028), and surgical delay (p = 0.021) was associated with a higher likelihood of medial meniscal tears. Sex and BMI were not significantly associated. Conclusions: Concomitant injuries are common in adolescents undergoing ACL reconstruction. Older age and delayed surgery were associated with a higher likelihood of meniscal damage, emphasizing the need for early diagnosis and timely surgical management as potentially relevant to limiting long-term degenerative changes in young athletes. Level of evidence: Level III, retrospective study. Full article

Background/Objectives: To date, few studies have reported the use of neurophysiological testing to assess the long-term progression of functional changes in median and ulnar nerve conduction in children and adolescents with mucopolysaccharidosis (MPS). This case series study aimed to perform an electroneurographic (ENG) assessment of the median and ulnar nerves in three young patients with MPS treated with enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) over a five-year observation period. Methods: Bilateral electroneurography of the motor and sensory fibers in the median and ulnar nerves, recording compound muscle action potential (CMAP) and sensory nerve action potential (SNAP), was performed twice in 5-, 7-, and 19-year-old males at two time points: before and five years after the application of ERT and HSCT. Results: In three MPS patients with Hurler or Hunter syndrome, ENG studies similarly demonstrated decreased amplitudes and prolonged distal latencies in their CMAP recordings, confirming the bilateral progression of axonal degeneration and demyelinating changes in the distal parts of the median nerves. The SNAP recordings revealed more severe degenerative processes of similar types in the sensory fibers of the median nerves. Nerve conduction studies in the ulnar nerve fibers bilaterally revealed analogous pathologies, but with a lesser degree of progression. Conclusions: This study confirms the progression of axonal degeneration and demyelinating changes in the distal parts of the median nerves, which were associated with decreased amplitudes and prolonged distal latencies in the CMAP recordings of the MPS patients. More expressed degeneration processes of a similar type were found in the sensory fibers of the median nerves. Ulnar nerve pathologies of neural conduction are less advanced in patients with Hurler and Hunter syndromes. It seems advisable to implement neurophysiological diagnostics as soon as possible to specify surgical or conservative therapy, which is crucial for maintaining hand function in the case of progressive peripheral neuropathies in patients with MPS. The timing of the treatment and the patient’s age may be factors influencing the effectiveness of treatment. Full article