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Background Currently, there is uncertainty regarding the long-term outcome of medial patellofemoral ligament reconstructions (MPFLr). Our objectives were: (1) to develop a parametric model of the patellofemoral joint (PFJ) enabling us to simulate different surgical techniques for MPFLr; (2) to determine the negative effects on the PFJ associated with each technique, which could be related to long-term deterioration of the PFJ. Methods A finite element model of the PFJ was created based on CT data from 24 knees with chronic lateral patellar instability. Patella contact pressure and maximum MPFL-graft stress at five angles of knee flexion (0, 30, 60, 90 and 120°) were analysed in three types of MPFLr: anatomic, non-anatomic with physiometric behaviour, and non-anatomic with non-physiometric behaviour. Results An increase in patella contact pressure was observed at 0 and 30° of knee flexion after both anatomic and non-anatomic MPFLr with physiometric behaviour. In both reconstructions, the ligament was tense between 0 and 30° of knee flexion, but at 60, 90 and 120°, it had no tension. In the third reconstruction, the behaviour was completely the opposite. Conclusion A parametric model of the PFJ enables us to evaluate different types of MPFLr throughout the full range of motion of the knee, regarding the effect on the patellofemoral contact pressure, as well as the kinematic behaviour of the MPFL-graft and the maximum MPFL-graft stress.

Background This study investigates the functional brain connectivity in patients with anterior knee pain (AKP). While biomechanical models are frequently employed to investigate AKP, it is important to recognize that pain can manifest even in the absence of structural abnormalities. Leveraging the capabilities of functional magnetic resonance imaging (fMRI), this research aims to investigate the brain mechanisms present in AKP patients. Methods Forty-five female subjects (24 AKP patients, 21 controls) underwent resting-state fMRI and T1-weighted structural MRI. Functional brain connectivity patterns were analyzed, focusing on pain network areas, and the influence of catastrophizing thoughts was evaluated. Results Comparing patients and controls, several findings emerged. First, patients with AKP exhibited increased correlation between the right supplementary motor area and cerebellum I, as well as decreased correlation between the right insula and the left rostral prefrontal cortex and superior frontal gyrus. Second, in AKP patients with catastrophizing thoughts, there was increased correlation of the left lateral parietal cortex with two regions of the right cerebellum (II and VII) and the right pallidum, and decreased correlation between the left medial frontal gyrus and the right thalamus. Furthermore, the correlation between these regions showed promising results for discriminating AKP patients from controls, achieving a cross-validation accuracy of 80.5%. Conclusions Resting-state fMRI revealed correlation differences in AKP patients compared to controls and based on catastrophizing thoughts levels. These findings shed light on neural correlates of chronic pain in AKP, suggesting that functional brain connectivity alterations may be linked to pain experience in this population. Relevance statement Etiopathogenesis of pain in anterior knee pain patients might not be limited to the knee, but also to underlying alterations in the central nervous system: cortical changes might lead a perpetuation of pain. Key points • Anterior knee pain patients exhibit distinct functional brain connectivity compared to controls, and among catastrophizing subgroups. • Resting-state fMRI reveals potential for discriminating anterior knee pain patients with 80.5% accuracy. • Functional brain connectivity differences improve understanding of pain pathogenesis and objective anterior knee pain identification. Graphical Abstract

Cervical cancer (CC) remains a significant public health problem. Despite the availability of standard treatment strategies, chemotherapy-resistant tumors persist, highlighting the need to explore new therapeutic approaches or adjuvant strategies. This underscores the importance of preclinical in vivo models. Conventional models, such as murine xenografts, patient-derived xenografts (PDXs), and patient-derived organoids (PDOs), provide valuable biological relevance but are often time-consuming, costly, and resource-intensive. In this context, the chick embryo chorioallantoic membrane (CAM) assay represents a rapid, low-cost, and technically accessible in vivo platform. The CAM is a non-innervated, highly vascularized extraembryonic structure that provides a suitable environment for tumor generation from xenografts. However, despite the broad use of the CAM assay for tumor xenografts, standardized and comparative methodological optimizations specifically addressing technical variables for cervical cancer tumor induction remain limited. Therefore, the aim of this study was to optimize the CAM assay for tumor generation using the HeLa and SiHa cell lines. The generated tumors are vascularized and exhibit Ki-67 expression. The CAM assay is an excellent short-term exploratory model based on developing chicken embryos for studying the developmental biology of cervical tumors, which would accelerate the preclinical investigation of new therapeutic molecules.

Background: A frequently used method to determine the anatomic femoral fixation point in the operating room during medial patellofemoral ligament (MPFL) reconstruction is the radiographic method. However, the ability of this radiological method to establish an anatomic femoral attachment point might not be as accurate as expected. Purpose: (1) To evaluate the accuracy of the radiological method to locate the anatomic femoral fixation point in MPFL reconstruction surgery and (2) to determine the factors influencing the predictability of this method to obtain this objective. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: A total of 100 consecutive 3-dimensional computed tomography (3D CT) knee examinations were performed at 0° of extension in 87 patients treated for chronic lateral patellar instability. For each knee, 2 virtual 7 mm–diameter femoral tunnels were created: 1 using the adductor tubercle as a landmark (anatomic tunnel) and the other according to the radiological method described by Schöttle et al (radiographic tunnel). We measured the percentage of overlap between both tunnels. Moreover, of the 100 included knees, 10 were randomly selected for a variability study. Results: Considering an overlap area greater than 50% as reasonable, the radiographic method achieved this in only 38 of the 100 knees. Intrarater and interrater reliability were excellent. There was a trend for female patients with severe trochlear dysplasia to have less overlap. This model accounted for 64.2% of the initial variability in the data. Conclusion: An exact anatomic femoral tunnel placement could not be achieved with the radiographic method. Radiography provided only an approximation and should not be the sole basis for the femoral attachment location. Moreover, in female patients with severe trochlear dysplasia, the radiographic method was less accurate in determining the anatomic femoral fixation point, although differences were not statistically significant.

Despite the extensive information available on the different genetic, epigenetic, and molecular features of cardiogenesis, the origin of congenital heart defects remains unknown. Most genetic and molecular studies have been conducted outside the context of the progressive anatomical and histological changes in the embryonic heart, which is one of the reasons for the limited knowledge of the origins of congenital heart diseases. We integrated the findings of descriptive studies on human embryos and experimental studies on chick, rat, and mouse embryos. This research is based on the new dynamic concept of heart development and the existence of two heart fields. The first field corresponds to the straight heart tube, into which splanchnic mesodermal cells from the second heart field are gradually recruited. The overall aim was to create a new vision for the analysis, diagnosis, and regionalized classification of congenital defects of the heart and great arteries. In addition to highlighting the importance of genetic factors in the development of congenital heart disease, this study provides new insights into the composition of the straight heart tube, the processes of twisting and folding, and the fate of the conus in the development of the right ventricle and its outflow tract. The new vision, based on in vivo labeling and cell tracking and enhanced by models such as gastruloids and organoids, has contributed to a better understanding of important errors in cardiac morphogenesis, which may lead to several congenital heart diseases.

Hyperglycemia during gestation can disrupt fetal heart development and increase postnatal cardiovascular disease risk. It is therefore imperative to identify early biomarkers of hyperglycemia during gestation-induced fetal heart damage and elucidate the underlying molecular pathomechanisms. Clinical investigations of diabetic adults with heart dysfunction and transgenic mouse studies have revealed that overexpression or increased expression of TNNI3K, a heart-specific kinase that binds troponin cardiac I, may contribute to abnormal cardiac remodeling, ventricular hypertrophy, and heart failure. Optimal heart function also depends on the precise organization of contractile and excitable tissues conferred by intercellular occlusive, adherent, and communicating junctions. The current study evaluated changes in embryonic heart development and the expression levels of sarcomeric proteins (troponin I, desmin, and TNNI3K), junctional proteins, glucose transporter-1, and Ki-67 under fetal hyperglycemia. Stage 22HH Gallus domesticus embryos were randomly divided into two groups: a hyperglycemia (HG) group, in which individual embryos were injected with 30 mmol/L glucose solution every 24 h for 10 days, and a no-treatment (NT) control group, in which individual embryos were injected with physiological saline every 24 h for 10 days (stage 36HH). Embryonic blood glucose, height, and weight, as well as heart size, were measured periodically during treatment, followed by histopathological analysis and estimation of sarcomeric and junctional protein expression by western blotting and immunostaining. Hyperglycemic embryos demonstrated delayed heart maturation, with histopathological analysis revealing reduced left and right ventricular wall thickness (−39% and −35% vs. NT). Immunoexpression levels of TNNI3K and troponin 1 increased (by 37% and 39%, respectively), and desmin immunofluorescence reduced (by 23%). Embryo-fetal hyperglycemia may trigger an increase in the expression levels of TNNI3K and troponin I, as well as dysfunction of occlusive and adherent junctions, ultimately inducing abnormal cardiac remodeling.

Purpose This study’s purpose was to investigate how an ideal anatomic femoral attachment affects the dynamic length change pattern of a virtual medial patellofemoral ligament (MPFL) from an extended to a highly flexed knee position; to determine the relative length and length change pattern of a surgically reconstructed MPFL; and to correlate femoral attachment positioning, length change pattern, and relative graft length with the clinical outcome. Methods Twenty-four knees with isolated nonanatomic MPFL reconstruction were analysed by three-dimensional computed tomography at 0°, 30°, 60°, 90°, and 120° of knee flexion. The lengths of the MPFL graft and a virtual anatomic MPFL were measured. The pattern of length change was considered isometric if the length distance changed <5 mm through the entire dynamic range of motion. Results Knee flexion significantly affected the path lengths between the femoral and patellar attachments. The length of the anatomic virtual MPFL decreased significantly from 60° to 120°. Its maximal length was 56.4 ± 6.8 mm at 30°. It was isometric between 0° and 60°. The length of the nonanatomic MPFL with a satisfactory clinical result decreased during flexion from 0° to 120°. Its maximal length was 51.6 ± 4.6 mm at 0° of knee flexion. The lengths measured at 0° and 30° were isometric and statistically greater than the lengths measured at higher flexion degrees. The failed nonanatomic MPFL reconstructions were isometric throughout the dynamic range, being significantly shorter (27.1 ± 13.3 %) than anatomic ligaments. Conclusion The femoral attachment point significantly influences the relative length and the dynamic length change of the grafts during knee flexion–extension and graft isometry. Moreover, it influences the long-term outcome of the MPFL reconstructive surgery. A nonanatomic femoral fixation point should not be considered the cause of persistent pain and instability after MPFL reconstruction in all cases. Level of evidence III.

Purpose To correlate the location of the medial patellofemoral ligament femoral fixation site in knees suffering a chronic lateral patellar instability, by using radiographic references and by using the most important anatomic reference point (i.e. the adductor tubercle) identified by means of 3-dimensional (3D) surface reconstructions by computed tomography (CT) imaging. Methods Thirty consecutive knee 3D-CT examinations at 0º of knee extension were obtained from patients (20 females, 10 males; median age of 23.5 years; range, 14–48 years) treated for chronic lateral patellar instability with at least two documented patellar dislocations. For each knee, three virtual 7-mm-diameter femoral tunnels were created. One of the tunnels used an anatomic fixation landmark (anatomic fixation), while the other two used established radiologic methods. We calculated the percentage of the anatomic tunnel covered by the tunnel created according to the method described by Schoettle, and the percentage of the anatomic tunnel covered by the tunnel created according to the method described by Stephen. These percentages were compared using paired Student’s t test. Results The percentage of anatomic tunnel area covered by the femoral tunnel created using Schoettle’s method was 36.7 ± 25.2 %. When using Stephen’s method, the percentage of overlap with the anatomic femoral tunnel was 25.5 ± 21.5 %. There were no significant differences between the two radiographic methods (n.s.). Conclusion None of the standard radiographic methods allowed a precise anatomic femoral placement. Conventional radiographic identification of the femoral graft placement site is only an approximation and should not be the sole basis for femoral attachment location. Level of evidence IV

Introduction Increased femoral anteversion (FAV) can have many clinical manifestations, including anterior knee pain (AKP). To our knowledge, no studies have measured the location of FAV in a cohort of female AKP patients. The objective of this research is to determine whether the increased FAV in AKP females originates above the lesser trochanter, below the lesser trochanter or at both levels. Materials and methods Thrity-seven consecutive AKP female patients ( n  = 66 femurs) were recruited prospectively. There were 17 patients ( n  = 26 femurs; mean age of 28 years) in whom the suspicion for the increased FAV of the femur was based on the clinical examination (pathological group—PG). The control group (CG) consisted of 20 patients ( n  = 40 femurs; mean age of 29 years) in whom there was no increased FAV from the clinical standpoint. All of them underwent a torsional computed tomography of the lower limbs. FAV was measured according to Murphy´s method. A segmental analysis of FAV was performed using the lesser trochanter as a landmark. Results Significant differences in the total FAV (18.7 ± 5.52 vs. 42.46 ± 6.33; p  < 0.001), the neck version (54.88 ± 9.64 vs. 64.27 ± 11.25; p  = 0.0006) and the diaphysis version (− 36.17 ± 8.93 vs. − 21.81 ± 11.73; p  < 0.001) were observed between the CG and the PG. The difference in the diaphyseal angle between CG and PG accounts for 60% of the total difference between healthy and pathological groups, while the difference between both groups in the angle of the neck accounts for 40%. Conclusion In chronic AKP female patients with increased FAV, the two segments of the femur contribute to the total FAV, with a different pattern among patients and controls, being the compensation mechanism of the diaphysis much lower in the pathological femurs than in the controls.

Sarcomas are rare malignant tumors of mesenchymal origin with a high misdiagnosis rate due to their heterogeneity and low incidence. Conventional diagnostic techniques, such as Fluorescence In Situ Hybridization (FISH) and Next-Generation Sequencing (NGS), have limitations in detecting structural variations (SVs), copy number variations (CNVs), and predicting clinical behavior. Optical genome mapping (OGM) provides high-resolution genome-wide analysis, improving sarcoma diagnosis and prognosis assessment. This study analyzed 53 sarcoma samples using OGM. Ultra-high molecular weight (UHMW) DNA was extracted from core and resection biopsies, and data acquisition was performed with the Bionano Saphyr platform. Bioinformatic pipelines identified structural variations, comparing them with known alterations for each sarcoma subtype. OGM successfully analyzed 62.3% of samples. Diagnostic-defining alterations were found in 95.2% of cases, refining diagnoses and revealing novel oncogenic and tumor suppressor gene alterations. The challenges included DNA extraction and quality issues from some tissue samples. Despite these limitations, OGM proved to be a powerful diagnostic and predictive tool for bone and soft tissue sarcomas, surpassing conventional methods in resolution and scope, enhancing the understanding of sarcoma genetics, and enabling better patient stratification and personalized therapies.