Search Results (2,622)

Digital twins (DTs) are dynamic, virtual representations of individual patients that could support predictive diagnostics and personalized therapeutic optimization. Their development depends on patient-level data from real-world data (RWD) sources and electronic medical record (EMR) data, but major barriers in data-stewardship, interoperability, provenance, and governance persist. This review examines critical bottlenecks within the current healthcare ecosystem, with particular attention to fragmented EMRs, limited longitudinal data continuity, and missing, incomplete, or inaccurate information. We address data availability, stewardship, and provenance rather than model construction itself. We also explore ethical imperatives of mitigating representational bias, where over-representation of European ancestry amplifies existing health inequalities. We evaluate blockchain technology as a decentralized trust anchor to ensure provenance, automate consent, and incentivize longitudinal data stewardship. In parallel, we acknowledge that clinically useful DTs also depend on substantial advances in model specification, calibration, and validation, especially for biologically complex diseases. By synthesizing computational, regulatory, and ethical challenges, we provide a roadmap for developing robust, equitable, and interoperable ecosystems for precision medicine. Full article

Background and Objectives: Traumatic brain injury (TBI) is one of the leading causes of long-term disability among adults, with consequences for balance, postural stability, and quality of life. Addressing balance disorders in TBI patients requires a tailored and continuous care approach; the existing literature underlines a general framework for physiotherapy treatments, but no clear profile of technique, dosage and timing of intervention emerges. The present scoping review, therefore, aimed at mapping physiotherapy approaches to balance in TBI population, highlighting their potential effects and role through care pathways. Materials and Methods: A scoping review was conducted, according to PRISMA Extension for Scoping Reviews, with the aim of mapping physical therapy approaches to treat balance disorders in adult patients with TBI. A specific search string for each database was formulated through a PCC (Population, Concept, Context) framework. The search, limited to articles in English and published between 2015 and 2025, was conducted across five databases (PubMed, PEDro, Scopus, Embase, and Web of Science), including experimental studies, observational designs, and `case reports. Results: From the initial selection of 1052 records, six studies were included: five randomized controlled trials and a case report, published between 2016 and 2022. Results presented high heterogeneity of physiotherapy programs and outcome variations; interventions identified included virtual reality, video game therapy, adapted physical exercise, ballistic training, rapid-resistance elliptical training, and rhythmic auditory stimulation. These studies reported variable improvements in balance and mobility, not even with significant inter-group differences. Conclusions: Several techniques showed preliminary evidence in pre/post improvements of balance for TBI patients, including strength exercise, aerobic training and virtual-mediated approaches such as video game therapy and virtual reality. Rhythmic auditory stimulation has unclear effects. Future studies are needed to define the impact of each balance recovery strategy according to the baseline characteristics of the patient. Full article

Background: Exercise rehabilitation (ER) has become an important treatment regimen during the recovery phase of acute ischemic stroke (AIS). Optimal exercise prescriptions for post-stroke motor recovery remain controversial. Methods: PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched through November 2025. The Cochrane risk-of-bias (RoB 1) assessment tool was utilized to assess the risk of bias in the original studies. Results: This study included 66 trials comprising 3675 patients. For balance, whole-body tilting postural training (WTPT), unilateral strength training (UST) and robot-assisted unilateral gait training (RAUGT) showed high SUCRA rankings. Activities of daily living likely improved most with robot-assisted Tai Chi training (RATCT), home rehabilitation guidance (HRG) and robot-assisted gait training (RAGT). Fugl-Meyer Assessment (FMA) gains appeared greatest following robot-assisted hand training with electrical stimulation (RAHT + ES), neural inhibition therapy (NIT) and graded motor imagery with electrical stimulation (GMI + ES). Walking endurance seemed most responsive to visual feedback training (VFT), UST and visual aids training (VAT), while functional mobility showed greatest improvement with tilt sensor-assisted gait training with electrical stimulation (TAGT + ES), gait training (GT) and virtual reality therapy with motor imagery (VRT + MI). Conclusions: This study provides the first comprehensive evidence synthesis evaluating the comparative effectiveness of specific exercise modalities across distinct recovery domains after AIS. Rather than supporting generic interventions, the findings highlight the distinct comparative advantages of various emerging technologies and traditional practices. These results offer an evidence-based framework for clinicians to optimize post-stroke rehabilitation protocols and highlight priority areas for future research on dose–response and long-term outcomes. Full article

Background: Patient-specific splints have become an integral component of virtual surgical planning in orthognathic surgery. However, transferring the virtually planned condylar position into the intraoperative setting remains technically challenging and typically requires labor-intensive manual modification of splint geometries. The aim of this study was to develop and describe an open-source Blender add-on that automates the generation of patient-specific splint extensions for condyle positioning and to evaluate its technical feasibility in a proof-of-concept clinical setting. Methods: A Python-based add-on for the open-source 3D modelling software Blender was developed to automate the generation of condyle-positioning splint extensions from stereolithography (STL) models exported by a commercial virtual surgical planning system. The software architecture and processing pipeline comprise facilitated data import, coordinate normalization, extension generation, Boolean processing, optional manual refinement, and STL export for additive manufacturing. The workflow was applied in three patients undergoing bilateral sagittal split osteotomy. Postoperative correspondence between the planned and achieved mandibular positions was assessed using translational and rotational transformation parameters together with qualitative surface distance heatmaps provided by the planning software. Results: The proposed add-on successfully generated patient-specific splint extensions in all three proof-of-concept cases while automating manual modelling steps. All splints were successfully manufactured and applied intraoperatively without redesign. Postoperative evaluation demonstrated good agreement between the virtually planned and achieved mandibular positions, with only small translational and rotational deviations. Descriptive statistical analysis supported the technical feasibility and reproducibility of the proposed workflow. Conclusions: The presented open-source Blender add-on provides a reproducible and extensible workflow for automated generation of patient-specific condyle-positioning splint extensions. The proposed approach successfully integrates virtual surgical planning with additive manufacturing and demonstrates technical feasibility in a proof-of-concept clinical setting. The software establishes a foundation for future validation studies in larger patient cohorts and illustrates the potential of open-source tools to improve transparency, reproducibility, and accessibility in digital orthognathic surgery workflows. Full article

Conventional typodonts for preclinical operative dentistry are idealised and lack the variability and tactile feedback of natural teeth; virtual-reality and haptic simulators remain costly for large cohorts. This study developed a reproducible, low-cost digital workflow for patient-specific, multi-material 3D-printed dental simulators and evaluated the models from a learner’s perspective. Intraoral and CBCT data from a single de-identified case were co-registered to a Virtual Patient. A modular tooth-socket architecture with trans-apical screw retention allowed repeatable individual tooth replacement; each tooth combined a variable-thickness enamel shell over a dentin core with multi-material carious lesions. Two fabrication routes (MSLA and PolyJet) and an adopted hybrid route (MSLA base, PolyJet teeth) were compared for cost, time and fidelity. The hybrid produced complete bimaxillary models at low consumable cost while preserving the source occlusion and contacts. Fifty dental students evaluated a PolyJet specimen hands-on: didactic utility scored highest (4.32 ± 0.65 on 1–5) and visual realism exceeded tactile realism (p < 0.001); 94% rated it at least comparable to a natural extracted tooth and 62% preferred it, while perceived hardness remained the main limitation. The workflow enables scalable in-house production of patient-specific simulators, with tactile realism the priority for material development. Full article

Background/Objectives: Miniscrew-assisted rapid palatal expansion (MARPE) is an effective treatment for maxillary transverse deficiency in skeletally mature patients. However, resistance of the midpalatal suture may limit treatment success. Surgical corticopunctures have been proposed to facilitate suture opening, while digital planning and 3D-printed surgical guides may improve procedural accuracy and safety. This study aims to evaluate the clinical effectiveness and safety of MARPE combined with surgically guided midpalatal corticopunctures in adult patients. Methods: A retrospective observational study was conducted on 15 adult patients (at least 20 years old) presenting with maxillary transverse deficiency and midpalatal suture maturation stages D or E. All patients underwent corticopuncture-assisted MARPE using patient-specific 3D-printed surgical guides designed through CBCT-based virtual planning. Treatment success was assessed by postoperative cone-beam computed tomography (CBCT), which evaluated midpalatal suture opening and transverse expansion. Clinical records were reviewed for complications, mini-implant stability, and postoperative outcomes. Results: Successful opening of the midpalatal suture was achieved in 13 of 15 patients, corresponding to a success rate of 86.7%. Among successful cases, the mean suture expansion measured on CBCT was 3.6 ± 0.9 mm. The customized surgical guides demonstrated adequate intraoral fit and enabled accurate execution of the planned corticopunctures in all cases. No intraoperative guide-related complications were reported. Postoperative healing was uneventful, with only mild and transient discomfort observed. No infections, excessive bleeding, significant soft-tissue injuries, damage to adjacent anatomical structures, or adverse events related to the corticopuncture procedure were recorded. Mini-implant stability was maintained in the majority of patients throughout the expansion phase. Conclusions: Within the limitations of this retrospective single-arm study, corticopuncture-assisted MARPE performed using customized 3D-printed surgical guides was feasible and associated with a high rate of successful midpalatal suture opening and few complications. The technique demonstrated a high rate of suture opening, clinically significant skeletal expansion, and a low incidence of complications. Digital planning and guided execution may enhance treatment precision and improve clinical outcomes in MARPE procedures. Full article

Background/Objectives: This study aimed to develop an artificial intelligence-based method for generating virtual post-contrast T1 maps and extracellular volume (ECV) maps from native T1 maps and to evaluate its performance. Methods: The proposed method was based on a modified self-consistent recursive diffusion bridge framework to generate virtual post-contrast T1 maps from native T1 maps. Cardiac magnetic resonance (CMR) data were collected from consecutive patients with suspected myocardial disease. A total of 813 well-registered image slices were selected for model development and evaluation. On an unseen test set of native T1 maps, the trained model generated virtual post-contrast T1 maps, which were subsequently combined with the corresponding native T1 maps to compute ECV maps. Results: The myocardial T1 values derived from the reference and virtual post-contrast T1 maps revealed similar distributions, although a systematic offset between the distribution peaks was observed. Following ECV transformation, this offset was substantially reduced. In the held-out test cohort, the virtual myocardial ECV showed acceptable agreement with the reference ECV, achieving a mean root mean square error (RMSE) of 3.05%, despite noticeable slice-to-slice variability (R² = 0.585; Bland–Altman 95% limits of agreement, −5.98% to +6.06%). Conclusions: The proposed method enabled the generation of post-contrast T1 and ECV maps directly from native T1 maps without the administration of gadolinium-based contrast agents during CMR. These findings suggest that the proposed approach represents a promising contrast-free, non-invasive alternative for myocardial tissue characterization, with the potential to reduce examination costs, eliminate contrast-agent-related risks, and improve patient safety. Full article

Salivary adenoid cystic carcinoma (SACC) is an immunologically cold malignancy with limited response to current immunotherapies. Integrated transcriptomic profiling of peripheral blood, primary tumors, lung metastases, and a two-donor single-cell dataset revealed compartment-specific expression signatures and, through computational inference, systemic immune dysregulation marked by hematopoietic suppression, T-cell exhaustion, compensatory myelopoiesis, and an immature B-cell expansion. To explore the transcriptional basis of this peripheral immune aberration, blood-derived RNA-seq was interrogated, identifying only 32 unique genes meeting |log2FC| > 1 and q < 0.05 among 34,999 transcripts; qPCR confirmed concordant upregulation of IL33 and CCL14, providing directional rather than confirmatory support, suggesting peripheral immune molecular aberrations that still require validation through broader differential gene expression validation. Complementing this transcriptomic signature, detection of MYB-NFIB fusion transcripts matching tumor tissue in one patient’s blood suggested that tumor-derived signals may access the circulation, although cohort validation remains necessary. Extending these peripheral observations to tissue compartments, we applied expression stratification, correlation networks, ligand-receptor mapping, and a virtual gain-loss model to computationally predict regulatory associations involving IL17RB/OLIG1/NOTCH1 in primary tumors and a CD24/IL17RB/MYB/MYBL2/CXCL13/CXCR5 module in lung metastases. At the single-cell level, cluster 10 emerged as a cell-cycle-high tumor population with transcriptional overlap with proliferating immune progenitors, providing a potential cellular basis for tumor cell entry into the circulation. Collectively, these computational inferences generate testable hypotheses for multicompartment immune dysregulation in SACC, positioning IL17RB as a candidate molecule that warrants prospective validation in SACC-specific preclinical models. Full article

Background/Objectives: Accurate visualization of peroneal perforator vessels prior to autologous transplantation of osteomyocutaneous fibular flap is essential for surgical success. Our aim was to improve and simplify pre-surgical diagnostics of peroneal perforators using a dedicated dual-energy Computed Tomography Angiography (CTA) protocol and semiautomatic Vessel Unfolding Reconstruction algorithm (VUR). Methods: CTA of both lower legs was performed in 22 patients using dual-energy acquisitions from a third-generation dual-source CT scanner and a high iodine flux (7 mL/s, 350 mg/mL). Low-energy virtual monoenergetic reconstructions (40 keV) were automatically reconstructed from the scanner and used for centerline labeling of the peroneal arteries and their perforators on a post-processing console using a dedicated vascular workflow. Separate segmentation and curved multiplanar reconstructions (MPRs) of each identified peroneal perforator vessel were regarded as the gold standard. Traditional visualization techniques of the entire volume like thin-slice maximum intensity projections (MIPs) or the volume rendering technique (VRT) were compared to a new VUR algorithm that aimed to adjust the visualization plane to the course of the vessels. The identified numbers and lengths of the perforator arteries were compared between curved MPRs, thin-slice MIPs in oblique coronal orientation, posterior-view VRT and coronal VUR of each lower leg. Results: The VUR algorithm was feasible in all patients and the same quantity of peroneal perforator vessels could be detected in comparison to the gold standard. The mean number of perforator vessels per lower leg was 2.6. Mean perforator length in VUR was slightly shorter by 1.6% and did not significantly differ from curved MPRs (p = 0.54), whereas length values from oblique coronal MIP and VRT reconstructions were significantly shorter (both p < 0.001). Conclusions: The combination of virtual monoenergetic reconstructions and the VUR algorithm enables comprehensive and precise depiction of small peroneal perforator vessels prior to autologous fibular flap transplantation, representing a diagnostic tool comparable to traditional visualization methods. Full article

Background: Stroke is a leading cause of neurological disability worldwide, with upper limb impairment affecting approximately 70% of survivors and only 5–20% achieving complete dexterity recovery at six months. Brain–computer interface (BCI) neurorehabilitation decodes motor intentions from electroencephalographic (EEG) signals to deliver synchronized functional electrical stimulation (FES) and virtual reality feedback, creating a closed-loop neurofeedback system that reinforces motor learning. While existing evidence supports BCI efficacy and safety in chronic stroke, its feasibility, safety, and cost-effectiveness during the acute and subacute phase (2 to 12 weeks post-stroke), when neuroplasticity is heightened, remain underexplored. Furthermore, there is a paucity of data regarding preliminary health economic analyses for BCI rehabilitation in acute stroke rehabilitation settings. Methods: This prospective, open-label, single-arm pragmatic feasibility pilot trial will recruit 12 patients with hemorrhagic or ischemic stroke (2–12 weeks post-stroke) undergoing inpatient rehabilitation from a public healthcare institution. Up to 15 sessions of BCI-rehabilitation of 30 min each using the recoveriX system will be supervised by a trained therapist or clinical research assistant (4–5 sessions/week over 3–4 weeks), followed by standard occupational therapy within 30–60 min of BCI-rehabilitation. Primary outcomes assessing feasibility and adherence include eligibility and recruitment rate (%/screened); tolerability using self-rated System Usability Scale (SUS) score; within-session adherence > 80%/240 trials, summated for completed trials per patient; programme completion number > 80% of scheduled (>12/15) sessions; and training-related adverse events per patient ≤ 17% (≤2/12 sessions). Secondary outcome measures include clinical efficacy by arm impairment scale using hemiplegic Upper Limb Fugl–Meyer Motor Assessment (FMA-UE), hand function using Action Research Arm Test (ARAT), admission and discharge functional status (Functional Independence Measure-FIM (18–126), Modified Barthel Index-MBI (0–100), stroke impact scale (SIS_3.0), arm, participation domains), and economic analysis. All outcomes will be measured by trained therapists/researchers at baseline week 0, week 3–4 (post-BCI-rehabilitation), and week 12 and 24 (follow-up). BCI-rehabilitation EEG-derived electrophysiological correlates of recovery will be extracted to better understand participant progress over time. An incremental cost-utility analysis will compare the BCI-rehabilitation participants against propensity-matched historical controls from the TTSH stroke rehabilitation registry (2017 to 2025), stratified by baseline motor severity. Discussion: This study will provide preliminary evidence on feasibility, tolerability, safety, clinical efficacy, and cost-effectiveness of early BCI-rehabilitation in acute/subacute stroke to better inform clinicians on its implementation. Full article

The gut microbiome has emerged as a critical determinant of health and disease across virtually all organ systems. In the context of chronic kidney disease (CKD) and renal transplantation, mounting evidence reveals a complex bidirectional relationship between the intestinal microbiota and kidney function—commonly referred to as the gut–kidney axis. Patients with CKD harbor a profoundly altered gut microbial ecosystem characterized by reduced diversity, depletion of beneficial commensal organisms, and expansion of pathobiont taxa capable of generating uremic toxins and pro-inflammatory mediators. These perturbations are further compounded by the uremic milieu itself, dietary restrictions, frequent antibiotic exposure, and the use of immunosuppressive agents following transplantation. The gut–liver–kidney axis adds an additional layer of complexity, linking hepatic metabolism, bile acid signaling, endotoxemia, and systemic immune activation to the progression of renal disease. Gut-derived metabolites—including short-chain fatty acids (SCFAs), bile acids, trimethylamine N-oxide (TMAO), and tryptophan-derived uremic solutes such as indoxyl sulfate and p-cresyl sulfate—serve as molecular mediators of inter-organ crosstalk and have been identified as both biomarkers and therapeutic targets. A growing body of literature supports the diagnostic and prognostic utility of microbiome composition and its metabolic signatures in patients with CKD and those undergoing renal replacement therapy. Therapeutic strategies aimed at restoring microbial homeostasis—encompassing dietary interventions, prebiotics, probiotics, synbiotics, fecal microbiota transplantation (FMT), bile acid–based therapies, and novel pharmacological approaches—hold considerable promise for improving outcomes in CKD and transplant recipients. Importantly, the bidirectional relationship between immunosuppressive drugs and the gut microbiota has emerged as a clinically significant determinant of both microbial ecology and drug pharmacokinetics: each major immunosuppressive agent class—corticosteroids, calcineurin inhibitors, mycophenolate mofetil, and mTOR inhibitors—induces characteristic dysbiotic patterns, while in turn, the microbiota modulates drug bioavailability through enzymatic biotransformation (notably bacterial beta-glucuronidase activity affecting mycophenolic acid enterohepatic recirculation) and modulation of host drug-metabolizing enzymes. This narrative review provides a comprehensive overview of the current understanding of microbiome dysbiosis in the setting of renal disease and transplantation, examines the mechanistic underpinnings of the gut–liver–kidney axis, details the multifaceted impact of dysbiosis on transplant outcomes—including allograft function and rejection, infection, post-transplant diabetes, and cardiovascular complications—and critically appraises the translational potential of microbiome-targeted interventions. We conclude by highlighting ongoing challenges and future directions toward personalized, microbiome-informed clinical care. Full article

Traditional speech therapy for children often faces challenges such as fear, a lack of patient motivation, unattractive supportive tools, and a critical shortage of specialized technological tools for under-resourced languages like Slovak. This paper presents a novel conceptual digital speech therapy ecosystem and core technological approaches developed within the 3PoCube project. To address the engagement gap, the proposed framework leverages gamification across five interconnected pillars which are integrating interactive, game-like environments for home practice with asynchronous offline telemedicine to support the parent–child–clinician dynamic. The technological core utilizes state-of-the-art Self-Supervised Learning (SSL) and Transformer-based Automatic Speech Recognition (ASR) models fine-tuned on a newly compiled Slovak children’s speech corpus, consisting of approximately 5 h of annotated speech from 303 speakers. In our experiments, the best-performing Wav2Vec 2.0 MMS architecture achieved a Word Error Rate (WER) of 15.10%, while the adapted Whisper Turbo achieved 16.33% on spontaneous pediatric speech. Several functional prototypes implementing these models are presented, including Neslovkáčik (a telemedicine portal), Hláskové superhrdinstvo (an articulation app), and LogoHra (a highly customizable virtual board game platform). Preliminary formative feedback from parents and speech-language pathologists indicates perceived acceptability during early prototype testing and suggests the potential to support engagement with the proposed solutions. However, while this study establishes a technical and conceptual foundation for home rehabilitation, rigorous clinical validation is required before definitive therapeutic efficacy can be claimed. Full article

Photodynamic therapy (PDT) is a cornerstone non-invasive modality for keratinocytic precancers and non-melanoma skin cancer (NMSC), leveraging selective photosensitizer accumulation, light activation, and reactive oxygen species (ROS) generation. This narrative review synthesized literature from major databases (2010–2025) to comprehensively evaluate PDT’s molecular mechanisms, innovative optimization protocols, and clinical efficacy across actinic keratosis (AK), field cancerization, Bowen’s disease (BD), basal cell carcinoma (BCC), and invasive squamous cell carcinoma (cSCC). The evidence highlights frontline clinical maturity and excellent cosmetic outcomes for superficial lesions (AK, field cancerization, superficial BCC, and BD), with daylight PDT offering a virtually painless alternative for widespread dysplasia. However, therapeutic reliability decreases in thick nodular, pigmented, or high-risk lesions due to optical barriers and tissue hypoxia. To overcome these limitations, advanced physical and chemical enhancements—such as ablative fractional lasers, iron chelators, epigenetically enhanced PDT (ePDT), and targeted nanocarriers—are actively reshaping drug delivery and cellular susceptibility. Furthermore, cyclic PDT serves as an indispensable tissue-sparing intervention for organ transplant recipients and Gorlin syndrome patients. In conclusion, while PDT is highly effective for superficial neoplasias, precise histopathological stratification and the integration of nanomedicine are critical to overcoming current biological barriers in aggressive dermatological malignancies. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by fluctuating symptoms, long-term medication use, bodily uncertainty, and complex self-management demands. These features can make patients’ experiences difficult to narrate, recognize, and integrate into everyday life. This study aimed to explore how Chinese women living with SLE use visual narratives to make sense of illness disruption, treatment burden, identity changes, and relational experience. Methods: This qualitative study used Virtual Photovoice, an online visual method in which participants generate and discuss photographs about lived experience, with eight Chinese women living with SLE. Data included participant-generated photographs, brief captions, SHOWeD-based written reflections structured around prompts that move from image description to broader reflection, and transcripts from three online Photovoice workshops. The data were analyzed using reflexive thematic analysis within a participatory-informed Virtual Photovoice design, informed by illness narrative theory. Results: Four themes were developed: Invisible Battlefield, Masks and Boundaries, Anchors of Order, and Longing to Be Seen. Participants used photographs and accompanying accounts to give form to fatigue, pain, and bodily uncertainty; negotiate the boundaries between concealment and disclosure; transform medication routines, dietary practices, and illness-related objects into anchors of order and agency; and contrast embodied relational support with clinical encounters experienced as distant or indicator-centered. Conclusions: The findings show how visual illness narratives can support meaning-making, self-recognition, and reflection on patient-centered communication among women living with SLE. Virtual Photovoice offers a narrative and participatory-informed approach for understanding psychological, embodied, and relational dimensions of chronic illness that are often difficult to express through routine clinical or everyday language. Full article

Background: Based on the available evidence, there are no published clinical trials that have analyzed the effectiveness of adding cross-education, mirror therapy, and virtual reality exercises (combined) to standard treatment to improve clinical outcomes in patients after anterior cruciate ligament (ACL) reconstruction. Methods: A total of 58 patients with ACL reconstruction, aged 18–50 years, will be randomized (1:1) to two treatment arms. The control group (n = 29) will receive a standard physiotherapy program based on a consensus developed by the Sport and Health Rehabilitation Guidelines. The experimental group (n = 29) will receive a novel physiotherapy program that includes cross-education exercise with visual biofeedback, mirror therapy, and virtual reality in addition to the standard exercise program. Five evaluations will be performed: at the beginning of physiotherapy treatment (baseline), at 6 weeks, 12 weeks, 24 weeks and 52 weeks after surgery. The primary outcome will be passive knee extension range of motion at 6 weeks (for sample size), assessed by goniometry; the remaining outcomes are secondary and exploratory. The secondary outcomes measures will be pain intensity, fear of movement, the level of anxiety, knee function, and isometric quadriceps strength. Discussion: We hypothesize that patients who receive a novel physiotherapy program that includes cross-education with visual biofeedback, mirror therapy, and virtual reality will show greater benefits in knee extension and other clinical outcomes than those who receive a standard physiotherapy program. Conclusions: The trial proposed in this protocol will provide new data on the effectiveness of the combination of cross-education, motor imagery, and virtual reality therapy added to a standard physiotherapy program compared with the standard physiotherapy program alone in patients who undergo ACL reconstruction. The findings will generate new insights into the effects of the interventions and expand the multimodal rehabilitation strategies available to patients who undergo this surgery. Full article