Citations

Abstract Background Machine perfusion represents the most significant breakthrough in liver transplantation (LT) since the discovery of cyclosporin. Yet, the optimal perfusion strategy remains unsettled. Randomized trials demonstrate that hypothermic oxygenated perfusion (HOPE) improves graft survival and function and reduces ischemic cholangiopathy, whereas normothermic machine perfusion (NMP) decreases post-transplant injury. Real-world comparisons are lacking and challenging due to heterogeneity in donor-recipient risk profiles and regional differences. Aims To compare real-world outcomes of HOPE and NMP in LT. Methods We analyzed consecutive NMP-preserved LTs from seven North American centers between 2021 and 2024. We compared NMP to the European HOPE-REAL cohort, comprising HOPE-treated LTs from 22 centers between 2012 and 2021. Analyses were stratifyied by graft type and risk category and adjusted for donor age, donor risk index, and balance of risk score using entropy balancing. Results A total of 470 NMP and 1202 HOPE-treated grafts were analyzed, revealing major differences in risk profiles (Figure 1). In NMP, death-censored graft survivals at 1, 2, and 3 years were >95% in donation after brain death (DBD) and >94% in donation after circulatory death (DCD) grafts. Comparable outcomes were observed in the HOPE cohort with >93%, in DBD, and >87% in DCD after up to 3 years, despite significantly higher donor age and longer functional warm ischemia in the HOPE DCD cohort (Figure 2). After risk adjustment, death-censored graft survival remained similar between both modalities (Table 1). Non-anastomotic biliary stricture rates after DCD-LT were comparable (8.5% vs. 12.4%), independent of whether continuous or end-ischemic NMP was performed. Conclusion This first transatlantic real-world report demonstrates excellent outcomes with both NMP and HOPE despite higher graft risk in Europe. Machine perfusion is the new standard of care in LT, while further understanding is needed regarding the distinct benefits of each modality across risk profiles.Figure 1.Graft risk in NMP and HOPE stratified by graft type. Benchmark case was defined as primary transplant with MELD <20 and BAR score <9, extended criteria as either BMI >30kg/m2, donor age >65 years, CIT >12h. DCD grafts were categorized as definedFor image description, please refer to the figure legend and surrounding text. Figure 2.Death-censored graft survival in liver transplantation following NMP and HOPE stratified by graft type. Abbreviations: NMP (Normothermic Machine Perfusion), HOPE (Hypothermic Oxygenated Perfusion), DBD (Donation after Brain Death), DCD (Donation after circulatory death)For image description, please refer to the figure legend and surrounding text. Table 1.Risk-adjusted comparison of death-censored graft survival between NMP and HOPE.For image description, please refer to the figure legend and surrounding text.

Abstract Background Indocyanine green (ICG) fluorescence imaging is increasingly incorporated into robotic liver resections (RLR), yet clinical practice regarding timing, dosage, and staining techniques is divergent. Aims This international expert survey aimed to characterize current practices for ICG in RLR. Methods Experts in RLR were invited to participate based on surgical volume (experience of 50 RLR and 30 annual RLR). A 74-item questionnaire was developed following a literature search and reviewed by a steering committee. The survey addressed indications, timing, dosage, imaging technology, benefits, limitations, training, and future directions of ICG use. Responses collected between September and October 2025 were analyzed. Results Seventy experts from 19 countries completed the survey, corresponding to an 88% response rate. Centers performed a median of 180 annual liver resections, including 55 RLR. Most experts used ICG (96%) during RLR. Anatomical demarcation (91%), tumor localization (60%), and biliary anatomy assessment (60%) were the most frequent indications. 60% of experts use preoperative ICG, while intraoperative ICG is mainly administered for demarcation (67%) and biliary tract visualization (40%). Considerable heterogeneity exists in dosage, timing, and staining techniques, particularly in cirrhotic livers and for tumor localization. Only half of the experts had standard operating procedures, whereas 64% expressed the need for a higher degree of standardization. Reported benefits of ICG use included improved anatomical orientation, margin assessment, lesion detection, and support during complex resections. Perceived limitations included background fluorescence, tissue penetration and variable staining in diseased parenchyma. 80% anticipated improved outcomes with combined ICG and three-dimensional image-guidance. Conclusion ICG fluorescence is widely used in RLR and is an important cornerstone for precision-guided robotic liver surgery. Standardized clinical practice guidelines, structured training, and technological improvements in imaging and navigation systems are claimed to optimize its clinical use.

BACKGROUND: The EARLY TAVR trial (Evaluation of TAVR Compared to Surveillance for Patients with Asymptomatic Severe Aortic Stenosis) demonstrated that early transcatheter aortic valve replacement (TAVR) was superior to clinical surveillance (CS) in asymptomatic severe aortic stenosis. The relative impact of early TAVR versus CS strategy by age is unknown. METHODS: The study population of the EARLY TAVR trial was stratified into 4 age groups: 65 to 69 years (n=141), 70 to 74 years (n=263), 75 to 79 years (n=250), and ≥80 years (n=247). Associations between age and the trial primary end point of death, stroke, or unplanned cardiovascular hospitalization; the composite end point of death, stroke, or heart failure hospitalization; and its individual components were examined. Interaction tests evaluated whether the treatment effect of early TAVR versus CS differed by age. RESULTS: No interaction was detected between age and the treatment effect of early TAVR versus CS for the composites or individual outcomes. We observed lower stroke rates with early TAVR compared with CS in the youngest (65–69 years, absolute risk reduction, 13%; P =0.008) and oldest (≥80 years; absolute risk reduction, 12.3%; P =0.029) age groups. The absolute difference in heart failure hospitalization rates between the early TAVR and CS arms at 2 years was greatest in the oldest patients (≥80 years, 9.1%; 75–79 years, 5.9%; 70–74 years, 5.1%; 65–69 years, 4.4%). In the CS group, time to conversion to AVR was similar across all age groups (median, 11 months; P =0.73). Approximately one-third of younger patients (65–69 years) in the CS arm presented with acute valve syndrome at the time of conversion, the frequency of which tended to increase with age ( P =0.06). CONCLUSIONS: In the EARLY TAVR trial, the relative benefit of early TAVR over CS was consistent among all age groups. The greatest absolute reduction in stroke rate with early TAVR compared with CS appeared in the youngest and oldest groups, whereas reduction in heart failure hospitalization was most pronounced in the oldest patients. These data suggest that early TAVR should be considered in all age groups above 65 years. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03042104.

Stroke is the second leading cause of death globally and a major contributor to lower-limb disability, affecting gait, balance, and functional independence in elderly populations. While robot-assisted rehabilitation has demonstrated effectiveness in motor recovery, access remains limited due to high costs and geographic barriers, particularly in Latin America. This study presents ExoKnee, a low-cost knee exoskeleton designed through biomimetic principles and 3D-printed fabrication as a proof-of-concept device targeting gait rehabilitation in elderly adults. The system integrates a single-degree-of-freedom pneumatic actuator controlled by electromyography (EMG) signals from the quadriceps muscle, enabling knee flexion and extension (90° to 180°). The design was evaluated through finite element analysis and dynamic simulations in MATLAB/Simulink R2024a under constant, stepwise, and sinusoidal reference inputs in a digital-twin environment. Expert validation using the Content Validity Coefficient yielded a mean score of 0.8747, reflecting preliminary expert agreement on the conceptual design’s coherence and relevance. The prototype demonstrated controlled movements through a 6-bar pneumatic system with EMG-triggered relay activation, validated at the proof-of-concept level through simulation and single-subject threshold calibration. ExoKnee addresses critical gaps by offering an anthropometrically informed, biosignal-driven, and locally manufacturable rehabilitation platform for low- and middle-income countries, pending clinical validation. Future work will focus on clinical trials and adaptive EMG control strategies.

Graph neural networks (GNNs) are increasingly used for medical imaging analysis and biological data modeling, where the integration of radiomics, topology, geometry, and generative artificial intelligence (AI) may improve representation learning from medical images and related biomedical data. Across the reviewed literature, GNNs show particular value for modeling spatial relationships, multimodal interactions, graph-structured biological networks, and non-Euclidean imaging features that are difficult to capture using conventional convolutional architectures alone. Topology- and geometry-aware approaches further expand this capability by encoding multi-scale structure, higher-order relationships, curvature, geodesic organization, and equivariant spatial priors. Hybrid graph–transformer models and generative graph methods represent emerging directions for modeling long-range dependencies, augmenting scarce datasets, supporting synthetic pretraining, and improving representation learning in low-label or heterogeneous biomedical settings. However, clinical translation remains limited by variability in graph construction, limited external validation, computational cost, scalability constraints, interpretability challenges, and uncertainty regarding the biological realism of synthetic data. Overall, this review highlights that GNN-based medical imaging analysis is most likely to advance when graph construction is biologically justified, model performance is evaluated across diverse clinical cohorts, and technical gains are paired with transparent validation, interpretability, and implementation strategies.

Abstract Background Wide-spread mast cell (MC)-associated symptoms and MC activation syndrome (MCAS) are often reported in patients with hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). The goal of this study was to develop a novel MC score based on 11 self-reported MC-related conditions with clinical and research utility to better understand MC symptoms in hEDS and HSD patients. Methods From November 1, 2019, to June 13, 2025, patients ( n =2,141) filled out an Intake Questionnaire at the Mayo Clinic Florida EDS Clinic that included 11 self-reported questions related to categories of MC-related conditions for a MC score ranging from 0/11 to 11/11. Based on the MC score distribution in hEDS and HSD patients, a MC score of 0-1 was considered a low MC score and ≥5 was considered a high MC score. Symptoms/comorbidities were compared between patients with high vs. low MC scores. Results From the 2,141 hEDS/HSD patients, 535 (25.0%) had a MC score ≥5 (Hi MC). MCAS-specific symptoms such as nausea and vomiting were reported more often in hEDS/HSD patients with a high vs. low MC score ( p <0.0001). Random clinical blood tryptase and urinary MC markers were not elevated in patients with high MC scores ( n =50/group), although high MC scores were found to significantly reduce urinary creatinine levels indicating that the protein used to normalize data was affected by MC activity. In contrast, random blood IgE, tryptase and major basic protein (MBP) by ELISA were increased in patients with high MC scores (e.g., IgE hEDS p =0.0004, HSD p =0.003). Of note, the percentage of patients reporting abuse or post-traumatic stress disorder was nearly doubled in patients with high vs. low MC scores (Abuse and PTSD: hEDS p < 0.0001; HSD p < 0.0001). Overall, 109/135 (80.7%) in hEDS and 129/135 (95.6%) in HSD reported more symptoms/comorbidities if they had a high MC score. Conclusions We found that hEDS/HSD patients with high MC scores self-reported more widespread symptoms/comorbidities and higher MC-related blood markers than patients with low MC scores indicating the utility of this tool to evaluate the level of widespread MC activity in hEDS, HSD and other patients.

Abstract Skull bone marrow (BM) is a recently identified site for immune activation responsive to CNS insults. The extent to which adaptive immunity is generated through skull BM is poorly understood. In this study, we evaluated how skull BM supports the early expansion of antiviral CD8 T cells during acute neurotropic virus infection. Virus antigen-specific CD8 T cells were rapidly identified in skull BM at a rate comparable to lymphoid compartments during acute Theiler’s murine encephalomyelitis viral (TMEV) infection. We therefore employed MHC class I conditional knockout mice and demonstrated the necessity of CD11c+ antigen-presenting cells (APCs) for the generation of various subsets of TMEV-specific CD8 T cells in skull BM. Importantly, the early expansion of skull BM-derived antiviral T cells was impeded by FTY720 treatment and restored upon shared circulation with a mouse exhibiting intact antigen presentation by CD11c+ APCs. Additionally, TMEV-specific CD8 T cells were retained in skull BM during both chronic CNS infection and long after infection has been resolved. Overall, we determined that skull BM responds to acute neurotropic viral infection through the rapid recruitment of virus-specific CD8 T cells primed in the periphery before serving as a reservoir for immunologic memory.

BACKGROUND Laser interstitial thermal therapy is a minimally invasive surgical technique commonly used for treating epileptogenic foci in patients with drug-resistant epilepsy. Densely calcified lesions pose a challenge because they prevent the placement of a laser cannula within them and act as a heat shield. A 22-year-old male presented with intractable epilepsy with imaging demonstrating a densely calcified lesion in the right medial occipitotemporal gyrus radiographically consistent with a polymorphous low-grade neuroepithelial tumor of the young. OBSERVATIONS Two laser cannulas were stereotactically positioned to flank the centrally calcified portion of the lesion at its anterior and posterior aspects. Intraoperative MR thermography during each ablation showed that the dense calcification shielded ablative heating from spreading to the other side of the lesion. The sum of the thermal ablation zones covered the entirety of the lesion. Postprocedure MRI demonstrated overlapping peripherally enhancing ablation zones, which subsumed the entirety of the calcified mass. The patient tolerated the procedure well and remained seizure free at the 14-month follow-up. LESSONS Using multiple stereotactically placed laser filaments to flank epileptogenic lesions that are densely calcified is a strategy to effectively encompass the entirety of the lesion within the combined ablation zones. https://thejns.org/doi/10.3171/CASE26184