Igor Maximillian Sauer

Normothermic machine perfusion (NMP) enables organ assessment and therapeutic intervention prior to transplantation. Evaluating treatment effects conventionally requires whole-organ transplantation, raising ethical and resource concerns. Precision-cut liver slices (PCLS) represent an established ex situ 3D tissue model, but their utility following NMP has not been characterized. We investigated whether PCLS prepared after NMP remain viable and reflect the injury state of the donor organ. Rat livers were allocated to four groups (n = 4/group): native controls, a warm ischemia injury model, and corresponding groups undergoing 6 h of NMP. PCLS were cultured for 48 h and sampled at 2, 24, and 48 h. Injury markers, synthetic function, metabolic activity, inflammatory and oxidative stress gene expression, and histology were assessed. Warm ischemia induction was confirmed by elevated perfusate injury markers during NMP. Alanine aminotransferase remained significantly higher in non-perfused damage-model slices compared with controls after 48 h of culture. Aspartate aminotransferase and lactate dehydrogenase did not differ. Metabolic activity and urea release persisted until 48 h. TUNEL positivity distinguished damage from control slices at 2 h but converged by 48 h. PCLS prepared after NMP remained viable and retained measurable injury- and perfusion-related differences, establishing a novel, 3R-compliant platform for perfusion research.

Background: The shortage of donor organs has increased the use of extended criteria donor (ECD) grafts in liver transplantation. Normothermic machine perfusion (NMP) could be used as a platform for real‐time quality assessment, which is crucial since ECD grafts are more susceptible to ischemia–reperfusion injury (IRI). As nicotinamide adenine dinucleotide (NAD ⁺ ) is a central mediator of cellular antioxidativedefense, reduced intracellular NAD (iNAD ⁺ ) levels in grafts sustaining greater injury may reflect diminished antioxidative capacity and could serve as a marker to assess graft quality. This study aimed to investigate iNAD ⁺ in comparison to existing damage‐associated parameters for liver graft quality in a small animal NMP model simulating ECD conditions through advanced donor age, prolonged cold ischemia time (CIT), and donation after circulatory death (DCD). Methods: Fifty‐nine male Sprague–Dawley rat livers were analyzed across six experimental groups defined by donor age (3 months [young] or 12 months [elderly]), procurement modality (standard procurement or donation after circulatory death [DCD]), and cold ischemia time (CIT; 6 h or 12 h), followed by 6 h of NMP. No livers were excluded from analysis. iNAD ⁺ levels were quantified using a colorimetric enzymatic assay. Results: Perfusate iNAD ⁺ levels continuously rose over time during NMP and differed significantly between intervention groups ( p = 0.003). iNAD+ correlated negatively with ALT levels (R = −0.36, p = 0.024) and liver tissue necrosis in grafts (perfusate R = −0.24, p = 0.17; tissue R = −0.19, p = 0.2), although these associations did not reach statistical significance. Long CIT, higher donor age, and DCD procurement were associated with lower iNAD+ levels. iNAD+ did not correlate with lactate clearance or bile production (both p > 0.05). A non‐significant trend toward a positive association between iNAD+ and glucose metabolism was observed ( R = 0.29, p = 0.077). Discussion: Higher perfusate iNAD+ levels were associated with better organ performance, consistent with iNAD+ reflecting the graft's antioxidative metabolic capacity. Lower iNAD+ levels in elderly and DCD grafts aligned with established damage markers. Perfusate iNAD+ may therefore offer a complementary tool for evaluating metabolic activity and organ performance during NMP, pending prospective validation.

Precise spatial understanding of complex anatomy is critical for preoperative planning in hepatobiliary surgery. Traditional CT and MRI imaging require mental reconstruction of anatomy from 2D slices, imposing substantial cognitive load. Although 3D reconstructions improve spatial understanding, they are typically displayed on 2D screens, limiting true depth perception. Virtual Reality (VR) visualization offers both stereoscopic depth and embodied interaction to improve spatial-anatomical understanding, yet its quantitative advantage over standard desktop visualization remains uncertain, especially regarding task complexity. In this randomized crossover study, 58 medical students analyzed 3D liver models of varying complexity using both VR and desktop visualization. Performance on lesion/vessel relations and lesion segment allocation tasks served as a measure of spatial-anatomical understanding, while visuospatial ability was assessed with the Mental Rotations Test. In complex models, VR significantly improved performance compared with desktop visualization (28.0 ± 3.3 vs. 26.4 ± 3.6; p = 0.002, d = 0.46), whereas results for simpler models were comparable. The VR advantage scaled with task complexity and correlated with higher visuospatial ability ( r = 0.31, p = 0.018). These findings indicate that VR is associated with measurable advantages under higher task complexity, supporting its potential role in surgical education and preoperative planning, although the present design cannot isolate which immersive features drive this benefit.

Human pancreatic islets are essential for studies in β-cell biology, cell transplantation, and tissue engineering, yet access to viable human islets remains limited because conventional isolation protocols primarily rely on whole pancreases from deceased donors. Surgical pancreatectomy specimens may represent an accessible alternative source, but factors influencing successful isolation and functional preservation remain poorly defined. In this study, we evaluated a standardized method for isolating human islets from pancreatic tissue obtained from surgical pancreatectomy specimens and investigated patient-, specimen-, and surgery-related factors affecting islet yield and functionality. Between March and October 2024, 50 consecutive islet isolations were performed from pancreatic specimens obtained during surgical resections. Following enzymatic digestion, tissue fractions were cultured for 24 h before handpicking of morphologically intact islets. Islet yield was quantified as islet equivalents (IEQ), and functional integrity was assessed by glucose-stimulated insulin secretion assays on culture days 1, 3, and 5. A mean yield of 6690 IEQ/g pancreatic tissue was obtained (range 0–56,500 IEQ/g). Exploratory analyses suggested potential associations between islet yield and factors such as younger patient age, shorter surgical duration, and preserved pancreatic parenchyma. However, these findings should be interpreted cautiously given the variability of the specimens and the exploratory design of the study. These findings support the feasibility of using surgical pancreatectomy specimens as an accessible source of functional human islets for experimental and translational research.

Compact, cost‐effective tabletop magnetic resonance elastography (ttMRE) is an emerging research tool for assessing bulk soft tissue biomechanics but still lacks spatially resolved imaging of viscoelastic properties in heterogeneous specimens like tumors. Here, we develop and validate ttMRE for quantifying intratumoral biomechanical heterogeneity in human colorectal liver metastasis (CRLM). We excite cylindrical, multifrequency shear waves and reconstruct viscoelastic maps using adaptive bandpass filters constrained by rheological Bessel‐fit priors. In this way, we obtain biophysical markers that agree with ground‐truth measurements in numerical and viscoelastic phantoms. In CRLM, shear‐wave‐speed and penetration‐rate maps – proxies of stiffness and attenuation, respectively – as well as their derived interquartile range and Shannon entropy, suggest markedly less viscous, stiffer, and more biomechanical heterogeneous tissue in specimens from responders to chemotherapy versus non‐responders, with heterogeneity metrics outperforming direct viscoelastic parameters in diagnostic accuracy. These findings establish compact, automated ttMRE as a low‐cost, scalable platform for spatial biomechanical profiling and quantitative assessment of treatment response in bulky colorectal liver metastasis specimens.

Robot-assisted surgery (RAS) has raised concerns within human-computer interaction, particularly regarding the socio-material configurations of robotic systems and their impact on surgical practices. To investigate these configurations in the context of the da Vinci robotic system, we used a research-through-design approach. Through this approach, we developed six Visual RAS (ViRAS) scenarios derived from RAS observations. These scenarios represent different configurations of interacting surgical team members and the robotic system in distinct adverse RAS events. In ViRAS-guided interviews with experienced RAS surgeons, we found that ViRAS scenarios help reflect on surgical practices and the specific material and spatial properties of RAS. Our findings indicated that the team’s cognitive engagement during surgery could be improved by providing sensory augmentation to facilitate task perception and individual skill development. Through our research, we show how ViRAS scenarios, as a tool for reflection, can reveal opportunities for designing socio-material configurations in RAS and beyond.

Background: Chemoresistance in treatment of colorectal liver metastases (CRLM) poses a major challenge in preventing disease relapse, with up to 80% of patients developing drug resistance over the course of treatment. Proteomic signatures of responsive vs. non-responsive metastases can provide insights into functional expression patterns, potentially identifying biomarkers for therapy efficacy. Methods: A total of 33 CRLM tissue samples from 31 patients were subjected to histopathological and proteomic analysis. The patients were included in the study after undergoing preoperative treatment ( n = 28), including platinum-based chemotherapy ( n = 19), non-platinum-based chemotherapy ( n = 8), as well as targeted therapies ( n = 20), or without preoperative therapy ( n = 5). Based on Rubbia-Brandt criteria and vital tumor cell percentage, CRLM were categorized to major (MR), partial (PR) and no response (NR) groups. Proteomic analysis was conducted using label-free mass spectrometry (LFQ-MS), followed by clustering according to histological response and distinct treatment regimens. Results: Proteomic analysis revealed significant differential protein expression of 607 proteins linked to distinct histopathological response types. CRLM responsive to chemotherapy displayed marked enrichment ( p ≤ 0.01) in pathways associated with immune infiltration, ECM matrix organization, the complement system, and apolipoprotein-associated processes, indicative of distinct stromal and immune invasion patterns with multimodal importance of cell adhesion proteins. In contrast, attenuated expression of proteins enriched in pathways of mitochondrial translation initiation, elongation and termination was detectable. Conclusion: CRLM exhibited distinct proteomic phenotypes based on their histopathological response to preoperative systemic therapy largely independent of chemotherapy regimens. This proteomic profiling establishes a foundation for identifying critical biomarker profiles by nominating protein markers for major chemotherapy response.

T-cell–mediated rejection (TCMR) remains a major cause of kidney transplant failure, despite being considered treatable. Its impact reflects a limited understanding of the underlying molecular mechanisms and their clinical consequences. To address this, we induced acute TCMR in mouse kidney transplants and profiled molecular changes using single-nucleus RNA sequencing (snRNA-seq), spatial transcriptomics and immunofluorescence. Results were compared with human snRNA-seq data from TCMR and stable allografts, as well as single-cell deconvolution analysis of bulk transcriptomic data from kidney transplant biopsies. Here we show that TCMR induces injured epithelial cell states in mouse kidney allografts, particularly in proximal tubules and thick ascending limbs. Spatial transcriptomics of these injured epithelial states demonstrated heterogeneous localization, interactions with immune cells and cellular microenvironments. Cross-species analysis confirmed similar severely injured epithelial states in human samples, whose abundances correlated with transplant survival and persisted despite TCMR resolution. Collectively, our results identify epithelial injury cell states as a determinant of outcome after TCMR.