Citations

Ex vivo liver perfusion (EVLP) sustains human or large animal livers outside the body under near-physiological conditions, enabling functional monitoring for lactate clearance, bile production, and oxygen consumption and allowing targeted therapeutic interventions. Originally developed to optimize donor grafts for transplantation, EVLP has evolved into a powerful translational research platform bridging preclinical discovery and early clinical translation. This review discusses EVLP as a platform for gene therapy, immunotherapy, pharmacology, and personalized medicine, with particular emphasis on gene- and immune-based interventions as mechanistically mature exemplars. We consolidate advances in pharmacological testing and toxicity modeling, viral and non-viral gene delivery, genome engineering, and immunomodulation using perfused livers. We further describe emerging applications, including autologous EVLP pathways for organ-confined therapy, ex vivo liver surgery, and bioengineering strategies such as biliary organoid repair, RNA interference, and mitochondrial transfer. We highlight how these applications align with a paradigm shift in biomedical research, including the NIH’s recent initiative to prioritize human-based experimental models over animal-only studies. By leveraging transplant-declined or surgically resected organs that would otherwise be unused, ex vivo perfusion bridges the gap between pre-clinical testing and clinical practice, enabling real-time evaluation of interventions in functional human tissue. We discuss both the scientific opportunities afforded by EVLP and the technical, biosafety, and ethical challenges that must be addressed to enable responsible clinical translation.

Background/Objectives: Cardiovascular disease (CVD) burden decreased in the North Africa and Middle East (NAME) region between 1990 and 2019. This study used Global Burden of Disease (GBD) 2023 data to examine whether trends in mortality, disability-adjusted life years (DALYs), incidence, and prevalence continued through 2023 across all 21 NAME countries. Methods: We analysed age-standardised CVD mortality, incidence, prevalence, and DALY rates from 1990 to 2023. Joinpoint regression identified changes in temporal trends and calculated the annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Results: Age-standardised CVD mortality decreased from 579.6 per 100,000 in 1990 to 358.2 in 2023 (AAPC: −1.42%; 95% CI: −1.48 to −1.35). However, no significant reduction occurred between 2019 and 2023 (APC: −0.33%; 95% CI: −1.37 to 1.75). DALY, incidence, and prevalence rates followed similar patterns, with no significant decline in the final years of this study. Egypt was the only country with a long-term increase in CVD mortality, which accelerated after 2020 (APC: +5.20%; 95% CI: 1.20 to 12.87). High systolic blood pressure, dietary risks, lead exposure, and air pollution were the leading modifiable risk factors. Conclusions: The earlier decline in CVD burden in the NAME region did not clearly continue after 2019. The region is currently off track to meet Sustainable Development Goal 3.4 by 2030. Future progress may depend on improved blood pressure control, lipid management, dietary habits, and environmental risk reduction.

Atelectasis, the partial or complete collapse of the lung, requires early diagnosis for effective treatment. This study investigates the effects of Region of Interest (ROI) cropping and transfer learning on the automatic classification of atelectasis from chest X-ray images. Four SqueezeNet-based models were developed using two image types (raw and cropped lung regions) and two training strategies (from-scratch and transfer learning). Models I and II were trained from scratch on raw and cropped images, respectively, while Models III and IV employed transfer learning on the same image sets. Performance was evaluated using standard classification metrics. Model IV, combining transfer learning and ROI-cropped images, achieved the best performance, with 98.43% accuracy, 0.984 F1-score, and 0.999 AUC. It also reached 0.9861 precision, 0.9828 sensitivity, and 0.9859 specificity. ROI-based cropping consistently improved classification performance. Combining transfer learning with ROI-focused preprocessing significantly enhances atelectasis detection and shows promise as a reliable clinical decision-support approach.

OBJECTIVE The optimal surgical treatment for lumbar spinal stenosis (LSS) with degenerative spondylolisthesis (DS) remains controversial. Posterior lumbar facet arthroplasty preserves motion after decompression and may address some of the limitations of fusion techniques. The Total Posterior Spine System (TOPS) investigational device exemption trial compared decompression with facet arthroplasty to decompression plus fusion (open with interbody). This study reports the 3-year outcomes from this trial. METHODS This randomized, controlled, multicenter trial enrolled 321 patients with LSS and grade I DS across 37 sites (2:1 randomization of arthroplasty to fusion). Eligible patients were 35–80 years old, had failed ≥ 6 months of nonsurgical treatment, and met thresholds for disability and leg pain. The primary endpoint was a composite clinical success score at 36 months, defined by four criteria: 1) no reoperation or lumbar injection, 2) no major device adverse events, 3) ≥ 15-point improvement in the Oswestry Disability Index (ODI), and 4) no new/progressive neurological deficit. Secondary outcomes included the ODI score, visual analog scale (VAS) scores for back and leg pain, the Zurich Claudication Questionnaire (ZCQ), device-related adverse events, and reoperations. RESULTS One hundred seventy-nine patients in the arthroplasty (TOPS) group and 74 in the fusion group were eligible for the 36-month analysis. The composite clinical success achievement rate was significantly higher in the arthroplasty group (76.0%) than in the fusion group (56.8%; p = 0.0038). The rate of reoperation or lumbar injection was significantly lower for the arthroplasty group (14.0%) compared to the fusion group (25.3%; p = 0.0222). Arthroplasty was associated with a significantly higher minimal clinically important difference (MCID) achievement rate for VAS back pain score compared with fusion (85.2% vs 72.2%; p = 0.041). Although there was no significant difference in ODI score, VAS leg pain score, or ZCQ component scores between groups, the arthroplasty group trended toward higher MCID achievement rates across all patient-reported outcome measures. There was no significant difference in reoperation failure rates between groups (5.8% for arthroplasty vs 9.5% for fusion; p = 0.329). CONCLUSIONS Decompression and dynamic stabilization with lumbar facet arthroplasty was associated with statistically significantly superior clinical outcomes and lower rates of secondary invasive procedures, including reoperations and injections, compared with decompression and fusion. Long-term follow-up is critical in defining the role of lumbar facet arthroplasty for the treatment of DS.

Précis: Glaucoma patients of similar age and educational level, compared with healthy individuals, exhibit a greater number of saccades and fixations during eye-tracking-aloud reading, resulting in reduced reading speed. Purpose: To evaluate reading performance in patients with glaucoma compared with controls using an eye tracker and to explore the potential confounding effects of patients’ contrast sensitivity and cognition. Materials and Methods: A cross-sectional study was conducted with 111 participants (57 with glaucoma and 54 controls) with a best-corrected visual acuity of ≥0.5 logMAR. Cognition was assessed using the Montreal Cognitive Assessment, and contrast sensitivity was measured with the Freiburg Visual Acuity and Contrast Test. A reading performance evaluation was conducted using the Minnesota Low Vision Reading Test displayed on slides on a computer screen. Reading speed was calculated in words per minute, and an eye tracker was used to analyze saccade and fixation patterns during the reading task. Results: Mean age was 61.8 (±11.6) and 66.5 (±13.7) in the glaucoma and control groups, respectively ( P =0.05). Best-corrected visual acuity was 0.18 (±0.16) and 0.04 (±0.10) logMAR in the glaucoma and control groups, respectively ( P <0.001). Montreal Cognitive Assessment score was 21.8 (±3.5) in the glaucoma and 21.4 (±4.0) in the control group ( P =0.566). A total of 26% of the glaucoma group and 33% of the control group had at least a primary education. Controls read faster and showed fewer saccades and fixations than patients with glaucoma ( P <0.05) across all 5 slides. Conclusions: Patients with glaucoma exhibit poorer reading performance, as evidenced by eye-tracking data, compared with controls of similar age, cognitive function, and educational level.