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Background: In Italy, 20 min of continuous, flat-line electrocardiogram are required for death declaration. Despite prolonged warm ischemia time, Italian centers reported good outcomes in controlled donation after circulatory death (cDCD) liver transplantation by combining normothermic regional and end-ischemic machine perfusion (MP). The aim of this study was to evaluate the safety and feasibility of the use of septuagenarian and octogenarian cDCD donors with this approach., Methods: All cDCD older than 70 y were evaluated during normothermic regional perfusion and then randomly assigned to dual hypothermic or normothermic MP., Results: In the period from April 2021 to December 2022, 17 cDCD older than 70 y were considered. In 6 cases (35%), the graft was not considered suitable for liver transplantation, whereas 11 (65%) were evaluated and eventually transplanted. The median donor age was 82 y, being 8 (73%) older than 80. Median functional warm ischemia and no-flow time were 36 and 28 min, respectively. Grafts were randomly assigned to ex situ dual hypothermic oxygenated MP in 6 cases (55%) and normothermic MP in 5 (45%). None was discarded during MP. There were no cases of primary nonfunction, 1 case of postreperfusion syndrome (9%) and 2 cases (18%) of early allograft dysfunction. At a median follow-up of 8 mo, no vascular complications or ischemic cholangiopathy were reported. No major differences were found in terms of postoperative hospitalization or complications based on the type of MP., Conclusions: The implementation of sequential normothermic regional and end-ischemic MP allows the safe use of very old donation after circulatory death donors., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Significance: This investigation reports for the first time the effects of different microperimetric biofeedback strategies in visually impaired subjects with central field loss., Purpose: This study aimed to evaluate the effects of two MP-3 microperimeter biofeedback strategies on the visual performance of subjects with central vision loss. Moreover, changes between the groups were compared to provide indications of practice with biofeedback stimulation in subjects with central vision loss., Methods: Using simple randomization, 19 participants were trained according to two different biofeedback stimulation approaches using the MP-3 microperimeter. Patients were assigned to two different groups: subjects trained for 2 days a week (group A) and 3 days a week (group B). The patients in each group were randomized to perform a total of 10 or 15 sessions., Results: Fixation stability increased from 4.5 ± 2.8 to 2.3 ± 2.2° 2 and from 8.2 ± 6.9 to 1.4 ± 1° 2 after 2 and 3 weekly biofeedback training sessions, respectively ( P < .05). Biofeedback training induced a significant improvement of 40.7 and 29.4% in reading speed for groups A and B, respectively ( P < .05). A comparison of two weekly biofeedback training sessions with three weekly biofeedback sessions demonstrated greater fixation stability in group B ( P < .05)., Conclusions: This study concludes that a biofeedback intervention is effective in enhancing oculomotor control in patients with central vision loss. In our study, a more intensive biofeedback strategy seemed to produce significantly better results in terms of functional vision parameters., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2023 American Academy of Optometry.)

Purpose of Review: The aim of this review is to outline disparities in liver and kidney transplantation across age spectrum. Disparities do not involve only recipients whose age may severely affect the possibility to access to a potentially life-saving procedure, but donors as well. The attitude of transplant centers to use older donors reflects on waiting list mortality and drop-out. This review examines which age categories are currently harmed and how different allocation systems may minimize disparities., Recent Findings: Specific age categories suffer disparities in the access to transplantation. A better understanding of how properly evaluate graft quality, a continuous re-evaluation of the most favorable donor-to-recipient match and most equitable allocation system are the three key points to promote 'justice and equality' among transplant recipients., Summary: The duty to protect younger patients waiting for transplantation and the request of older patients to have access to potentially life-saving treatment urge the transplant community to use older organs thus increasing the number of available grafts, to evaluate new allocation systems with the aim to maximize 'utility' while respecting 'equity' and to avoid 'futility' thus minimizing waiting list mortality and drop-out, and improving the survival benefits for all patients requiring a transplant., Video Abstract: http://links.lww.com/COOT/A9., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Cancer angiogenesis can be imaged by using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Pharmacokinetic modeling can be used to assess vascular perfusion and permeability, but the assessment of angiogenic changes in the microvascular architecture remains challenging. This article presents 2 models enabling the characterization of the microvascular architecture by DCE-MRI., Theory: The microvascular architecture is reflected in the dispersion coefficient according to the convective dispersion equation. A solution of this equation, combined with the Tofts model, permits defining a dispersion model for magnetic resonance imaging. A reduced dispersion model is also presented., Methods: The proposed models were evaluated for prostate cancer diagnosis. Dynamic contrast-enhanced magnetic resonance imaging was performed, and concentration-time curves were calculated in each voxel. The simultaneous generation of parametric maps related to permeability and dispersion was obtained through model fitting. A preliminary validation was carried out through comparison with the histology in 15 patients referred for radical prostatectomy., Results: Cancer localization was accurate with both dispersion models, with an area under the receiver operating characteristic curve greater than 0.8. None of the compared parameters, aimed at assessing vascular permeability and perfusion, showed better results., Conclusions: A new DCE-MRI method is proposed to characterize the microvascular architecture through the assessment of intravascular dispersion, without the need for separate arterial-input-function estimation. The results are promising and encourage further research.

Objective: The interaction of advanced glycation end products (AGEs) with their main receptor RAGE in endothelial cells induces intracellular generation of reactive oxygen species (ROS) and the expression of vascular cell adhesion molecule (VCAM)-1. We investigated the role of distinct sources of ROS, including the mitochondrial electron transport chain, NAD(P)H oxidase, xanthine oxidase, and arachidonic acid metabolism, in AGE-induced VCAM-1 expression., Methods and Results: The induction of ROS and VCAM-1 by AGEs in cultured human umbilical vein endothelial cells was specifically blocked by an anti-RAGE antibody. The inhibition of NAD(P)H oxidase by apocynin and diphenylene iodonium, and of the mitochondrial electron transport system at complex II by thenoyltrifluoroacetone (TTFA), significantly inhibited both AGE-induced ROS production and VCAM-1 expression, whereas these effects were potentiated by rotenone and antimycin A, specific inhibitors of mitochondrial complex I and III, respectively. The inhibition of Cu/Zn superoxide dismutase inhibited both ROS and VCAM-1 induction, indicating that H2O2 by this source is involved as a mediator of VCAM-1 expression by AGEs., Conclusions: Altogether, these results demonstrate that ROS generated by both NAD(P)H-oxidase and the mitochondrial electron transport system are involved in AGE signaling through RAGE, and indicate potential targets for the inhibition of the atherogenic signals triggered by AGE-RAGE interaction.

In HIV-1 infection, the appearance of syncytia-inducing (SI) isolates is associated with a more rapid decline of CD4+ cells and progression to AIDS. Agents that inhibit either virus infection or syncytia formation have the potential to be therapeutically useful. Lipophosphoglycan (LPG), the major glycoconjugate of Leishmania, was recently shown to be a potent nonspecific inhibitor of viral membrane fusion. In this study, LPG demonstrated a dose-dependent inhibition of HIV-1-induced syncytia formation in CD4+ MT-2 cells infected with distinct SI isolates. Fragments of LPG were used to show that inhibition of syncytia formation was dependent on the length of the LPG fragment. Treatment of CD4+ cells or HIV-1 isolates with LPG inhibited infection in vitro. Furthermore, LPG inhibited the replication of SI viral isolates in CD4+ T cells in vitro. LPG had no toxic effects on peripheral blood mononuclear cells at the highest concentrations used in these assays. Further, LPG rapidly associated with the surface membrane of a human T cell line and subsequently disassociated over a 24-h period. The development of compounds capable of inhibiting HIV-induced syncytia formation should provide novel therapeutic approaches to control the spread of virus and disease progression.