Diagnostic Performance of Two Different Techniques to Quantify CMV-Specific Cell-Mediated Immunity in Intermediate-Risk Seropositive Kidney Transplant Recipients.

Background: Kidney transplant (KT) recipients at intermediate risk for cytomegalovirus (CMV) infection constitute a potential target for individualized prevention strategies informed by the CMV-specific cell-mediated immunity (CMV-CMI). The optimal method for the functional assessment of CMV-CMI in this group remains unclear.

Methods: We included 74 CMV-seropositive KT recipients that did not receive T-cell-depleting induction and were managed by preemptive therapy.

Outcomes of liver transplantation with donors older than 80 years in HCV patients treated with direct-action antivirals vs. non-HCV patients.

Background: Multiple studies have shown good results with the use of octogenarian donors in non-HCV recipients and its use is universally accepted worldwide. There are no studies analyzing differences between hepatitis C virus (HCV) and non-HCV recipients transplanted with donors≥80 years in the direct-action antivirals (DAA) period. The rate of liver transplantation (LT) using old donors is still low, and a change in the acceptance of these grafts could increase the liver pool available for LT.

Performance of a Global Functional Assay Based on Interferon-γ Release to Predict Infectious Complications and Cancer After Kidney Transplantation.

The QuantiFERON-Monitor assay (QTF-Monitor) is intended to assess innate and adaptive immune responses by quantifying interferon (IFN)-γ release upon whole blood stimulation with a TLR7/8 agonist and an anti-CD3 antibody. We performed the QTF-Monitor in 126 kidney transplant recipients (KTRs) at different points during the first 6 post-transplant months. The primary outcome was overall infection, whereas secondary outcomes included bacterial infection, opportunistic infection and cancer.

Efficacy and safety of a preventive strategy against tuberculosis in liver transplantation recipients including the treatment of latent infection with moxifloxacin.

Background: Preventive management of tuberculosis in liver transplantation (LT) is challenging due to difficulties in detecting and treating latent tuberculosis infection (LTBI). The aim of this study was to analyze the safety and efficacy of a screening strategy for LTBI with the inclusion of moxifloxacin as treatment.

Methods: We performed a retrospective single-center study of all LTs performed between 2016 and 2019 with a minimum 4-year follow-up and a standardized protocol for the evaluation of LTBI.

Valproic acid-induced teratogenicity is driven by senescence and prevented by Rapamycin in human spinal cord and animal models.

Valproic acid (VPA) is an effective and widely used anti-seizure medication but is teratogenic when used during pregnancy, affecting brain and spinal cord development for reasons that remain largely unclear. Here we designed a genetic recombinase-based SOX10 reporter system in human pluripotent stem cells that enables tracking and lineage tracing of Neural Crest cells (NCCs) in a human organoid model of the developing neural tube. We found that VPA induces extensive cellular senescence and promotes mesenchymal differentiation of human NCCs.

Novel intervention based on an individualized bundle of care to decrease infection in kidney transplant recipients.

Background: Infection remains a relevant complication after kidney transplantation (KT). A well-established strategy in modern medicine is the application of bundles of evidence-based practice in clinical settings. The objective of this study is to explore the application of a personalized bundle of measures aimed to reduce the incidence of infection in the first 12 months after KT.

Effect of Different Durations of Treatment With Antihypertensive Drugs With Anticholinergic Effects on the Risk of Dementia: A Target Trial Emulation Study.

Studying the effect of duration of treatment on prognostic outcomes using real-world data is challenging because only people who survive for a long time can receive a treatment for a long time. Specifying a target trial helps overcome such challenge. We aimed to estimate the effect of different durations of treatment with antihypertensive drugs with anticholinergic properties (AC AHT) on the risk of vascular dementia and Alzheimer's disease by emulating a target trial using the UK CPRD GOLD database (2001-2017).

Ataxia Telangiectasia patient-derived neuronal and brain organoid models reveal mitochondrial dysfunction and oxidative stress.

Ataxia Telangiectasia (AT) is a rare disorder caused by mutations in the ATM gene and results in progressive neurodegeneration for reasons that remain poorly understood. In addition to its central role in nuclear DNA repair, ATM operates outside the nucleus to regulate metabolism, redox homeostasis and mitochondrial function. However, a systematic investigation into how and when loss of ATM affects these parameters in relevant human neuronal models of AT was lacking.

Donor-Dependent Variations in Systemic Oxidative Stress and Their Association with One-Year Graft Outcomes in Kidney Transplantation.

Introduction: Oxidative stress has been implicated in complications after kidney transplantation (KT), including delayed graft function (DGF) and rejection. However, its role in long-term posttransplant outcomes remains unclear.

Methods: We investigated oxidative damage and antioxidant defense dynamics, and their impact on the graft outcomes, in 41 KT recipients categorized by type of donation over 12 months.

Cytomegalovirus UL44 protein induces a potent T-cell immune response in mice.

Due to the severity of CMV infection in immunocompromised individuals the development of a vaccine has been declared a priority. However, despite the efforts made there is no yet a vaccine available for clinical use. We designed an approach to identify new CMV antigens able to inducing a broad immune response that could be used in future vaccine formulations.

Survey on the approach to antibiotic prophylaxis in liver and kidney transplant recipients colonized with "difficult to treat" Gram-negative bacteria.

Background: Performance of active screening for multidrug-resistant Gram-negative bacteria (MDR-GNB) and administration of targeted antibiotic prophylaxis (TAP) in colonized patients undergoing liver (LT) and/or kidney transplantation (KT) are controversial issues.

Methods: Self-administered electronic cross-sectional survey disseminated from January to February 2022. Questionnaire consisted of four parts: hospital/transplant program characteristics, standard screening and antibiotic prophylaxis, clinical vignettes asking for TAP in patients undergoing LT and KT with prior infection/colonization with four different MDR-GNB (extended-spectrum cephalosporin-resistant Enterobacterales [ESCR-E], carbapenem-resistant Enterobacterales [CRE], multidrug-resistant Pseudomonas aeruginosa [MDR-Pa], and carbapenem-resistant Acinetobacter baumannii [CRAb]).

Isavuconazole for Treating Invasive Mould Disease in Solid Organ Transplant Recipients.

Solid organ transplant (SOT) recipients have a higher risk of developing invasive mould diseases (IMD). Isavuconazole is a novel broad-spectrum azole active against spp. and Mucor, well tolerated, with an excellent bioavailability and predictable pharmacokinetics, that penetrates in most tissues rapidly, and has few serious adverse effects, including hepatic toxicity.

Predictive value of fecal calprotectin and lactoferrin levels for negative outcomes in Clostridioides difficile infection.

Purpose: We investigated the role of fecal calprotectin (FC) and lactoferrin (FL) as predictive biomarkers in Clostridioides difficile infection (CDI).

Methods: We assembled a prospective cohort including all patients with a laboratory-confirmed CDI diagnosis between January and December 2017. FL and FC levels were measured at diagnosis by commercial ELISA and EIA kits.

Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology.

Aging is a major risk factor for neurodegenerative diseases, and coronavirus disease 2019 (COVID-19) is linked to severe neurological manifestations. Senescent cells contribute to brain aging, but the impact of virus-induced senescence on neuropathologies is unknown. Here we show that senescent cells accumulate in aged human brain organoids and that senolytics reduce age-related inflammation and rejuvenate transcriptomic aging clocks.

Incidence of refractory CMV infection with or without antiviral resistance in Spain: A systematic literature review.

Introduction: Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients are susceptible to cytomegalovirus (CMV) infection. The incidence of refractoriness to antivirals, with or without resistance, is unclear. The purpose of this review was to describe the epidemiology of refractory CMV infection in Spain to understand the current unmet needs.