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Background: Despite superiority of preemptive therapy (PET) compared to universal prophylaxis for prevention of cytomegalovirus (CMV) disease in the CAPSIL randomized trial among CMV D+R‐ liver transplant recipients (LTxRs), real‐world effectiveness may be lower because of logistical concerns about feasibility of PET. Methods: We retrospectively assessed PET as standard clinical care at a single transplant center among 50 consecutive adult CMV D+R‐ LTxRs undergoing a first liver transplant between 4/4/2019 and 5/18/2021 and compared outcomes and adherence to those randomized to PET in the CAPSIL study (N = 100). The primary outcome was CMV disease and secondary outcomes were biopsy‐confirmed acute allograft rejection, retransplant, invasive fungal infections, and death, all assessed by 1‐year post‐transplant. Exploratory outcomes included virologic parameters and measures of adherence to protocol‐specified CMV qPCR monitoring. Results: Baseline characteristics were similar between groups. The cumulative incidence of CMV disease at 1‐year post‐transplant was 4/50 (8%) versus 9/100 (9%) in the real‐world and CAPSIL cohorts, respectively, p = 1.0. The rate of breakthrough CMV disease during the 100‐day PET period was low (2/50 [4%]) and similar to the PET cohort from the CAPSIL study (3/100 [3%]). All secondary and exploratory outcomes were not significantly different between the real‐world and CAPSIL PET cohorts. Conclusions: In this first reported study of real‐world PET, the feasibility and effectiveness for CMV disease prevention and for other clinical outcomes in CMV D+R‐ LTxRs were similar to those reported with PET in a clinical trial. Additional studies to confirm feasibility and generalizability in other settings are warranted. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury (IRI), a pathological condition resulting from prolonged cessation and subsequent restoration of blood flow to a tissue, is an inevitable consequence of solid organ transplantation. Current organ preservation strategies, such as static cold storage (SCS), are aimed at reducing IRI. However, prolonged SCS exacerbates IRI. Recent research has examined pre-treatment approaches to more effectively attenuate IRI. Hydrogen sulfide (H2S), the third established member of a family of gaseous signaling molecules, has been shown to target the pathophysiology of IRI and thus appears to be a viable candidate that can overcome the transplant surgeon's enemy. This review discusses pre-treatment of renal grafts and other transplantable organs with H2S to mitigate transplantation-induced IRI in animal models of transplantation. In addition, ethical principles of pre-treatment and potential applications of H2S pre-treatment in the prevention of other IRI-associated conditions are discussed. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV), a ubiquitous β-herpes virus, mostly causes asymptomatic infections in adults with healthy immune systems. Due to immunosuppressive therapy, solid organ transplantation (SOT) recipients are at increased risk of HCMV infection. In recent years, the interdisciplinary, filed of immunoinformatics, based on computer science, and modern immunology, has emerged. In this study, we designed three types of recombinant subunit vaccines, which are expressed by the E. coli BL21 strain according to immunoinformatics prediction. Subsequently, we evaluated the innate and cellular immune responses of recombinant subunit vaccines in vivo and/or in vitro. Flow cytometry analysis, revealed that recombinant subunit vaccines enhanced both innate and cellular immune responses in vivo and/or in vitro. We also found that the novel herb adjuvant hesperetin (HES) increased memory T cell inflation. Overall, we developed three types of recombinant subunit vaccines based on HCMV antigen fragments containing multiple T-cell epitopes and assessed the innate and cellular immune responses in vivo and/or in vitro., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ischemia-reperfusion injury (IRI), a pathological condition resulting from prolonged cessation and subsequent restoration of blood flow to a tissue, is an inevitable consequence of solid organ transplantation. Current organ preservation strategies, such as static cold storage (SCS), are aimed at reducing IRI. However, prolonged SCS exacerbates IRI. Recent research has examined pre-treatment approaches to more effectively attenuate IRI. Hydrogen sulfide (H2S), the third established member of a family of gaseous signaling molecules, has been shown to target the pathophysiology of IRI and thus appears to be a viable candidate that can overcome the transplant surgeon’s enemy. This review discusses pre-treatment of renal grafts and other transplantable organs with H2S to mitigate transplantation-induced IRI in animal models of transplantation. In addition, ethical principles of pre-treatment and potential applications of H2S pre-treatment in the prevention of other IRI-associated conditions are discussed.

Cytomegaloviruses (CMVs), members of the β-subfamily of the herpesvirus family, have co-speciated with their respective mammalian hosts resulting in a mutual virus–host adaptation reflected by sets of 'private' viral genes that a particular CMV species does not share with other CMVs and that define the host-species specificity of CMVs. Nonetheless, based on "biological convergence" in evolution, fundamental rules in viral pathogenesis and immune control are functionally analogous between different virus–host pairs. Therefore, the mouse model of infection with murine CMV (mCMV) has revealed generally valid principles of CMV–host interactions. Specifically, the mouse model has paved the way to cellular immunotherapy of CMV disease in immunocompromised recipients of hematopoietic cell transplantation (HCT). Precisely in the context of HCT, however, current view assumes that there exists a major difference between hCMV and mCMV regarding "latent virus reservoirs" in that only hCMV establishes latency in hematopoietic lineage cells (HLCs), whereas mCMV establishes latency in endothelial cells. This would imply that only hCMV can reactivate from transplanted HLCs of a latently infected donor. In addition, as viral transcriptional activity during latency is discussed as a driver of clonal T-cell expansion over lifetime, a phenomenon known as "memory inflation", it is important to know if hCMV and mCMV establish latency in the same cell type(s) for imprinting the immune system. Here, we review the currently available evidence to propose that the alleged difference in latent virus reservoirs between hCMV and mCMV may rather relate to a difference in the focus of research. While studies on hCMV latency in HLCs likely described a non-canonical, transient type-2 latency, studies in the mouse model focussed on canonical, lifelong type-1 latency. [ABSTRACT FROM AUTHOR]

Urinary Extracellular Vesicles in Allograft Assessment: Biomarker analysis. HC (Healthy Control); Tx (Transplant recipients with normal allografts); AGD (Allograft dysfunction patients). Created using BioRender.com. [Display omitted] • Allograft dysfunction (AGD) poses a significant risk to graft survival following solid organ transplantation. • Early detection is crucial for preserving graft function; however, current diagnostic methods are invasive and inadequate. • Urinary extracellular vesicles (UEVs) offer benefits: stable biological activity, higher sensitivity and enhanced specificity. • Therefore, UEVs are a promising avenue for accurate and non-invasive liquid biopsy in organ allograft assessment. • Our study employed UEV-mRNA analysis to suggest a gene signature classifying allograft dysfunction from normal allografts. Allograft dysfunction (AGD) is a common complication following solid organ transplantation (SOT). This study leverages the potential of urinary extracellular vesicles (UEVs) for the non-invasive detection of AGD. We aimed to assess the diagnostic value of T-cell and B-cell markers characteristic of T-cell-mediated and antibody-mediated rejection in UEV-mRNA using renal transplantation as a model. UEVs were isolated from 123 participants, spanning healthy controls, functional transplant recipients, and biopsy-proven AGD patients. T-cell and B-cell marker mRNA expressions were evaluated using RT-qPCR. We observed significant differences in marker expression between healthy controls and AGD patients. ROC analysis revealed an AUC of 0.80 for T-cell markers, 0.98 for B-cell markers, and 0.94 for combined markers. T-cell markers achieved 81.3 % sensitivity, 80 % specificity, and 80.4 % efficiency. A triad of T-cell markers (PRF1 , OX40 , and CD3e) increased sensitivity to 87.5 % and efficiency to 82.1 %. B-cell markers (CD20 , CXCL3 , CD46 , and CF3) delivered 100 % sensitivity and 97.5 % specificity. The combined gene signature of T-cell and B-cell markers offered 93.8 % sensitivity and 95 % specificity. Our findings underscore the diagnostic potential of UEV-derived mRNA markers for T-cells and B-cells in AGD, suggesting a promising non-invasive strategy for monitoring graft health. [ABSTRACT FROM AUTHOR]

Highlights: [•] TLR mediated activation of NK cells impacts on the quality of immune responses. [•] An aberrant CD56neg NK cell subset is greatly expanded in HIV-viremic individuals. [•] NK cell receptor repertoire is skewed toward late differentiation stages by HCMV. [•] HCMV infection favors the differentiation of “memory-like” NKG2C+ KIR+ NK cells. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hepatitis E virus (HEV) has long been known as a major cause of acute hepatitis in developing countries with occasional travel-related cases in developed countries, most of them belonging to genotype 1. Currently, genotype 3 HEV is recognized as an emerging public health issue in developed countries and can cause a chronic hepatitis in immunocompromised patients. Objectives: The aim of this study was to get an overview of the clinical course of HEV infection, from July 2007 to December 2012, and further characterize HEV in patients of the University Medical Center Groningen (UMCG) over a 5-year time period. Methods: Since the second half of 2007, patients in the UMCG with unexplained hepatitis were screened for HEV and clinical data were collected. HEV was characterized by sequencing of the ORF1 and ORF2 regions. Results: In total, 34 patients of the 1129 tested patients showed HEV viremia. The majority of the infected patients were immunocompromised; 18 were solid organ transplant (SOT) patients and 9 were patients immunocompromised for other reasons. Seven patients diagnosed with HEV were immunocompetent. Viral genotyping revealed genotype 3 isolates, mostly genotype 3c. Conclusion: Non-travel related HEV hepatitis is an important diagnosis. In immunocompromised patients HEV infection often has major clinical impact, necessitating medical intervention including antiviral treatment. In immunocompetent patients, the detection could expand our understanding about the route of transmission and the relation with the zoonotic origin. Therefore, besides an increasing awareness for HEV among clinicians and medical microbiologists, diagnostics should be routinely incorporated into standard patients care. [Copyright &y& Elsevier]

Abstract: Background: Valganciclovir preemptive therapy guided by the viral load is the current strategy recommended for preventing CMV disease in CMV-seropositive Solid Organ Transplant Recipients (SOTR) at lower risk for developing CMV infection. However, universal viral load cut-off has not been established for initiating therapy. Objectives: Our goal was to define and validate a standardized cut-off determined in plasma by real-time PCR assay for initiating preemptive therapy in this population. Study design: A prospective cohort study of consecutive cases of CMV-seropositive SOTR was carried out. The cut-off value was determined in a derivation cohort and was validated in the validation cohort. Viral loads were determined using the Quant CMV LightCycler 2.0 real-time PCR System (Roche Applied Science) and results were standardized using the WHO International Standard for human CMV. Results: A viral load of 3983IU/ml (2600copies/ml) was established as the optimal cut-off for initiating preemptive therapy in a cohort of 141 patients with 982 tests and validated in a cohort of 252 recipients with a total of 2022 test. This cut-off had a 99.6% NPV indicating that the great majority of patients at lower risk will not develop CMV disease without specific antiviral therapy. The high sensitivity and specificity (89.9% and 88.9%, respectively) and the relatively small numbers of patients with CMV disease confirm that real-time PCR was optimal. Conclusions: We have established a cut-off viral load for starting preemptive therapy for CMV-seropositive SOT recipients. Our results emphasized the importance of a mandatory follow-up protocol for CMV-seropositive patients receiving preemptive treatment. [Copyright &y& Elsevier]

Background: Solid organ transplantation (SOT), which is the best remedy for end-stage organ failure, is accompanied by the risk of developing a postoperative malignant tumor. To date, assessments of the changes in the increased risk of thyroid cancer (TC) after SOT remain controversial. This study sought to reevaluate the risk of TC after SOT based on the latest literature. Our findings could improve the early diagnosis of tumors and the overall prognosis of patients after SOT., Methods: A computerized search of four major English-language databases (i.e., PubMed, EMBASE, Cochrane Library, and Web of Science) was performed to retrieve cohort studies on the risk of developing TC after SOT. The standardized incidence ratio (SIR) was used as the pooled-effect size and expressed as the 95% confidence interval (CI)., Results: In total, 20 cohort studies, comprising 362,079 patients who underwent SOT, were included in the meta-analysis. We found that the patients all had an increased risk of developing TC after the transplantation of different solid organs, including the kidney, heart, lung, and liver (P<0.05), and patients had the highest risk of developing TC after kidney transplantation (SIR =5.28, 95% CI: 4.03-6.92, P<0.01)., Conclusions: Patients have an increased risk of developing TC after SOT. Aggressive and regular tumor screenings after SOT for early detection and timely treatment may improve patient prognosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-137/coif). The authors have no conflicts of interest to declare., (2022 Gland Surgery. All rights reserved.)

Cold ischemia-reperfusion injury (IRI) is an inevitable and unresolved problem that poses a great challenge in solid organ transplantation (SOT). It represents a major factor that increases acute tubular necrosis, decreases graft survival, and delays graft function. This complicates graft quality, post-transplant patient care and organ transplantation outcomes, and therefore undermines the success of SOT. Herein, we review recent advances in research regarding novel pharmacological strategies involving the use of different donor molecules of hydrogen sulfide (H 2 S), the third established member of the gasotransmitter family, against cold IRI in different experimental models of SOT (kidney, heart, lung, liver, pancreas and intestine). Additionally, we discuss the molecular mechanisms underlying the effects of these H 2 S donor molecules in SOT, and suggestions for clinical translation. Our reviewed findings showed that storage of donor organs in H 2 S-supplemented preservation solution or administration of H 2 S to organ donor prior to organ procurement and to recipient at the start and during reperfusion is a novel, simple and cost-effective pharmacological approach to minimize cold IRI, limit post-transplant complications and improve transplantation outcomes. In conclusion, experimental evidence demonstrate that H 2 S donors can significantly mitigate cold IRI during SOT through inhibition of a complex cascade of interconnected cellular and molecular events involving microcirculatory disturbance and microvascular dysfunction, mitochondrial injury, inflammatory responses, cell damage and cell death, and other damaging molecular pathways while promoting protective pathways. Translating these promising findings from bench to bedside will lay the foundation for the use of H 2 S donor molecules in clinical SOT in the future. [ABSTRACT FROM AUTHOR]

Background: The increasing occurrence of multidrug-resistant organisms (MDROs) infections has posed major challenge to solid organ transplantation (SOT). For SOT recipients, high-dose immunosuppressants and broad-spectrum antibiotics can markedly increase the risk of early postoperative MDRO infections and thus have adverse effects on the outcomes of SOT. Here, we analyzed the incidence and clinical features of early MDRO infections after SOT, in an attempt to provide new evidence for the control and treatment of early MDROs., Methods: The clinical data of 133 patients with MDRO infections after SOT in our department from 2017 to 2020 were retrospectively collected, and clinical features including incidence, etiologies, infection sites, and complications, were analyzed., Results: The incidence of MDRO infections after SOT was 9.9%. Simultaneous liver and kidney transplantation patients had the highest incidence of MDRO infections, followed by the recipients of liver transplantation and simultaneous pancreas-kidney transplantation; patients undergoing renal transplantation had the lowest incidence of MDRO infections. The most common pathogen was extended spectrum beta-lactamase (ESBL)-producing organisms (n=88, 66.2%), the most common infection site was the urinary system (n=58, 43.6%), and the main postoperative complications were urinary tract infections (n=44, 33.1%) and lung infections (n=41, 30.8%). MDRO infections were cured in most cases., Conclusions: A sound knowledge of the clinical features of MDRO infection after SOT is important for the successful prevention and treatment of these infections.

Cryptococcosis is an invasive mycosis caused by pathogenic encapsulated yeasts in the genus Cryptococcus. Cryptococcus gained prominence as a pathogen capable of widespread disease outbreaks in vulnerable populations. We have gained insight into the pathobiology of Cryptococcus, including the yeast' s capacity to adapt to environmental pressures, exploit new geographic environments, and cause disease in both immunocompromised and apparently immunocompetent hosts. Inexpensive, point-of-care testing makes diagnosis more feasible than ever. The associated worldwide burden and mortality remains unacceptably high. Novel screening strategies and preemptive therapy offer promise at making a sustained and much needed impact on this sugar-coated opportunistic mycosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)