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Cureus Dec 2023Polyomavirus nephropathy (PVN) is a rare kidney disease caused by the BK virus, a strain of polyomavirus. The disease primarily affects transplant recipients, which is...
BACKGROUND
Polyomavirus nephropathy (PVN) is a rare kidney disease caused by the BK virus, a strain of polyomavirus. The disease primarily affects transplant recipients, which is related to intensive immunosuppression protocol and can lead to kidney allograft failure.
OBJECTIVES
The objective of this study is to analyze histopathological features of PVN using the Banff 2018 PVN classification and to determine clinical features and outcomes of patients with PVN in each histologic class.
MATERIALS AND METHODS
The study included 44 patients who had been diagnosed with PVN by renal allograft biopsy in a large tertiary care hospital in Thailand from January 2011 to January 2020. The kidney biopsy slides were reviewed for Banff 2018 PVN classification and other histologic features. Patient demographic information, clinical data, and laboratory results were retrospectively collected.
RESULTS
Nine (20.45%), 27 (61.36%), and eight (18.18%) cases of PVN were Class I, Class II, and Class III, respectively. The time from transplant to PVN diagnosis for Classes I, II, and III was four, 19, and 33.5 months, respectively. Class III had the worst clinical outcomes in terms of deterioration of allograft function, the lowest rate of resolution, and the highest rate of graft failure.
CONCLUSIONS
PVN classification provides prognostic information in renal allograft biopsy. Our study confirmed the validity of the three-tier histologic PVN classification put forward by the Banff Working Group in 2018.
PubMed: 38249254
DOI: 10.7759/cureus.50910 -
Vaccines May 2024The safety and immunogenicity of the two-dose Ebola vaccine regimen MVA-BN-Filo, Ad26.ZEBOV, 14 days apart, was evaluated in people without HIV (PWOH) and living with...
The safety and immunogenicity of the two-dose Ebola vaccine regimen MVA-BN-Filo, Ad26.ZEBOV, 14 days apart, was evaluated in people without HIV (PWOH) and living with HIV (PLWH). In this observer-blind, placebo-controlled, phase 2 trial, healthy adults were randomized (4:1) to receive MVA-BN-Filo (dose 1) and Ad26.ZEBOV (dose 2), or two doses of saline/placebo, administered intramuscularly 14 days apart. The primary endpoints were safety (adverse events (AEs)) and immunogenicity (Ebola virus (EBOV) glycoprotein-specific binding antibody responses). Among 75 participants (n = 50 PWOH; n = 25 PLWH), 37% were female, the mean age was 44 years, and 56% were Black/African American. AEs were generally mild/moderate, with no vaccine-related serious AEs. At 21 days post-dose 2, EBOV glycoprotein-specific binding antibody responder rates were 100% among PWOH and 95% among PLWH; geometric mean antibody concentrations were 6286 EU/mL (n = 36) and 2005 EU/mL (n = 19), respectively. A total of 45 neutralizing and other functional antibody responses were frequently observed. Ebola-specific CD4+ and CD8+ T-cell responses were polyfunctional and durable to at least 12 months post-dose 2. The regimen was well tolerated and generated robust, durable immune responses in PWOH and PLWH. Findings support continued evaluation of accelerated vaccine schedules for rapid deployment in populations at immediate risk. Trial registration: NCT02598388 (submitted 14 November 2015).
PubMed: 38793748
DOI: 10.3390/vaccines12050497 -
Medicina (Kaunas, Lithuania) Jul 2023C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we...
C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we describe the case of a kidney transplant recipient who developed recurrent C3GN along with BK-virus-associated nephropathy (BKVAN) following KT. A 33-year-old man diagnosed with membranoproliferative glomerulonephritis 17 years ago underwent preemptive KT with a donor kidney from his aunt. Proteinuria gradually increased after 3 months following KT, and graft biopsy was performed 30 months after KT. Histopathological examination revealed recurrent C3GN. The dosages of triple immunosuppressive maintenance therapy agents were increased. Subsequently, serum C3 levels recovered to normal levels. However, at 33 months following KT, the BK viral load increased and graft function gradually deteriorated; a second graft biopsy was performed at 46 months following KT, which revealed BKVAN and decreased C3GN activity. The dosages of immunosuppressive agents were decreased; subsequently, BKVAN improved and graft function was maintained with normal serum C3 levels at 49 months following KT. This case indicates that C3GN is highly prone to recurrence following KT and that immunosuppressive therapy for C3GN increases the risk of BKVAN.
Topics: Male; Humans; Adult; Kidney Transplantation; Glomerulonephritis; Immunosuppressive Agents; Glomerulonephritis, Membranoproliferative; Nephritis, Interstitial
PubMed: 37512118
DOI: 10.3390/medicina59071308 -
Biomolecules Jun 2024The Ebola virus (EBOV) is a lethal pathogen causing hemorrhagic fever syndrome which remains a global health challenge. In the EBOV, two multifunctional proteins, VP35...
The Ebola virus (EBOV) is a lethal pathogen causing hemorrhagic fever syndrome which remains a global health challenge. In the EBOV, two multifunctional proteins, VP35 and VP40, have significant roles in replication, virion assembly, and budding from the cell and have been identified as druggable targets. In this study, we employed in silico methods comprising molecular docking, molecular dynamic simulations, and pharmacological properties to identify prospective drugs for inhibiting VP35 and VP40 proteins from the myxobacterial bioactive natural product repertoire. Cystobactamid 934-2, Cystobactamid 919-1, and Cittilin A bound firmly to VP35. Meanwhile, 2-Hydroxysorangiadenosine, Enhypyrazinone B, and Sorangiadenosine showed strong binding to the matrix protein VP40. Molecular dynamic simulations revealed that, among these compounds, Cystobactamid 919-1 and 2-Hydroxysorangiadenosine had stable interactions with their respective targets. Similarly, molecular mechanics Poisson-Boltzmann surface area (MMPBSA) calculations indicated close-fitting receptor binding with VP35 or VP40. These two compounds also exhibited good pharmacological properties. In conclusion, we identified Cystobactamid 919-1 and 2-Hydroxysorangiadenosine as potential ligands for EBOV that target VP35 and VP40 proteins. These findings signify an essential step in vitro and in vivo to validate their potential for EBOV inhibition.
Topics: Ebolavirus; Molecular Docking Simulation; Biological Products; Molecular Dynamics Simulation; Antiviral Agents; Myxococcales; Humans; Viral Regulatory and Accessory Proteins; Viral Matrix Proteins; Nucleocapsid Proteins
PubMed: 38927063
DOI: 10.3390/biom14060660 -
Cell Reports. Medicine Jun 2024Descendants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant now account for almost all SARS-CoV-2 infections. The Omicron variant and...
Descendants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant now account for almost all SARS-CoV-2 infections. The Omicron variant and its sublineages have spike glycoproteins that are highly diverged from the pandemic founder and first-generation vaccine strain, resulting in significant evasion from monoclonal antibody therapeutics and vaccines. Understanding how commonly elicited antibodies can broaden to cross-neutralize escape variants is crucial. We isolate IGHV3-53, using "public" monoclonal antibodies (mAbs) from an individual 7 months post infection with the ancestral virus and identify antibodies that exhibit potent and broad cross-neutralization, extending to the BA.1, BA.2, and BA.4/BA.5 sublineages of Omicron. Deep mutational scanning reveals these mAbs' high resistance to viral escape. Structural analysis via cryoelectron microscopy of a representative broadly neutralizing antibody, CAB-A17, in complex with the Omicron BA.1 spike highlights the structural underpinnings of this broad neutralization. By reintroducing somatic hypermutations into a germline-reverted CAB-A17, we delineate the role of affinity maturation in the development of cross-neutralization by a public class of antibodies.
Topics: SARS-CoV-2; Humans; Antibodies, Viral; COVID-19; Spike Glycoprotein, Coronavirus; Antibodies, Neutralizing; Antibodies, Monoclonal; Cross Reactions; Cryoelectron Microscopy; Neutralization Tests
PubMed: 38761799
DOI: 10.1016/j.xcrm.2024.101577 -
ACS Infectious Diseases Jul 2023The development of safe and potent insecticides remains an integral part of a multifaceted strategy to effectively control human-disease-transmitting insect vectors....
The development of safe and potent insecticides remains an integral part of a multifaceted strategy to effectively control human-disease-transmitting insect vectors. Incorporating fluorine can dramatically alter the physiochemical properties and bioavailability of insecticides. For example, 1,1,1-trichloro-2,2-bis(4-fluorophenyl)ethane (DFDT)─a difluoro congener of trichloro-2,2-bis(4-chlorophenyl)ethane (DDT)─was demonstrated previously to be 10-fold less toxic to mosquitoes than DDT in terms of LD values, but it exhibited a 4-fold faster knockdown. Described herein is the discovery of fluorine-containing 1-aryl-2,2,2-trichloro-ethan-1-ols (FTEs, for luorophenyl-richloromethyl-thanols). FTEs, particularly per-fluorophenyl-trichloromethyl-ethanol (PFTE), exhibited rapid knockdown not only against but also against susceptible and resistant mosquitoes, major vectors of Dengue, Zika, yellow fever, and Chikungunya viruses. The enantiomer of any chiral FTE, synthesized enantioselectively, exhibited faster knockdown than its corresponding enantiomer. PFTE does not prolong the opening of mosquito sodium channels that are characteristic of the action of DDT and pyrethroid insecticides. In addition, pyrethroid/DDT-resistant strains having enhanced P450-mediated detoxification and/or carrying sodium channel mutations that confer knockdown resistance were not cross-resistant to PFTE. These results indicate a mechanism of PFTE insecticidal action distinct from that of pyrethroids or DDT. Furthermore, PFTE elicited spatial repellency at concentrations as low as 10 ppm in a hand-in-cage assay. PFTE and MFTE were found to possess low mammalian toxicity. These results suggest the substantial potential of FTEs as a new class of compounds for controlling insect vectors, including pyrethroid/DDT-resistant mosquitoes. Further investigations of FTE insecticidal and repellency mechanisms could provide important insights into how incorporation of fluorine influences the rapid lethality and mosquito sensing.
Topics: Animals; Humans; Insecticides; Aedes; Fluorine; DDT; Fluorine Compounds; Drosophila melanogaster; Insecticide Resistance; Pyrethrins; Zika Virus; Zika Virus Infection; Mammals
PubMed: 37311068
DOI: 10.1021/acsinfecdis.3c00161 -
Transplantation Proceedings Nov 2023Protocol biopsies are performed to detect subclinical pathologies that may lead to future graft dysfunction. However, they are not routinely performed interventions in... (Observational Study)
Observational Study
BACKGROUND
Protocol biopsies are performed to detect subclinical pathologies that may lead to future graft dysfunction. However, they are not routinely performed interventions in every transplant center. There is no established regimen for performing them.
PURPOSE
The study aimed to evaluate if protocol biopsies can improve long-term patient outcomes after detecting early disorders and modifying treatment.
MATERIAL AND METHODS
Our observational study included 61 patients who underwent protocol biopsy 12 months after the transplantation. Based on the biopsy results, patients with abnormal histologic material (n = 37) were divided into 3 study groups as follows: patients with mild inflammatory lesions (n = 21), patients with interstitial fibrosis and tubular atrophy (IFTA) grade II to III (n = 12), and patients with BK virus nephropathy (n = 4). The control group (n = 24) included kidney recipients with IFTA 0 to I grade. Outcomes after 5-year follow-up were evaluated.
RESULTS
Five years after the biopsy, patients in the control group had stable graft function (5-year change in serum creatinine was -0.09 mg/dL). An increase in serum creatinine levels was observed in patients with IFTA II to III compared with the control group (0.14 mg/dL, P = .04). Immunosuppressive treatment was modified in the group with mild inflammatory changes and in the BKV group after the biopsy result. In the group with mild inflammatory lesions, renal function was stable (change of serum creatinine was -0.01 mg/dL, P = .51). In the BKV nephropathy group, there was a significant reduction in serum creatine levels (-0.48 mg/dL, P = .016). The analysis showed no diagnostic value for serum creatinine concentration (95% CI 0.49-0.78, P = .08).
CONCLUSIONS
Protocol biopsies are useful for detecting early pathologies and preventing allograft failure. They greatly benefit patients with detectable pathology that can be treated or in whom therapy modification is possible.
Topics: Humans; Biopsy; Creatinine; Follow-Up Studies; Graft Rejection; Kidney; Kidney Transplantation; Nephritis, Interstitial; Prognosis
PubMed: 37778932
DOI: 10.1016/j.transproceed.2023.08.022 -
Journal of Clinical Virology : the... Apr 2024BK Polyomavirus is of particular concern for kidney transplant recipients, due to their immunosuppression. This problem is exacerbated by the high effectiveness of... (Review)
Review
BK Polyomavirus is of particular concern for kidney transplant recipients, due to their immunosuppression. This problem is exacerbated by the high effectiveness of antirejection therapies, which also compromise the organism's ability to fight viral infections. The long-term risk is loss of graft function through BKPyV-associated nephropathy (BKPyVAN). The assessment of host immunity and its link to the control of viral infections is a major challenge. In terms of humoral immunity, researchers have highlighted the prognostic value of the pre-transplantation anti-BKPyV immunoglobulin G titer. However, humoral immunity alone does not guarantee viral clearance, and the correlation between the humoral response and the time course of the infection remains weak. In contrast, cellular immunity variables appear to be more closely associated with viral clearance, given that the cellular immune response to the kidney transplant is the main target of immunosuppressive treatments in recipients. However, the assessment of the cellular immune response to BK Polyomavirus is complex, and many details still need to be characterized. Here, we review the current state of knowledge about BKPyV cellular immunity, as well as the difficulties that may be encountered in studying it in kidney transplant recipient. This is an essential area of research for optimizing the management of transplant recipients and minimizing the risks associated with insidious BKPyV disease.
Topics: Humans; Kidney Transplantation; BK Virus; Transplant Recipients; Polyomavirus Infections; Kidney Diseases; Tumor Virus Infections
PubMed: 38412681
DOI: 10.1016/j.jcv.2024.105656 -
Clinical Infectious Diseases : An... Mar 2024During the 2022-2023 influenza season, the United States experienced the highest influenza-associated pediatric hospitalization rate since 2010-2011. Influenza A/H3N2...
BACKGROUND
During the 2022-2023 influenza season, the United States experienced the highest influenza-associated pediatric hospitalization rate since 2010-2011. Influenza A/H3N2 infections were predominant.
METHODS
We analyzed acute respiratory illness (ARI)-associated emergency department or urgent care (ED/UC) encounters or hospitalizations at 3 health systems among children and adolescents aged 6 months-17 years who had influenza molecular testing during October 2022-March 2023. We estimated influenza A vaccine effectiveness (VE) using a test-negative approach. The odds of vaccination among influenza-A-positive cases and influenza-negative controls were compared after adjusting for confounders and applying inverse-propensity-to-be-vaccinated weights. We developed overall and age-stratified VE models.
RESULTS
Overall, 13 547 of 44 787 (30.2%) eligible ED/UC encounters and 263 of 1862 (14.1%) hospitalizations were influenza-A-positive cases. Among ED/UC patients, 15.2% of influenza-positive versus 27.1% of influenza-negative patients were vaccinated; VE was 48% (95% confidence interval [CI], 44-52%) overall, 53% (95% CI, 47-58%) among children aged 6 months-4 years, and 38% (95% CI, 30-45%) among those aged 9-17 years. Among hospitalizations, 17.5% of influenza-positive versus 33.4% of influenza-negative patients were vaccinated; VE was 40% (95% CI, 6-61%) overall, 56% (95% CI, 23-75%) among children ages 6 months-4 years, and 46% (95% CI, 2-70%) among those 5-17 years.
CONCLUSIONS
During the 2022-2023 influenza season, vaccination reduced the risk of influenza-associated ED/UC encounters and hospitalizations by almost half (overall VE, 40-48%). Influenza vaccination is a critical tool to prevent moderate-to-severe influenza illness in children and adolescents.
Topics: Adolescent; Child; Humans; United States; Influenza, Human; Influenza A Virus, H3N2 Subtype; Seasons; Vaccine Efficacy; Influenza Vaccines; Hospitalization; Vaccination; Emergency Service, Hospital; Hospitals
PubMed: 37972288
DOI: 10.1093/cid/ciad704 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Oct 2023Currently, patients with pre-exsiting donor-specific antibody (DSA) are prone to antibody-mediated rejection (AMR) after surgery and are at a relatively high risk of...
OBJECTIVES
Currently, patients with pre-exsiting donor-specific antibody (DSA) are prone to antibody-mediated rejection (AMR) after surgery and are at a relatively high risk of postoperative complications and graft failure. The risk of postoperative complications and graft failure is relatively high. This study aims to discuss the clinical outcome of DSA-positive kidney transplantation and analyze the role and safety of preoperative pretreatment in DSA-positive kidney transplantation, providing single-center treatment experience for DSA-positive kidney transplantation.
METHODS
We retrospectively analyzed the clinical data of 15 DSA-positive kidney transplants in the Department of Renal Transplantation of First Affiliated Hospital of Zhengzhou University from August 2017 to July 2022. Eight cases were organ donation after citizen's death (DCD) kidney transplant recipients, of which 3 cases in the early stage were not treated with preoperative desensitisation therapy (DCD untreated group, =3), and 5 recipients were treated with preoperative rituximab desensitisation (DCD preprocessing group, =5). The remaining 7 cases were living related donors recipients (LRD) who received preoperative desensitisation treatment with rituximab and plasma exchange (LRD preprocessing group, =7). We observed and recorded the incidence of complications with changes in renal function and DSA levels in the recipients and the survival of the recipients and transplanted kidneys at 1, 3 and 5 years, and to compare the differences in recovery and postoperative complications between 3 groups.
RESULTS
All 15 recipients were positive for preoperative panel reactive antibody (PRA) and DSA and were treated with methylprednisolone+rabbit anti-human thymocyte immunoglobulin induction before kidney transplantation. DCD untreated group all suffered from DSA level rebound, delayed renal graft function (DGF) and rejection reaction after surgery. After the combined treatment, DSA level was reduced and the graft renal function returned to normal. The DCD preprocessing group were all without antibody rebound, 1 recipient developed DGF and the renal function returned to normal after plasmapheresis, and the remaining 4 recipients recovered their renal function to normal within 2 weeks after the operation. In the LRD preprocessing group, 2 cases had antibody rebound and 1 case had rejection, but all of them recovered to normal after treatment, and DSA was maintained at a low level or even disappeared. The incidence of DGF and rejection in the DCD untreated group were significantly higher than that in the DCD preprocessing group and the LRD preprocessing group; and there were no significant difference in the incidence of postoperative haematuria, proteinuria, bacterial and fungal infections, and BK virus infection between the 3 groups (all >0.05). A total of 11 of the 15 recipients were followed up for more than 1 year, 6 for more than 3 years, and 1 for more than 5 years, and the survival rates of both the recipients and the transplanted kidneys were 100%.
CONCLUSIONS
Effective preoperative pretreatment with desensitization therapy can effectively prevent antibody rebound in DSA-positive kidney transplantation and reduce perioperative complications.
Topics: Animals; Rabbits; Humans; Kidney Transplantation; Retrospective Studies; Rituximab; Tissue Donors; Antibodies; Postoperative Complications
PubMed: 38432887
DOI: 10.11817/j.issn.1672-7347.2023.230144