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Medical Science Monitor : International... Jul 2024BACKGROUND Thrombosis poses a grave threat to patients undergoing kidney transplants, with a heightened risk of mortality. While previous studies have established a link...
BACKGROUND Thrombosis poses a grave threat to patients undergoing kidney transplants, with a heightened risk of mortality. While previous studies have established a link between COVID-19 and thrombosis, the specific association between COVID-19 and thrombosis in this patient population remains unexplored. MATERIAL AND METHODS We conducted a retrospective analysis utilizing data from 394 individuals who underwent kidney transplantation within the period of September 1, 2015, to April 1, 2023. To evaluate overall survival, we employed Kaplan-Meier analysis and utilized a logistic regression model for risk analysis. Furthermore, we developed a prediction model and assessed its accuracy through calibration curves. RESULTS Out of the 394 patients included in our study, a total of 51 individuals experienced thrombosis, resulting in 2 deaths. Our analysis revealed that COVID-19 infection significantly increased the risk of thrombosis (odds ratio [OR] 8.60, 95% confidence interval 3.13-24.74, P<0.01). Additionally, the use of cyclosporine was found to elevate the risk of death (OR 20.86, 95% CI 7.93-59.24, P<0.01) according to multifactorial analysis. Logistic models were employed to screen variables, and predictive models were constructed based on the presence of COVID-19 infection and the usage of cyclosporine. A nomogram was developed, demonstrating promising accuracy in estimating the risk of thrombosis during internal validation, with a corrected C-index of 0.869. CONCLUSIONS Our study suggests that both COVID-19 infection and the use of cyclosporine can serve as reliable predictors of thrombosis risk in patients undergoing renal transplantation. Furthermore, we developed a mortality risk prediction model based on COVID-19 in assessing thrombosis.
Topics: Humans; Kidney Transplantation; COVID-19; Thrombosis; Male; Female; Middle Aged; Retrospective Studies; Incidence; Adult; Prognosis; Risk Factors; Transplant Recipients; SARS-CoV-2; Logistic Models; Aged; Cyclosporine; Kaplan-Meier Estimate
PubMed: 38946121
DOI: 10.12659/MSM.944285 -
Mycoses Jul 2024The impact of COVID-19 on paracoccidioidomycosis (PCM) in Argentina and the consequences generated by the pandemic are discussed. From 2018 to 3 years after the...
The impact of COVID-19 on paracoccidioidomycosis (PCM) in Argentina and the consequences generated by the pandemic are discussed. From 2018 to 3 years after the pandemic declaration, 285 proven PCM patients were registered. No association between both diseases was documented. PCM frequency decreased to extremely low levels in 2020. Mandatory social isolation and the emotional and psychological effects generated under pandemic circumstances led to delays in diagnosis, severe disseminated cases, and other challenges for diagnosis in subsequent years. Probable underdiagnosis should be considered due to the overlap of clinical manifestations, the low index of suspicion and the lack of sensitive diagnostic tools.
Topics: Paracoccidioidomycosis; Humans; COVID-19; Argentina; Male; Adult; Middle Aged; Female; SARS-CoV-2; Aged; Young Adult; Pandemics; Adolescent; Delayed Diagnosis
PubMed: 38946016
DOI: 10.1111/myc.13761 -
Retrovirology Jul 2024Since the introduction of combination antiretroviral therapy (cART) the brain has become an important human immunodeficiency virus (HIV) reservoir due to the relatively...
BACKGROUND
Since the introduction of combination antiretroviral therapy (cART) the brain has become an important human immunodeficiency virus (HIV) reservoir due to the relatively low penetration of many drugs utilized in cART into the central nervous system (CNS). Given the inherent limitations of directly assessing acute HIV infection in the brains of people living with HIV (PLWH), animal models, such as humanized mouse models, offer the most effective means of studying the effects of different viral strains and their impact on HIV infection in the CNS. To evaluate CNS pathology during HIV-1 infection in the humanized bone marrow/liver/thymus (BLT) mouse model, a histological analysis was conducted on five CNS regions, including the frontal cortex, hippocampus, striatum, cerebellum, and spinal cord, to delineate the neuronal (MAP2ab, NeuN) and neuroinflammatory (GFAP, Iba-1) changes induced by two viral strains after 2 weeks and 8 weeks post-infection.
RESULTS
Findings reveal HIV-infected human cells in the brain of HIV-infected BLT mice, demonstrating HIV neuroinvasion. Further, both viral strains, HIV-1 and HIV-1, induced neuronal injury and astrogliosis across all CNS regions following HIV infection at both time points, as demonstrated by decreases in MAP2ab and increases in GFAP fluorescence signal, respectively. Importantly, infection with HIV-1 had more prominent effects on neuronal health in specific CNS regions compared to HIV-1 infection, with decreasing number of NeuN neurons, specifically in the frontal cortex. On the other hand, infection with HIV-1 demonstrated more prominent effects on neuroinflammation, assessed by an increase in GFAP signal and/or an increase in number of Iba-1 microglia, across CNS regions.
CONCLUSION
These findings demonstrate that CNS pathology is widespread during acute HIV infection. However, neuronal loss and the magnitude of neuroinflammation in the CNS is strain dependent indicating that strains of HIV cause differential CNS pathologies.
Topics: Animals; Mice; HIV-1; HIV Infections; Humans; Neurons; Neuroinflammatory Diseases; Disease Models, Animal; Brain; Glial Fibrillary Acidic Protein; Calcium-Binding Proteins; Microfilament Proteins
PubMed: 38945996
DOI: 10.1186/s12977-024-00644-z -
Journal of Oleo Science 2024Handwashing represents an important personal hygiene measure for preventing infection. Herein, we report the persistence of antibacterial and antiviral effects after...
Handwashing represents an important personal hygiene measure for preventing infection. Herein, we report the persistence of antibacterial and antiviral effects after handwashing with fatty acid salt-based hand soap. To this end, we developed a new in vitro test method to measure persistence, utilizing coacervation formed by anionic surfactants and cationic polymers to retain highly effective soap components against each bacterium and virus on the skin. Coacervation with fatty acid salts and poly diallyldimethylammonium chloride (PDADMAC) as a cationic polymer allowed the persistence of antibacterial and antiviral effects against E. coli, S. aureus, and influenza virus even 4 h after handwashing. Furthermore, we confirmed an increase in the number of residual components effective against each bacterium and virus on the skin. In summary, the current findings describe an effective approach for enhancing the protective effects of handwashing.
Topics: Soaps; Escherichia coli; Hand Disinfection; Quaternary Ammonium Compounds; Anti-Bacterial Agents; Staphylococcus aureus; Antiviral Agents; Polyethylenes; Skin; Surface-Active Agents; Humans; Fatty Acids; Time Factors; Orthomyxoviridae
PubMed: 38945924
DOI: 10.5650/jos.ess23266 -
Nihon Yakurigaku Zasshi. Folia... 2024Ensitrelvir fumaric acid (Xocova hereafter ensitrelvir) is a novel anti-SARS-CoV-2 drug for COVID-19. Hokkaido University and Shionogi & Co., Ltd. engaged in joint... (Review)
Review
Ensitrelvir fumaric acid (Xocova hereafter ensitrelvir) is a novel anti-SARS-CoV-2 drug for COVID-19. Hokkaido University and Shionogi & Co., Ltd. engaged in joint research targeting SARS-CoV-2 3C-like (3CL) protease at an early stage and started clinical trials in July 2021. In February 2022, an application was filed for manufacture and sales approval for the indication of "SARS-CoV-2 infection,". Ensitrelvir recieved the first emergency regulatory approval from the Ministry of Health, Labour and Welfare (MHLW) in Japan in November 2022, and has obtained standard approval in March 2024. This emergency approval was based on the confirmed safety in a Phase 2/3 study (T1221) conducted in Japan and other Asian countries (Korea and Vietnam) in patients with mild/moderate COVID-19 and the presumed efficacy in Phase 3 Part (SCORPIO-SR), and the standard approval is based on efficacy from the Phase 3 part. In the Phase 3 part, ensitrelvir administered orally 375/125 mg once daily for five days, in patients with irrespective of risk factors for severe complications and vaccination status, demonstrating a significant reduction vs placebo in the time to resolution of five typical Omicron-related symptoms (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness), and also showed a significant reduction in viral RNA on day 4 relative to placebo (P < 0.001). In the Phase 2/3 study, there were no serious adverse events or deaths, indicating good tolerability and safety. We hope that ensitrelvir will contribute as a new treatment option for patients suffering from COVID-19 symptoms.
Topics: Humans; COVID-19 Drug Treatment; SARS-CoV-2; Tablets; Clinical Trials as Topic; COVID-19; Antiviral Agents; Treatment Outcome; Fumarates; Indazoles; Triazines; Triazoles
PubMed: 38945910
DOI: 10.1254/fpj.24017 -
American Journal of Critical Care : An... Jul 2024Use of noninvasive ventilation in patients with acute respiratory distress syndrome (ARDS) is debated. The COVID-19 pandemic posed challenges due to high patient volumes...
BACKGROUND
Use of noninvasive ventilation in patients with acute respiratory distress syndrome (ARDS) is debated. The COVID-19 pandemic posed challenges due to high patient volumes and worldwide resource strain.
OBJECTIVES
To determine associations between use of noninvasive ventilation in adult patients with moderate to severe ARDS due to SARS-CoV-2 pneumonia, progression to intubation, and hospital mortality.
METHODS
This retrospective cohort study included patients in an institutional COVID-19 registry. Adult patients were included if they were admitted for COVID-19 between March 1, 2020, and March 31, 2022, and developed moderate to severe ARDS. Primary outcomes were progression to intubation and hospital mortality in patients who received noninvasive ventilation or mechanical ventilation. A secondary outcome was successful treatment with noninvasive ventilation without intubation.
RESULTS
Of 823 patients who met inclusion criteria, 454 (55.2%) did not receive noninvasive ventilation and 369 (44.8%) received noninvasive ventilation. Patients receiving noninvasive ventilation were more likely to require mechanical ventilation than were patients not receiving noninvasive ventilation. Among patients requiring endotracheal intubation, those receiving noninvasive ventilation had a higher likelihood of mortality. Patients receiving noninvasive ventilation had lower severity-adjusted odds of survival to discharge without intubation than did patients not receiving noninvasive ventilation.
CONCLUSION
Patients with moderate to severe ARDS due to SARS-CoV-2 pneumonia treated with noninvasive ventilation had increased likelihood of progression to endotracheal intubation and hospital mortality.
Topics: Humans; COVID-19; Male; Female; Retrospective Studies; Middle Aged; Noninvasive Ventilation; Respiratory Distress Syndrome; Hospital Mortality; Aged; Intubation, Intratracheal; SARS-CoV-2; Severity of Illness Index; Respiration, Artificial; Adult
PubMed: 38945818
DOI: 10.4037/ajcc2024663 -
Chinese Medical Journal Jun 2024Chronic hepatitis B virus (HBV) infection is a global public health concern. Existing antiviral drugs, including nucleos(t)ide analogs and interferon-α, can suppress...
Chronic hepatitis B virus (HBV) infection is a global public health concern. Existing antiviral drugs, including nucleos(t)ide analogs and interferon-α, can suppress HBV replication and improve the prognosis. However, the persistence of covalently closed circular DNA (cccDNA), the integration of HBV-DNA into the host genome, and compromised immune responses impede the successful treatment of hepatitis B. While achieving a functional cure of HBV remains elusive with the current treatment methods, this is the goal of new therapeutic approaches. Therefore, developing novel antiviral drugs is necessary for achieving a functional or complete cure for chronic hepatitis B. In recent years, substantial progress has been made in drug discovery and development for HBV infection. Direct-acting antiviral agents such as entry inhibitors, capsid assembly modulators, subviral particle release inhibitors, cccDNA silencers, and RNA interference molecules have entered clinical trials. In addition, several immunomodulatory agents, including toll-like receptor agonists, therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also making their way toward clinical use. In this review, we summarize the recent progress and limitations of chronic hepatitis B treatment and discuss perspectives on approaches to achieving functional cure. Although it will take some time for these new antiviral drugs to be widely used in clinical practice, combination therapy may become a preferable treatment option in the future.
PubMed: 38945693
DOI: 10.1097/CM9.0000000000003178 -
Journal of Thrombosis and Haemostasis :... Jul 2024
Topics: COVID-19; Humans; Blood Coagulation; SARS-CoV-2; Gastrointestinal Microbiome; Host-Pathogen Interactions
PubMed: 38945665
DOI: 10.1016/j.jtha.2024.03.023 -
The Journal of Biological Chemistry Jun 2024The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness...
The development of safe and effective broad-spectrum antivirals that target the replication machinery of respiratory viruses is of high priority in pandemic preparedness programs. Here, we studied the mechanism of action of a newly discovered nucleotide analog against diverse RNA-dependent RNA polymerases (RdRp) of prototypic respiratory viruses. GS-646939 is the active 5'-triphosphate (TP) metabolite of a 4'-cyano modified C-adenosine analog phosphoramidate prodrug GS-7682. Enzyme kinetics show that the RdRps of human rhinovirus type 16 (HRV-16) and enterovirus 71 (EV-71) incorporate GS-646939 with unprecedented selectivity; GS-646939 is incorporated 20-50-fold more efficiently than its natural ATP counterpart. The RdRp complex of respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) incorporate GS-646939 and ATP with similar efficiency. In contrast, influenza B RdRp shows a clear preference for ATP and human mitochondrial RNA polymerase (h-mtRNAP) does not show significant incorporation of GS-646939. Once incorporated into the nascent RNA strand, GS-646939 acts as a chain-terminator although higher NTP concentrations can partially overcome inhibition for some polymerases. Modeling and biochemical data suggest that the 4'-modification inhibits RdRp translocation. Comparative studies with GS-443902, the active triphosphate form of the 1'-cyano modified prodrugs remdesivir and obeldesivir, reveal not only different mechanisms of inhibition, but also differences in the spectrum of inhibition of viral polymerases. In conclusion, 1'-cyano and 4'-cyano modifications of nucleotide analogs provide complementary strategies to target the polymerase of several families of respiratory RNA viruses.
PubMed: 38945449
DOI: 10.1016/j.jbc.2024.107514 -
Gene Jun 2024The adeno-associated virus (AAV) is a defective single-stranded DNA virus with the simplest structure reported to date. It constitutes a capsid protein and... (Review)
Review
The adeno-associated virus (AAV) is a defective single-stranded DNA virus with the simplest structure reported to date. It constitutes a capsid protein and single-stranded DNA. With its high transduction efficiency, low immunogenicity, and tissue specificity, it is the most widely used and promising gene therapy vector. The clustered regularly interspaced short palindromic sequence (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing system is an emerging technology that utilizes cas9 nuclease to specifically recognize and cleave target genes under the guidance of small guide RNA and realizes gene editing through homologous directional repair and non-homologous recombination repair. In recent years, an increasing number of animal experiments and clinical studies have revealed the great potential of AAV as a vector to deliver the CRISPR/cas9 system for treating genetic diseases and viral infections. However, the immunogenicity, toxicity, low transmission efficiency in brain and ear tissues, packaging size limitations of AAV, and immunogenicity and off-target effects of Cas9 protein pose several clinical challenges. This research reviews the role, challenges, and countermeasures of the AAV-CRISPR/cas9 system in gene therapy.
PubMed: 38945310
DOI: 10.1016/j.gene.2024.148733