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Blood Advances May 2024Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic... (Meta-Analysis)
Meta-Analysis
Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic benefits. However, no systematic data support this approach. To support objective risk/benefit assessment of cytoreductive drugs in patients with PV aged <60 years (PV<60), this systematic review and meta-analysis was conducted to evaluate toxicity and disease-related complications in PV<60 treated with interferon alfa (rIFN-α) or hydroxyurea (HU). A search of PubMed, Scopus, Web of Science and Embase identified 693 unique studies with relevant keywords, of which 14 met inclusion criteria and were selected for analysis. The weighted average age of patients treated with rIFN-α was 48 years (n = 744 patients; 12 studies) and for HU was 56 years (n = 1397; 8 studies). The weighted average duration of treatment for either drug was 4.5 years. Using a Bayesian hierarchical model, the pooled annual rate of discontinuation due to toxicity was 5.2% for patients receiving rIFN-α (n = 587; 95% confidence interval [CI], 2.2-8.2) and 3.6% for HU (n = 1097; CI, 1-6.2). The average complete hematologic response for rIFN-α and HU was 62% and 52%, respectively. Patients experienced thrombotic events at a pooled annual rate of 0.79% and 1.26%; secondary myelofibrosis at 1.06% and 1.62%; acute myeloid leukemia at 0.14% and 0.26%; and death at 0.87% and 2.65%, respectively. No treatment-related deaths were reported. With acceptable rates of nonfatal toxicity, cytoreductive treatment, particularly with disease-modifying rIFN-α, may benefit PV<60. Future randomized trials prioritizing inclusion of PV<60 are needed to establish a long-term benefit of early cytoreductive treatment in these patients.
Topics: Humans; Polycythemia Vera; Treatment Outcome; Interferon-alpha; Hydroxyurea; Adult; Middle Aged; Cytoreduction Surgical Procedures; Age Factors
PubMed: 38507746
DOI: 10.1182/bloodadvances.2023012459 -
Lipids in Health and Disease Mar 2024Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to investigate the effects of DAAs in treating hepatitis C to achieve a sustained viral response (SVR) on lipid parameters.
METHODS
PubMed,Web of science, Embase and Central databases were searched, with a deadline of September 2023. Studies on the effects of sustained viral response on lipid parameters after DAAs treatment for hepatitis C were selected. The required information was extracted from the included studies, and then the Stata 12.0 was used to analyze the data quantitatively.
RESULTS
Of 32 studies, the results showed that total cholesterol (TC) levels increased from the end of treatment (WMD = 20.144, 95%CI = 3.404, 36.884,P = 0.018) to one year after treatment (WMD = 24.900, 95%CI = 13.669, 36.131, P < 0.001). From the end of treatment (WMD = 17.728, 95%CI = 4.375, 31.082, P = 0.009) to one year after treatment (WMD = 18.528, 95%CI = 7.622, 29.433, P < 0.001), the levels of low-density lipoprotein (LDL) were also increased. High-density lipoprotein (HDL) levels were elevated from 4 weeks after treatment (WMD = 6.665, 95%CI = 3.906, 9.424, P < 0.001) to 24 weeks after treatment (WMD = 3.159,95% CI = 0.176, 6.142, P = 0.038). Triglyceride (TG) levels showed no significant change after the treatment.
CONCLUSIONS
Hepatitis C patients who achieved SVR on DAAs showed the increase of lipid levels and the improvement of hepatic inflammation indicators AST and ALT. This may provide evidence-based medical evidence for the follow-up and monitoring of blood lipids and hyperlipidemia treatment.
REGISTRATION
PROSPERO CRD42020180793.
Topics: Humans; Antiviral Agents; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Lipids
PubMed: 38461262
DOI: 10.1186/s12944-023-01957-2 -
Hepatology International Apr 2024
Meta-Analysis
Topics: Humans; Hepatitis B, Chronic; Adenine; Tenofovir; Dyslipidemias
PubMed: 38424394
DOI: 10.1007/s12072-024-10664-8 -
Current Topics in Medicinal Chemistry 2024SARS-CoV-2, the unique coronavirus that causes COVID-19, has wreaked damage around the globe, with victims displaying a wide range of difficulties that have encouraged...
BACKGROUND
SARS-CoV-2, the unique coronavirus that causes COVID-19, has wreaked damage around the globe, with victims displaying a wide range of difficulties that have encouraged medical professionals to look for innovative technical solutions and therapeutic approaches. Artificial intelligence-based methods have contributed a significant part in tackling complicated issues, and some institutions have been quick to embrace and tailor these solutions in response to the COVID-19 pandemic's obstacles. Here, in this review article, we have covered a few DL techniques for COVID-19 detection and diagnosis, as well as ML techniques for COVID-19 identification, severity classification, vaccine and drug development, mortality rate prediction, contact tracing, risk assessment, and public distancing. This review illustrates the overall impact of AI/ML tools on tackling and managing the outbreak.
PURPOSE
The focus of this research was to undertake a thorough evaluation of the literature on the part of Artificial Intelligence (AI) as a complete and efficient solution in the battle against the COVID-19 epidemic in the domains of detection and diagnostics of disease, mortality prediction and vaccine as well as drug development.
METHODS
A comprehensive exploration of PubMed, Web of Science, and Science Direct was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) regulations to find all possibly suitable papers conducted and made publicly available between December 1, 2019, and August 2023. COVID-19, along with AI-specific words, was used to create the query syntax.
RESULTS
During the period covered by the search strategy, 961 articles were published and released online. Out of these, a total of 135 papers were chosen for additional investigation. Mortality rate prediction, early detection and diagnosis, vaccine as well as drug development, and lastly, incorporation of AI for supervising and controlling the COVID-19 pandemic were the four main topics focused entirely on AI applications used to tackle the COVID-19 crisis. Out of 135, 60 research papers focused on the detection and diagnosis of the COVID-19 pandemic. Next, 19 of the 135 studies applied a machine-learning approach for mortality rate prediction. Another 22 research publications emphasized the vaccine as well as drug development. Finally, the remaining studies were concentrated on controlling the COVID-19 pandemic by applying AI AI-based approach to it.
CONCLUSION
We compiled papers from the available COVID-19 literature that used AI-based methodologies to impart insights into various COVID-19 topics in this comprehensive study. Our results suggest crucial characteristics, data types, and COVID-19 tools that can aid in medical and translational research facilitation.
Topics: Humans; COVID-19; Artificial Intelligence; SARS-CoV-2; COVID-19 Vaccines; COVID-19 Drug Treatment; Drug Development; Antiviral Agents
PubMed: 38318824
DOI: 10.2174/0115680266282179240124072121 -
Liver International : Official Journal... Mar 2024We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines.
METHODS
We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach.
RESULTS
A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%).
CONCLUSIONS
All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes.
PROSPERO RECORD
CRD42020146752.
Topics: Adult; Child; Adolescent; Humans; Child, Preschool; Sofosbuvir; Hepatitis C, Chronic; Antiviral Agents; Hepatitis C; Sustained Virologic Response; Hepacivirus; Drug Therapy, Combination; Genotype; Treatment Outcome; Carbamates; Imidazoles; Pyrrolidines; Valine
PubMed: 38293756
DOI: 10.1111/liv.15827 -
Molecular Biology Reports Jan 2024Various viruses cause viral infection, and these viruses have different microscopic sizes, genetic material, and morphological forms. Due to a viral infection, the host... (Review)
Review
Various viruses cause viral infection, and these viruses have different microscopic sizes, genetic material, and morphological forms. Due to a viral infection, the host body induces defense mechanisms that activate the innate and adaptive immune system. sncRNAs are involved in various biological processes and play an essential role in antiviral response in viruses including ZIKV, HCV, DENV, SARS-CoV, and West Nile virus, and regulate the complex interactions between the viruses and host cells. This review discusses the role of miRNAs, siRNAs, piRNAs, and tiRNAs in antiviral response. Cellular miRNAs bind with virus mRNA and perform their antiviral response in multiple viruses. However, the chemical modifications of miRNA necessary to avoid nuclease attack, which is then involved with intracellular processing, have proven challenging for therapeutic replacement of miRNAs. siRNAs have significant antiviral responses by targeting any gene of interest along the correct nucleotide of targeting mRNA. Due to this ability, siRNAs have valuable characteristics in antiviral response for therapeutic purposes. Additionally, the researchers noted the involvement of piRNAs and tiRNAs in the antiviral response, yet their findings were deemed insignificant.
Topics: Humans; RNA, Small Untranslated; Piwi-Interacting RNA; Zika Virus Infection; Zika Virus; MicroRNAs; RNA, Small Interfering; RNA, Messenger; Antiviral Agents
PubMed: 38227137
DOI: 10.1007/s11033-023-09141-6 -
Virulence Dec 2024Newcastle disease virus (NDV) typically induces severe illness in poultry and results in significant economic losses for the worldwide poultry sector. NDV, an RNA virus...
Newcastle disease virus (NDV) typically induces severe illness in poultry and results in significant economic losses for the worldwide poultry sector. NDV, an RNA virus with a single-stranded negative-sense genome, is susceptible to mutation and immune evasion during viral transmission, thus imposing enormous challenges to avian health and poultry production. NDV is composed of six structural proteins and two nonstructural proteins that exert pivotal roles in viral infection and antiviral responses by interacting with host proteins. Nowadays, there is a particular focus on the mechanisms of virus-host protein interactions in NDV research, yet a comprehensive overview of such research is still lacking. Herein, we briefly summarize the mechanisms regarding the effects of virus-host protein interaction on viral infection, pathogenesis, and host immune responses. This review can not only enhance the present comprehension of the mechanism underlying NDV and host interplay, but also furnish a point of reference for the advancement of antiviral measures.
Topics: Animals; Antiviral Agents; Host Microbial Interactions; Immune Evasion; Newcastle disease virus; Virus Diseases
PubMed: 38193514
DOI: 10.1080/21505594.2023.2299182 -
Cytokine Mar 2024The COVID-19 (coronavirus disease 2019) is a well-defined viral infection, resulting from SARS-CoV-2 (severe acute respiratory syndrome- coronavirus-2). The innate... (Review)
Review
Do chemokine/chemokine receptor axes play paramount parts in trafficking and oriented locomotion of monocytes/macrophages toward the lungs of COVID-19 infected patients? A systematic review.
The COVID-19 (coronavirus disease 2019) is a well-defined viral infection, resulting from SARS-CoV-2 (severe acute respiratory syndrome- coronavirus-2). The innate immune system serves as the first line of defense to limit viral spreading and subsequently stimulate adaptive immune responses by the prominent aids of its cellular and molecular arms. Monocytes are defined as the most prominent innate immune cells (IICs) that are reactive against invading pathogens. These cells support host protection against the virus that is mediated by several non-specific mechanisms such as phagocytosis, producing antiviral enzymes, and recruitment of immune cells toward and into the infected tissues. They have the ability to egress from blood and migrate to the SARS-CoV-2 infected regions by the aid of some defense-related functions like chemotaxis, which is mediated by chemical compounds, e.g., chemokines. Chemokines, in addition to their related ligands are categorized within the most important and deserved agents involved in oriented trafficking of monocytes/macrophages towards and within the lung parenchyma in both steady state and pathological circumstances, including COVID-19-raised infection. However, the overexpression of chemokines could have deleterious effects on various organs through the induction of cytokine storm and may be the most important leading mechanisms in the pathogenesis of COVID-19. Authors have aimed the current review article to describe present knowledge about the interplay between monocytes/macrophages and SARS-CoV-2 with a focus on the ability of IICs to migrate and home into the lung of COVID-19 patients through various chemokine-chemokine receptor axes to promote our understanding regarding this disease.
Topics: Humans; COVID-19; Monocytes; Receptors, Chemokine; SARS-CoV-2; Chemokines; Lung; Macrophages; Cytokines
PubMed: 38190792
DOI: 10.1016/j.cyto.2023.156497 -
The American Journal of the Medical... Apr 2024Influenza infection is rarely associated with cardiac conduction disorder. Cardiac arrhythmias due to such an infection have a full spectrum with ventricular arrythmias...
BACKGROUND
Influenza infection is rarely associated with cardiac conduction disorder. Cardiac arrhythmias due to such an infection have a full spectrum with ventricular arrythmias being the most common.
METHODS
In our systematic review from PubMed, OVID Medline and EMBASE we have identified 23 articles describing arrythmias associated with different influenza infection. Most of them were case reports where ventricular arrhythmias were the most common.
RESULTS
Complete heart block after influenza infection is usually temporary and a permanent pacemaker is rarely needed. There are reports of Influenza associated with arrhythmias in adults, neonates, and even fetuses in pregnant woman. Different mechanisms were described in literatures by which influenza causes arrhythmias such as interleukin 6 & tumor necrosis factor-alpha mediated inflammatory response, sympathetic overactivation, focal myocarditis and cleavage of angiotensin converting enzyme 2 protein which is cardioprotective.
CONCLUSIONS
ACE 2 binder influenza viruses have more prone to be associated with cardiac conduction disorder. Oseltamivir for influenza infection is also associated with bradycardia and can shorten or lengthen QT segment. Influenza vaccination has found to be protective from cardiac arrhythmia.
Topics: Adult; Infant, Newborn; Pregnancy; Female; Humans; Influenza, Human; Arrhythmias, Cardiac; Bradycardia; Oseltamivir; Myocarditis
PubMed: 38185405
DOI: 10.1016/j.amjms.2024.01.004 -
European Journal of Medical Research Jan 2024During the COVID-19 pandemic, some populations, including immunocompromised patients, could not tolerate COVID-19 vaccination or had low responses. Evusheld is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
During the COVID-19 pandemic, some populations, including immunocompromised patients, could not tolerate COVID-19 vaccination or had low responses. Evusheld is a combined neutralizing monoclonal antibody containing tixagevimab and cilgavimab. The World Health Organization (WHO) has approved this combination as pre-exposure prophylaxis (PrEP) and treatment for immunocompromised patients. With the new variant, the (WHO) recommended an increase in dose from 300 to 600 mg with a booster dose after 6 months. The target of this review was to compare the efficacy of the two doses, 300 mg and 600 mg of tixagevimab/cilgavimab (Evusheld) as prophylaxis for higher-risk individuals to reveal if there is a significant difference in efficacy between those two doses of the drug.
METHODS
In this study, electronic databases (PubMed, Web of Science core collection, Scopus, and Cochran) were investigated for articles up to 31/12/2022 in English using a well-established search strategy. We included studies conducted in immunocompromised patients (aged ≥ 12 years) (WHO) received Evusheld as prophylaxis or treatment for COVID-19. After excluding studies inconsistent with the selection criteria, 24 were involved, 22 of which were included in the meta-analysis. We analyzed the data by using RevMan 5.4 program software.
RESULTS
In the double-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed no significant difference in the COVID-19 infection rate, mortality rate, or needed hospitalization rate compared with the dose of 300 mg (p = 0.13, p = 0.29, and p = 0.25, respectively). In the single-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed a significant decrease in the COVID-19 infection rate and the hospitalization rate compared with the dose of 300 mg (p = 0.0001, p = 0.007, respectively). As a treatment, Evusheld showed a significant decrease in the mortality rate over the placebo group (p = 0.01) in COVID-19 patients.
CONCLUSION
This result indicated that Evusheld was an effective prophylactic and therapeutic drug for COVID-19 infection, especially for immunocompromised patients, but there was no considerable variation between the high and low doses. Further prospective and randomized controlled trials (RCTs) with increased population sizes are necessary to show the valuable benefit of the high dose of Evusheld in COVID-19 prevention and treatment and to compare the difference between the two doses within adverse events.
Topics: Humans; Antibodies, Monoclonal; COVID-19; Immunocompromised Host; COVID-19 Drug Treatment; Drug Combinations; Antibodies, Neutralizing
PubMed: 38183123
DOI: 10.1186/s40001-023-01549-x