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International Immunopharmacology Jan 2022Animal diarrhea due to diarrheagenic Escherichia coli (E. coli) has been a major concern in the field of livestock farming leading to a severe loss of domesticated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Animal diarrhea due to diarrheagenic Escherichia coli (E. coli) has been a major concern in the field of livestock farming leading to a severe loss of domesticated animals. This systematic review aims to analyze medical shreds of evidence available in the literature and to discover the effect of IgY in treatment and protection against E. coli diarrhea.
METHODS AND RESULTS
Research reports that aimed to evaluate the effect of IgY against E. coli diarrhea were searched and collected from several databases (Science Direct, Springer link, Wiley, T&F). The collected studies were screened based on the inclusion criteria. 19 studies were identified and included in the meta-analysis. The pooled relative risk ratios were calculated for the studies and found to be statistically significant to support the therapeutic effect of IgY against E. coli diarrhea but the 95% confidence interval of a majority of studies includes a relative risk of 1. This variability between the effect of IgY in the overall estimate and individual studies accounts due to the presence of methodological heterogeneity. In addition, subgroup analysis revealed the grounds for heterogeneity.
CONCLUSIONS
This systematic review and meta-analysis provide concrete evidence for the favorable effect of IgY as a prophylactic and therapeutic modality against E. coli diarrhea. Yet, more research pieces of evidence with standardized animal studies aimed to utilize IgY against E. coli are vital. Further studies and trials on human subjects could open new perspectives in the application IgY as a therapeutic agent.
Topics: Animals; Chickens; Diarrhea; Egg Yolk; Escherichia coli; Escherichia coli Infections; Immunization, Passive; Immunoglobulins
PubMed: 34810126
DOI: 10.1016/j.intimp.2021.108381 -
Scientific Reports Aug 2023Insight into the clinical potential of convalescent plasma in patients with coronavirus disease (COVID-19) is important given the severe clinical courses in unvaccinated... (Meta-Analysis)
Meta-Analysis
Insight into the clinical potential of convalescent plasma in patients with coronavirus disease (COVID-19) is important given the severe clinical courses in unvaccinated and seronegative individuals. The aim of the study was to investigate whether there is a survival benefit of convalescent plasma therapy in COVID-19 patients. The authors independently assessed randomized controlled trials (RCTs) identified by the search strategy for inclusion, extracted data, and assessed risk of bias. The binary primary outcome was all-cause mortality. Risk ratio (RR) of the convalescent plasma treatment (vs. best standard care) and its associated standard error (effect size) were calculated. A random-effects model was employed to statistically pool the effect sizes of the selected studies. We included 19 RCTs with 17,021 patients. The random-effects model resulted in an estimated pooled RR of 0.94 (95% CI 0.81-1.08, p = 0.33), showing no statistical evidence of the benefit of convalescent plasma therapy on all-cause mortality. Convalescent plasma therapy was not found to be effective in reducing all-cause mortality in COVID-19 patients. Further studies are needed to determine in which patients convalescent plasma therapy may lead to a reduction in mortality.
Topics: Humans; COVID-19; COVID-19 Serotherapy; SARS-CoV-2; Immunization, Passive; Bias
PubMed: 37558729
DOI: 10.1038/s41598-023-40009-8 -
Frontiers in Immunology 2022Convalescent plasma is a suggested treatment for Coronavirus disease 2019 (Covid-19), but its efficacy is uncertain. We aimed to evaluate whether the use of convalescent... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Convalescent plasma is a suggested treatment for Coronavirus disease 2019 (Covid-19), but its efficacy is uncertain. We aimed to evaluate whether the use of convalescent plasma is associated with improved clinical outcomes in patients with Covid-19.In this systematic review and meta-analysis, we searched randomized controlled trials investigating the use of convalescent plasma in patients with Covid-19 in Medline, Embase, Web of Science, Cochrane Library, and medRxiv from inception to October 17, 2021. Two reviewers independently extracted the data. The primary efficacy outcome was all-cause mortality. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. This study was registered with PROSPERO, CRD42021284861. Of the 8874 studies identified in the initial search, sixteen trials comprising 16 317 patients with Covid-19 were included. In the overall population, the all-cause mortality was 23.8% (2025 of 8524) with convalescent plasma and 24.4% (1903 of 7769) with standard of care (risk ratio (RR) 0.97, 95% CI 0.90-1.04) (high-certainty evidence). All-cause mortality did not differ in the subgroups of noncritically ill (21.7% [1288 of 5929] vs. 22.4% [1320 of 5882]) and critically ill (36.9% [518 of 1404] vs. 36.4% [455 of 1247]) patients with Covid-19. The use of convalescent plasma in patients who tested negative for anti-SARS-CoV-2 antibodies at baseline was not associated with significantly improved survival (RR 0.94, 95% CI 0.87-1.02). In the overall study population, initiation of mechanical ventilation (RR 0.97, 95% CI 0.88-1.07), time to clinical improvement (HR 1.09, 95% CI 0.91-1.30), and time to discharge (HR 0.95, 95% CI 0.89-1.02) were similar between the two groups. In patients with Covid-19, treatment with convalescent plasma, as compared with control, was not associated with lower all-cause mortality or improved disease progression, irrespective of disease severity and baseline antibody status.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021284861).
Topics: COVID-19; Critical Illness; Humans; Immunization, Passive; Respiration, Artificial; SARS-CoV-2; COVID-19 Serotherapy
PubMed: 35197981
DOI: 10.3389/fimmu.2022.817829 -
Journal of Experimental & Clinical... Jan 2023CAR-T cells are widely recognized for their potential to successfully treat hematologic cancers and provide durable response. However, severe adverse events such as... (Review)
Review
CAR-T cells are widely recognized for their potential to successfully treat hematologic cancers and provide durable response. However, severe adverse events such as cytokine release syndrome (CRS) and neurotoxicity are concerning. Our goal is to assess CAR-T cell clinical trial publications to address the question of whether administration of CAR-T cells as dose fractions reduces toxicity without adversely affecting efficacy. Systematic literature review of studies published between January 2010 and May 2022 was performed on PubMed and Embase to search clinical studies that evaluated CAR-T cells for hematologic cancers. Studies published in English were considered. Studies in children (age < 18), solid tumors, bispecific CAR-T cells, and CAR-T cell cocktails were excluded. Data was extracted from the studies that met inclusion and exclusion criteria. Review identified a total of 18 studies that used dose fractionation. Six studies used 2-day dosing schemes and 12 studies used 3-day schemes to administer CAR-T cells. Three studies had both single dose and fractionated dose cohorts. Lower incidence of Grade ≥ 3 CRS and neurotoxicity was seen in fractionated dose cohorts in 2 studies, whereas 1 study reported no difference between single and fractionated dose cohorts. Dose fractionation was mainly recommended for high tumor burden patients. Efficacy of CAR-T cells in fractionated dose was comparable to single dose regimen within the same or historical trial of the same agent in all the studies. The findings suggest that administering dose fractions of CAR-T cells over 2-3 days instead of single dose infusion may mitigate the toxicity of CAR-T cell therapy including CRS and neurotoxicity, especially in patients with high tumor burden. However, controlled studies are likely needed to confirm the benefits of dose fractionation.
Topics: Child; Humans; Immunotherapy, Adoptive; Hematologic Neoplasms; Neurotoxicity Syndromes; Cytokine Release Syndrome; T-Lymphocytes
PubMed: 36627710
DOI: 10.1186/s13046-022-02540-w -
Biomedicine & Pharmacotherapy =... May 2024Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues... (Review)
Review
Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability to recognize and eliminate cancer cells. This review paper explores the intricate interplay between CAR-T therapy and radiotherapy (RT), investigating their synergistic potential. Radiotherapy, a standard cancer treatment, involves using high doses of radiation to target and damage cancer cells, disrupting their ability to grow and divide. We highlight that RT modulates the TME, augments antigen presentation, and promotes immune cell infiltration, bolstering CAR-T cell-mediated tumor eradication. Molecular insights shed light on RT-induced alterations in tumor stroma, T cell recruitment promotion, and induction of immunogenic cell death. Noteworthy, strategies, such as combining hypofractionated radiotherapy with myeloid-derived suppressor cell blockade, underscore innovative approaches to enhance CAR-T cell therapy in solid tumors. Bridging indications for RT and CAR-T cells in hematological malignancies are discussed, emphasizing scenarios where RT strategically enhances CAR-T cell efficacy. The paper critically evaluates the RT as a bridge compared to traditional chemotherapy, highlighting timing and dosage considerations crucial for optimizing CAR-T therapy outcomes. In summary, the paper provides valuable insights into the intricate molecular mechanisms activated by RT and innovative strategies to improve CAR-T cell therapy, fostering a deeper understanding of their combined potential in cancer treatment.
Topics: Humans; Neoplasms; Tumor Microenvironment; Immunotherapy, Adoptive; Animals; Receptors, Chimeric Antigen; Combined Modality Therapy; Radiotherapy
PubMed: 38574625
DOI: 10.1016/j.biopha.2024.116532 -
The AAPS Journal Apr 2021Chimeric antigen receptor (CAR) T-cell therapy is an immunotherapy that has recently become highly instrumental in the fight against life-threatening diseases. A variety...
Chimeric antigen receptor (CAR) T-cell therapy is an immunotherapy that has recently become highly instrumental in the fight against life-threatening diseases. A variety of modeling and computational simulation efforts have addressed different aspects of CAR T-cell therapy, including T-cell activation, T- and malignant cell population dynamics, therapeutic cost-effectiveness strategies, and patient survival. In this article, we present a systematic review of those efforts, including mathematical, statistical, and stochastic models employing a wide range of algorithms, from differential equations to machine learning. To the best of our knowledge, this is the first review of all such models studying CAR T-cell therapy. In this review, we provide a detailed summary of the strengths, limitations, methodology, data used, and data gap in currently published models. This information may help in designing and building better models for enhanced prediction and assessment of the benefit-risk balance associated with novel CAR T-cell therapies, as well as with the data need for building such models.
Topics: Computer Simulation; Humans; Immunotherapy, Adoptive; Machine Learning; Models, Immunological; Neoplasms; Receptors, Chimeric Antigen; Risk Assessment
PubMed: 33835308
DOI: 10.1208/s12248-021-00579-9 -
3 Biotech Mar 2022has emerged as one of major nosocomial pathogen and global emergence of multidrug-resistant strains has become a challenge for developing effective treatment options.... (Review)
Review
has emerged as one of major nosocomial pathogen and global emergence of multidrug-resistant strains has become a challenge for developing effective treatment options. has developed resistance to almost all the antibiotics viz beta-lactams, carbapenems, tigecycline and now colistin, a last resort of antibiotics. The world is on the cusp of post antibiotic era and the evolution of multi-, extreme- and pan-drug-resistant strains is its obvious harbinger. Various combinations of antibiotics have been investigated but no successful treatment option is available. All these failed efforts have led researchers to develop and implement prophylactic vaccination for the prevention of infections caused by this pathogen. In this review, the advantages and disadvantages of active and passive immunization, the types of sub-unit and multi-component vaccine candidates investigated against viz whole cell organism, outer membrane vesicles, outer membrane complexes, conjugate vaccines and sub-unit vaccines have been discussed. In addition, the benefits of Reverse vaccinology are emphasized here in which the potential vaccine candidates are predicted using bioinformatic online tools prior to in vivo validations.
PubMed: 35261870
DOI: 10.1007/s13205-022-03148-9 -
Immunotherapy Aug 2023The article explores the possibility of using nanoparticles and IgY technology together for biosensing and antibody delivery to fight mammalian infections. The use of... (Review)
Review
The article explores the possibility of using nanoparticles and IgY technology together for biosensing and antibody delivery to fight mammalian infections. The use of IgG in passive immunotherapy has drawbacks; however, nanoparticles and IgY technology offer new opportunities for diagnostic and therapeutic applications. The primary selection of reports was based on the title and abstract, and potential studies were selected based on predefined inclusion criteria such as nanoparticle/nanomaterials and IgY, studies that have employed nanoparticles-IgY for diagnostic and therapeutic applications and animal experiments. Nanoparticle-IgY conjugates have great potential in diagnostics and therapeutics, but translation of nanotechnology-based IgY technology from laboratory settings to clinical setup is still a challenge. As science advances, nanoimmunotherapy can be explored in modern-day medicine.
Topics: Animals; Chickens; Immunoglobulins; Antibodies; Immunization, Passive; Nanotechnology; Mammals
PubMed: 37222153
DOI: 10.2217/imt-2022-0304 -
Daru : Journal of Faculty of Pharmacy,... Dec 2020A recent survey has shown that the COVID-19 pandemic has culminated in dramatical and critical treatment particularly in acute infected patients. In fact, this... (Meta-Analysis)
Meta-Analysis
PURPOSE
A recent survey has shown that the COVID-19 pandemic has culminated in dramatical and critical treatment particularly in acute infected patients. In fact, this systematic review-meta-analysis was directly pertained to estimation at the efficient value of some clinical managements to confront the COVID-19 infection.
METHODS
Pubmed, Embase, Scopus, Cochrane, and Scholar databases were searched from inception to July 1, 2020, to identify studies reporting the current treatment process and medications (e.g. hydroxychloroquine, antiviral therapy, convalescent plasma, and immunomodulatory agents) for COVID-19. A random-effects model meta-analysis was performed to calculate the relative risk (RR) with 95% confidence intervals (CI). The outcomes of this study were the frequency of negative conversion cases, clinical improvements, mechanical ventilation demand, intensive care unit (ICU) entry, and mortality. The standard treatment refers to the published guidelines and specialist experience which varies in different articles, and the proposed treatment refers to the kind of interest suggested in the included studies.
RESULTS
A number of 45 articles met the eligibility criteria (out of 6793 articles). Among them, 26 articles involving 3263 patients were included in quantitative analysis. Anti-COVID-19 interventions could significantly increase clinical improvement (RR 1.17, 95% CI 1.08-1.27; I = 49.8%) and reduce the mortality rate (RR 0.58, 95% CI 0.35-0.95; I = 74.8%). Although in terms of negative conversion, ICU entry, and mechanical ventilation demand, clinical intervention had no beneficial effect. The clinical effect of immunomodulatory agents (especially tocilizumab and anakinra) was noticeable compared to other medications with RR of 0.22 (95% CI 0.09-0.53; I = 40.9%) for mortality and 1.25 (95% CI 1.07-1.46; I = 45.4%) for clinical improvement. Moreover, Antivirals (RR 1.13, 95% CI 1.01-1.26; I = 47.0%) and convalescent plasma therapy (RR 1.41, 95% CI 1.01-1.98; I = 66.6%) had significant beneficial effects on clinical improvement.
CONCLUSION
Based on our findings, all the included interventions significantly declined the mortality and enhanced clinical improvements with no effect on negative conversion and mechanical ventilation demand. Especially, immunomodulators and plasma therapy showed favorable outcomes. An evaluation on the efficacy of proposed treatment against COVID-19.
Topics: Antiviral Agents; COVID-19; Humans; Immunization, Passive; Immunologic Factors; Intensive Care Units; Respiration, Artificial; COVID-19 Serotherapy
PubMed: 32812187
DOI: 10.1007/s40199-020-00367-4 -
Journal of Autoimmunity Nov 2023This systematic review aimed to characterise the cognitive outcomes of patients who received chimeric antigen receptor T-cell therapy. (Review)
Review
BACKGROUND
This systematic review aimed to characterise the cognitive outcomes of patients who received chimeric antigen receptor T-cell therapy.
METHODS
A systematic search of the literature was performed using PubMed, PsycINFO, SCOPUS, EMBASE, Medline, and CINAHL (February 2023). Risk of bias was assessed using the JBI Checklist for Case Reports and the Risk of Bias Assessment Tool for Non-randomised Studies.
RESULTS
Twenty-two studies met inclusion criteria with a total of 1104 participants. There was considerable methodological heterogeneity with differing study designs (e.g., cohort studies, clinical trials, case studies, a qualitative interview, and a focus group), measures of cognition (e.g., self-report, neuropsychological measures, clinician assessed/neurological examinations), and longest follow-up time points (i.e., five days to five years).
DISCUSSION
Results of the studies were heterogenous with studies demonstrating stable, improved, or reduced cognition across differing time points. Overall, cognitive symptoms are common particularly in the acute stage (<2 weeks) post-infusion. Most deficits that arise in the acute stage resolve within one to two weeks, however, there is a subset of patients who continue to experience and self-report persistent deficits in the subacute and chronic stages. Future studies are needed to comprehensively analyse cognition using a combination of self-report and psychometric measures following chimeric antigen receptor T-cell therapy in the acute, subacute, and chronic settings.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Cognition; Treatment Outcome
PubMed: 37837807
DOI: 10.1016/j.jaut.2023.103126