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Systematic Reviews Apr 2024Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA.
METHODS
We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis.
RESULTS
A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics.
CONCLUSION
EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.
Topics: Humans; Immunosuppressive Agents; Anemia, Aplastic; Immunosuppression Therapy; Benzoates; Pathologic Complete Response; Treatment Outcome; Hydrazines; Pyrazoles
PubMed: 38576005
DOI: 10.1186/s13643-024-02515-2 -
Skin Health and Disease Apr 2024To assess current evidence of effectiveness of sequential lines of biologic and targeted small molecule drugs for psoriasis beyond first line. A systematic search of the...
To assess current evidence of effectiveness of sequential lines of biologic and targeted small molecule drugs for psoriasis beyond first line. A systematic search of the literature (Medline, Embase and bibliographic) was undertaken in October and December 2022 to find all studies assessing effectiveness of biologics and targeted small molecules when used beyond first-line in adults with psoriasis (PROSPERO CRD42022365298). Data extraction and a bias assessment (Risk Of Bias In Non-randomized Studies-of Interventions/Cochrane RoB2) were undertaken for all included studies. A random effects proportional meta-analysis was undertaken for PASI75/90/100 at 12-16 weeks for each line of treatment (1st to 4th). Of 2666 abstracts identified, a full text review was undertaken of 177 studies; 20 manuscripts met eligibility criteria. Twenty studies were included in the analysis: 19 observational studies and one sub analysis of a RCT; = 6495 (average age 49.7 years, female 35.1%). Eleven studies assessed second line biologic, nine assessed third + line. A meta-analysis of PASI75 at 12-16 weeks found pooled effect percentage achieving PASI75 of 61%, 56%, 79% and 61% in 1st, 2nd, 3rd and 4th line biologics respectively. Meta-analyses of PASI90/100 also found no evidence of diminished effectiveness with sequential lines (PASI90 46.1%, 39.9%, 55.8% and 33.7% and PASI100 36.7%, 30.3%, 46.7% and 30.4% in 1st to 4th line respectively). Available evidence for effectiveness of biologics beyond first line in psoriasis is predominantly observational, at high risk of bias and of low quality. There is very limited data for effectiveness beyond second line. Evidence indicates that biologics can be effective to fourth-line.
PubMed: 38577060
DOI: 10.1002/ski2.350 -
Journal of Crohn's & Colitis Feb 2024Randomised controlled trials historically under-represent marginalised racial and ethnic populations. As incidence and prevalence of Crohn's disease in these groups... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Randomised controlled trials historically under-represent marginalised racial and ethnic populations. As incidence and prevalence of Crohn's disease in these groups rise, it is important to characterise their inclusion in randomised controlled trials on first-line and pipe-line medications.
METHODS
PubMed was searched systematically for randomised controlled trials of biologic and small molecule inhibitor [SMI] medications, with a primary outcome related to efficacy following PRISMA guidelines. We used descriptive statistics to summarise demographic variables and meta-regression analyses to estimate temporal trends in racial inclusion.
RESULTS
More than a half of trials did not report any racial/ethnic demographics [53.7%] and several reported racial demographics for only one race [20.9%]. When racial data were reported, Whites made up 90.2% of participants. Percentages of Black, Asian, Native American/Pacific Islander, and participants considered 'Other' averaged 2.9%, 11.6%, 0.5%, and 1.6% out of the total sample sizes of 3901, 3742, 828 and 4027, respectively. Proportional representation of White participants decreased over time [p <0.01] and proportional representation of Asian participants increased over time [p = 0.047]. In ordinal logistic regression, mean year of trial enrolment significantly increased the number of racial groups reported [p <0.001].
CONCLUSIONS
Half of published randomised controlled trials in Crohn's disease contain no racial or ethnic demographics, and the remaining often only have limited inclusion of Black, Native American/Pacific Islander, and Hispanic patients. Further work should characterise representation in observational and prospective trials. Researchers should work to: 1] increase reporting of racial and ethnic demographics; and 2] improve recruitment and retention of marginalised populations.
Topics: Humans; United States; Crohn Disease; Prospective Studies; Ethnicity; Hispanic or Latino; Racial Groups
PubMed: 37586091
DOI: 10.1093/ecco-jcc/jjad138 -
Nutrition, Metabolism, and... Oct 2023Grape consumption-associated improvements in cardiovascular health have received significant attention over the last few years; however, major gaps have remained in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Grape consumption-associated improvements in cardiovascular health have received significant attention over the last few years; however, major gaps have remained in the meta-evidence related to this topic. This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to explore the effect of whole grapes and its products on blood pressure, endothelial function, heart rate, and pulse rate.
METHODS AND RESULTS
Four database (PubMed, Scopus, Web of Sciences, and the Cochrane Library) were searched until the 14th of January 2022. The pooled effect size of interested outcomes was calculated using the random-effects model. Thirty eligible RCTs were identified. Pooled results indicated that compared to the control group, consumption of grape products significantly decreased systolic blood pressure (SBP) (WMD = -3.17 mmHg; 95% CI: -5.36, -0.99 mmHg; P = 0.004; I = 64%; P-heterogeneity<0.001); while, vascular cell adhesion molecule-1 (VCAM-1) increased (WMD = 34.11 ng/ml; 95% CI: 0.98, 67.25 ng/ml; P = 0.04; I = 2%; P-heterogeneity = 0.4). Although, the certainty of evidence was low and very low, respectively. No significant effect was observed on diastolic blood pressure, endothelial function, heart rate, pulse rate, and soluble intercellular adhesion molecule-1 (sICAM-1). In a subgroup analysis, consumption of whole grape products (raisin and grape powder) induced a significant decrease in SBP (WMD = -2.69 mmHg; 95% CI: -4.81, -0.57; P = 0.01; I = 18.1%; P-heterogeneity < 0.001), while grape juice did not.
CONCLUSION
The low certainty of evidence from RCTs revealed that consumption of grape products, especially in whole forms, resulted in a small reduction of SBP but did not influence other markers of cardiovascular health.
PROSPERO REGISTRATION CODE
CRD42022379231.
Topics: Humans; Blood Pressure; Vitis; Randomized Controlled Trials as Topic; Heart Rate; Hypertension
PubMed: 37482483
DOI: 10.1016/j.numecd.2023.05.001 -
Clinical Gastroenterology and... Mar 2024There are limited data on the safety of immunosuppressive therapy use in individuals with immune-mediated diseases with a history of malignancy, particularly with newer... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
There are limited data on the safety of immunosuppressive therapy use in individuals with immune-mediated diseases with a history of malignancy, particularly with newer biologic and small-molecule treatments.
METHODS
We performed a systematic search of PubMed and Embase databases to identify studies examining the impact of immunosuppressive therapies on cancer recurrence across several immune-mediated diseases. Studies were pooled together using random-effects meta-analysis and stratified by type of treatment. Primary outcome was occurrence of incident cancers, defined as new or recurrent.
RESULTS
Our meta-analysis included 31 studies (17 inflammatory bowel disease, 14 rheumatoid arthritis, 2 psoriasis, and 1 ankylosing spondylitis) contributing 24,328 persons and 85,784 person-years (p-y) of follow-up evaluation. Rates of cancer recurrence were similar among individuals not on immunosuppression (IS) (1627 incident cancers, 43,765 p-y; 35 per 1000 p-y; 95% CI, 27-43), receiving an anti-tumor necrosis factor (571 incident cancers, 17,772 p-y; 32 per 1000 p-y; 95% CI, 25-38), immunomodulators (1104 incident cancers, 17,018 p-y; 46 per 1000 p-y; 95% CI, 31-61), combination immunosuppression (179 incident cancers, 2659 p-y; 56 per 1000 p-y; 95% CI, 31-81). Patients receiving ustekinumab (5 incident cancers, 213 p-y; 21 per 1000 p-y; 95% CI, 0-44) and vedolizumab (37 incident cancers, 1951 p-y; 16 per 1000 p-y; 95% CI, 5-26) had numerically lower rates of cancer. There were no studies on Janus kinase inhibitors. Stratification of studies by timing of immunosuppression initiation did not reveal a medication effect based on early (<5 years) or delayed treatment initiation.
CONCLUSIONS
In patients with immune-mediated diseases and a history of malignancy, we observed similar rates of cancer recurrence in those on no immunosuppression compared with different immunosuppressive treatments.
Topics: Humans; Immunosuppressive Agents; Immunosuppression Therapy; Immunologic Factors; Ustekinumab; Recurrence; Neoplasms; Inflammatory Bowel Diseases
PubMed: 37579866
DOI: 10.1016/j.cgh.2023.07.027 -
Asian Journal of Surgery May 2024The gut microbiome is the entirety of microorganisms and their genomes residing in the gut, characterised by diversity, stability, and resilience. Disrupted gut... (Review)
Review
The gut microbiome is the entirety of microorganisms and their genomes residing in the gut, characterised by diversity, stability, and resilience. Disrupted gut microbiome has been implicated in multiple disease entities. The aim of this paper is to summarise the rapidly evolving contemporary evidence of gut dysbiosis on the development and progression of abdominal aortic aneurysm (AAA), discuss possible mechanisms, and explore potential microbiota-targeted interventions and prognostic markers for AAA. A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using PubMed, ScienceDirect, Web of Science, Ovid, Embase. Search terms of "microbiome" OR "dysbiosis" OR "microorganism"; AND "aneurysm" OR "dilatation" OR "aorta" were used. Study endpoints included effects of microbiota on AAA formation, effects of specific type of bacteria and its metabolite on AAA formation, and pre- or post-treatment by novel small-molecules/inhibitors. From May to August 2023, a total of twelve animal studies and eight human studies were included. Akkermansia muciniphila, Lactobacillus acidophilus and species from the Bacteroidetes phylum were associated with lower AAA incidence in both animal and human studies, while Proteobacteria phylum, Campylobacter, Fusobacterium and Faecalibacterium prausnitzii were found to be in abundance in the AAA group and were associated with larger aneurysms. The diversity of gut microbiota was inversely correlated with AAA diameter. Three important mechanisms were identified: including trimethylamine N-oxide pathway, butyric acid pathway, and aberrant tryptophan metabolism. With our expanding knowledge of the downstream pathogenic mechanisms of gut dysbiosis, novel therapeutics such as short-chain fatty acids and spermidine, as well as prognostic biomarkers such as TMAO have yielded promising preclinical results. In conclusion, there is strong evidence corroborating the role of gut dysbiosis in the pathogenesis of AAA, wherein its therapeutic and prognostic potential deserves further exploration.
PubMed: 38772822
DOI: 10.1016/j.asjsur.2024.05.058 -
Viruses Jul 2023Whether RNA-RNA interactions of cytoplasmic RNA viruses, such as , might end in the biogenesis of putative virus-derived small RNAs as miRNA-like molecules has been...
Computational Prediction of RNA-RNA Interactions between Small RNA Tracks from Nonstructural Protein 3 and Neurotrophin Genes during Infection of an Epithelial Lung Cancer Cell Line: Potential Role of Novel Small Regulatory RNA.
Whether RNA-RNA interactions of cytoplasmic RNA viruses, such as , might end in the biogenesis of putative virus-derived small RNAs as miRNA-like molecules has been controversial. Even more, whether RNA-RNA interactions of wild animal viruses may act as virus-derived small RNAs is unknown. Here, we address these issues in four ways. First, we use conserved RNA structures undergoing negative selection in the genomes of SARS-CoV, MERS-CoV, and SARS-CoV-2 circulating in different bat species, intermediate animals, and human hosts. Second, a systematic literature review was conducted to identify -targeting hsa-miRNAs involved in lung cell infection. Third, we employed sophisticated long-range RNA-RNA interactions to refine the seed sequence homology of hsa-miRNAs with conserved RNA structures. Fourth, we used high-throughput RNA sequencing of a -infected epithelial lung cancer cell line (Calu-3) to validate the results. We proposed nine potential virus-derived small RNAs: two vsRNAs in SARS-CoV (Bats: SB-vsRNA-ORF1a-3p; SB-vsRNA-S-5p), one vsRNA in MERS-CoV (Bats: MB-vsRNA-ORF1b-3p), and six vsRNAs in SARS-CoV-2 (Bats: S2B-vsRNA-ORF1a-5p; intermediate animals: S2I-vsRNA-ORF1a-5p; and humans: S2H-vsRNA-ORF1a-5p, S2H-vsRNA-ORF1a-3p, S2H-vsRNA-ORF1b-3p, S2H-vsRNA-ORF3a-3p), mainly encoded by nonstructural protein 3. Notably, -derived small RNAs targeted 74 differentially expressed genes in infected human cells, of which 55 upregulate the molecular mechanisms underlying acute respiratory distress syndrome (ARDS), and the 19 downregulated genes might be implicated in neurotrophin signaling impairment. These results reveal a novel small RNA-based regulatory mechanism involved in neuropathogenesis that must be further studied to validate its therapeutic use.
Topics: Animals; Humans; Chiroptera; SARS-CoV-2; COVID-19; Lung Neoplasms; MicroRNAs; Middle East Respiratory Syndrome Coronavirus; Cell Line; Lung; Nerve Growth Factors
PubMed: 37631989
DOI: 10.3390/v15081647 -
Heliyon Mar 2024Diabetes mellitus (DM) is one of the fastest-growing diseases worldwide; however, its pathogenesis remains unclear. Complications seriously affect the quality of life of... (Review)
Review
CONTEXT
Diabetes mellitus (DM) is one of the fastest-growing diseases worldwide; however, its pathogenesis remains unclear. Complications seriously affect the quality of life of patients in the later stages of diabetes, ultimately leading to suffering. Natural small molecules are an important source of antidiabetic agents.
OBJECTIVE
Astragaloside IV (AS-IV) is an active ingredient of Astragalus mongholicus (Fisch.) Bunge. We reviewed the efficacy and mechanism of action of AS-IV in animal and cellular models of diabetes and the mechanism of action of AS-IV on diabetic complications in animal and cellular models. We also summarized the safety of AS-IV and provided ideas and rationales for its future clinical application.
METHODS
Articles on the intervention in DM and its complications using AS-IV, such as those published in SCIENCE, PubMed, Springer, ACS, SCOPUS, and CNKI from the establishment of the database to February 2022, were reviewed. The following points were systematically summarized: dose/concentration, route of administration, potential mechanisms, and efficacy of AS-IV in animal models of DM and its complications.
RESULTS
AS-IV has shown therapeutic effects in animal models of DM, such as alleviating gestational diabetes, delaying diabetic nephropathy, preventing myocardial cell apoptosis, and inhibiting vascular endothelial dysfunction; however, the potential effects of AS-IV on DM should be investigated.
CONCLUSION
AS-IV is a potential drug for the treatment of diabetes and its complications, including diabetic vascular disease, cardiomyopathy, retinopathy, peripheral neuropathy, and nephropathy. In addition, preclinical toxicity studies indicate that it appears to be safe, but the safe human dose limit is yet to be determined, and formal assessments of adverse drug reactions among humans need to be further investigated. However, additional formulations or structural modifications are required to improve the pharmacokinetic parameters and facilitate the clinical use of AS-IV.
PubMed: 38439832
DOI: 10.1016/j.heliyon.2024.e26863 -
Therapeutic Advances in Medical Oncology 2024Compared with anti-infective drugs, immunosuppressants and other fields, the application of therapeutic drug monitoring (TDM) in oncology is somewhat limited. (Review)
Review
BACKGROUND
Compared with anti-infective drugs, immunosuppressants and other fields, the application of therapeutic drug monitoring (TDM) in oncology is somewhat limited.
OBJECTIVE
We aimed to provide a comprehensive understanding of TDM guidelines for antineoplastic drugs and to promote the development of individualized drug therapy in oncology.
DESIGN
This study type is a systematic review.
DATA SOURCES AND METHODS
This study was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Databases including PubMed, Embase, the official websites of TDM-related associations and Chinese databases were comprehensively searched up to March 2023. Two investigators independently screened the literature and extracted data. The methodological and reporting quality was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) and the Reporting Items for Practice Guidelines in Healthcare (RIGHT), respectively. Recommendations and quality evaluation results were presented by visual plots. This study was registered in PROSPERO (No. CRD42022325661).
RESULTS
A total of eight studies were included, with publication years ranging from 2014 to 2022. From the perspective of guideline development, two guidelines were developed using evidence-based methods. Among the included guidelines, four guidelines were for cytotoxic antineoplastic drugs, three for small molecule kinase inhibitors, and one for antineoplastic biosimilars. Currently available guidelines and clinical practice provided recommendations of individualized medication in oncology based on TDM, as well as influencing factors. With regard to methodological quality based on AGREE II, the average overall quality score was 55.21%. As for the reporting quality by RIGHT evaluation, the average reporting rate was 53.57%.
CONCLUSION
From the perspective of current guidelines, TDM in oncology is now being expanded from cytotoxic antineoplastic drugs to newer targeted treatments. Whereas, the types of antineoplastic drugs involved are still small, and there is still room for quality improvement. Furthermore, the reflected gaps warrant future studies into the exposure-response relationships and population pharmacokinetics models.
PubMed: 38812991
DOI: 10.1177/17588359241250130 -
Frontiers in Cellular Neuroscience 2023Limb-girdle muscular dystrophies (LGMD) constitute a heterogeneous group of neuromuscular disorders in which there are alterations in proteins responsible for the... (Review)
Review
Limb-girdle muscular dystrophies (LGMD) constitute a heterogeneous group of neuromuscular disorders in which there are alterations in proteins responsible for the preservation of muscle architecture and function, leading to proximal and progressive muscle weakness. There is, however, significant phenotypic and genotypic variation, as well as difficulty in establishing biomarkers that help to define pathogenic mechanisms and assess disease severity and progression. In this field, there is special attention to microRNAs, small non-coding RNA molecules related to the regulation of gene expression and, consequently, the production of proteins. Thus, this research aimed to verify the correlation between the expression of microRNAs and the severity, progression, and therapeutic response of LGMD animal models. A search was carried out in the PubMed, Embase, Scopus, ScienceDirect, Cochrane, and SciELO databases, with articles in English and without a time limit. The PRISMA 2020 checklist was used, and the protocol of this review was submitted to PROSPERO. The bibliographic survey of the 434 records found that 5 original articles met the inclusion criteria. The studies explored myomicroRNAs or miRNA panels with gene expression analysis. The analysis demonstrates that miR-1, 133a, and 206 are differentially expressed in serum and muscle. They change according to the degree of inflammation, fibrosis, muscle regeneration, and progression of the dystrophic process. MicroRNAs are up-regulated in dystrophic muscles, which are reversed after treatment in a dose-dependent manner. The present study inferred that miRs are essential in severity, progression, and therapeutic response in LGMD models and may be a useful biomarker in clinical research and prognosis. However, the practical application of these findings should be further explored.
PubMed: 38130868
DOI: 10.3389/fncel.2023.1233181