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JAMA Network Open May 2021Hematopoietic stem cell transplant (HSCT) is an advisable option for refractory or relapsed peripheral T-cell lymphoma (R/R-PTCL), but whether allogeneic HSCT or... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of Allogeneic Stem Cell Transplant and Autologous Stem Cell Transplant in Refractory or Relapsed Peripheral T-Cell Lymphoma: A Systematic Review and Meta-analysis.
IMPORTANCE
Hematopoietic stem cell transplant (HSCT) is an advisable option for refractory or relapsed peripheral T-cell lymphoma (R/R-PTCL), but whether allogeneic HSCT or autologous HSCT is more beneficial is unknown.
OBJECTIVE
To compare the effectiveness and safety of allogeneic HSCT vs autologous HSCT in patients with R/R-PTCL.
DATA SOURCES
A systematic search of the PubMed, Embase, the Cochrane Central Register of Controlled Trials, Wanfang, and China National Knowledge Infrastructure databases with the search items refractory or relapsed peripheral T-cell lymphoma, ASCT/autologous stem-cell transplantation, allo-HSCT/allogeneic stem-cell transplantation, therapeutic effect, and treatment was conducted for articles published from January 12, 2001, to October 1, 2020.
STUDY SELECTION
After duplicate and irrelevant publications were discarded, 329 were ineligible according to the inclusion (clinical trials or retrospective studies with >10 samples) and exclusion criteria (articles without overall survival [OS], progression-free survival [PFS], and transplantation-related mortality [TRM]). Thirty trials were included in the meta-analysis. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
DATA EXTRACTION AND SYNTHESIS
Data on study design, individual characteristics, and outcomes were extracted. All statistics were pooled by applying a random-effects model.
MAIN OUTCOMES AND MEASURES
The prespecified main outcomes were OS, PFS, and TRM.
RESULTS
Of 6548 articles, data extracted from the 30 studies (including 880 patients who underwent allogeneic HSCT and 885 who underwent autologous HSCT) were included in this meta-analysis. In the allogeneic HSCT group, a 3-year OS of 50% (95% CI, 41%-60%) and PFS of 42% (95% CI, 35%-51%), a 5-year OS of 54% (95% CI, 47%-62%) and PFS of 48% (95% CI, 40%-56%), and a 3-year TRM of 32% (95% CI, 27%-37%) were observed. In the autologous HSCT group, a 3-year OS of 55% (95% CI, 48%-64%) and PFS of 41% (95% CI, 33%-51%), a 5-year OS of 53% (95% CI, 44%-64%) and PFS of 40% (95% CI, 24%-58%), and a 3-year TRM of 7% (95% CI, 2%-23%) were observed.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, OS and PFS were similar in the allogeneic HSCT and autologous HSCT groups; however, allogeneic HSCT was associated with specific survival benefits among patients with R/R-PTCL.
Topics: Humans; Lymphoma, T-Cell, Peripheral; Neoplasm Recurrence, Local; Stem Cell Transplantation; Transplantation, Autologous; Transplantation, Homologous; Treatment Failure
PubMed: 34042995
DOI: 10.1001/jamanetworkopen.2021.9807 -
Frontiers in Cardiovascular Medicine 2022Several studies have investigated the value of the systemic immune-inflammation index (SII) for predicting cardiovascular disease (CVD), but the results were...
BACKGROUND
Several studies have investigated the value of the systemic immune-inflammation index (SII) for predicting cardiovascular disease (CVD), but the results were inconsistent. Therefore, a meta-analysis and systematic review were conducted to assess the correlation between SII and risk of CVD.
MATERIALS AND METHODS
Two investigators systematically searched PubMed, Embase, Web of Science, Cochrane library, and CINAHL databases to identify all studies that examined the association between SII levels and CVD. The risk estimates of CVD for people with high SII compared to those with low SII levels and the weighted mean difference (WMD) between the CVD and control groups were pooled using fixed- or random-effects models based on the heterogeneity test. We used the Newcastle-Ottawa Scale to assess the risk of bias in eligible studies, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was applied to rate the certainty of evidence.
RESULTS
A total of 13 studies with 152,996 participants were included for analysis. The overall pooled results showed that higher SII was significantly associated with an increased risk of CVD (HR = 1.39, 95%CI: 1.20-1.61, < 0.001). This increased risk could be observed in almost all CVD subtypes, including ischemic stroke (HR = 1.31, 95%CI: 1.06-1.63, = 0.013), hemorrhagic stroke (HR = 1.22, 95%CI: 1.10-1.37, < 0.001), myocardial infarction (HR = 1.11, 95%CI: 1.01-1.23, = 0.027), and peripheral arterial disease (HR = 1.51, 95%CI: 1.18-1.93, = 0.001). There were no significant but still similar trends in venous thrombosis (HR = 4.65, 95%CI: 0.66-32.71, = 0.122), cerebral small vessel disease (HR = 1.09, 95%CI: 0.95-1.25, = 0.233), and acute coronary syndrome (HR = 1.08, 95%CI: 0.96-1.22, = 0.200). Furthermore, the pooled results showed that SII levels at the onset of CVD were significantly higher than that in the general population (WMD = 355.2, 95%CI: 234.8-475.6, < 0.001), which was consistent across different CVD subtypes. The GRADE assessment suggested that the quality of current evidence from observational studies was low or very low.
CONCLUSION
This study indicated that SII may be a potential biomarker for CVD development and elevated SII is associated with an increased risk of CVD. However, the quality of evidence is generally low. Additional well-designed studies are necessary to determine the optimal cutoff value and to characterize the benefited population.
PubMed: 36003917
DOI: 10.3389/fcvm.2022.933913 -
Cells Feb 2022The anti-thymic stromal lymphopoietin antibody (tezepelumab) has therapeutical potential for inadequately controlled asthma. However, evidence comparing tezepelumab with... (Meta-Analysis)
Meta-Analysis
Comparative Efficacy and Safety of Tezepelumab and Other Biologics in Patients with Inadequately Controlled Asthma According to Thresholds of Type 2 Inflammatory Biomarkers: A Systematic Review and Network Meta-Analysis.
The anti-thymic stromal lymphopoietin antibody (tezepelumab) has therapeutical potential for inadequately controlled asthma. However, evidence comparing tezepelumab with other biologics is scarce. To address this issue, we performed a network meta-analysis to compare and rank the efficacy of five treatments (tezepelumab, dupilumab, benralizumab, mepolizumab, and placebo) in overall participants and in subgroups stratified by the thresholds of type 2 inflammatory biomarkers, including peripheral blood eosinophil count (PBEC) and fractional exhaled nitric oxide (FeNO). The primary endpoints were annualized exacerbation rate (AER) and any adverse events (AAEs). In the ranking assessment using surface under the cumulative ranking curve (SUCRA) of AER, tezepelumab ranked the highest overall and across subgroups (based on PBEC and FeNO level thresholds). A significant difference was observed between tezepelumab and dupilumab in the patient subgroup with PBEC < 150, and between tezepelumab and benralizumab in overall participants and the patient subgroup with PBEC ≥ 300 and ≥150, respectively. There was no significant difference in the incidence of AAEs in the overall participants between each pair of five treatment arms. These results provide a basis for the development of treatment strategies for asthma and may guide basic, clinical, or translational research.
Topics: Antibodies, Monoclonal, Humanized; Asthma; Biological Products; Biomarkers; Humans; Network Meta-Analysis
PubMed: 35269440
DOI: 10.3390/cells11050819 -
Nutrients Oct 2020Citicoline is a chemical compound involved in the synthesis of cell membranes. It also has other, not yet explained functions. Research on the use of citicoline is...
Citicoline is a chemical compound involved in the synthesis of cell membranes. It also has other, not yet explained functions. Research on the use of citicoline is conducted in neurology, ophthalmology, and psychiatry. Citicoline is widely available as a dietary supplement. It is often used to enhance cognitive functions. In our article, accessible databases were searched for articles regarding citicoline use in neurological diseases. This article has a systemic review form. After rejecting non-eligible reports, 47 remaining articles were reviewed. The review found that citicoline has been proven to be a useful compound in preventing dementia progression. It also enhances cognitive functions among healthy individuals and improves prognosis after stroke. In an animal model of nerve damage and neuropathy, citicoline stimulated regeneration and lessened pain. Among patients who underwent brain trauma, citicoline has an unclear clinical effect. Citicoline has a wide range of effects and could be an essential substance in the treatment of many neurological diseases. Its positive impact on learning and cognitive functions among the healthy population is also worth noting.
Topics: Animals; Brain Injuries, Traumatic; Cognition; Cytidine Diphosphate Choline; Dementia; Disease Models, Animal; Humans; Meta-Analysis as Topic; Nervous System Diseases; Neuralgia; Neurotransmitter Agents; Peripheral Nervous System; Stroke
PubMed: 33053828
DOI: 10.3390/nu12103113 -
Molecular Psychiatry Mar 2023Meta-analyses implicate immune dysfunction in depression confirming increased levels of circulating immune proteins (e.g., cytokines) in depression cases compared to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Meta-analyses implicate immune dysfunction in depression confirming increased levels of circulating immune proteins (e.g., cytokines) in depression cases compared to controls. White blood cells (WBC) both produce and are influenced by cytokines, and play key roles in orchestrating innate and adaptive immune responses, but their role in depression remains unclear. Therefore, a systematic review of studies of various WBC subsets in depression is required for a greater understanding of the nature of immune dysfunction in this illness.
METHODS
We searched PubMed and PsycINFO databases (inception to 5 April 2022) and conducted a systematic review and meta-analysis of identified studies comparing absolute count and/or relative percentage of flow cytometry-derived WBC subsets between depression cases and controls. Selected studies were quality assessed. Random-effect meta-analysis was performed.
RESULTS
Thirty-three studies were included and 27 studies (n = 2277) were meta-analysed. We report an increase in mean absolute counts of WBC (seven studies; standardised mean difference [SMD] = 1.07; 95% CI, 0.61-1.53; P < 0.01; I = 64%), granulocytes (two studies; SMD = 2.07; 95% CI, 1.45-2.68; P < 0.01; I = 0%), neutrophils (four studies; SMD = 0.91; 95% CI, 0.23-1.58; P < 0.01; I = 82%), monocytes (seven studies; SMD = 0.60; 95% CI, 0.19-1.01; P < 0.01; I = 66%), CD4 helper T cells (11 studies; SMD = 0.30; 95% CI, 0.15-0.45; P < 0.01; I = 0%), natural killer cells (11 studies; SMD = 1.23; 95% CI, 0.38-2.08; P < 0.01; I = 95%), B cells (10 studies; SMD = 0.30; 95% CI, 0.03-0.57; P = 0.03; I = 56%), and activated T cells (eight studies; SMD = 0.45; 95% CI, 0.24-0.66; P < 0.01; I = 0%) in depression, compared to controls. Fewer studies reported relative percentage, indicating increased neutrophils and decreased total lymphocytes, Th1, and Th2 cells in depression.
CONCLUSIONS
Depression is characterised by widespread alterations in circulating myeloid and lymphoid cells, consistent with dysfunction in both innate and adaptive immunity. Immune cells could be useful biomarkers for illness subtyping and patient stratification in future immunotherapy trials of depression, along with cytokines, other biomarkers, and clinical measures.
Topics: Humans; Depression; Biomarkers
PubMed: 36577838
DOI: 10.1038/s41380-022-01919-7 -
NPJ Parkinson's Disease Feb 2023Neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD), but controversies persist. Studies reporting concentrations of blood or... (Review)
Review
Neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD), but controversies persist. Studies reporting concentrations of blood or cerebrospinal fluid (CSF) markers for patients with PD and controls were included and extracted. Pooled Hedges'g was adopted to illustrate comparisons, and covariates were used to explore sources of heterogeneity. Finally, 152 studies were included. Increased IL-6, TNF-α, IL-1β, STNFR1, CRP, CCL2, CX3CL1, and CXCL12 levels and decreased INF-γ and IL-4 levels were noted in the PD group. In addition, increased CSF levels of IL-6, TNF-α, IL-1β, CRP and CCL2 were revealed in patients with PD compared to controls. Consequently, significantly altered levels of inflammatory markers were verified between PD group and control, suggesting that PD is accompanied by inflammatory responses in both the peripheral blood and CSF. This study was registered with PROSPERO, CRD42022349182.
PubMed: 36739284
DOI: 10.1038/s41531-023-00449-5 -
EBioMedicine Mar 2023Mass vaccination has dramatically reduced the incidence of severe COVID-19, with most cases now presenting as self-limiting upper respiratory tract infections. However,...
BACKGROUND
Mass vaccination has dramatically reduced the incidence of severe COVID-19, with most cases now presenting as self-limiting upper respiratory tract infections. However, those with co-morbidities, the elderly and immunocompromised, as well as the unvaccinated, remain disproportionately vulnerable to severe COVID-19 and its sequelae. Furthermore, as the effectiveness of vaccination wanes with time, immune escape SARS-CoV-2 variants could emerge to cause severe COVID-19. Reliable prognostic biomarkers for severe disease could be used as early indicator of re-emergence of severe COVID-19 as well as for triaging of patients for antiviral therapy.
METHODS
We performed a systematic review and re-analysis of 7 publicly available datasets, analysing a total of 140 severe and 181 mild COVID-19 patients, to determine the most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients. In addition, we included an independent cohort where blood transcriptomics of COVID-19 patients were prospectively and longitudinally monitored previously, to track the time in which these gene expression changes occur before nadir of respiratory function. Single cell RNA-sequencing of peripheral blood mononuclear cells from publicly available datasets was then used to determine the immune cell subsets involved.
FINDINGS
The most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients were MCEMP1, HLA-DRA and ETS1 across the 7 transcriptomics datasets. Moreover, we found significantly heightened MCEMP1 and reduced HLA-DRA expression as early as four days before the nadir of respiratory function, and the differential expression of MCEMP1 and HLA-DRA occurred predominantly in CD14+ cells. The online platform which we developed is publicly available at https://kuanrongchan-covid19-severity-app-t7l38g.streamlitapp.com/, for users to query gene expression differences between severe and mild COVID-19 patients in these datasets.
INTERPRETATION
Elevated MCEMP1 and reduced HLA-DRA gene expression in CD14+ cells during the early phase of disease are prognostic of severe COVID-19.
FUNDING
K.R.C is funded by the National Medical Research Council (NMRC) of Singapore under the Open Fund Individual Research Grant (MOH-000610). E.E.O. is funded by the NMRC Senior Clinician-Scientist Award (MOH-000135-00). J.G.H.L. is funded by the NMRC under the Clinician-Scientist Award (NMRC/CSAINV/013/2016-01). S.K. is funded by the NMRC under the Transition Award. This study was sponsored in part by a generous gift from The Hour Glass.
Topics: Humans; Aged; HLA-DR alpha-Chains; COVID-19; SARS-CoV-2; Leukocytes, Mononuclear; Prognosis
PubMed: 36801619
DOI: 10.1016/j.ebiom.2023.104472 -
ACR Open Rheumatology Apr 2023Biomarkers have been proposed as tools to aid in the identification and prognostication of interstitial lung disease (ILD) in rheumatoid arthritis (RA). We performed a...
BACKGROUND
Biomarkers have been proposed as tools to aid in the identification and prognostication of interstitial lung disease (ILD) in rheumatoid arthritis (RA). We performed a systematic review of studies evaluating peripheral blood biomarkers and their association with RA-ILD and its prognosis.
METHODS
Medline, Embase, the Cochrane Library, and Scopus were queried for relevant studies, with the final search update on July 12, 2021. We included studies evaluating peripheral blood biomarkers for the identification and/or prognostication of RA-ILD, extracting the performance of individual biomarkers for identifying RA-ILD, and predicting prognosis. Modified versions of the Quality Assessment of Diagnostic Accuracy Studies 2 and the Quality in Prognosis Studies tools were used for quality assessment.
RESULTS
Seventy studies met eligibility criteria. Study and patient characteristics, analytical methods, strength and consistency of associations, and study quality were heterogeneous. A total of 92 biomarkers were positively associated and 12 were negatively associated with RA-ILD among patients with RA in one or more report. Only a small number of biomarkers were evaluated in multiple cohorts using adjusted analyses. Biomarkers most strongly associated with RA-ILD overlapped with those identified for idiopathic pulmonary fibrosis. Few prognostic biomarkers of RA-ILD were identified.
CONCLUSION
Several peripheral blood biomarkers are associated with the presence of RA-ILD, but few have been assessed in multivariable models, have been externally validated, have discriminated RA-ILD from other lung disease, or have prognosticated the disease course. High-quality studies investigating and validating peripheral biomarkers in RA-ILD are needed before they can be employed in clinical care.
PubMed: 36852564
DOI: 10.1002/acr2.11535 -
Biomedicines Sep 2023Psychotic disorders are a heterogenous class of mental illness, with an intricate pathophysiology, involving genetics and environmental factors, and their interaction.... (Review)
Review
Psychotic disorders are a heterogenous class of mental illness, with an intricate pathophysiology, involving genetics and environmental factors, and their interaction. The identification of accessible biomarkers in bodily systems such as blood may lead to more accurate diagnosis, and more effective treatments targeting dysfunctional pathways, and could assist in monitoring the disease evolution. This systematic review aims to highlight the dysregulated microRNAs (miRNAs) in the peripheral blood of patients with psychotic disorders. Using the PRISMA protocol, PubMed and Science Direct databases were investigated and 22 articles were included. Fifty-five different miRNAs were found differentially expressed in the blood of psychotic patients compared to controls. Seventeen miRNAs (miR-34a, miR-181b, miR-432, miR-30e, miR-21, miR-137, miR-134, miR-7, miR-92a, miR-1273d, miR-1303, miR-3064-5p, miR-3131, miR-3687, miR-4428, miR-4725-3p, and miR-5096) were dysregulated with the same trend (up- or down-regulation) in at least two studies. Of note, miR-34a and miR-181b were up-regulated in the blood of psychotic patients in seven and six studies, respectively. Moreover, the level of miR-181b in plasma was found to be positively correlated with the amelioration of negative symptoms. The panel of miRNAs identified in this review could be validated in future studies in large and well-characterized cohorts of psychotic patients.
PubMed: 37760977
DOI: 10.3390/biomedicines11092536 -
Molecular Psychiatry Sep 2022(R,S)-ketamine (ketamine) and its enantiomer (S)-ketamine (esketamine) can produce rapid and substantial antidepressant effects. However, individual response to... (Meta-Analysis)
Meta-Analysis
(R,S)-ketamine (ketamine) and its enantiomer (S)-ketamine (esketamine) can produce rapid and substantial antidepressant effects. However, individual response to ketamine/esketamine is variable, and there are no well-accepted methods to differentiate persons who are more likely to benefit. Numerous potential peripheral biomarkers have been reported, but their current utility is unclear. We conducted a systematic review/meta-analysis examining the association between baseline levels and longitudinal changes in blood-based biomarkers, and response to ketamine/esketamine. Of the 5611 citations identified, 56 manuscripts were included (N = 2801 participants), and 26 were compatible with meta-analytical calculations. Random-effect models were used, and effect sizes were reported as standardized mean differences (SMD). Our assessments revealed that more than 460 individual biomarkers were examined. Frequently studied groups included neurotrophic factors (n = 15), levels of ketamine and ketamine metabolites (n = 13), and inflammatory markers (n = 12). There were no consistent associations between baseline levels of blood-based biomarkers, and response to ketamine. However, in a longitudinal analysis, ketamine responders had statistically significant increases in brain-derived neurotrophic factor (BDNF) when compared to pre-treatment levels (SMD [95% CI] = 0.26 [0.03, 0.48], p = 0.02), whereas non-responders showed no significant changes in BDNF levels (SMD [95% CI] = 0.05 [-0.19, 0.28], p = 0.70). There was no consistent evidence to support any additional longitudinal biomarkers. Findings were inconclusive for esketamine due to the small number of studies (n = 2). Despite a diverse and substantial literature, there is limited evidence that blood-based biomarkers are associated with response to ketamine, and no current evidence of clinical utility.
Topics: Humans; Ketamine; Brain-Derived Neurotrophic Factor; Antidepressive Agents; Biomarkers; Depressive Disorder, Treatment-Resistant
PubMed: 35760879
DOI: 10.1038/s41380-022-01652-1