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Frontiers in Immunology 2023Optimal biomarkers to select patients who will benefit most from immunotherapy remain lacking in nasopharyngeal cancer (NPC). This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Optimal biomarkers to select patients who will benefit most from immunotherapy remain lacking in nasopharyngeal cancer (NPC). This systematic review and meta-analysis aimed to evaluate the association between various biomarkers and clinical outcomes in NPC patients treated with immune checkpoint inhibitors (ICIs).
METHODS
Systematic searches of PubMed, Embase, Cochrane Library, and Web of Science databases were performed up to October 2022. Studies evaluating the association between biomarkers and intended outcomes of ICIs were included. The pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) were calculated, respectively, for the objective response rate (ORR) and progression-free survival (PFS) under fixed or random-effect models.
RESULTS
A total of 15 studies involving 1,407 patients were included. The pooled analysis indicated that NPC patients with lower plasma Epstein-Barr virus (EBV) DNA level at baseline (OR = 2.14, 95% CI: 1.46-3.14, < 0.001), decreased EBV DNA load during immunotherapy (OR = 4.57, 95% CI: 2.24-9.34, = 0.002) and higher programmed cell death-ligand 1 (PD-L1) expression (OR = 2.35, 95% CI: 1.36-4.09, = 0.002) had superior ORR than the counterparts. No significant differences of ORR were observed between positive PD-L1 expression and negative PD-L1 expression (OR = 1.50, 95% CI: 0.92-2.45, = 0.104), as well as higher tumor mutation burden (TMB) and lower TMB (OR = 1.62, 95% CI: 0.41-6.44, = 0.494). Patients with lower plasma EBV DNA level at baseline obtained a significant benefit on PFS than those with higher plasma EBV DNA level (HR = 0.52, 95% CI: 0.42-0.63, < 0.001). There were no differences in PFS between decreased EBV DNA load and increased EBV DNA load during immunotherapy (HR = 0.51, 95% CI: 0.22-1.17, = 0.109), higher PD-L1 expression and lower PD-L1 expression (HR = 0.65, 95% CI: 0.42-1.01, = 0.054), positive PD-L1 expression and negative PD-L1 expression (HR = 0.90, 95% CI: 0.64-1.26, = 0.531), lower TMB and higher TMB (HR = 0.84, 95% CI: 0.51-1.38, = 0.684).
CONCLUSION
Lower baseline plasma EBV DNA level, decreased plasma EBV DNA during immunotherapy, and higher PD-L1 expression are reliable biomarkers predicting better response to ICIs treatment. Lower baseline plasma EBV DNA level was also associated with longer PFS. It is warranted to further explore and better illuminate the utility of these biomarkers in future clinical trials and real-world practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022324434.
Topics: Humans; Immune Checkpoint Inhibitors; Nasopharyngeal Neoplasms; Epstein-Barr Virus Infections; B7-H1 Antigen; Biomarkers, Tumor; Herpesvirus 4, Human; Nasopharyngeal Carcinoma
PubMed: 37063822
DOI: 10.3389/fimmu.2023.1146898 -
Saudi Journal of Anaesthesia 2023The utility of instantaneous evaluation of coagulation during primary postpartum haemorrhage (PPH) is paramount in the context of empirical blood product...
BACKGROUND
The utility of instantaneous evaluation of coagulation during primary postpartum haemorrhage (PPH) is paramount in the context of empirical blood product transfusion-related risk of dilutional and consumptive coagulopathy and circulatory overload.
METHODS
A profound screening of electronic databases till August 15, 2022 was carried out after being enlisted in PROSPERO (CRD42021275514). Randomized control studies, comparative cohort studies, and cross-sectional studies comparing point-of-care viscoelastic test guided blood product transfusion with empirical transfusion in patients with PPH were included.
RESULTS
We retrieved five studies, with a total of 1914 parturient with PPH. Patients receiving transfusion based upon point of care viscoelastic tests had lesser risk of having emergency hysterectomy (Odds ratio (OR) = 0.55, 95% CI 0.32-0.95, I = 7%), transfusion-associated circulatory overload (TACO) (OR = 0.03, 95% CI 0.00-0.50), reduced transfusion of fresh frozen plasma (OR = 0.07, 95% CI 0.04-0.14, I = 89%), platelets (OR = 0.51, 95% CI 0.28-0.91, I = 89%), packed red blood cell transfusion (OR = 0.70, 95% CI 0.55-0.88, I = 89%), and had better cost-effective treatment [Mean difference (MD) = -357.5, 95% CI - 567.75 to -147.25, I = 93%] than patient received empirical transfusion. However, there was no significant difference in the requirement of ICU admissions (OR = 0.77, 95% CI = 0.46-1.29, I = 82%). No mortality was detected across the studies.
CONCLUSIONS
Point of care viscoelastic assessment guided transfusion in PPH confederates with reduced morbidity. Nevertheless, more studies on the triggering values for transfusion, long-term survival, and cost-benefit in patients with PPH are warranted to establish its utility.
PubMed: 37032697
DOI: 10.4103/sja.sja_529_22 -
Animal Nutrition (Zhongguo Xu Mu Shou... Jun 2023The goal of this review article, based on a systematic literature search, is to critically assess the state of knowledge and experimental methodologies used to delineate... (Review)
Review
The goal of this review article, based on a systematic literature search, is to critically assess the state of knowledge and experimental methodologies used to delineate the conversion and metabolism of the 2 methionine (Met) sources DL-methionine (DL-Met) and DL-2-hydroxy-4-(methylthio) butanoic acid (HMTBa). The difference in the chemical structures of HMTBa and DL-Met indicates that these molecules are absorbed and metabolized differently in animals. This review explores the methodologies used to describe the 2-step enzymatic conversion of the 3 enantiomers (D-HMTBa, L-HMTBa and D-Met) to L-Met, as well as the site of conversion at the organ and tissue levels. Extensive work was published documenting the conversion of HMTBa and D-Met into L-Met and, consequently, the incorporation into protein using a variety of in vitro techniques, such as tissue homogenates, cell lines, primary cell lines, and everted gut sacs of individual tissues. These studies illustrated the role of the liver, kidney, and intestine in the conversion of Met precursors into L-Met. A combination of in vivo studies using stable isotopes and infusions provided evidence of the wide conversion of HMTBa to L-Met by all tissues and how some tissues are net users of HMTBa, whereas others are net secreters of L-Met derived from HMTBa. Conversion of D-Met to L-Met in organs other than the liver and kidney is poorly documented. The methodology cited in the literature to determine conversion efficiency ranged from measurements of urinary, fecal, and respiratory excretion to plasma concentration and tissue incorporation of isotopes after intraperitoneal and oral infusions. Differences observed between these methodologies reflect differences in the metabolism of Met sources rather than differences in conversion efficiency. The factors affecting conversion efficiency are explored in this paper and are mostly associated with extreme dietary conditions, such as noncommercial crystalline diets that are very deficient in total sulfur amino acids with respect to requirements. Implications in the diversion of the 2 Met sources toward transsulfuration over transmethylation pathways are discussed. The strengths and weaknesses of some methodologies used are discussed in this review. From this review, it can be concluded that due to the inherent differences in conversion and metabolism of the 2 Met sources, the experimental methodologies (e.g., selecting different organs at different time points or using diets severely deficient in Met and cysteine) can impact the conclusions of the study and may explain the apparent divergences of conclusion found in the literature. It is recommended when conducting studies or reviewing the literature to properly select the experimental models that allow for differences in how the 2 Met precursors are converted to L-Met and metabolized by the animal to enable a proper comparison of their bioefficacy.
PubMed: 37009071
DOI: 10.1016/j.aninu.2023.01.009 -
Therapeutic Advances in Neurological... 2023Intravenous immunoglobulin (IVIg) and therapeutic plasma exchange (TPE) are among the main immunotherapies for neurological disorders. Their benefit is greatest in... (Review)
Review
BACKGROUND
Intravenous immunoglobulin (IVIg) and therapeutic plasma exchange (TPE) are among the main immunotherapies for neurological disorders. Their benefit is greatest in immune-mediated conditions, but their distinct efficacy cannot be simply explained.
OBJECTIVES
This review aimed to systematically identify studies comparing the efficacy of TPE and IVIg treatments for selected autoimmune neurological disorders and identify optimal therapies for each condition.
DATA SOURCES AND METHODS
PubMed, MEDLINE and Embase databases were searched for original publications from 1990 to 2021. Additional publications were identified expert recommendations. Conference abstracts older than 2017, review articles and articles without information on TPE and IVIg comparison in title and abstract were excluded. Risks of bias were descriptively addressed, without a meta-analysis.
RESULTS
Forty-four studies were included on Guillain-Barré syndrome (20 studies - 12 adult, 5 paediatric, 3 all ages), myasthenia gravis (11 studies -8 adult, 3 paediatric), chronic immune-mediated polyradiculoneuropathy (3 studies -1 adult, 2 paediatric), encephalitis (1 study in adults), neuromyelitis optica spectrum disorders (5 studies -2 adult, 3 all ages) and other conditions (4 studies - all ages). TPE and IVIg were mostly similarly efficacious, measured by clinical outcomes and disease severity scores. Some studies recommended IVIg as easy to administer. TPE procedures, however, have been simplified and the safety has been improved. TPE is currently recommended for management of neuromyelitis optica spectrum disorder relapses and some myasthenia gravis subtypes, in which rapid removal of autoantibodies is crucial.
CONCLUSION
Despite some limitations (e.g. the low evidence levels), this review provides an extensive 30-year-long overview of treatments for various conditions. Both IVIg and TPE are usually comparably efficacious options for autoimmune neurological disorders, with few exceptions. Treatment choices should be patient-tailored and based on available clinical resources. Better designed studies are needed to provide higher-level quality of evidence regarding clinical efficacy of TPE and IVIg treatments.
PubMed: 37006460
DOI: 10.1177/17562864231154306 -
World Journal of Emergency Surgery :... Mar 2023The occurrence of massive haemorrhages in various emergency situations increases the need for blood transfusions and increases the risk of mortality. Fibrinogen... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The occurrence of massive haemorrhages in various emergency situations increases the need for blood transfusions and increases the risk of mortality. Fibrinogen concentrate (FC) use may increase plasma fibrinogen levels more rapidly than fresh-frozen product or cryoprecipitate use. Previous several systematic reviews and meta-analyses have not effectively demonstrated FC efficacy in significantly improving the risk of mortality and reducing transfusion requirements. In this study, we investigated the use of FC for haemorrhages in emergency situations.
METHODS AND ANALYSIS
In this systematic review and meta-analysis, we included controlled trials, but excluded randomized controlled trials (RCTs) in elective surgeries. The study population consisted of patients with haemorrhages in emergency situations, and the intervention was emergency supplementation of FC. The control group was administered with ordinal transfusion or placebo. The primary and secondary outcomes were in-hospital mortality and the amount of transfusion and thrombotic events, respectively. The electronic databases searched included MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials.
RESULTS
Nine RCTs in the qualitative synthesis with a total of 701 patients were included. Results showed a slight increase in in-hospital mortality with FC treatment (RR 1.24, 95% CI 0.64-2.39, p = 0.52) with very low certainty of the evidence. There was no reduction in the use of red blood cells (RBC) transfusion in the first 24 h after admission with FC treatment (mean difference [MD] 0.0 Unit in the FC group, 95% CI - 0.99-0.98, p = 0.99) with very low certainty of the evidence. However, the use of fresh-frozen plasma (FFP) transfusion significantly increased in the first 24 h after admission with FC treatment (MD 2.61 Unit higher in the FC group, 95% CI 0.07-5.16, p = 0.04). The occurrence of thrombotic events did not significantly differ with FC treatment.
CONCLUSIONS
The present study indicates that the use of FC may result in a slight increase in in-hospital mortality. While FC did not appear to reduce the use of RBC transfusion, it likely increased the use of FFP transfusion and may result in a large increase in platelet concentrate transfusion. However, the results should be interpreted cautiously due to the unbalanced severity in the patient population, high heterogeneity, and risk of bias.
Topics: Humans; Fibrinogen; Hemorrhage; Hemostatics; Blood Transfusion; Elective Surgical Procedures
PubMed: 36998084
DOI: 10.1186/s13017-023-00497-5 -
Frontiers in Endocrinology 2023Leptin (LEP) acts as a proinflammatory cytokine and may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to assess the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Leptin (LEP) acts as a proinflammatory cytokine and may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to assess the quantitative difference in leptin status between CF patients and non-CF controls.
METHODS
In this study, the researchers conducted systematic searches of various databases, such as PubMed, Excerpta Medica Database, Google Scholar, Web of Science, and the China National Knowledge Infrastructure. The data collected from the above databases were assessed using the Stata 11.0 and R 4.1.3 software. The correlation coefficients and the Standardized Mean Differences (SMD) were employed to assess the effect size. A combination analysis was also carried out with the help of either a fixed-effects or random-effects model. In addition, the single-cell sequencing GSE193782 dataset was obtained to determine the mRNA expression levels of LEP and leptin receptor (LEPR) in the bronchoalveolar lavage fluid, to verify the different leptin expression between the CF patients and healthy controls.
RESULTS
A total of 919 CF patients and 397 controls from 14 articles were included in this study. CF patients and non-CF controls showed similar serum/plasma leptin levels. Gender, specimen testing, age, and study design were all taken into account for carrying out subgroup analyses. The results revealed no variations in serum/plasma leptin levels between the controls and CF patients in the various subgroups. Female CF patients exhibited higher leptin concentrations compared to male CF patients, and male healthy individuals showed lower leptin levels than female healthy participants. Aside from the fact that serum/plasma leptin appeared to be favorably linked to fat mass and BMI, the findings in this study also indicated that serum/plasma concentrations were not associated with Forced Expiratory Volume in the first second (FEV1). No statistically significant differences were observed in the leptin and leptin receptor mRNA expression levels between the healthy controls and CF patients. The leptin receptor and leptin expression levels in alveolar lavage fluid were low in various cells, without any distinctive distribution patterns.
CONCLUSIONS
The current meta-analysis indicated the absence of significant differences in leptin levels between CF patients and healthy individuals. Gender, fat mass, and BMI may all be correlated with leptin concentrations.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022380118.
Topics: Humans; Male; Female; Leptin; Cystic Fibrosis; Receptors, Leptin; RNA, Messenger; China
PubMed: 36992806
DOI: 10.3389/fendo.2023.1126129 -
EClinicalMedicine Apr 2023Biomarker-defined patients with smoldering multiple myeloma (SMM) were included in the diagnostic category of multiple myeloma (MM) by the International Myeloma Working...
SLiM CRAB criteria revisited: temporal trends in prognosis of patients with smoldering multiple myeloma who meet the definition of 'biomarker-defined early multiple myeloma'-a systematic review with meta-analysis.
BACKGROUND
Biomarker-defined patients with smoldering multiple myeloma (SMM) were included in the diagnostic category of multiple myeloma (MM) by the International Myeloma Working Group (IMWG) in 2014. This includes ≥60% bone marrow plasma cells (BMPCs), free light chain ratio (FLCratio) ≥100, and >1 MRI-defined ≥5 mm focal lesion, also called SLiM CRAB MM. We examined whether the risk of progression of SLiM CRAB MM patients to CRAB positive MM described in recent studies differs from that reported in earlier studies published before the introduction of the new diagnostic criteria.
METHODS
We conducted a systematic review with meta-analysis, and included studies on Embase and PubMed (01/01/2010-01/11/2022), selecting studies with digitizable progression curves. Inconsistent studies were excluded. We created forest plots using random effects models from digitized and published data and Kaplan-Meier curves. Main outcomes were median time to progression (TTP), 2-year progression risk, and odds ratios (ORs) comparing 2-year progression risks.
FINDINGS
Our meta-analysis including 11 studies with 3482 patients found an approximately 3-fold longer TTP and 50% lower 2-year progression risk of SliM CRAB MM patients in recent (published after 2014) compared with earlier studies. Median TTP in patients with ≥60% BMPCs was 30.31 months [18.71-62.93] in recent compared with 9.20 months [6.02-15.56] in earlier studies; the 2-year progression risk was 45.45% [20.12-62.75] compared with 86.21% [65.74-94.45] in the respective time periods. In patients with a FLCratio ≥ 100, the median TTP was 48.06 months [40.51-64.91] vs. 15.33 months [9.38-19.10], and the 2-year progression risk was 31.61% [25.30-37.39] vs. 73.00% [62.39-80.62] in recent and earlier studies, respectively. Tests for heterogeneity showed that the two time periods differed significantly in their ORs when comparing patients who met the high-and low risk criteria. No appropriate recent studies on focal lesions have been published.
INTERPRETATION
Recent studies show significantly improved prognosis of biomarker-defined MM with ≥60% BMPCs and FLCratio ≥ 100. This warrants careful evaluation for signs of progression before treatment initiation.
FUNDING
Funding was provided by the Austrian Forum against Cancer.
PubMed: 36969337
DOI: 10.1016/j.eclinm.2023.101910 -
Frontiers in Aging Neuroscience 2023Alzheimer's disease (AD) is the most common neurodegenerative disease in elderly people. Many researches have reported that neuroinflammation is related to AD....
BACKGROUND
Alzheimer's disease (AD) is the most common neurodegenerative disease in elderly people. Many researches have reported that neuroinflammation is related to AD. Chemokines are a class of small cytokines that play important roles in cell migration and cell communication, which involved in neuroinflammation. Up to now there is no meta-analysis to explore the difference of chemokines between AD patients and healthy elderly individuals.
METHOD
We searched PubMed, Web of science, Cochrane library, EMBASE and Scopus databases from inception to January 2022. Data were extracted by two independent reviewers, and the Review Manager 5.3 was used for the meta-analysis.
RESULT
Thirty-two articles were included and analyzed. The total number of participants in the included study was 3,331. We found that the levels of CCL5 (SMD = 2.56, 95% CI: 1.91-3.21), CCL15 (SMD = 3.30, 95% CI: 1.48-5.13) and IP-10 (SMD = 3.88, 95% CI: 1.84-5.91) in the plasma of AD patients were higher than healthy people. MCP-1 protein (SMD = 0.67, 95% CI: 0.29-1.05) in the AD patients' CSF was higher than healthy controls.
CONCLUSION
These results suggested that chemokines may play an important role in AD. These findings could provide evidences for the diagnosis and treatment of AD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021278736, identifier: CRD42021278736.
PubMed: 36967827
DOI: 10.3389/fnagi.2023.1047810 -
Therapeutic Advances in Gastroenterology 2023Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need.... (Review)
Review
BACKGROUND
Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need. Neutrophil-related biomarkers have been mainly studied in the feces, but blood analyses have inherent advantages.
OBJECTIVE
To review the recent learnings on the ability of blood-based neutrophil-expressed biomarkers to predict treatment outcomes in IBD.
DESIGN
Systematic scoping review.
DATA SOURCES AND METHODS
We performed a literature search in Pubmed, EMBASE, SCOPUS, Web of Science, ScienceDirect, and Cochrane Central Register of Controlled Trials from inception until May 2022 according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. All human studies associating blood-based neutrophil-related compounds with the prediction of disease progression, complication onset, or treatment outcomes were included.
RESULTS
From 1032 retrieved entries, 34 studies were selected, 32 published in 2013 or later. In all, 17 biomarkers from granules, cytoplasm, plasmatic membrane, and plasma were explored. In total, 1850 Crohn's disease (CD) and 1122 ulcerative colitis non-duplicated patients were included. The most mentioned biomarkers were nCD64, serum calprotectin (SC), oncostatin M (OSM), neutrophil elastase-generated calprotectin fragment (CPa9-HNE), and triggering receptor expressed on myeloid cells 1 (TREM1). Six biomarkers showed promising results: OSM, SC, eNAMPT, nCD64, TREM1, and CPa9-HNE. Variable positive signals were found for human neutrophil peptide 1-3, LL-37, S100A12, and neutrophil gelatinase-associated lipocalin. No predictive ability was found for the remaining markers. Sharing a neutrophil compartment did not indicate similar behavior.
CONCLUSION
Advances in the last decade began to unveil the untapped potential of the readily accessible blood neutrophil-expressed biomarkers, especially nCD64, TREM1, and CPa9-HNE. Current evidence suggests that future research should focus on well-defined subpopulations instead of a one-size-fits-all biomarker.
REGISTRATION
https://osf.io/kes9a.
PubMed: 36923488
DOI: 10.1177/17562848231155987 -
MedRxiv : the Preprint Server For... Feb 2023Type 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to...
AIMS
Type 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to track this evolution are limited, with development of islet autoantibodies marking the onset of autoimmunity and metabolic tests used to detect dysglycemia. Therefore, additional biomarkers are needed to better track disease initiation and progression. Multiple clinical studies have used proteomics to identify biomarker candidates. However, most of the studies were limited to the initial candidate identification, which needs to be further validated and have assays developed for clinical use. Here we curate these studies to help prioritize biomarker candidates for validation studies and to obtain a broader view of processes regulated during disease development.
METHODS
This systematic review was registered with Open Science Framework (DOI 10.17605/OSF.IO/N8TSA). Using PRISMA guidelines, we conducted a systematic search of proteomics studies of T1D in the PubMed to identify putative protein biomarkers of the disease. Studies that performed mass spectrometry-based untargeted/targeted proteomic analysis of human serum/plasma of control, pre-seroconversion, post-seroconversion, and/or T1D-diagnosed subjects were included. For unbiased screening, 3 reviewers screened all the articles independently using the pre-determined criteria.
RESULTS
A total of 13 studies met our inclusion criteria, resulting in the identification of 251 unique proteins, with 27 (11%) being identified across 3 or more studies. The circulating protein biomarkers were found to be enriched in complement, lipid metabolism, and immune response pathways, all of which are found to be dysregulated in different phases of T1D development. We found a subset of 3 proteins (C3, KNG1 & CFAH), 6 proteins (C3, C4A, APOA4, C4B, A2AP & BTD) and 7 proteins (C3, CLUS, APOA4, C6, A2AP, C1R & CFAI) have consistent regulation between multiple studies in samples from individuals at pre-seroconversion, post-seroconversion and post-diagnosis compared to controls, respectively, making them strong candidates for clinical assay development.
CONCLUSIONS
Biomarkers analyzed in this systematic review highlight alterations in specific biological processes in T1D, including complement, lipid metabolism, and immune response pathways, and may have potential for further use in the clinic as prognostic or diagnostic assays.
PubMed: 36865103
DOI: 10.1101/2023.02.21.23286132