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Signal Transduction and Targeted Therapy Oct 2020Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named coronavirus disease (COVID-19). Currently, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Vaccines, such as inactivated vaccines, nucleic acid-based vaccines, and vector vaccines, have already entered clinical trials. In this review, we provide an overview of the experimental and clinical data obtained from recent SARS-CoV-2 vaccines trials, and highlight certain potential safety issues that require consideration when developing vaccines. Furthermore, we summarize several strategies utilized in the development of vaccines against other infectious viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), with the aim of aiding in the design of effective therapeutic approaches against SARS-CoV-2.
Topics: Angiotensin-Converting Enzyme 2; Antibodies, Viral; Betacoronavirus; COVID-19; COVID-19 Vaccines; Clinical Trials as Topic; Coronavirus Infections; Gene Expression Regulation; Humans; Immunity, Innate; Immunization Schedule; Immunogenicity, Vaccine; Middle East Respiratory Syndrome Coronavirus; Pandemics; Patient Safety; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Binding; Receptors, Virus; Severe acute respiratory syndrome-related coronavirus; SARS-CoV-2; Severe Acute Respiratory Syndrome; Spike Glycoprotein, Coronavirus; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Subunit; Vaccines, Virus-Like Particle; Viral Vaccines
PubMed: 33051445
DOI: 10.1038/s41392-020-00352-y -
Annals of the Rheumatic Diseases Jun 2020To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).
Pharmacological treatment of psoriatic arthritis: a systematic literature research for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis.
OBJECTIVE
To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).
METHODS
This is a systematic literature research of 2015-2018 publications on all DMARDs in patients with PsA, searching Medline, Embase and the Cochrane Library. Efficacy was assessed in randomised controlled trials. For safety, cohort studies, case-control studies and long-term extensions (LTEs) were analysed.
RESULTS
56 publications (efficacy: n=33; safety n=23) were analysed. The articles were on tumour necrosis factor (TNF) inhibitors (n=6; golimumab, etanercept and biosimilars), interleukin (IL)-17A inhibitors (n=10; ixekizumab, secukinumab), IL-23-p19 inhibitors (n=2; guselkumab, risankizumab), clazakizumab (IL-6 inhibitor), abatacept (CD80/86 inhibitor) and ABT-122 (anti-TNF/IL-17A), respectively. One study compared ustekinumab (IL-12/23i) with TNF inhibitor therapy in patients with entheseal disease. Three articles investigated DMARD tapering. Trials on targeted synthetic DMARDs investigated apremilast (phosphodiesterase-4 inhibitor) and Janus kinase inhibitors (JAKi; tofacitinib, filgotinib). Biosimilar comparison with bio-originator showed non-inferiority. Safety was evaluated in 13 LTEs, 9 cohort studies and 1 case-control study investigating malignancies, infections, infusion reactions, multiple sclerosis and major cardiovascular events, as well as efficacy and safety of vaccination. No new safety signals were identified; however, warnings on the risk of venous thromboembolic events including pulmonary embolism when using JAKi were issued by regulators based on other studies.
CONCLUSION
Many drugs in PsA are available and have demonstrated efficacy against placebo. Efficacy varies across PsA manifestations. Safety must also be taken into account. This review informed the development of the European League Against Rheumatism 2019 updated PsA management recommendations.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Biological Products; Humans; Interleukin-17; Interleukin-23 Subunit p19; Molecular Targeted Therapy; Synthetic Drugs; Tumor Necrosis Factor-alpha
PubMed: 32381564
DOI: 10.1136/annrheumdis-2020-217163 -
European Review For Medical and... Jun 2017Osteoarthritis (OA) is the most common joint disease, and in recent years has become a major public health problem. The hallmark of OA is cartilage destruction with... (Review)
Review
Osteoarthritis (OA) is the most common joint disease, and in recent years has become a major public health problem. The hallmark of OA is cartilage destruction with local commitment of subchondral bone and the synovial membrane. Hypoxia-inducible factors (HIFs) are transcriptional factors and key regulators of the cellular response to hypoxia. To date, three members of the human HIF-α protein family have been described: HIF-1α, HIF-2α, and HIF-3α. HIF-1α plays an essential role in the articular cartilage (a hypoxic tissue), as it has a protective effect in the maintenance of the articular cartilage matrix, HIF-2α has a harmful effect on the articular cartilage matrix, and HIF-3α acts as a negative regulator of HIF-1α and HIF-2α. Due to the recent growing interest in the role of HIFs in rheumatic diseases, we focused this review on the potential role of these key regulators in articular cartilage maintenance as the central axis in OA development.
Topics: Basic Helix-Loop-Helix Transcription Factors; Cartilage, Articular; Cell Hypoxia; Chondrocytes; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Osteoarthritis
PubMed: 28682438
DOI: No ID Found -
Journal of Dermatological Science May 2018Dupilumab, a fully human monoclonal antibody against the interleukin-4-receptor α subunit, has been developed and used in clinical trials to treat atopic dermatitis (AD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dupilumab, a fully human monoclonal antibody against the interleukin-4-receptor α subunit, has been developed and used in clinical trials to treat atopic dermatitis (AD).
OBJECTIVE
We aimed to assess the overall efficacy and safety of dupilumab treatment in AD.
METHODS
PubMed, Embase, Cochrane library databases, and the Chinese Biological Medicine (CBM) published up to September 2017 were searched. All randomized controlled trials (RCTs) of dupilumab treatment on adult patients with AD were included. Fixed- or random-effects models were used to calculate pooled standard mean differences or relative risks (SMD or RR, respectively).
RESULTS
Six trials involving 2447 patients were identified. Pooled analysis revealed significant improvements in Eczema Area and Severity Index (EASI) score (SMD = -0.89, 95% CI: -1.0 to -0.78), percentage of body surface area (BSA) (SMD = -0.83, 95% CI: -0.90 to -0.75), pruritus numeric rating scale (NRS) scores (SMD = -0.81, 95% CI: -0.96 to -0.66), and Dermatology Life Quality Index (DLQI) scores (SMD = -0.78, 95% CI: -0.89 to -0.66). Dupilumab treatment was also associated with a significant increase in the proportion of patients achieving Investigator's Global Assessment (IGA) response (RR = 3.82; 95% CI: 3.23 to 4.51) and a similar incidence of adverse events (RR = 1.0; 95% CI: 0.96 to 1.04).
CONCLUSIONS
Our analysis provided evidence that dupilumab had an acceptable safety profile and resulted in clinically relevant improvements in signs and symptoms of AD. Dose regimens of 300 mg qw and q2 w seemed to have similar benefits. Further long-term trials are required for confirmation.
Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Dermatitis, Atopic; Humans; Injections, Subcutaneous; Interleukin-4 Receptor alpha Subunit; Pruritus; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 29472119
DOI: 10.1016/j.jdermsci.2018.01.016 -
Genetic Testing and Molecular Biomarkers Mar 2016Inflammation plays an important role in the pathophysiology of coronary artery disease (CAD). NF-κB is a central regulator of inflammation. Thus the aim of this study... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inflammation plays an important role in the pathophysiology of coronary artery disease (CAD). NF-κB is a central regulator of inflammation. Thus the aim of this study was to conduct a systematic review and meta-analysis investigating whether the polymorphism in the NFKB1 promoter region (NFKB1-94ins(I)/del(D)ATTG, rs28362491) is associated with CAD susceptibility.
METHODS
PubMed, Embase, Cochrane Library and CNKI databases were searched up to 30 July 2015. All observational case-control studies that investigated the association of NFKB1 I/D polymorphism and CAD risk were included. Two reviewers independently selected the studies and extracted the data.
RESULTS
A total of 7 studies were included in this meta-analysis. Comparison between alleles showed a 13% increased risk of CAD for D vs. I (OR = 1.13, 95% CI 1.06-1.19, PH = 0.318), and comparisons among genotypes showed a 26% increased risk of CAD for DD vs. II (OR = 1.26, 95% CI 1.12-1.43, PH = 0.125) and in the heterozygote model ID vs. II had an 11% increased risk (OR = 1.11, 95% CI 1.01-1.21, PH = 0.751). In the dominant model the risk of CAD risk was reduced by 13% (OR = 0.87, 95%CI 0.80-0.95, PH = 0.814) across the total population. Subgroup analysis by ethnicity indicated that the additive model was associated with a 21% increased risk for CAD in the Caucasian population (OR = 1.21, 95% CI 1.09-1.34, PH = 0.522), while the homozygote model gave a 47% increased risk for CAD in Asian population (OR = 1.47, 95% CI 1.21-1.78, PH = 0.314).
CONCLUSIONS
Our results indicated that the NFKB1-94ins/del ATTG polymorphism was associated with susceptibility to CAD in both Asian and Caucasian populations.
Topics: Case-Control Studies; Coronary Artery Disease; Genetic Predisposition to Disease; Humans; INDEL Mutation; NF-kappa B p50 Subunit; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Risk Factors
PubMed: 26799199
DOI: 10.1089/gtmb.2015.0242 -
Epigenomics Jul 2017Evidence points to the role of DNA methylation in ulcerative colitis (UC)-associated cancer (UCC), the most serious complication of ulcerative colitis. A better... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence points to the role of DNA methylation in ulcerative colitis (UC)-associated cancer (UCC), the most serious complication of ulcerative colitis. A better understanding of the etiology of UCC may facilitate the development of new therapeutic targets and help to identify biomarkers of the disease risk.
METHODS
A search was performed in three databases following PRISMA protocol. DNA methylation in UCC was compared with sporadic colorectal cancer (SCRC), and individual genes differently methylated in UCC identified.
RESULTS
While there were some similarities in the methylation patterns of UCC compared with SCRC, generally lower levels of hypermethylation in promoter regions of individual genes was evident in UCC. Certain individual genes are, however, highly methylated in colitis-associated cancer: RUNX3, MINT1, MYOD and p16 exon1 and the promoter regions of EYA4 and ESR.
CONCLUSION
Patterns of DNA methylation differ between UCC and SCRC. Seven genes appear to be promising putative biomarkers.
Topics: Adaptor Proteins, Signal Transducing; Biomarkers, Tumor; Colitis, Ulcerative; Colorectal Neoplasms; Core Binding Factor Alpha 3 Subunit; DNA Methylation; Female; Humans; Male; MyoD Protein; Nerve Tissue Proteins; Trans-Activators
PubMed: 28621161
DOI: 10.2217/epi-2017-0025 -
Annals of Allergy, Asthma & Immunology... Jun 2024Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in...
A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.
BACKGROUND
Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians.
OBJECTIVE
To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab.
METHODS
A systematic review of the literature was performed, and an expert Delphi Panel was assembled.
RESULTS
The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective.
CONCLUSION
Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.
PubMed: 38848870
DOI: 10.1016/j.anai.2024.05.014 -
Journal of Neurotrauma Apr 2021Accurate diagnosis of traumatic brain injury (TBI) is critical to effective management and intervention, but can be challenging in patients with mild TBI. A substantial... (Meta-Analysis)
Meta-Analysis
Blood-Based Protein Biomarkers for the Management of Traumatic Brain Injuries in Adults Presenting to Emergency Departments with Mild Brain Injury: A Living Systematic Review and Meta-Analysis.
Accurate diagnosis of traumatic brain injury (TBI) is critical to effective management and intervention, but can be challenging in patients with mild TBI. A substantial number of studies have reported the use of circulating biomarkers as signatures for TBI, capable of improving diagnostic accuracy and clinical decision making beyond current practice standards. We performed a systematic review and meta-analysis to comprehensively and critically evaluate the existing body of evidence for the use of blood protein biomarkers (S100 calcium binding protein B [S100B], glial fibrillary acidic protein [GFAP], neuron specific enolase [NSE], ubiquitin C-terminal hydrolase-L1 [UCH-L1]. tau, and neurofilament proteins) for diagnosis of intracranial lesions on CT following mild TBI. Effects of potential confounding factors and differential diagnostic performance of the included markers were explored. Further, appropriateness of study design, analysis, quality, and demonstration of clinical utility were assessed. Studies published up to October 2016 were identified through searches of MEDLINE, Embase, EBM Reviews, the Cochrane Library, World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP), and clinicaltrials.gov. Following screening of the identified articles, 26 were selected as relevant. We found that measurement of S100B can help informed decision making in the emergency department, possibly reducing resource use; however, there is insufficient evidence that any of the other markers is ready for clinical application. Our work pointed out serious problems in the design, analysis, and reporting of many of the studies, and identified substantial heterogeneity and research gaps. These findings emphasize the importance of methodologically rigorous studies focused on a biomarker's intended use, and defining standardized, validated, and reproducible approaches. The living nature of this systematic review, which will summarize key updated information as it becomes available, can inform and guide future implementation of biomarkers in the clinical arena.
Topics: Adult; Biomarkers; Blood Proteins; Brain Concussion; Brain Injuries, Traumatic; Disease Management; Emergency Service, Hospital; Glial Fibrillary Acidic Protein; Humans; Neurofilament Proteins; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit
PubMed: 29020853
DOI: 10.1089/neu.2017.5182 -
Gastrointestinal Endoscopy May 2021Although molecular analysis of pancreatic cyst fluid may aid pancreatic cyst classification, clinical practice remains highly variable. Therefore, we performed a... (Meta-Analysis)
Meta-Analysis
Molecular analysis of EUS-acquired pancreatic cyst fluid for KRAS and GNAS mutations for diagnosis of intraductal papillary mucinous neoplasia and mucinous cystic lesions: a systematic review and meta-analysis.
BACKGROUND AND AIMS
Although molecular analysis of pancreatic cyst fluid may aid pancreatic cyst classification, clinical practice remains highly variable. Therefore, we performed a systematic review and meta-analysis to evaluate the diagnostic performance of KRAS and GNAS mutations in EUS-acquired pancreatic cyst fluid for diagnosis of intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic lesions (MCLs).
METHODS
Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and meta-analysis analyzed according to the Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute the pooled sensitivity and specificity and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI).
RESULTS
Six studies (785 lesions) were included. For IPMNs and MCLs, KRAS + GNAS (combination) had significantly higher diagnostic accuracy than KRAS alone and GNAS alone (all P < .001). The pooled sensitivity, specificity, and diagnostic accuracy of KRAS + GNAS mutations for diagnosis of IPMNs were 94% (95% CI, 72-99; I = 86.74%), 91% (95% CI, 72-98; I = 89.83), and 97% (95% CI, 95-98), respectively, with each significantly higher compared with carcinoembryonic antigen (CEA) alone (all P < .001). For diagnosis of MCLs, KRAS + GNAS had a similar sensitivity and specificity compared with CEA alone; however, diagnostic accuracy was significantly improved (97% [95% CI, 95-98] vs 89% [95% CI, 86-91]; P < .001).
CONCLUSIONS
Molecular analysis for KRAS + GNAS mutations in EUS-acquired pancreatic cyst fluid has high sensitivity and specificity with significantly improved diagnostic accuracy for diagnosis of IPMNs and MCLs when compared with CEA alone.
Topics: Biomarkers, Tumor; Chromogranins; Cyst Fluid; GTP-Binding Protein alpha Subunits, Gs; Humans; Mutation; Pancreatic Cyst; Pancreatic Neoplasms; Proto-Oncogene Proteins p21(ras)
PubMed: 33359054
DOI: 10.1016/j.gie.2020.12.014 -
Clinical Immunology (Orlando, Fla.) Sep 2016Regulatory T lymphocyte cells (Treg) associated with interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) have implicated in the development of type 1... (Meta-Analysis)
Meta-Analysis Review
Regulatory T lymphocyte cells (Treg) associated with interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) have implicated in the development of type 1 diabetes mellitus (T1DM), yet the existing evidence remains unclear. Hereby we performed a systematic review and meta-analysis to characterize the changes in T1DM patients. A total of 1407 T1DM patients and 1373 healthy controls from 40 case-control studies were eventually included in the pooling analysis. Compared with the controls, T1DM patients had decreased frequency of CD4(+)CD25(+)Treg (p=0.0003), CD4(+)CD25(+)Foxp3(+)Treg (p=0.020), and the level of TGF-β (p=0.030). Decrease in IL-10 (p=0.14) was not significant. All the changes remained significant when the studies with low NOS scores and publication bias were excluded. In conclusion, peripheral Treg and serum TGF-β are reduced in type 1 diabetes mellitus whereas changes in serum IL-10 are not significant.
Topics: Case-Control Studies; Diabetes Mellitus, Type 1; Female; Forkhead Transcription Factors; Humans; Interleukin-10; Interleukin-2 Receptor alpha Subunit; Male; T-Lymphocytes, Regulatory; Transforming Growth Factor beta
PubMed: 27498109
DOI: 10.1016/j.clim.2016.08.004