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Frontiers in Immunology 2023There is an increasing interest in the pathophysiological role of the kynurenine pathway of tryptophan metabolism in the regulation of immune function and inflammation.... (Meta-Analysis)
Meta-Analysis
UNLABELLED
There is an increasing interest in the pathophysiological role of the kynurenine pathway of tryptophan metabolism in the regulation of immune function and inflammation. We sought to address the link between this pathway and the presence rheumatic diseases (RD) by conducting a systematic review and meta-analysis of studies reporting the plasma or serum concentrations of tryptophan, kynurenine, and other relevant metabolites in RD patients and healthy controls. We searched electronic databases for relevant articles published between inception and the 30 of June 2023. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system. In 24 studies selected for analysis, compared to controls, RD patients had significantly lower tryptophan (standard mean difference, SMD= -0.71, 95% CI -1.03 to -0.39, p<0.001; I = 93.6%, p<0.001; low certainty of evidence), and higher kynurenine (SMD=0.69, 95% CI 0.35 to 1.02, p<0.001; I = 93.2%, p<0.001; low certainty), kynurenine to tryptophan ratios (SMD=0.88, 95% CI 0.55 to 1.21, p<0.001; I = 92.9%, p<0.001; moderate certainty), 3-hydroxykynurenine (SMD=0.74, 95% CI 0.30 to 1.18, p=0.001; I = 87.7%, p<0.001; extremely low certainty), and quinolinic acid concentrations (SMD=0.71, 95% CI 0.31 to 1.11, p<0.001; I = 88.1%, p<0.001; extremely low certainty). By contrast, there were non-significant between-group differences in kynurenic acid, 3-hydroxyanthranilic acid, kynurenic acid to kynurenine ratio, or quinolinic acid to kynurenine acid ratio. In meta-regression, the SMD of tryptophan, kynurenine, and kynurenine to tryptophan ratio were not associated with age, publication year, sample size, RD duration, C-reactive protein, or use of anti-rheumatic drugs and corticosteroids. In subgroup analysis, the SMD of tryptophan, kynurenine, and kynurenine to tryptophan ratio was significant across different types of RD, barring rheumatoid arthritis. Therefore, we have observed significant alterations in tryptophan, kynurenine, 3-hydroxykynurenine, and quinolinic acid concentrations in RD patients. Further research is warranted to determine whether these biomarkers can be useful for diagnosis and management in this patient group. (PROSPERO registration number: CRD CRD42023443718).
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD CRD42023443718.
Topics: Humans; Kynurenine; Tryptophan; Quinolinic Acid; C-Reactive Protein; Rheumatic Diseases
PubMed: 37936702
DOI: 10.3389/fimmu.2023.1257159 -
Canadian Family Physician Medecin de... Oct 2023To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe,...
OBJECTIVE
To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe, fibrates, niacin, omega-3 supplements, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and statins.
DATA SOURCES
MEDLINE, the Cochrane Database of Systematic Reviews, and a grey literature search.
STUDY SELECTION
Systematic reviews of randomized controlled trials published between January 2017 and March 2022 looking at statins, ezetimibe, PCSK9 inhibitors, fibrates, BAS, niacin, and omega-3 supplements for preventing cardiovascular outcomes were selected. Outcomes of interest included major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, and adverse events.
SYNTHESIS
A total of 76 systematic reviews were included. Four randomized controlled trials were also included for BAS because no efficacy systematic review was identified. Statins significantly reduced MACE (6 systematic reviews; median risk ratio [RR]=0.74; interquartile range [IQR]=0.71 to 0.76), cardiovascular mortality (7 systematic reviews; median RR=0.85, IQR=0.83 to 0.86), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.88 to 0.92). Major adverse cardiovascular events were also significantly reduced by ezetimibe (3 systematic reviews; median RR=0.93, IQR=0.93 to 0.94), PCSK9 inhibitors (14 systematic reviews; median RR=0.84, IQR=0.83 to 0.87), and fibrates (2 systematic reviews; mean RR=0.86), but these interventions had no effect on cardiovascular or all-cause mortality. Fibrates had no effect on any cardiovascular outcomes when added to a statin. Omega-3 combination supplements had no effect on MACE or all-cause mortality but significantly reduced cardiovascular mortality (5 systematic reviews; median RR=0.93, IQR=0.93 to 0.94). Eicosapentaenoic acid ethyl ester alone significantly reduced MACE (1 systematic review, RR=0.78) and cardiovascular mortality (2 systematic reviews; RRs of 0.82 and 0.82). In primary cardiovascular prevention, only statins showed consistent benefits on MACE (6 systematic reviews; median RR=0.75, IQR=0.73 to 0.78), cardiovascularall-cause mortality (7 systematic reviews, median RR=0.83, IQR=0.81 to 0.90), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.87 to 0.91).
CONCLUSION
Statins have the most consistent evidence for the prevention of cardiovascular complications with a relative risk reduction of about 25% for MACE and 10% to 15% for mortality. The addition of ezetimibe, a PCSK9 inhibitor, or eicosapentaenoic acid ethyl ester to a statin provides additional MACE risk reduction but has no effect on all-cause mortality.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9; Cardiovascular Diseases; PCSK9 Inhibitors; Niacin; Systematic Reviews as Topic; Ezetimibe; Lipids; Fibric Acids; Primary Health Care; Anticholesteremic Agents
PubMed: 37833094
DOI: 10.46747/cfp.6910701 -
Nutrients Dec 2023Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products. It participates in cellular energy metabolism and modulates multiple cellular survival and death pathways. Nicotinamide has been widely studied as a safe chemopreventive agent that reduces actinic keratosis (AKs) and non-melanoma skin cancers (NMSC).
METHODS
We used the Medline, EMBASE, PubMed, and Cochrane databases to search the concepts "nicotinamide", "chemoprevention", and "skin cancer" up to August 2023. Three independent authors screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. The primary outcome was the impact of oral nicotinamide on the incidence of NMSC in high-risk patients. We also conducted a systematic search to identify relevant epidemiological studies published evaluating dietary niacin intake and the risk of NMSC.
RESULTS
Two hundred and twenty-five studies were reviewed, and four met the inclusion criteria. There was no association between NAM consumption and risk for squamous cell carcinoma (SCC) (rate ratio (RR) 0.81, 95% CI 0.48-1.37; I = 0%), basal cell carcinoma (BCC) (RR 0.88, 95% CI 0.50-1.55; I = 63%), and NMSC (RR 0.82, 95% CI 0.61-1.12; I = 63%). Adverse events were rare and acceptable, allowing optimal compliance of patients to the treatment. We found only one article evaluating the association between niacin dietary intake and NMSC risk, supporting a potential beneficial role of niacin intake concerning SCC but not BCC or melanoma.
CONCLUSIONS
The present meta-analysis shows, by pooling immunocompetent and immunosuppressed patients, that there is insufficient evidence that oral nicotinamide therapy significantly reduces the number of keratinocyte cancers.
Topics: Animals; Humans; Niacinamide; Niacin; Chemoprevention; Skin Neoplasms; Carcinoma, Basal Cell; Carcinoma, Squamous Cell
PubMed: 38201930
DOI: 10.3390/nu16010100 -
Medicine Sep 2023A systematic review and network meta-analysis (NMA) were conducted to explore the optimal administration route of nimodipine for treatment subarachnoid hemorrhage. (Meta-Analysis)
Meta-Analysis
BACKGROUND
A systematic review and network meta-analysis (NMA) were conducted to explore the optimal administration route of nimodipine for treatment subarachnoid hemorrhage.
METHODS
Electronic databases (Pubmed, Embase, Web of Science and Cochrane databases) were systematically searched to identify randomized controlled trials evaluating different administration route of nimodipine (intravenous and enteral) versus placebo for treatment subarachnoid hemorrhage. Outcomes included case fatality at 3 months, poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), incidence of delayed cerebral ischemia (DCI), delayed ischemic neurological deficit. A random-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as odds ratios (ORs) and 95% credible intervals. The NMA was performed using R Software with a GeMTC package. A Bayesian NMA was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities.
RESULTS
Nine randomized controlled trials met criteria for inclusion and finally included in this NMA. There was no statistically significant between intravenous and enteral in terms of case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P > .05). Both intravenous and enteral could reduce case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P < .05). The SUCRA shows that enteral ranked first, intravenous ranked second and placebo ranked the last for case fatality, the occurrence of DCI and poor outcomes. The SUCRA shows that intravenous ranked first, enteral ranked second and placebo ranked the last for delayed ischemic neurologic deficit.
CONCLUSIONS
It is possible that both enteral and intravenous nimodipine have comparable effectiveness in preventing poor outcomes, DCI, and delayed ischemic neurological deficits. However, further investigation may be necessary to determine the exact role of intravenous nimodipine in current clinical practice.
Topics: Humans; Nimodipine; Subarachnoid Hemorrhage; Network Meta-Analysis; Bayes Theorem; Administration, Intravenous; Brain Ischemia; Cerebral Infarction
PubMed: 37773855
DOI: 10.1097/MD.0000000000034789 -
Sleep & Breathing = Schlaf & Atmung Oct 2023Insomnia is highly prevalent in modern society. However, the hierarchical selection of hypnotics in young and middle-aged adults with insomnia remains unclear. We aimed... (Meta-Analysis)
Meta-Analysis
OBJECTIVE/BACKGROUND
Insomnia is highly prevalent in modern society. However, the hierarchical selection of hypnotics in young and middle-aged adults with insomnia remains unclear. We aimed to compare the efficacy and daytime drowsiness associated with different hypnotics for treating insomnia in young and middle-aged adults.
METHODS
We searched Embase, PubMed, Cochrane Library, and ProQuest Dissertations and Theses A&I databases from inception until December 15, 2021. We also manually searched reference lists and relevant publications. The literature search, data collection, and risk of bias evaluation were all carried out separately by pairs of reviewers. We included randomized control trials (RCTs) that compared hypnotics approved by the Food and Drug Administration. The R and Stata software were both used to perform the meta-analysis.
RESULTS
In total, 117 RCTs comprising 22,508 participants with the age of 18 to 65 years were included. Assessment of the efficacy of the hypnotics and adverse events (drowsiness) revealed that zolpidem improved all objective sleep parameters (oTST, oSOL, oWASO, and oSE), zopiclone increased oTST and oSE and reduced oSOL, and daridorexant increased oTST and reduced oWASO. Regarding subjective sleep outcomes, zolpidem exhibited beneficial effects on sTST, sSOL, and sWASO. Zaleplon reduced sSOL, and zopiclone was the recommended hypnotic for improving SQ. Zolpidem was associated with drowsiness effect (odds ratio = 1.82; 95% confidence interval = 1.25 to 2.65). The results of sensitivity analysis remained unchanged after the exclusion of studies reporting long-term effects.
CONCLUSION
Zolpidem is recommended for managing sleep-onset insomnia and sleep maintenance insomnia but should be used with caution because of daytime drowsiness effects. Daridorexant is recommended as a promising agent for managing sleep maintenance insomnia.
Topics: Middle Aged; Adult; Humans; Adolescent; Young Adult; Aged; Sleep Initiation and Maintenance Disorders; Hypnotics and Sedatives; Zolpidem; Network Meta-Analysis
PubMed: 36928548
DOI: 10.1007/s11325-023-02812-5 -
European Journal of Clinical... May 2024Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the literature and conducted meta-analyses to assess the efficacy and safety of these agents.
METHODS
PubMed, Embase, and Scopus were searched from inception to September 2023 for studies examining dabrafenib and/or trametinib for gliomas. Outcomes included response rates (ORR, CR, PR), progression rates (PD), 6- and 12-month PFS, adverse events, and dosing modifications. Meta-analyses were conducted using random effect models.
RESULTS
Nine studies met the inclusion criteria. Meta-analysis demonstrated overall response rates (ORR) of 50% (95% confidence interval (CI): 35-65%) for low-grade gliomas (LGG) and 40% (95% CI: 29-51%) for high-grade gliomas (HGG). Pooled ORR was 45% (95% CI: 36-54%) for both glioma grades. The complete response rate was 13% (95% CI: 05-27%) for HGG and 5% (95% CI: 1-10%) for both LGG and HGG. Six-month progression-free survival (PFS) rates reached 87% in LGG and 67% in HGG and a pooled 6-month PFS 78% (95% CI: 58-98%), declining at 12 months to 67% and 44%, respectively, with a pooled 12-month PFS 56% (95% CI: 34-79%). Grade 1-4 adverse events occurred in 100% of LGG and 63% of HGG patients.
CONCLUSIONS
Dabrafenib and trametinib demonstrate promising anti-tumor efficacy in gliomas, particularly low-grade tumors, achieving durable disease stabilization in many patients. However, toxicity significantly limited tolerability. Additional research should further examine efficacy and refine safe administration protocols across glioma subtypes.
Topics: Humans; Imidazoles; Glioma; Oximes; Pyridones; Mutation; Antineoplastic Combined Chemotherapy Protocols; Pyrimidinones
PubMed: 38345637
DOI: 10.1007/s00228-024-03635-3 -
The Journal of Urology Nov 2023Ureteral stents are commonly used for the treatment of ureteral obstruction, most often urolithiasis. Their use may be associated with significant bothersome symptoms... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Ureteral stents are commonly used for the treatment of ureteral obstruction, most often urolithiasis. Their use may be associated with significant bothersome symptoms and discomfort. Prior studies have examined the effects of various medication regimens on ureteral stent symptoms. This study utilized Bayesian network meta-analysis to analyze all available evidence on the pharmacological management of ureteral stent-related symptoms.
MATERIALS AND METHODS
In December 2022 a systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines on randomized prospective studies on pharmacological management of ureteral stent-related symptoms reporting outcomes using the Ureteral Stent Symptom Questionnaire score on urinary symptoms and pain. The data were analyzed in Review Manager 5.3 and R Studio where a Bayesian network meta-analysis was performed. Treatments were ranked using surface under the cumulative ranking curve and mean difference vs placebo with 95% credible intervals.
RESULTS
A total of 26 studies were analyzed. These were used to build networks which were modeled to run 100,000 Markov Chain Montecarlo simulations each. Drug-class analysis revealed the most effective class for each domain: for urinary symptoms, sexual performance, general health, and work performance-combined α-blocker and anticholinergic and phosphodiesterase 5 inhibitors; for pain-combined anticholinergic and pregabalin. The following were the most effective drugs and dosages for specific symptoms: for urinary symptoms-combined silodosin 8 mg+solifenacin 10 mg; for pain-combined silodosin 8 mg+solifenacin 10 mg; for sexual performance-tadalafil 5 mg. Combined silodosin 8 mg+solifenacin 10 mg+tadalafil 5 mg has the best general health scores while solifenacin 10 mg had the best work experience scores.
CONCLUSIONS
This network meta-analysis demonstrated that the most effective drug therapy is different for each symptom domain. It is important to consider a patient's chief complaint and domains in order to ascertain the optimal medication regimen for each patient. Further iterations of this analysis can be strengthened by trials that directly compare more of these drugs instead of relying on indirect evidence.
Topics: Humans; Solifenacin Succinate; Tadalafil; Network Meta-Analysis; Prospective Studies; Bayes Theorem; Quality of Life; Ureter; Pain; Cholinergic Antagonists; Stents
PubMed: 37428119
DOI: 10.1097/JU.0000000000003616 -
Neuroscience and Biobehavioral Reviews Oct 2023The use of electronic cigarettes by young people has increased exponentially in the past decade due to various health and social influences. E-cigarettes, particularly... (Meta-Analysis)
Meta-Analysis Review
The use of electronic cigarettes by young people has increased exponentially in the past decade due to various health and social influences. E-cigarettes, particularly those containing nicotine, can cause health complications and addiction, which may result in a subsequent initiation of psychoactive substance use. This systematic review and meta- analysis evaluated the prospective association between e-cigarette use and subsequent use of psychoactive substances in young people aged 10-24 years. Pooling of data from the identified longitudinal studies showed that ever e-cigarette users have an increased likelihood for subsequent cannabis, alcohol, and unprescribed Ritalin/Adderall use compared to never e-cigarette users. The findings indicate a need for interventions to reduce e-cigarette use in adolescents and young adults.
Topics: Adolescent; Young Adult; Humans; Electronic Nicotine Delivery Systems; Vaping; Nicotine; Cognition; Hallucinogens
PubMed: 37714228
DOI: 10.1016/j.neubiorev.2023.105392 -
Food and Chemical Toxicology : An... Mar 2024This systematic review evaluated the health risks of electronic cigarettes (e-cigarettes) compared to traditional cigarettes. It examines various studies and research on... (Review)
Review
BACKGROUND
This systematic review evaluated the health risks of electronic cigarettes (e-cigarettes) compared to traditional cigarettes. It examines various studies and research on the subject to provide a comprehensive analysis of potential health risks associated with both smoking methods.
METHODS
The systematic review, incorporating searches in PubMed, Scopus, Web of Science, and the Cochrane Library up to July 2023, examines the results obtained in relevant studies, and provides a critical discussion of the results.
RESULTS
E-cigarettes exhibit reduced exposure to harmful toxins compared to traditional cigarettes.
CONCLUSION
However, concerns persist regarding respiratory irritation and potential health risks, especially among youth, emphasizing the need for comprehensive, long-term research and protective legislation.
Topics: Adolescent; Humans; Nicotine; Electronic Nicotine Delivery Systems; Tobacco Products; Smoking
PubMed: 38331086
DOI: 10.1016/j.fct.2024.114507 -
Frontiers in Immunology 2023Over 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders,...
BACKGROUND
Over 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders, tobacco consumption is associated with a variety of chronic-inflammatory diseases. Although neutrophilic granulocytes (neutrophils) play a role in the pathogenesis of many of these diseases, the impact of nicotine on neutrophils has not been systematically reviewed so far.
OBJECTIVES
The aim of this systematic review was to evaluate the direct influence of nicotine on human neutrophil functions, specifically on cell death/damage, apoptosis, chemotaxis, general motility, adhesion molecule expression, eicosanoid synthesis, cytokine/chemokine expression, formation of neutrophil extracellular traps (NETs), phagocytosis, generation of reactive oxygen species (ROS), net antimicrobial activity, and enzyme release.
MATERIAL AND METHODS
This review was conducted according to the PRISMA guidelines. A literature search was performed in the databases NCBI Pubmed and Web of Science™ in February 2023. Inclusion criteria comprised English written research articles, showing studies on the direct impact of nicotine on specified human neutrophil functions.
RESULTS
Of the 532 originally identified articles, data from 34 articles were finally compiled after several evaluation steps. The considered studies highly varied in methodological aspects. While at high concentrations (>3 mmol/l) nicotine started to be cytotoxic to neutrophils, concentrations typically achieved in blood of smokers (in the nmol/l range) applied for long exposure times (24-72h) supported the survival of neutrophils. Smoking-relevant nicotine concentrations also increased the chemotaxis of neutrophils towards several chemoattractants, elevated their production of elastase, lipocalin-2, CXCL8, leukotriene B4 and prostaglandin E2, and reduced their integrin expression. Moreover, while nicotine impaired the neutrophil phagocytotic and anti-microbial activity, a range of studies demonstrated increased NET formation. However, conflicting effects were found on ROS generation, selectin expression and release of β-glucuronidase and myeloperoxidase.
CONCLUSION
Nicotine seems to support the presence in the tissue and the inflammatory and selected tissue-damaging activity of neutrophils and reduces their antimicrobial functions, suggesting a direct contribution of nicotine to the pathogenesis of chronic-inflammatory diseases via influencing the neutrophil biology.
Topics: Humans; Extracellular Traps; Neutrophils; Nicotine; Reactive Oxygen Species; Granulocytes
PubMed: 38077313
DOI: 10.3389/fimmu.2023.1281685