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Medicine Jan 2024Apatinib, a novel tyrosine kinase inhibitor independently developed by China, has been widely used in the treatment of advanced hepatocellular carcinoma (HCC) in recent... (Meta-Analysis)
Meta-Analysis
The long-term efficacy and safety of apatinib are inferior to sorafenib in the first-line treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis.
BACKGROUND
Apatinib, a novel tyrosine kinase inhibitor independently developed by China, has been widely used in the treatment of advanced hepatocellular carcinoma (HCC) in recent years. For more than a decade, sorafenib has been the classic first-line treatment option for patients with advanced HCC. However, the results of clinical studies comparing the efficacy and safety of these 2 drugs are still controversial. Therefore, the aim of this meta-analysis is to evaluate the efficacy and safety of apatinib versus sorafenib as first-line treatment for advanced HCC.
METHODS
Up to August 14, 2023, the databases of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang were searched, and clinical studies of experimental group (apatinib or apatinib plus transarterial chemoembolization [TACE]) versus control group (sorafenib or sorafenib plus TACE) in the first-line treatment of advanced HCC were included. Two researchers evaluated the quality of the included studies and extracted the data. Revman 5.4 software was used for meta-analysis.
RESULTS
A total of 12 studies involving 1150 patients were included. Five studies are apatinib alone versus sorafenib alone, and the other 7 studies are apatinib plus TACE versus sorafenib plus TACE. The results of the meta-analysis showed that compared with sorafenib alone, apatinib could improve (OR = 3.06, 95%CI: 1.76-5.31), had no advantage in improving DCR (OR = 1.52, 95%CI: 0.86-2.68) and prolonging PFS (HR = 1.35, 95%CI: 0.94-1.96), and was significantly worse in prolonging OS (HR = 1.43, 95%CI: 1.08-1.88). Similarly, apatinib plus TACE was inferior to sorafenib plus TACE in prolonging OS (HR = 1.15, 95%CI: 1.03-1.28), although it improved ORR (OR = 1.49, 95%CI: 1.03-2.16). In terms of adverse drug events, the overall incidence of adverse events, and the incidence of drug reduction and discontinuation in the experimental group were significantly higher than those in the control group (P < .05). The incidence of hypertension, proteinuria, and oral mucositis in the experimental group was significantly higher than that in the control group (P < .05).
CONCLUSION
In the setting of first-line treatment of advanced HCC, apatinib has improved short-term efficacy (ORR) compared with sorafenib, but the safety and long-term efficacy of apatinib are inferior to sorafenib.
Topics: Humans; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Liver Neoplasms; Pyridines; Sorafenib
PubMed: 38241568
DOI: 10.1097/MD.0000000000036865 -
Journal of the International Society of... Dec 2024Previous research has established that nicotine withdrawal can ameliorate cardiovascular and pulmonary function in smokers. Nevertheless, the impact on physical fitness... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous research has established that nicotine withdrawal can ameliorate cardiovascular and pulmonary function in smokers. Nevertheless, the impact on physical fitness and athletic performance remains under-investigated.
OBJECTIVE
To evaluating the impacts of nicotine withdrawal on both exercise performance and exercise-associated physical capabilities in nicotine-dependent individuals.
STUDY DESIGN
A comprehensive systematic review and meta-analysis.
DATA SOURCES
The data was compiled from databases such as PubMed, Scopus, Web of Science, Cochrane Central, and EBSCO.
STUDY SELECTION
The selection criteria required studies to elucidate the effects of nicotine withdrawal on exercise performance or exercise-related physical abilities. Moreover, the selected studies needed to provide discernible experimental results.
DATA SYNTHESIS AND ANALYSIS
The random effects model was employed in data analysis, utilizing the standardized mean difference (SMD) and the 95% confidence intervals (95% CIs) to estimate participants' exercise performance and physical abilities, referencing the Mean ±SD during baseline and withdrawal states.
RESULTS
Out of the selected studies, 10 trials were included, encompassing 13,538 participants aged 18 to 65 years. The findings suggest that nicotine withdrawal could potentially enhance sports performance (SMD = 0.45, 95% CI: 0.03 to 0.88; I^2 = 83%), particularly in terms of aerobic capacity. Short-term nicotine withdrawal (spanning 12 to 24 hours) might lead to a decline in participants' physical abilities in certain aspects like reaction time and sustained attention (SMD = -0.83, 95% CI: -1.91 to 0.25; I^2 = 79%), whereas long-term withdrawal (lasting 48 hours or more) demonstrated an opposing trend (SMD = 0.25, 95% CI: 0.12 to 0.39; I^2 = 81%). Overall, the results show that long-term nicotine withdrawal exhibited some positive impacts on sports performance and exercise-related physical ability, with the withdrawal duration being an indicator of subsequent physical performance.
CONCLUSIONS
Mid- to long-term (≥3 months) nicotine withdrawal significantly improved the exercisers' exercise-related physical ability and sports performance. Conversely, short-term (≤24 hours) nicotine withdrawal considerably hampered exercisers' performance and physical cognition. It is suggested that exercises avoid abrupt nicotine cessation prior to competitions, as long-term nicotine withdrawal has been shown to significantly enhance exercise-related physiological capacities and athletic performance. By referring to existing literatures we also found that athletes with existing nicotine addiction may could consume nicotine 15-30 minutes before competition to enhance athletic performance and physical function.PROSPERO registration number CRD42023411381.
Topics: Humans; Exercise; Nicotine; Physical Fitness; Athletic Performance; Tobacco Use Disorder
PubMed: 38213003
DOI: 10.1080/15502783.2024.2302383 -
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 -
Dental Press Journal of Orthodontics 2024Bisphosphonates have an inhibitory impact on osteoclastic activity, reducing bone resorption. However, the influence of risedronate on tooth movement is not well-defined.
INTRODUCTION
Bisphosphonates have an inhibitory impact on osteoclastic activity, reducing bone resorption. However, the influence of risedronate on tooth movement is not well-defined.
OBJECTIVE
This systematic review assessed the effect of risedronate intake on orthodontic tooth movement. A case report was also provided.
METHODS
Two independent reviewers searched six databases (PubMed, Web of Science, Ovid, Lilacs, Scopus, and Open Grey). The searches were carried out in April/2020, and an update was set in place in June/2023. Therefore, the searches considered a timeline from the databases' inception date until June/2023, with no publication date and/or language restrictions. The clinical question focused on evaluating the orthodontic tooth movement and relapse movement (Outcome) in animals (Population) exposed to risedronate (Exposure), compared to control groups (Comparison). The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were applied, and the protocol was registered in PROSPERO (CRD42020168581). The risk of bias was determined using the Systematic Review Centre for Laboratory Animal Experimentation protocol (SYRCLE).
RESULTS
Two studies in rats and one in guinea pigs were included in the systematic review. The studies reported a decrease in orthodontic tooth movement, a reduction in the relapse movement, and a reduced number of positive tartrate-resistant acid phosphatase (TRAP) cells, with a significantly reduced number of bone gaps after the administration of risedronate in rats. A case report illustrated the effects of risedronate administration in one patient.
CONCLUSION
Based on the systematic review, risedronate seems to impair orthodontic tooth movement and relapse due to a decrease in bone resorption cells.
Topics: Animals; Guinea Pigs; Humans; Rats; Bone Resorption; Recurrence; Risedronic Acid; Rodentia; Tooth Movement Techniques
PubMed: 38198389
DOI: 10.1590/2177-6709.28.6.e2322280.oar -
Jornal Brasileiro de Pneumologia :... 2024To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis.
METHODS
This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, -0.16; 95% CI, -0.28 to -0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, -0.03; 95% CI, -0.08 to 0.01), and none of the studies reported deaths.
CONCLUSIONS
Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.
Topics: Humans; Alleles; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis; Quality of Life; Pyridines; Indoles; Pyrazoles; Aminophenols; Quinolones; Pyrrolidines; Benzodioxoles
PubMed: 38198345
DOI: 10.36416/1806-3756/e20230187 -
International Journal of Clinical... Apr 2024Ibandronate is effective in reducing the risk of vertebral fractures, but experimental evidence offers conflicting results regarding nonvertebral fractures. Real-world... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ibandronate is effective in reducing the risk of vertebral fractures, but experimental evidence offers conflicting results regarding nonvertebral fractures. Real-world evidence has been published evaluating the anti-nonvertebral fracture effect of ibandronate.
AIM
This meta-analysis of observational studies assessed the effectiveness of ibandronate in reducing the risk of nonvertebral fractures in women with osteoporosis.
METHOD
Pubmed/Embase databases were searched for observational studies. Risks of nonvertebral fractures and hip fractures were the outcomes. Meta-analyses were performed pooling rate ratios (RRs), using random-effects models. Data were reanalysed in sensitivity analyses considering Knapp-Hartung method and Bayesian random-effects.
RESULTS
Six cohort studies were included. Overall, once-monthly 150 mg oral ibandronate reduced the risk of nonvertebral fractures (RR 0.84; 95% CI 0.76-0.94). Similar results were obtained when the comparison was restricted to once-monthly 150 mg risedronate, but no differences were found when the comparator was other oral bisphosphonates (weekly alendronate/risedronate). Ibandronate didn't significantly change the risk of hip fractures (RR 1.25; 95% CI 0.89-1.76). The risk of hip fracture was comparable between once monthly, 150 mg oral ibandronate and other oral bisphosphonates. Intravenous ibandronate was not effective in reducing hip fractures comparing to intravenous zoledronate. The low number of studies diminished the robustness of sensitivity analyses.
CONCLUSION
Results suggest that once-monthly 150 mg oral ibandronate may be as effective as other oral bisphosphonates in reducing the risk of nonvertebral fractures. However, uncertainty associated to the small number of included studies, which are characterized by heterogeneous demographics and methodologies, precluded definitive conclusions.
Topics: Female; Humans; Ibandronic Acid; Risedronic Acid; Bone Density Conservation Agents; Diphosphonates; Bayes Theorem; Osteoporosis; Hip Fractures; Osteoporosis, Postmenopausal; Observational Studies as Topic
PubMed: 38112890
DOI: 10.1007/s11096-023-01666-x -
Neurological Sciences : Official... May 2024Masitinib, originally developed as a tyrosine kinase inhibitor for cancer treatment, has shown potential neuroprotective effects in various neurological disorders by... (Review)
Review
OBJECTIVES
Masitinib, originally developed as a tyrosine kinase inhibitor for cancer treatment, has shown potential neuroprotective effects in various neurological disorders by modulating key pathways implicated in neurodegeneration. This scoping review aimed to summarize the current evidence of masitinib's neuroprotective activities from preclinical to clinical studies.
METHODS
This scoping review was conducted following the guidelines described by Arksey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria covered all original studies reporting on the neuroprotective effects of masitinib, including clinical studies, animal studies, and in vitro studies.
RESULTS
A total of 16 studies met the inclusion criteria and were included in the review. These comprised five randomized controlled trials (RCTs), one post-hoc analysis study, one case report, and nine animal studies. The RCTs focused on Alzheimer's disease (two studies), multiple sclerosis (two studies), and amyotrophic lateral sclerosis (one study). Across all included studies, masitinib consistently demonstrated neuroprotective properties. However, the majority of RCTs reported concerns regarding the safety profile of masitinib. Preclinical studies revealed the neuroprotective mechanisms of masitinib, which include inhibition of certain kinases interfering with cell proliferation and survival, reduction of neuroinflammation, and exhibition of antioxidant activity.
CONCLUSION
The current evidence suggests a promising therapeutic benefit of masitinib in neurodegenerative diseases. However, further research is necessary to validate and expand upon these findings, particularly regarding the precise mechanisms through which masitinib exerts its therapeutic effects. Future studies should also focus on addressing the safety concerns associated with masitinib use.
Topics: Animals; Neuroprotective Agents; Piperidines; Pyridines; Benzamides; Thiazoles
PubMed: 38105307
DOI: 10.1007/s10072-023-07259-w -
Clinical Genitourinary Cancer Feb 2024Real-world cabozantinib use has increased since its approval to treat patients with advanced renal cell carcinoma (RCC) in 2016. We reviewed cabozantinib use in... (Review)
Review
Real-world cabozantinib use has increased since its approval to treat patients with advanced renal cell carcinoma (RCC) in 2016. We reviewed cabozantinib use in real-world clinical practice and compared outcomes with pivotal cabozantinib randomized control trials (RCTs). This PRISMA-standard systematic literature review evaluated real-world effectiveness and tolerability of cabozantinib in patients with RCC (PROSPERO registration: CRD42021245854). Systematic MEDLINE, Embase, and Cochrane database searches were conducted on November 2, 2022. Eligible publications included ≥ 20 patients with RCC receiving cabozantinib. After double-screening for eligibility, standardized data were abstracted, qualitatively summarized, and assessed for risk of bias using the Newcastle-Ottawa Scale. Of 353 screened publications, 41 were included, representing approximately 11,000 real-world patients. Most publications reported cabozantinib monotherapy cohort studies (40/41) of retrospective (39/41) and multicenter (32/41) design; most included patients from North America and/or Europe (30/41). Baseline characteristics were demographically similar between real-world and pivotal RCT populations, but real-world populations showed greater variation in prevalence of prior nephrectomy, multiple-site/brain metastasis, and nonclear-cell RCC histology. Cabozantinib activity was reported across real-world treatment lines and tumor types. Overall survival, progression-free survival, and objective response rate values from pivotal RCTs were within the ranges reported for equivalent outcomes across real-world studies. Common real-world grade ≥ 3 adverse events were consistent with those in pivotal RCTs (fatigue, palmar-plantar erythrodysesthesia syndrome, diarrhea, hypertension), but less frequent. No new tolerability concerns were identified. Real-world RCC survival outcomes for cabozantinib monotherapy were broadly consistent with pivotal RCTs, despite greater heterogeneity in real-world populations.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Pyridines; Anilides; Multicenter Studies as Topic
PubMed: 38101983
DOI: 10.1016/j.clgc.2023.11.001 -
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 -
Mechanisms of Ageing and Development Feb 2024The kynurenine pathway (KP) is gaining more attention as a common pathway involved in age-related conditions. However, which changes in the KP occur due to normal ageing...
BACKGROUND
The kynurenine pathway (KP) is gaining more attention as a common pathway involved in age-related conditions. However, which changes in the KP occur due to normal ageing is still largely unclear. The aim of this systematic review was to summarize the available evidence for associations of KP metabolites with age.
METHODS
We used an broad search strategy and included studies up to October 2023.
RESULTS
Out of 8795 hits, 55 studies were eligible for the systematic review. These studies suggest that blood levels of tryptophan decrease with age, while blood and cerebrospinal fluid levels of kynurenine and its ratio with tryptophan increase. Studies investigating associations between cerebrospinal fluid and blood levels of kynurenic acid and quinolinic acid with age reported either positive or non-significant findings. However, there is a large heterogeneity across studies. Additionally, most studies were cross-sectional, and only few studies investigated associations with other downstream kynurenines.
CONCLUSIONS
This systematic review suggests that levels of kynurenines are positively associated with age. Larger and prospective studies are needed that also investigate a more comprehensive panel of KP metabolites and changes during the life-course.
Topics: Kynurenine; Quinolinic Acid; Tryptophan; Aging
PubMed: 38056721
DOI: 10.1016/j.mad.2023.111890