-
Journal of Orthopaedic Surgery and... Mar 2024Many KOA patients have not reached indications for surgery, thus we need to find effective non-surgical treatments. Acupuncture is thought to have the potential to... (Meta-Analysis)
Meta-Analysis
Efficacy and immune-inflammatory mechanism of acupuncture-related therapy in animal models of knee osteoarthritis: a preclinical systematic review and network meta-analysis.
BACKGROUND
Many KOA patients have not reached indications for surgery, thus we need to find effective non-surgical treatments. Acupuncture is thought to have the potential to modulate inflammation and cytokines in KOA through the immune system. However, the mechanisms have not been elucidated, and there is no network Meta-analysis of acupuncture on KOA animals. So we evaluate the effect and mechanism of acupuncture-related therapy in KOA animals.
METHODS
A comprehensive search was conducted in multiple databases including PubMed, Web of Science, Embase, CBM, CNKI, WanFang, and VIP Database to identify relevant animal studies focusing on acupuncture therapy for KOA. The included studies were assessed for risk of bias using SYRCLE's Risk of Bias tool. Subsequently, pair-wise meta-analysis and network meta-analysis were performed using Stata 15.0 software, evaluating outcomes such as Lequesne index scale, Mankin score, IL-1β, TNF-α, MMP3, and MMP13.
RESULTS
56 RCTs with 2394 animals were included. Meta-analysis showed that among the 6 outcomes, there were significant differences between acupuncture and model group; the overall results of network meta-analysis showed that the normal group or sham operation group performed the best, followed by the acupotomy, acupuncture, and medicine group, and the model group had the worst effect, and there were significant differences between 6 interventions.
CONCLUSIONS
Acupuncture-related therapy can be a possible treatment for KOA. The mechanism involves many immune-inflammatory pathways, which may be mediated by DAMPs/TLR/NF-κB/MAPK,PI3K/Akt/NF-κB pathway, or IFN-γ/JAK-STAT pathway. It needs to be further confirmed by more high-quality animal experiments or meta-analysis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO identifier: CRD42023377228.
Topics: Animals; Humans; Osteoarthritis, Knee; Network Meta-Analysis; Janus Kinases; NF-kappa B; Phosphatidylinositol 3-Kinases; STAT Transcription Factors; Signal Transduction; Acupuncture Therapy; Models, Animal
PubMed: 38459553
DOI: 10.1186/s13018-024-04660-9 -
European Journal of Cancer (Oxford,... May 2024The first-line treatment choice of EGFRIs plus doublet chemotherapy vs. bevacizumab plus doublet chemotherapy remains a topic of interest for patients with left-sided... (Meta-Analysis)
Meta-Analysis Review
A meta-analysis of efficacy and safety data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in adult patients with RAS wild-type metastatic colorectal cancer by sidedness.
The first-line treatment choice of EGFRIs plus doublet chemotherapy vs. bevacizumab plus doublet chemotherapy remains a topic of interest for patients with left-sided RAS WT mCRC. We conducted a systematic literature review and meta-analysis of clinical trial data published between 2015 and 2024. We evaluated the relative efficacy and safety of first-line EGFRIs plus doublet chemotherapy (FOLFIRI or FOLFOX) vs. bevacizumab plus doublet chemotherapy for patients with RAS WT left-sided mCRC, as well as in all- and right-sided tumors. We identified eight trials with 2624 patients. Five trials reported outcomes by tumor sidedness. In the left-sided population, overall survival (OS) (Hazard Ratio (HR) = 0.80, 95% Confidence Interval (CI): 0.71-0.90) and objective response rate (ORR) (Odds ratio [OR]=1.61, 95% CI: 1.30-1.99) favored EGFRI plus chemotherapy, while no statistically significant differences were observed for progression-free survival (PFS) (HR=0.93, 95% CI: 0.84-1.04) or resection rate (RR). Similar results were found in the all-sided population. In the right-sided population, PFS favored bevacizumab plus chemotherapy (HR=1.45, 95% CI: 1.19-1.78), while no statistically significant differences were observed for OS (HR=1.17, 95% CI: 0.95-1.44), ORR (OR=0.99, 95% CI: 0.69-1.41), and RR. Early tumor shrinkage in the all-sided population favored EGFRI plus chemotherapy (OR=1.72; 95% CI: 1.36-2.17); limited data precluded evaluation by sidedness. Safety was available in 6 trials for all-sided tumors and 1 trial for left-sided tumors, each demonstrating typical class-specific adverse events. This most comprehensive meta-analysis indicates a benefit for first-line EGFRI plus chemotherapy over bevacizumab plus chemotherapy in patients with left-sided RAS WT mCRC.
Topics: Adult; Humans; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; ErbB Receptors
PubMed: 38442645
DOI: 10.1016/j.ejca.2024.113975 -
PeerJ 2024To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment.
METHODOLOGY
PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias.
RESULTS
Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor- (PDGFR-) ( = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) ( < 0.0001), matrix metalloproteinase (MMP) 9 ( < 0.0001), MMP 11 ( < 0.0001) and MMP 13 ( = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of -smooth muscle actin (-SMA) ( = 0.0002), podoplanin (PDPN) ( = 0.0008), and PDGFR- ( = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR- expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2).
CONCLUSIONS
The high expression of -SMA, PDPN, PDGFR- in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.
Topics: Humans; Female; Breast Neoplasms; Cancer-Associated Fibroblasts; Tissue Inhibitor of Metalloproteinase-2; Biomarkers, Tumor; Breast; Receptor, Platelet-Derived Growth Factor beta
PubMed: 38410801
DOI: 10.7717/peerj.16958 -
American Journal of Obstetrics &... Mar 2024In recent years, the ratio of soluble fms-like tyrosine kinase 1 to placental growth factor for use in predicting preeclampsia has been explored extensively. Despite... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In recent years, the ratio of soluble fms-like tyrosine kinase 1 to placental growth factor for use in predicting preeclampsia has been explored extensively. Despite extensive research, available data on its effectiveness in predicting preeclampsia in twin pregnancies are limited and conflicting. This meta-analysis aimed to assess the diagnostic accuracy of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio in distinguishing cases with preeclampsia in twin pregnancies from healthy controls.
DATA SOURCES
Studies that evaluated the use of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio in predicting preeclampsia were searched in PubMed, Embase, and Cochrane databases from inception to August 6, 2023, without language restriction.
STUDY ELIGIBILITY CRITERIA
The following population, exposure, comparators, outcomes, and study designs were included: women with twin pregnancies; an increased soluble fms-like tyrosine kinase 1 to placental growth factor ratio with preeclampsia as the outcome; women without preeclampsia; a 2 × 2 diagnostic table, diagnostic accuracy data, and the incidence of preeclampsia; and prospective cohort studies and observational comparative studies, respectively.
STUDY APPRAISAL AND SYNTHESIS METHODS
The quality of the included studies was evaluated. Key parameters, including the specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, were calculated using the random- and fixed-effects models. In addition, the area under the receiver operating characteristic curve and the summary receiver operating characteristic curve were evaluated.
RESULTS
A total of 7 studies were included, including 442 women with twin pregnancies (115 patients with preeclampsia and 327 controls without preeclampsia). The results highlighted the promising effectiveness of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio in predicting preeclampsia in twin pregnancies with a pooled specificity of 0.89 (95% confidence interval, 0.80-0.95), a sensitivity of 0.84 (95% confidence interval, 0.73-0.93), a positive likelihood ratio of 32.76 (95% confidence interval, 12.82-83.74), and a negative likelihood ratio of 0.03 (95% confidence interval, 0.01-0.08). The combined diagnostic odds ratio was 35.72 (95% confidence interval, 12.92-98.76), and the area under the receiver operating characteristic curve was 0.92.
CONCLUSION
These collective findings underscore the potential of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio as an accurate marker for identifying preeclampsia among women with twin pregnancies.
Topics: Female; Humans; Pregnancy; Placenta Growth Factor; Pre-Eclampsia; Pregnancy, Twin; Prospective Studies; Vascular Endothelial Growth Factor Receptor-1
PubMed: 38401234
DOI: 10.1016/j.ajogmf.2024.101290 -
Medicine Feb 2024To evaluate the efficacy and safety of dorzagliatin for the treatment of type 2 diabetes (T2DM). (Meta-Analysis)
Meta-Analysis
OBJECT
To evaluate the efficacy and safety of dorzagliatin for the treatment of type 2 diabetes (T2DM).
METHODS
Seven databases were systematically searched, spanning the interval from 2016 to August 2023. Randomized controlled trials (RCTS) comparing dorzagliatin with placebo for the treatment of T2DM were applicable for containing this study. The relevant data were extracted, and a meta-analysis was implemented using RevMan 5.4 software.
RESULTS
A total of 3 studies involving 1332 patients were included. We use glycated hemoglobin (HbA1c) levels as the major indicator of efficacy, FBG, 2h postprandial blood glucose, Homa-β and Homa-IR to be Secondary outcome measures. Compared with placebo group, dorzagliatin significantly reduced blood glucose levels as well as enhanced insulin resistance. In terms of safety, no serious adverse events occurred. However, lipid-related indicators, especially triglycerides levels, and the incidence of hypoglycemia were higher in patients in the dorzagliatin group compared with those in the control group, but the increase from baseline was mild.
CONCLUSIONS
Dorzagliatin exerted favorable effects in hypoglycemic control, effectively reduced the HbA1c, FBG, and 2h postprandial blood glucose levels in T2DM patients, stimulated the secretion of insulin during the initial phase, and exerted a consistent hypoglycemic effect. However, the incidence of adverse events such as elevated blood lipids and cardiovascular risk warrants further investigations through long-term clinical trials.
Topics: Humans; Glucokinase; Glycated Hemoglobin; Blood Glucose; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Pyrazoles
PubMed: 38394489
DOI: 10.1097/MD.0000000000036916 -
Phytomedicine : International Journal... Apr 2024Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and... (Review)
Review
BACKGROUND
Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and have been shown to improve gastric disorders in preclinical and clinical studies. The finding that PBAs exhibit low oral bioavailability but potent pharmacological activity has attracted great interest.
PURPOSE
This review aims to provide a systematic review of the molecular mechanisms of PBAs in the treatment of gastric disorders and to discuss the current understanding of the pharmacokinetics and toxicity of PBAs.
METHODS
The articles related to PBAs were collected from the Web of Science, Pubmed, and China National Knowledge Infrastructure databases using relevant keywords. The collected articles were screened and categorized according to their research content to focus on the gastroprotective effects, pharmacokinetics, and toxicity of PBAs.
RESULTS
Based on the results of preclinical studies, PBAs have demonstrated therapeutic effects on chronic atrophic gastritis and gastric cancer by activating interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) pathway and suppressing transforming growth factor-beta 1 (TGF-β1)/phosphoinositide 3-kinase (PI3K), Janus kinase-2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) pathways. The major PBAs exhibit similar pharmacokinetic properties, including rapid absorption, slow elimination, and low bioavailability. Notably, the natural organ-targeting property of PBAs may account for the finding of their low blood levels and high pharmacological activity. PBAs interact with other compounds, including conventional drugs and natural products, by modulation of metabolic enzymes and transporters. The potential tissue toxicity of PBAs should be emphasized due to their high tissue accumulation.
CONCLUSION
This review highlights the gastroprotective effects, pharmacokinetics, and toxicity of PBAs and will contribute to the evaluation of drug properties and clinical translational studies of PBAs, accelerating their transfer from the laboratory to the bedside.
Topics: Phosphatidylinositol 3-Kinases; Alkaloids; Berberine Alkaloids; Drugs, Chinese Herbal
PubMed: 38367423
DOI: 10.1016/j.phymed.2024.155444 -
Pediatric Neurology Apr 2024To systematically evaluate the diagnostic accuracy of the creatine kinase isoenzyme-MM (CK-MM) test in newborn screening for Duchenne muscular dystrophy (DMD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To systematically evaluate the diagnostic accuracy of the creatine kinase isoenzyme-MM (CK-MM) test in newborn screening for Duchenne muscular dystrophy (DMD).
METHODS
A comprehensive literature search was conducted up to October 31, 2022, in PubMed, Embase, Cochrane Library, Web of Science, and Scopus Database. To evaluate the diagnostic value, the sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and Q∗ index were pooled. Threshold effect followed by subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was used to verify the robustness of the findings.
RESULTS
A total seven studies with 248,853 newborns was included in our meta-analysis. The pooled SEN and SPE were 1.00 (95% confidence interval [CI]: 0.89∼1.00) and 1.00 (95% CI: 1.00 to 1.00), respectively; the PLR and NLR were 1004.59 (95% CI: 251.37∼4014.91) and 0.13 (95% CI: 0.05∼0.34), respectively; the DOR was 877.96 (95% CI: 983.24∼78,366.32); the AUC and Q index were 0.8683 and 0.9326, respectively. Sensitivity analysis showed that two studies had an impact on the pooled results and mainly contributed to the heterogeneity.
CONCLUSIONS
CK-MM test demonstrated high accuracy in newborn screening for DMD and may be a valuable alternative in the early diagnosis of the disease followed by confirmatory genetic testing.
Topics: Humans; Infant, Newborn; Muscular Dystrophy, Duchenne; Neonatal Screening; Isoenzymes; Sensitivity and Specificity; Creatine Kinase
PubMed: 38350306
DOI: 10.1016/j.pediatrneurol.2024.01.010 -
International Journal of Sports Medicine Jun 2024This review aimed to verify the effects of vitamin E supplementation on oxidative stress, inflammatory response, muscle damage, soreness, and strength in healthy adults... (Meta-Analysis)
Meta-Analysis
This review aimed to verify the effects of vitamin E supplementation on oxidative stress, inflammatory response, muscle damage, soreness, and strength in healthy adults after exercise. We searched the MEDLINE, EMBASE, SPORTDiscus, Cochrane CENTRAL, and Web of Science from inception to August 2023, with no language restrictions. We included randomized placebo-controlled trials evaluating the supplementation of vitamin E on the abovementioned outcomes after a bout of physical exercise in healthy participants (no restriction for publication year or language). Meta-analyses were conducted to compare vitamin E and placebo supplementations to obtain a 95% confidence interval (95%IC). Twenty studies were included (n=298 participants). The effect of supplementation was assessed between 0 h and 96 h after the exercise. Compared to placebo, vitamin E had no effects on lipid (95%IC= -0.09 to 0.42), protein (-2.44 to 3.11), SOD (-1.05 to 0.23), interleukin-6 (-0.18 to 1.16), creatine kinase (-0.33 to 0.27), muscle soreness (-1.92 to 0.69), and muscle strength (-1.07 to 0.34). Heterogeneity for the analyses on carbonyls, interleukin-6 (1 h and 3 h), and muscle soreness ranged between 70 to 94%. Supplementing with vitamin E should not be recommended to support the recovery process in healthy individuals after exercise, given the lack of efficacy in the analyzed variables following an exercise session.
Topics: Humans; Antioxidants; Creatine Kinase; Dietary Supplements; Exercise; Inflammation; Interleukin-6; Muscle Strength; Muscle, Skeletal; Myalgia; Oxidative Stress; Randomized Controlled Trials as Topic; Vitamin E
PubMed: 38346687
DOI: 10.1055/a-2221-5688 -
BMC Cancer Feb 2024To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung... (Meta-Analysis)
Meta-Analysis
Identifying optimal ALK inhibitors in first- and second-line treatment of patients with advanced ALK-positive non-small-cell lung cancer: a systematic review and network meta-analysis.
OBJECTIVES
To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung cancer (NSCLC).
METHODS
The included RCTs were identified through a systematic search of PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and major cancer conferences. The assessment of progression-free survival (PFS), intracranial PFS, overall survival (OS), and patient-reported outcomes (PROs) was carried out using restricted mean survival time (RMST) model, fractional polynomial model and Royston-Parmar model. Time-invariant hazard ratio (HR) models were also used to validate and supplement the primary analysis. Objective response rate (ORR) and adverse events with any grade, grade 3-5 were assessed through a Bayesian network meta-analysis. The primary measures for OS, PFS, and PROs were HR and RMST. The odds ratio was the metric for evaluating safety, ORR, 12-month PFS rate, 24-month OS rate, and the 12-month non-deterioration rate of PROs. Subgroup analyses based on patient characteristics were performed.
RESULTS
A total of fourteen studies (ten for first-line, four for second-line) consisting of nine treatments (chemotherapy, crizotinib, alectinib [600mg BID], low-dose alectinib [300mg BID], brigatinib, ceritinib, ensartinib, envonalkib, and lorlatinib) were included. In the first-line setting, alectinib showed a significant advantage over crizotinib and had the longest OS among all ALK-inhibitors. Compared to crizotinib, lorlatinib had the best efficacy regarding PFS for global patients, followed closely by alectinib and brigatinib. For Asian patients, alectinib significantly improved PFS compared to other treatments. In second-line, alectinib had the highest PFS for patients pretreated with crizotinib, followed by brigatinib, ceritinib and chemotherapy. Alectinib, irrespective of the dose, was the safest first-line option, whereas lorlatinib, brigatinib, and ceritinib showed poorer safety profiles. Alectinib was also the safest ALK-inhibitor for crizotinib-resistant patients. Brigatinib had the best performance in terms of PROs.
CONCLUSIONS
Considering both efficacy and safety, alectinib appears to be the preferable treatment in first-line and second-line, particularly for Asian patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Crizotinib; Lung Neoplasms; Network Meta-Analysis; Bayes Theorem; Quality of Life; Anaplastic Lymphoma Kinase; Protein Kinase Inhibitors; Carbazoles; Sulfones; Aminopyridines; Lactams; Pyrimidines; Pyrazoles; Organophosphorus Compounds
PubMed: 38331773
DOI: 10.1186/s12885-024-11916-4 -
Scientific Reports Feb 2024Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall... (Meta-Analysis)
Meta-Analysis
Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall survival (OS). A robust comparative evaluation of OS, safety, and tolerability of the three drugs is warranted. A systematic literature search identified phase 3 randomized clinical trials reporting OS of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy in ER-positive/HER2-negative advanced breast cancer. Trial-level data on OS and common and serious adverse events (AE) were extracted for each drug. In the absence of direct comparisons, a network meta-analysis was performed to evaluate pairwise comparative efficacy, safety, and tolerability of each of the CDK4/6i. Seven studies comprising of 4415 patients met the inclusion criteria. Median follow-up was 73.3 months (range: 48.7-97.2 months). There were no statistically significant differences in OS between any of the CDK4/6i. Compared to palbociclib, ribociclib and abemaciclib both showed significantly higher GI toxicity (grade 1-2 vomiting OR 1.87 [95% CI 1.37-2.56] and OR 2.27 [95% CI 1.59-3.23] respectively). Compared to palbociclib, abemaciclib was associated with more grade 3-4 diarrhea OR 118.06 [95% CI 7.28-1915.32]. In contrast, palbociclib was associated with significantly more neutropenia than ribociclib and abemaciclib but significantly lower risk of grade 3-4 infections. Abemaciclib had significantly less grade 3-4 transaminitis and grade 3-4 neutropenia than ribociclib. Treatment discontinuation and death due to AE were significantly higher with abemaciclib than palbociclib and ribociclib. There is no statistically significant difference in OS between CDK4/6i despite differing statistical significance levels of individual trials. Real-world data analyses may help to identify if there is a meaningful inter-drug difference in efficacy. Significant differences between CDK4/6i are observed for safety and tolerability outcomes.
Topics: Female; Humans; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinase Inhibitor Proteins; Neutropenia; Purines; Clinical Trials, Phase III as Topic; Randomized Controlled Trials as Topic
PubMed: 38326452
DOI: 10.1038/s41598-024-53151-8