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Revista Da Associacao Medica Brasileira... 2024The objective of this study was to explore the relationship between serum soluble fms-like tyrosine kinase 1 and the severity of acute pancreatitis and its diagnostic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to explore the relationship between serum soluble fms-like tyrosine kinase 1 and the severity of acute pancreatitis and its diagnostic utility.
METHODS
This study was carried out by searching Chinese and English literature from the establishment of the database to July 9, 2023, systematically, and assessing the quality and heterogeneity of the articles included.
RESULTS
Thirteen studies with a total of 986 patients were included. Patients with severe acute pancreatitis showed higher levels of soluble fms-like tyrosine kinase 1 compared with mild acute pancreatitis [weighted mean difference=76.64 pg/mL, 95% confidence interval (95%CI 50.39-102.89, p<0.001)]. Soluble fms-like tyrosine kinase 1 predicted pooled sensitivity, specificity, and area under the curve were 79%, 74%, and 0.85 for severe acute pancreatitis, with some heterogeneity (I2>50% or p<0.05). In the subgroup analysis, cutoff >150 pg/mL was found to be a heterogeneous factor.
CONCLUSION
Soluble fms-like tyrosine kinase 1 is a reliable tool for identifying acute pancreatitis severity, but only as a screening tool.
Topics: Humans; Pancreatitis; Severity of Illness Index; Acute Disease; Biomarkers; Vascular Endothelial Growth Factor Receptor-1; Sensitivity and Specificity; Predictive Value of Tests
PubMed: 38775515
DOI: 10.1590/1806-9282.20231694 -
American Journal of Physiology. Heart... Jul 2024The reduced uterine perfusion pressure (RUPP) model is frequently used to study preeclampsia and fetal growth restriction. An improved understanding of influential... (Meta-Analysis)
Meta-Analysis Review
The reduced uterine perfusion pressure (RUPP) model is frequently used to study preeclampsia and fetal growth restriction. An improved understanding of influential factors might improve reproducibility and reduce animal use considering the variability in RUPP phenotype. We performed a systematic review and meta-analysis by searching Medline and Embase (until 28 March, 2023) for RUPP studies in murine. Primary outcomes included maternal blood pressure (BP) or proteinuria, fetal weight or crown-rump length, fetal reabsorptions, or antiangiogenic factors. We aimed to identify influential factors by meta-regression analysis. We included 155 studies. Our meta-analysis showed that the RUPP procedure results in significantly higher BP (MD = 24.1 mmHg; [22.6; 25.7]; = 148), proteinuria (SMD = 2.3; [0.9; 3.8]; = 28), fetal reabsorptions (MD = 50.4%; [45.5; 55.2]; = 42), circulating soluble FMS-like tyrosine kinase-1 (sFlt-1) (SMD = 2.6; [1.7; 3.4]; = 34), and lower fetal weight (MD = -0.4 g; [-0.47; -0.34]; = 113. The heterogeneity (variability between studies) in primary outcomes appeared ≥90%. Our meta-regression identified influential factors in the method and time point of BP measurement, randomization in fetal weight, and type of control group in sFlt-1. The RUPP is a robust model considering the evident differences in maternal and fetal outcomes. The high heterogeneity reflects the observed variability in phenotype. Because of underreporting, we observed reporting bias and a high risk of bias. We recommend standardizing study design by optimal time point and method chosen for readout measures to limit the variability. This contributes to improved reproducibility and thereby eventually improves the translational value of the RUPP model.
Topics: Fetal Growth Retardation; Female; Pregnancy; Pre-Eclampsia; Animals; Disease Models, Animal; Mice; Uterus; Blood Pressure; Vascular Endothelial Growth Factor Receptor-1; Fetal Weight
PubMed: 38758122
DOI: 10.1152/ajpheart.00056.2024 -
Lung Cancer (Amsterdam, Netherlands) Jun 2024Crizotinib was approved to treat patients with advanced non-small cell lung cancer (aNSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion in 2016. We conducted a... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of crizotinib in the treatment of advanced non-small cell lung cancer with ROS1 gene fusion: a systematic literature review and meta-analysis of real-world evidence.
BACKGROUND
Crizotinib was approved to treat patients with advanced non-small cell lung cancer (aNSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion in 2016. We conducted a systematic literature review to identify real-world evidence (RWE) studies and estimated the efficacy and safety of crizotinib using meta-analyses (MA) for objective response rate (ORR), real-world progression-free survival (PFS), and overall survival (OS).
METHODS
We searched MEDLINE®, Embase, and Cochrane CENTRAL from January 2016 to March 2023 using Ovid® for published single-arm or comparative RWE studies evaluating patients (N ≥ 20) receiving crizotinib monotherapy for aNSCLC with ROS1 gene fusion. Pooled estimates for ORR and grade 3/4 adverse events (AEs) were derived using the metafor package in R while pooled estimates for median real-world PFS (rwPFS) and OS were derived using reconstructed individual patient data from published Kaplan-Meier curves. The primary analysis included all studies regardless of crizotinib line of therapy; a subgroup analysis (SA) was conducted using studies evaluating patients receiving first-line crizotinib.
RESULTS
Fourteen studies met the eligibility criteria and were considered feasible for MA. For the primary analysis, the pooled ORR (N = 9 studies) was 70.6 % (95 % confidence interval [CI]: 57.0, 81.3), median rwPFS was 14.5 months (N = 11 studies), and OS was 40.2 months (N = 9 studies). In the SA, the pooled ORR (N = 4 studies) was 81.1 % (95 % CI: 76.1, 85.2) and the median rwPFS (N = 4 studies) and OS (N = 2 studies) were 18.1 and 60 months, respectively. All MAs were associated with significant heterogeneity (I > 25 %). Grade 3/4 AEs occurred in 18.7 % of patients (pooled estimate).
CONCLUSION
The results from this study are consistent with clinical trial data and, taken collectively, supports crizotinib as a safe and effective treatment across different lines of therapy in patients with ROS1 aNSCLC in the real-world setting.
Topics: Crizotinib; Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Proto-Oncogene Mas; Proto-Oncogene Proteins; Protein-Tyrosine Kinases; Protein Kinase Inhibitors; Oncogene Proteins, Fusion; Treatment Outcome; Antineoplastic Agents; Gene Fusion
PubMed: 38749072
DOI: 10.1016/j.lungcan.2024.107816 -
Expert Review of Pharmacoeconomics &... Jun 2024This study aims to provide a comprehensive assessment of economic and health-related quality of life (HRQoL) outcomes for human epidermal growth factor receptor 2... (Review)
Review
Quality-adjusted life years for HER2-positive, early-stage breast cancer using trastuzumab-containing regimens in the context of cost-effectiveness studies: a systematic review.
INTRODUCTION
This study aims to provide a comprehensive assessment of economic and health-related quality of life (HRQoL) outcomes for human epidermal growth factor receptor 2 (HER2)-positive, early-stage breast cancer patients treated with trastuzumab-containing regimens, by focusing on both Incremental Cost-Effectiveness Ratios (ICERs) and quality-adjusted life years (QALYs).
METHODS
A systematic search was conducted across PubMed, Embase, and Scopus databases without language or publication year restrictions. Two independent reviewers screened eligible studies, extracted data, and assessed methodology and reporting quality using the Drummond checklist and Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022), respectively. Costs were converted to US dollars (US$) for 2023 for cross-study comparison.
RESULTS
Twenty-two articles, primarily from high-income countries (HICs), were included, with ICERs ranging from US$13,176/QALY to US$254,510/QALY, falling within country-specific cost-effectiveness thresholds. A notable association was observed between higher QALYs and lower ICERs, indicating a favorable cost-effectiveness and health outcome relationship. EQ-5D was the most utilized instrument for assessing health state utility values, with diverse targeted populations.
CONCLUSIONS
Studies reporting higher QALYs tend to have lower ICERs, indicating a positive relationship between cost-effectiveness and health outcomes. However, challenges such as methodological heterogeneity and transparency in utility valuation persist, underscoring the need for standardized guidelines and collaborative efforts among stakeholders.
REGISTRATION
PROSPERO ID: CRD42021259826.
Topics: Humans; Cost-Benefit Analysis; Breast Neoplasms; Trastuzumab; Quality-Adjusted Life Years; Female; Receptor, ErbB-2; Quality of Life; Antineoplastic Agents, Immunological; Neoplasm Staging; Developed Countries
PubMed: 38738869
DOI: 10.1080/14737167.2024.2352006 -
Radiotherapy and Oncology : Journal of... Jul 2024We performed this systematic review and meta-analysis to investigate the performance of ML in detecting genetic mutation status in NSCLC patients. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
We performed this systematic review and meta-analysis to investigate the performance of ML in detecting genetic mutation status in NSCLC patients.
MATERIALS AND METHODS
We conducted a systematic search of PubMed, Cochrane, Embase, and Web of Science up until July 2023. We discussed the genetic mutation status of EGFR, ALK, KRAS, and BRAF, as well as the mutation status at different sites of EGFR.
RESULTS
We included a total of 128 original studies, of which 114 constructed ML models based on radiomic features mainly extracted from CT, MRI, and PET-CT data. From a genetic mutation perspective, 121 studies focused on EGFR mutation status analysis. In the validation set, for the detection of EGFR mutation status, the aggregated c-index was 0.760 (95%CI: 0.706-0.814) for clinical feature-based models, 0.772 (95%CI: 0.753-0.791) for CT-based radiomics models, 0.816 (95%CI: 0.776-0.856) for MRI-based radiomics models, and 0.750 (95%CI: 0.712-0.789) for PET-CT-based radiomics models. When combined with clinical features, the aggregated c-index was 0.807 (95%CI: 0.781-0.832) for CT-based radiomics models, 0.806 (95%CI: 0.773-0.839) for MRI-based radiomics models, and 0.822 (95%CI: 0.789-0.854) for PET-CT-based radiomics models. In the validation set, the aggregated c-indexes for radiomics-based models to detect mutation status of ALK and KRAS, as well as the mutation status at different sites of EGFR were all greater than 0.7.
CONCLUSION
The use of radiomics-based methods for early discrimination of EGFR mutation status in NSCLC demonstrates relatively high accuracy. However, the influence of clinical variables cannot be overlooked in this process. In addition, future studies should also pay attention to the accuracy of radiomics in identifying mutation status of other genes in EGFR.
Topics: Humans; Lung Neoplasms; Machine Learning; Mutation; Carcinoma, Non-Small-Cell Lung; Positron Emission Tomography Computed Tomography; ErbB Receptors; Proto-Oncogene Proteins p21(ras)
PubMed: 38734145
DOI: 10.1016/j.radonc.2024.110325 -
Frontiers in Pharmacology 2024The European League of Rheumatology(EULAR)guidelines recommend Janus kinase (JAK) inhibitors for patients with moderate to severe rheumatoid arthritis (RA) who are... (Review)
Review
Comparative efficacy of five approved Janus kinase inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
The European League of Rheumatology(EULAR)guidelines recommend Janus kinase (JAK) inhibitors for patients with moderate to severe rheumatoid arthritis (RA) who are insensitive or under-responsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). But there was no recommendation for which one was preferred in five currently approved JAK inhibitors. The objective of this network meta-analysis study was to evaluate the efficacy of five JAK inhibitors as monotherapy and combination therapy in patients with moderate-to-severe active rheumatoid arthritis.
METHODS
The randomized controlled trials (RCTs) of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy or combined with csDMARD in the treatment of active RA were searched in database of PubMed, Embase, Web of Science and Cochrane Library, up to December 2023. The control group included placebo or csDMARD. Outcome indicators included American College of Rheumatology 20% response (ACR20), ACR50, ACR70 and the percentage of patients achieving 28-joint disease activity score using C-reactive protein (DAS28(CRP))<2.6 at 12 weeks and 24 weeks. The statistical analysis was performed by Stata14 and RevMan5.4. Data processing, network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots and funnel plots were generated. Risk ratio (RR) and 95% confidence interval (95%CI) as effect sizes to analyze the statistics.
RESULTS
This study included thirty-six RCTs with 16,713 patients. All JAK inhibitors were more effective than placebo in ACR20 (RRs ranging between 1.74 and 3.08), ACR50 (RRs ranging between 2.02 and 7.47), ACR70 (RRs ranging between 2.68 and 18.13), DAS28(CRP) < 2.6 (RRs ranging between 2.70 and 7.09) at 12 weeks. Upadacitinib 30 mg and upadacitinib 15 mg showed relatively good efficacy according to their relative SUCRA ranking. All JAK inhibitors were more effective than csDMARD or placebo in ACR20 (RRs ranging between 1.16 and 1.86), ACR50 (RRs ranging between 1.69 and 2.84), ACR70 (RRs ranging between 1.50 and 4.47), DAS28(CRP) < 2.6 (RRs ranging between 2.28 and 7.56) at 24 weeks. Upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD showed relatively good efficacy according to their relative SUCRA ranking. The safety analysis results such as serious infection, malignancy, major adverse cardiovascular event (MACE), and venous thromboembolic events (VTE) showed no statistical difference.
CONCLUSION
This NMA study indicated that all JAK inhibitors performed better than placebo. Based on the results of this study, upadacitinib 30 mg, upadacitinib 15 mg, upadacitinib 15 mg + csDMARD and baricitinib 4 mg + csDMARD were recommended treatment options with relatively good efficacy and safety. However, attention should be paid to monitoring the occurrence of adverse events in high-risk RA patients with medication. Combination therapy with csDMARD might be more suitable for the maintenance of long-term efficacy. However, in clinical practice, it is still necessary to select the appropriate therapeutic regimen based on the actual clinical situation.
PubMed: 38725657
DOI: 10.3389/fphar.2024.1387585 -
Oral Oncology Jun 2024Exploration into the use of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) inhibitors alongside programmed cell death protein 1 (PD-1)/programmed... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Exploration into the use of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) inhibitors alongside programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has been undertaken for treating recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). We conducted a meta-analysis to provide a more precise assessment of the efficacy and safety of this integrated approach in managing R/M HNSCC.
METHODS
A systematic exploration encompassing PubMed, Embase, the Cochrane Library, and Web of Science databases was undertaken to figure out relevant studies. It was attempted to analyze critical endpoints, such as overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) utilizing a random-effects model.
RESULTS
Eleven studies, encompassing 413 patients, were analyzed. The combined data revealed an ORR of 41 % (95 % CI: 34-49 %), a DCR of 67 % (95 % CI: 51-83 %), a median PFS of 5.87 months (95 % CI: 3.90-7.85), and a median OS of 9.63 months (95 % CI: 6.78-12.49). Furthermore, the rates for 1-year PFS and OS were 45 % (95 % CI: 27-64 %) and 65 % (95 % CI: 49-81 %), respectively. The occurrence of grade 3 or higher adverse events related to the drugs was 20 % (95 % CI: 10-30 %). Subgroup analysis within the tyrosine kinase inhibitor (TKI) group revealed an ORR of 47 % (95 % CI: 39 %-55 %) and a DCR of 67 % (95 % CI: 46 %-88 %).
CONCLUSIONS
In summary, combining VEGF/VEGFR inhibitors with PD-1/PD-L1 inhibitors shows considerable effectiveness with manageable side effects in cases with R/M HNSCC.
SYSTEMATIC REVIEW REGISTRATION
Registered with the International Prospective Register of Systematic Reviews, identifier CRD42023486345.
Topics: Humans; Vascular Endothelial Growth Factor A; Receptors, Vascular Endothelial Growth Factor; Squamous Cell Carcinoma of Head and Neck; Immune Checkpoint Inhibitors; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Head and Neck Neoplasms; Male; Female
PubMed: 38714115
DOI: 10.1016/j.oraloncology.2024.106814 -
Expert Review of Anticancer Therapy Jul 2024Neoadjuvant treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is controversial and requires a... (Meta-Analysis)
Meta-Analysis Comparative Study Review
BACKGROUND
Neoadjuvant treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is controversial and requires a comprehensive analysis for optimal therapy assessment. Therefore, a two-step Bayesian network meta-analysis (NMA) was performed to compare the efficacy and safety of different neoadjuvant regimens.
RESEARCH DESIGN AND METHODS
Phase II/III randomized clinical trials comparing various neoadjuvant therapies for HR+/HER2- breast cancer were included. NMA and pairwise meta-analyses were conducted using Stata (version 14), R (version 4.2.3), and Review Manager 5.4.
RESULTS
Twenty-eight studies (5,625 patients) were eligible. NMA of objective response rate (ORR) indicated the highest SUCRA for chemotherapy (CT) and chemotherapy with anthracycline (CT(A)). Pathologic complete response (PCR) NMA demonstrated significant PCR improvement with chemotherapy regimens containing programmed cell death protein-1 and programmed cell death ligand-1 inhibitors (PD-1i/PD-L1i) and poly ADP-ribose polymerase inhibitors (PARPi). Combined analysis considering both the ORR and safety highlighted CT(A)'s efficacy and toxicity balance.
CONCLUSIONS
CT(A) and CT showed improved ORR compared with alternative regimens. CT(A) combined with PD-1/PD-L1 or PARP inhibitors significantly increased PCR rates. Comprehensive assessment of both ORR and safety indicated that CT(A) represents an optimal neoadjuvant therapy for HR+/HER2- breast cancer, whereas AI + CDK4/6 inhibitors rank solely behind chemotherapy.
REGISTRATION
PROSPERO Registration: CRD42024538948. International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) registration number INPLASY202440092.
Topics: Humans; Female; Neoadjuvant Therapy; Bayes Theorem; Breast Neoplasms; Network Meta-Analysis; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase III as Topic; Clinical Trials, Phase II as Topic
PubMed: 38693054
DOI: 10.1080/14737140.2024.2350105 -
Leukemia Research Jun 2024Acute myeloid leukemia (AML) is a complex disease with diverse mutations, including prevalent mutations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene that lead... (Review)
Review
BACKGROUND
Acute myeloid leukemia (AML) is a complex disease with diverse mutations, including prevalent mutations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene that lead to poor prognosis. Recent advancements have introduced FLT3 inhibitors that have improved outcomes for FLT3-mutated AML patients, however, questions remain on their application in complex conditions such as relapsed/refractory (R/R) disease. Therefore, we aimed to evaluate the clinical effectiveness of second-generation FLT3 inhibitors in treating patients with R/R AML.
METHODS
A systematic literature search of PubMed, MEDLINE, SCOPUS and Google Scholar databases was made to identify relevant studies up to January 30, 2024. This study was conducted following the guidelines of the PRISMA.
RESULTS
The ADMIRAL trial revealed significantly improved overall survival and complete remission rates with gilteritinib compared to salvage chemotherapy, with manageable adverse effects. Ongoing research explores its potential in combination therapies, showing synergistic effects with venetoclax and promising outcomes in various clinical trials. The QuANTUM-R trial suggested longer overall survival with quizartinib compared to standard chemotherapy, although concerns were raised regarding trial design and cardiotoxicity. Ongoing research explores combination therapies involving quizartinib, such as doublet or triplet regimens with venetoclax, showing promising outcomes in FLT3-mutated AML patients.
CONCLUSION
These targeted therapies offer promise for managing this subgroup of AML patients, but further research is needed to optimize their use. This study underscores the importance of personalized treatment based on genetic mutations in AML, paving the way for more effective and tailored approaches to combat the disease.
Topics: Humans; fms-Like Tyrosine Kinase 3; Leukemia, Myeloid, Acute; Protein Kinase Inhibitors; Drug Resistance, Neoplasm; Mutation; Aniline Compounds; Phenylurea Compounds; Neoplasm Recurrence, Local; Pyrazines; Benzothiazoles
PubMed: 38692232
DOI: 10.1016/j.leukres.2024.107505 -
Human Psychopharmacology Apr 2024Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, primarily used in breast cancer treatment, has recently emerged as a potential... (Review)
Review
BACKGROUND
Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, primarily used in breast cancer treatment, has recently emerged as a potential therapeutic option for managing manic episodes associated with bipolar disorder (BD). This review aims to assess the existing evidence base for endoxifen in BD treatment and evaluate the strengths and limitations of current research findings.
METHODS
A systematic search was conducted on Medline, Embase, and Web of Science databases. We included studies published in English that used endoxifen in BD, alongside any relevant studies identified through manual searching and conference papers with full-text availability. Information pertaining to dose, duration, clinical effects, and safety profiles was extracted from the included studies. The Cochrane Risk of Bias 2 tool was used to assess the risk of bias in clinical trials.
RESULTS
The final review included seven case reports (including two conference presentations), two clinical trials, and one prospective study. Most studies administered endoxifen 8 mg and reported an improvement in manic symptoms. Several case reports included patients with comorbid substance use, and most patients received mood stabilizers concurrently. Few reports lacked any structured outcome measures. The clinical trials used divalproex 1000 mg as an active comparator, which was deemed sub-therapeutic. Despite being multicentric, the first trial lacked data on center-wise recruitment, and certain methodological concerns were observed across the included trials. There were no serious adverse effects noted, except for a significant elevation in lipid profile within a 3-week period. Limited data were available regarding endoxifen efficacy and safety in mixed episodes, depressive episodes, and maintenance treatment.
CONCLUSION
There is a paucity of research on the efficacy and safety of endoxifen in BD. While existing evidence suggests short-term efficacy in manic episodes, significant limitations were identified in most of the included studies. Further research is imperative to establish the efficacy and safety of endoxifen in BD before considering its recommendation as a viable treatment option.
PubMed: 38683854
DOI: 10.1002/hup.2899