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Lung Cancer (Amsterdam, Netherlands) May 2024The aim of this study was to investigate the clinical benefit and necessity of neoadjuvant programmed cell death (or ligand) (PD-(L)1) blockades in resectable non-small... (Meta-Analysis)
Meta-Analysis
Is neoadjuvant immunotherapy necessary in patients with programmed death ligand 1 expression-negative resectable non-small cell lung cancer? A systematic review and meta-analysis.
OBJECTIVES
The aim of this study was to investigate the clinical benefit and necessity of neoadjuvant programmed cell death (or ligand) (PD-(L)1) blockades in resectable non-small cell lung cancer (NSCLC) patients with negative PD-L1 expression.
MATERIALS AND METHODS
Randomized control trials (RCTs) that compared event-free survival (EFS), overall survival (OS), major pathological response (MPR), and/or pathological complete response (pCR) between neoadjuvant chemo-immunotherapy (nCIT) and neoadjuvant chemotherapy (nCT) for patients with resectable NSCLC stratified by PD-L1 expression were eligible for inclusion in the study. Data regarding the pathological response and EFS were evaluated by the odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) using random and fixed models.
RESULTS
A total of six RCTs involving 3,194 patients with resectable NSCLC with or without neoadjuvant immunotherapy were included. Compared with nCT alone, nCIT significantly improved pCR (18.3 % vs. 3.0 %; OR, 5.64; 95 % CI, 3.22-9.89; P < 0.001), MPR (38.9 % vs. 15.5 %; OR, 3.57; 95 % CI, 2.10-6.05; P < 0.001), and EFS (HR, 0.75; 95 % CI, 0.62-0.90; P = 0.002) in PD-L1 <1 % NSCLC patients. In addition, PD-L1 ≥1 % was associated with higher rates of pCR (32.8 % vs. 18.3 %; OR, 2.28; 95 % CI, 1.40-3.73; P = 0.001) and MPR (53.9 % vs. 38.9 %; OR, 1.84; 95 % CI, 1.22-2.79; P = 004) and longer EFS (HR, 0.44 vs. 0.75) in the setting of nCIT compared with PD-L1 <1 %. nCIT improved only OS in NSCLC patients with PD-L1 ≥1 % but not in patients with PD-L1 <1 %.
CONCLUSIONS
The use of nCIT should be recommended for resectable NSCLC patients with negative PD-L1 expression, as nCIT significantly improved the pathological response and EFS in these patients. The benefit to PD-L1-negative patients treated with nCIT on OS remains to be validated.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoadjuvant Therapy; B7-H1 Antigen; Immunotherapy; Randomized Controlled Trials as Topic; Immune Checkpoint Inhibitors
PubMed: 38669725
DOI: 10.1016/j.lungcan.2024.107799 -
Transfusion and Apheresis Science :... Jun 2024Haemorrhage is a significant cause of death in trauma patients. There is evidence that individuals with blood group O have higher rates of non-traumatic haemorrhage. It... (Review)
Review
BACKGROUND
Haemorrhage is a significant cause of death in trauma patients. There is evidence that individuals with blood group O have higher rates of non-traumatic haemorrhage. It has been suggested that blood group O may be associated with higher mortality in trauma, however existing evidence is limited and conflicting.
OBJECTIVE
A systematic review was conducted to evaluate the impact of ABO blood group on mortality in trauma patients.
METHODS
MEDLINE via OVID, the Cochrane library and grey literature were searched to identify studies investigating the effect of ABO blood group on mortality of trauma patients admitted to hospital. PRISMA guidelines were followed throughout, study quality was assessed using CASP checklists and certainty of evidence was evaluated using GRADE. Meta-analysis was precluded by significant study heterogeneity.
RESULTS
180 relevant records were screened and seven studies met inclusion criteria, representing 12,240 patients. Two studies found that there was a higher mortality in blood group O compared to other ABO groups. Included studies had substantial variability in methods and population. Study quality was variable with certainty of evidence rated as very low.
CONCLUSIONS
There is insufficient evidence to definitively establish an association between mortality and ABO group in trauma patients. In an age of increasingly individualised care, there is a need to determine the existence and cause for any association through further studies across multiple settings, trauma mechanisms and populations.
Topics: Humans; ABO Blood-Group System; Wounds and Injuries
PubMed: 38653629
DOI: 10.1016/j.transci.2024.103925 -
Journal of Clinical Apheresis Jun 2024Gemtuzumab ozogamicin (GO) is a CD33 monoclonal antibody-drug conjugate currently in use to treat myeloid malignancies. A unique adverse effect of this medication is...
Gemtuzumab ozogamicin (GO) is a CD33 monoclonal antibody-drug conjugate currently in use to treat myeloid malignancies. A unique adverse effect of this medication is destruction of CD33 positive macrophages resulting in reduced clearance of free hemoglobin leading to grossly red plasma. This build-up of free hemoglobin can potentially lead to end organ damage and prevent performance of clinically necessary laboratory evaluation. We present a case of a pediatric patient who developed this adverse effect and was successfully treated with therapeutic plasma exchange (TPE). We also present results from a systematic review of the medical literature and share data from a query of the United States Food and Drug Administration (FDA) Adverse Event Reporting system for GO-related hemoglobin scavenging impairment. Among reported cases, patients undergoing TPE and those receiving steroids had improved outcomes. Practitioners should be aware of this rare drug side-effect and the potential utility of TPE for these patients.
Topics: Humans; Gemtuzumab; Plasma Exchange; Hemoglobins; Sialic Acid Binding Ig-like Lectin 3; Male; Aminoglycosides; Female; Antibodies, Monoclonal, Humanized
PubMed: 38647036
DOI: 10.1002/jca.22116 -
Multiple Sclerosis and Related Disorders Jun 2024Use of natalizumab (NTZ) is precluded in many Multiple Sclerosis (MS) patients by the risk of progressive multifocal leukoencephalopathy (PML). Regardless, some patients...
BACKGROUND
Use of natalizumab (NTZ) is precluded in many Multiple Sclerosis (MS) patients by the risk of progressive multifocal leukoencephalopathy (PML). Regardless, some patients may commence natalizumab for short term disease control in spite of being seropositive, and others may seroconvert whilst on treatment. In these circumstances, discontinuation of NTZ should not occur until a clear exit strategy is established to prevent post-NTZ disease reactivation, which often exceeds the severity of disease activity prior to NTZ treatment. The objective of this systematic review was to summarise the available evidence for CD20-monoclonal antibodies (CD20mAb) as a suitable NTZ exit strategy, and to identify whether a superior switch protocol can be established.
METHODS
In accordance with PRISMA guidelines, a total of 2393 references were extracted from a search of three online databases (PubMed, Scopus, MEDLINE). Following the application of inclusion/exclusion criteria, a total of 5 studies representing 331 patients were included.
RESULTS
The overall incidence of clinical relapse during washout periods ranging from 4.4-10.7 weeks was 0 %. The incidence of clinical relapse during two-year follow-up ranged from 1.8 % to 10 % for switches to all types of CD20 monoclonal antibody. The weighted mean for clinical relapse at 12 months was 8.8 %. Three studies reported an annualised relapse rate (ARR) ranging from 0.02-0.12 with a weighted mean ARR of 0.07. The overall incidence of PML during washout was 0 % and the overall incidence of PML within 6 months follow-up was 0.6 %.
CONCLUSIONS
This systematic review provides the first attempt at identifying a superior switch protocol in patients at risk of PML transitioning from NTZ to a CD20mAb. Our results indicate that CD20mAb's are a suitable transitional option for patients who discontinue NTZ, with our cohort demonstrating very low rates of carryover PML and low rates of clinical relapse. The most appropriate washout period is unclear due to confounding factors but is likely between 4 and 12 weeks.
Topics: Humans; Natalizumab; Multiple Sclerosis, Relapsing-Remitting; Immunologic Factors; Antigens, CD20; Drug Substitution; Leukoencephalopathy, Progressive Multifocal
PubMed: 38640586
DOI: 10.1016/j.msard.2024.105605 -
Transfusion May 2024Anti-D can be formed after D-incompatible platelet transfusions due to contaminating D+ red blood cells. These antibodies are of particular importance in women of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anti-D can be formed after D-incompatible platelet transfusions due to contaminating D+ red blood cells. These antibodies are of particular importance in women of childbearing potential, because anti-D is most often involved in severe cases of hemolytic disease of the fetus and newborn. This systematic review determined the frequency of anti-D after D+ platelet transfusions and risk factors for D alloimmunization.
STUDY DESIGN AND METHODS
Relevant literature was searched using PubMed, Embase and Web of Science until December 2022. Overall anti-D frequency and risk factors were estimated using a random effects meta-analysis.
RESULTS
In 22 studies, a total of 3028 D- patients received a mean of six D+ platelet transfusions. After a mean follow-up of seven months 106 of 2808 eligible patients formed anti-D. The pooled anti-D frequency was 3.3% (95% CI 2.0-5.0%; I 71%). After including only patients with an undoubtable follow-up of at least 4 weeks, 29 of 1497 patients formed anti-D with a pooled primary anti-D rate of 1.9% (95% CI 0.9-3.2%, I 44%). Women and patients receiving whole blood derived platelets had two and five times higher anti-D rates compared with men and patients receiving apheresis derived platelets, respectively.
DISCUSSION
Anti-D immunization is low after D incompatible platelet transfusions and dependent on recipients' sex and platelet source. We propose anti-D prophylaxis in girls and women, capable of becoming pregnant in the future, that received D+ platelets, regardless of platelet source, to reduce the risk of anti-D induced hemolytic disease of the fetus and newborn.
Topics: Humans; Platelet Transfusion; Rho(D) Immune Globulin; Female; Isoantibodies; Rh-Hr Blood-Group System; Risk Factors; Pregnancy; Blood Group Incompatibility
PubMed: 38634345
DOI: 10.1111/trf.17833 -
High Blood Pressure & Cardiovascular... Mar 2024Coenzyme Q10 (CoQ10) has gained attention as a potential therapeutic agent for improving endothelial function. Several randomized clinical trials have investigated CoQ10... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Coenzyme Q10 (CoQ10) has gained attention as a potential therapeutic agent for improving endothelial function. Several randomized clinical trials have investigated CoQ10 supplementation's effect on endothelial function. However, these studies have yielded conflicting results, therefore this systematic review and meta-analysis were conducted.
AIM
This systematic review and meta-analysis were conducted to assess the effects of CoQ10 supplementation on endothelial factors.
METHODS
A comprehensive search was done in numerous databases until July 19th, 2023. Quantitative data synthesis was performed using a random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis, and publication bias.
RESULTS
12 studies comprising 489 subjects were included in the meta-analysis. The results demonstrated significant increases in Flow Mediated Dilation (FMD) after CoQ10 supplementation (WMD: 1.45; 95% CI: 0.55 to 2.36; p < 0.02), but there is no increase in Vascular cell adhesion protein (VCAM), and Intercellular adhesion molecule (ICAM) following Q10 supplementation (VCAM: SMD: - 0.34; 95% CI: - 0.74 to - 0.06; p < 0.10) (ICAM: SMD: - 0.18; 95% CI: - 0.82 to 0.46; p < 0.57). The sensitivity analysis showed that the effect size was robust in FMD and VCAM. In meta-regression, changes in FMD percent were associated with the dose of supplementation (slope: 0.01; 95% CI: 0.004 to 0.03; p = 0.006).
CONCLUSIONS
CoQ10 supplementation has a positive effect on FMD in a dose-dependent manner. Our findings show that CoQ10 has an effect on FMD after 8 weeks of consumption. Additional research is warranted to establish the relationship between CoQ10 supplementation and endothelial function.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Young Adult; Dietary Supplements; Endothelium, Vascular; Randomized Controlled Trials as Topic; Treatment Outcome; Ubiquinone; Vascular Cell Adhesion Molecule-1; Vasodilation
PubMed: 38630421
DOI: 10.1007/s40292-024-00630-8 -
JAMA Network Open Apr 2024Randomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Randomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) have reported consistent associations with event-free survival (EFS) and pathologic complete response (pCR) pending longer follow-up for overall survival data.
OBJECTIVE
To assess the pooled benefit of ICI-chemotherapy in 2-year EFS and pCR among patients with NSCLC and examine the impact of clinical, pathologic, and treatment-related factors.
DATA SOURCES
Full-text articles and abstracts in English were searched in EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through November 1, 2023, and in oncology conference proceedings from January 1, 2008, to November 1, 2023.
STUDY SELECTION
Phase 2 or 3 RCTs with neoadjuvant ICI-chemotherapy with or without adjuvant ICIs vs neoadjuvant chemotherapy alone with or without placebo or observation in patients with previously untreated NSCLC staged IB to IIIB were included.
DATA EXTRACTION AND SYNTHESIS
Data extraction of prespecified data elements was performed by 2 reviewers using a structured data abstraction electronic form. A random-effects model was used for meta-analysis. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.
MAIN OUTCOMES AND MEASURES
Two-year EFS and pCR were the outcomes of interest in patients who received neoadjuvant ICI-chemotherapy (experimental arm) or neoadjuvant chemotherapy alone (control arm). Aggregated pooled hazard ratios (HRs) for time-to-event outcomes (2-year EFS) and risk ratios (RRs) for dichotomous outcomes (pCR) with their respective 95% CIs were calculated.
RESULTS
Eight trials with 3387 patients were included, with some concerns of risk of bias as assessed by the Cochrane Collaboration method, mainly related to outcomes measurements. Neoadjuvant ICI-chemotherapy was associated with improved 2-year EFS (HR, 0.57; 95% CI, 0.50-0.66; P < .001) and increased pCR rate (RR, 5.58; 95% CI, 4.27-7.29; P < .001) in the experimental vs control treatment arms. This association was not significantly modified by the main patient characteristics; tumor- or treatment-related factors, including tumor programmed cell death ligand 1 (PD-L1) status; type of platinum-compound chemotherapy; number of cycles of neoadjuvant ICI-chemotherapy; or addition of adjuvant ICIs. Patients whose tumor cells were negative for PD-L1 were at higher risk of relapse (HR, 0.75; 95% CI, 0.62-0.91) than were those with low (HR, 0.61; 95% CI, 0.37-0.71) or high PD-L1 (HR, 0.40; 95% CI, 0.27-0.58) (P = .005).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis of neoadjuvant ICI-chemotherapy RCTs in patients with early-stage NSCLC, 3 cycles of neoadjuvant platinum-based ICI-chemotherapy were associated with a meaningful improvement in 2-year EFS and pCR.
Topics: Humans; Neoadjuvant Therapy; Carcinoma, Non-Small-Cell Lung; B7-H1 Antigen; Neoplasm Recurrence, Local; Immunotherapy; Small Cell Lung Carcinoma; Adjuvants, Immunologic; Lung Neoplasms
PubMed: 38625698
DOI: 10.1001/jamanetworkopen.2024.6837 -
Critical Reviews in Oncology/hematology Jun 2024Whether PD-L1 testing is needed to identify patients receiving PD-1/PD-L1 inhibitors is an area of debate. (Meta-Analysis)
Meta-Analysis Review
Association of PD-L1 expression with survival benefit from PD-1/PD-L1 inhibitors in advanced cancer: Systematic review and meta-analysis of phase III randomized clinical trials.
BACKGROUND
Whether PD-L1 testing is needed to identify patients receiving PD-1/PD-L1 inhibitors is an area of debate.
METHODS
PubMed and Embase were searched for phase III randomized clinical trials. We assessed the heterogeneity of overall survival (OS) between patients with high and low PD-L1 expression using an interaction test.
RESULTS
Seventy studies representing 44791 patients were included. Both the CPS and TPS can predict better survival from anti-PD-1/PD-L1 therapy in patients with high PD-L1 expression. However, only CPS 1 has the ability to select patients who are unlikely to respond to anti-PD-1/PD-L1 therapy, while an OS advantage can be obtained from PD-1/PD-L1 inhibitors both in patients with high and low PD-L1 expression defined by CPS 5, CPS 10 and TPS.
CONCLUSION
CPS 1 is recommended to select patients with the likelihood of benefiting from PD-1/PD-L1 inhibitors while excluding patients who may not respond.
Topics: Humans; Neoplasms; B7-H1 Antigen; Randomized Controlled Trials as Topic; Clinical Trials, Phase III as Topic; Programmed Cell Death 1 Receptor; Immune Checkpoint Inhibitors
PubMed: 38614270
DOI: 10.1016/j.critrevonc.2024.104357 -
Phytomedicine : International Journal... Jul 2024Over years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Over years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer.
OBJECTIVE
Our study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer.
METHODS
Researchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes.
RESULTS
Following screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE.
CONCLUSION
The NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.
Topics: Male; Prostatic Neoplasms; Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor Binding Protein 3; Network Meta-Analysis; Prostate-Specific Antigen; Plant Extracts; Biological Products
PubMed: 38608596
DOI: 10.1016/j.phymed.2024.155598 -
Frontiers in Immunology 2024Recently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC). However, patients show highly heterogeneous responses to treatment, and predictive biomarkers are lacking. We performed a systematic review and meta-analysis to assess the potential of PD-L1 expression as a biomarker for treatment response and survival in patients with BTC undergoing anti-PD-1/PD-L1 therapy.
METHODS
We conducted a comprehensive systematic literature search through June 2023, utilizing the PubMed, EMBASE, and Cochrane Library databases. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) according to PD-L1 expression. Subgroup analyses and meta-regression were performed to identify possible sources of heterogeneity.
RESULTS
A total of 30 studies was included in the final analysis. Pooled analysis showed no significant differences in ORR (odds ratio [OR], 1.56; 95% confidence intervals [CIs], 0.94-2.56) and DCR (OR, 1.84; 95% CIs, 0.88-3.82) between PD-L1 (+) and PD-L1 (-) patients. In contrast, survival analysis showed improved PFS (hazard ratio [HR], 0.54, 95% CIs, 0.41-0.71) and OS (HR, 0.58; 95% CI, 0.47-0.72) among PD-L1 (+) patients compared to PD-L1 (-) patients. Sensitivity analysis excluding retrospective studies showed no significant differences with the primary results. Furthermore, meta-regression demonstrated that drug target (PD-1 PD-L1), presence of additional intervention (monotherapy combination therapy), and PD-L1 cut-off level (1% ≥5%) significantly affected the predictive value of PD-L1 expression.
CONCLUSION
PD-L1 expression might be a helpful biomarker for predicting PFS and OS in patients with BTC undergoing anti-PD-1/PD-L1 therapy. The predictive value of PD-L1 expression can be significantly influenced by diagnostic or treatment variables.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023434114.
Topics: Humans; B7-H1 Antigen; Biliary Tract Neoplasms; Ligands; Programmed Cell Death 1 Receptor
PubMed: 38605964
DOI: 10.3389/fimmu.2024.1321813