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European Journal of Clinical... Apr 2024Long COVID is highly heterogeneous, often debilitating, and may last for years after infection. The aetiology of long COVID remains uncertain. Examination of potential... (Review)
Review
BACKGROUND
Long COVID is highly heterogeneous, often debilitating, and may last for years after infection. The aetiology of long COVID remains uncertain. Examination of potential serological markers of long COVID, accounting for clinical covariates, may yield emergent pathophysiological insights.
METHODS
In adherence to PRISMA guidelines, we carried out a rapid review of the literature. We searched Medline and Embase for primary observational studies that compared IgG response in individuals who experienced COVID-19 symptoms persisting ≥12 weeks post-infection with those who did not. We examined relationships between serological markers and long COVID status and investigated sources of inter-study variability, such as severity of acute illness, long COVID symptoms assessed and target antigen(s).
RESULTS
Of 8018 unique records, we identified 29 as being eligible for inclusion in synthesis. Definitions of long COVID varied. In studies that reported anti-nucleocapsid (N) IgG (n = 10 studies; n = 989 participants in aggregate), full or partial anti-Spike IgG (i.e. the whole trimer, S1 or S2 subgroups, or receptor binding domain, n = 19 studies; n = 2606 participants), or neutralizing response (n = 7 studies; n = 1123 participants), we did not find strong evidence to support any difference in serological markers between groups with and without persisting symptoms. However, most studies did not account for severity or level of care required during acute illness, and other potential confounders.
CONCLUSIONS
Pooling of studies would enable more robust exploration of clinical and serological predictors among diverse populations. However, substantial inter-study variations hamper comparability. Standardized reporting practices would improve the quality, consistency and comprehension of study findings.
Topics: Humans; COVID-19; SARS-CoV-2; Post-Acute COVID-19 Syndrome; Acute Disease; Immunoglobulin G; Antibodies, Viral
PubMed: 38083997
DOI: 10.1111/eci.14149 -
Frontiers in Oncology 2024The low rates of durable response against relapsed/refractory multiple myeloma (RRMM) in recent studies prompt that chimeric antigen receptor (CAR)-T cell therapies are...
BACKGROUND
The low rates of durable response against relapsed/refractory multiple myeloma (RRMM) in recent studies prompt that chimeric antigen receptor (CAR)-T cell therapies are yet to be optimized. The combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high clinical efficacy in several clinical trials for RRMM. We here conducted a meta-analysis to confirm its efficacy and safety.
METHODS
We collected data from Embase, Web of Science, PubMed, CNKI, Wanfang and Cochrane databases up to April 2023. We extracted and evaluated data related to the efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapies in RRMM patients. The data was then analyzed using RevMan5.4 and StataSE-64 software. PROSPERO number was CRD42023455002.
RESULTS
Our meta-analysis included 12 relevant clinical trials involving 347 RRMM patients who were treated with combined anti-BCMA and anti-CD19 CAR-T cell therapies. For efficacy assessment, the pooled overall response rate (ORR) was 94% (95% CI: 91%-98%), the complete response rate (CRR) was 50% (95% CI: 29%-71%), and the minimal residual disease (MRD) negativity rate within responders was 73% (95% CI: 66%-80%). In terms of safety, the pooled all-grade cytokine release syndrome (CRS) rate was 98% (95% CI: 97%-100%), grade≥3 CRS rate was 9% (95% CI: 4%-14%), and the incidence of neurotoxicity was 8% (95% CI: 4%-11%). Of hematologic toxicity, neutropenia was 82% (95% CI: 75%-89%), anemia was 71% (95% CI: 53%-90%), thrombocytopenia was 67% (95% CI: 40%-93%) and infection was 42% (95% CI: 9%-76%). The median progression-free survival (PFS) was 12.97 months (95% CI: 6.02-19.91), and the median overall survival (OS) was 26.63 months (95% CI: 8.14-45.11).
CONCLUSIONS
As a novel immunotherapy strategy with great potential, the combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high efficacy in RRMM, but its safety needs further improvement. This meta-analysis suggests possible optimization of combined CAR-T therapy.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023455002.
PubMed: 38651157
DOI: 10.3389/fonc.2024.1355643 -
International Journal of Molecular... Nov 2023Behçet's disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD's... (Review)
Review
Behçet's disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD's pathogenesis, focusing on established genetic factors. Studies reveal that is the primary genetic risk factor, but non-HLA genes (, , ), as well as innate immunity genes (, , ), also contribute. Genome-wide studies emphasize the significance of and HLA-I epistasis. These variants influence antigen presentation, enzymatic activity, and HLA-I peptidomes, potentially leading to distinct autoimmune responses. We conducted a systematic review of the literature to identify studies exploring the association between and BD and further highlighted the roles of innate and adaptive immunity in BD. Dysregulations in Th1/Th2 and Th17/Th1 ratios, heightened clonal cytotoxic (CD8+) T cells, and reduced T regulatory cells characterize BD's complex immune responses. Various immune cell types (neutrophils, γδ T cells, natural killer cells) further contribute by releasing cytokines (IL-17, IL-8, GM-CSF) that enhance neutrophil activation and mediate interactions between innate and adaptive immunity. In summary, this review advances our understanding of BD pathogenesis while acknowledging the research limitations. Further exploration of genetic interactions, immune dysregulation, and immune cell roles is crucial. Future studies may unveil novel diagnostic and therapeutic strategies, offering improved management for this complex disease.
Topics: Humans; Behcet Syndrome; Antigen Presentation; Genetic Predisposition to Disease; HLA-B Antigens; Risk Factors; Aminopeptidases; Minor Histocompatibility Antigens
PubMed: 38003572
DOI: 10.3390/ijms242216382 -
Critical Reviews in Oncology/hematology Apr 2024To summarize and indirectly compare the efficacy and safety of different second-line systematic therapies after first-line androgen-receptor targeting therapies (ARTs)... (Meta-Analysis)
Meta-Analysis Review
Second-line treatment options in metastatic castration-resistant prostate cancer after progression on first-line androgen-receptor targeting therapies: A systematic review and Bayesian network analysis.
OBJECTIVE
To summarize and indirectly compare the efficacy and safety of different second-line systematic therapies after first-line androgen-receptor targeting therapies (ARTs) for biomarker-unselected metastatic castration-resistant prostate cancer (mCRPC) patients.
METHODS
Studies published in English up to May 2023 were identified in PubMed, Web of Science and ASCO-GU 2023. Studies accessing the efficacy and safety of second-line systematic therapies after first-line ARTs for biomarker-unselected mCRPC patients were eligible for current systematic review and network meta-analysis (NMA).
RESULTS
Thirty-two studies with 5388 patients and 10 unique treatment modalities met our inclusion criteria. Current evidence suggested that docetaxel (DOC) combined with the same ART as first-line (ART1) (ART1 + DOC) were associated with significantly improved PSA response, PSA progression-free survival (PFS) and clinical or radiographic PFS (rPFS) compared with other reported second-line systematic therapies, including DOC. An increase in toxicity was observed with ART1 + DOC. Our NMA indicated that DOC monotherapy was only inferior to ART1 + DOC in improvement disease outcomes. The incidence of toxicity between patients received second-line DOC and an alternative ART (ART2) was similar.
CONCLUSION
The available evidence reviewed in our work suggested a clinical benefit of DOC nomotherapy and DOC plus ART1 as the second-line systematic therapy for biomarker-unselected mCRPC patients progressed on a first-line ART. More studies and RCTs are needed to evaluate the optimal second-line treatments for mCRPC patients with one prior first-line ART.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Androgens; Prostate-Specific Antigen; Treatment Outcome; Bayes Theorem; Docetaxel; Biomarkers; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38316286
DOI: 10.1016/j.critrevonc.2024.104286 -
Journal of Thrombosis and Haemostasis :... Jul 2024Chimeric antigen receptor T-cell (CAR T-cell) therapy is increasingly utilized for treatment of hematologic malignancies. Hematologic toxicities including thrombosis and... (Meta-Analysis)
Meta-Analysis
A meta-analysis to assess the risk of bleeding and thrombosis following chimeric antigen receptor T-cell therapy: Communication from the ISTH SSC Subcommittee on Hemostasis and Malignancy.
BACKGROUND
Chimeric antigen receptor T-cell (CAR T-cell) therapy is increasingly utilized for treatment of hematologic malignancies. Hematologic toxicities including thrombosis and bleeding complications have been reported. Accurate estimates for thrombotic and bleeding outcomes are lacking.
OBJECTIVES
We performed a systematic review and meta-analysis in patients who received CAR T-cell therapy for an underlying hematologic malignancy with the objective to: a) assess the thrombosis and bleeding risk associated with CAR T-cell therapy, b) assess the impact of CRS and ICANS on the risks of thrombosis and bleeding, and c) assess the safety of anticoagulant or antiplatelet use in the period following treatment with CAR T-cell therapy.
METHODS
We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to February 2022 for studies reporting thrombotic or bleeding outcomes in patients receiving CAR T-cell therapy. Pooled event rates were calculated using a random-effects model. We performed subgroup analyses stratified by follow-up duration, CAR T-cell target antigen, and underlying hematologic malignancy.
RESULTS
We included 47 studies with a total of 7040 patients. High heterogeneity between studies precluded reporting of overall pooled rates of thrombotic and bleeding events. In studies with follow-up duration of ≤6 months, the pooled incidence of venous thrombotic events was 2.4% (95% CI, 1.4%-3.4%; I = 0%) per patient-month, whereas the rate was 0.1% (95% CI, 0%-0.1%; I = 0%) per patient-month for studies with longer follow-up periods (>6 months). The pooled incidences of any bleeding events per patient-month in studies with follow-up duration of ≤6 months and >6 months were 1.9% (95% CI, 0.6%-3.1%; I = 78%) and 0.3% (95% CI: 0%-0.8%, I = 40%), respectively. Secondary analyses by CAR T-cell target antigen, underlying malignancy, and primary outcome of the studies did not reveal significant differences in the rates of thromboembolism, any bleeding events, or major bleeding events.
CONCLUSION
The risk of both thrombosis and bleeding following CAR T-cell therapy appears to be highest in the initial months following infusion.
Topics: Humans; Hemorrhage; Immunotherapy, Adoptive; Thrombosis; Hematologic Neoplasms; Risk Assessment; Risk Factors; Treatment Outcome; Hemostasis; Receptors, Chimeric Antigen; Anticoagulants; Male; Female; Middle Aged; Platelet Aggregation Inhibitors; Adult; Aged
PubMed: 38574863
DOI: 10.1016/j.jtha.2024.03.021 -
World Journal of Surgical Oncology Nov 2023The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors as neoadjuvant therapy for malignant solid tumors.
METHODS
This study has been registered with the number CRD42023407275 on PROSPERO. Systematic searches were conducted in PubMed, Embase, Web of Science and Cochrane Library databases until March 17, 2023. In addition, manual searches were performed. The inclusion criteria encompassed randomized controlled trials (RCTs) that assessed the utilization of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors PD-1/PD-L1 inhibitors for patients with solid malignancies. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials (ROB1) were used. Risk ratios (RRs), hazared ratios (HRs) and their respective 95% confidence intervals were calculated using Stata17.0 MP and Review Manager 5.4 software.
RESULTS
A total of 2780 records were identified, and ultimately 10 studies involving 273 patients were included. The meta-analysis showed that the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors did not demonstrate a significant effect on overall response rate, main pathological response, pathological complete response, surgical resection, radical resection, overall survival, progression-free survival, recurrence-free survival, grade 3-4 adverse events, all-cause mortality, and completed treatment (P > 0.05). However, further subgroup analysis indicated that the combination of PD-1 with CTLA-4 inhibitors significantly increased the occurrence of grade 3-4 adverse events in patients (P < 0.05).
CONCLUSIONS
As neoadjuvant therapy for malignant solid tumors, the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors does not appear to enhance efficacy.Moreover, there is a potential increase in the risk of grade 3-4 adverse events associated with this combination. However, it is important to note that the studies included in this analysis suffer from limitations such as small samples and single-center designs, which are inherent constrains with the available published literature. Further research involving large-sample and multicenter RCTs are warranted to obtain more reliable results.
Topics: Humans; Immune Checkpoint Inhibitors; Neoadjuvant Therapy; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Neoplasms; Multicenter Studies as Topic
PubMed: 37926852
DOI: 10.1186/s12957-023-03212-5 -
Journal of Infection and Public Health Apr 2024Dengue hemorrhagic fever (DHF) is a severe condition resulting from the dengue virus, with four serotypes known as DEN-1, DEN-2, DEN-3, and DEN-4. Genetic variations... (Meta-Analysis)
Meta-Analysis Review
Dengue hemorrhagic fever (DHF) is a severe condition resulting from the dengue virus, with four serotypes known as DEN-1, DEN-2, DEN-3, and DEN-4. Genetic variations play a crucial role in influencing susceptibility to DHF. Therefore, this investigation conducted a meta-analysis to uncover genetic changes that might have remained undetected in individual studies due to small sample sizes or methodological differences. Among 2212 initially identified studies, 23 were deemed suitable for analysis based on PRISMA guidelines. Toll-like receptors (TLR) and CD209 showed significant association with DHF (odds ratios: TLR=0.56, CD209 =0.55), indicating protective effects. However, tumor necrosis factor (TNF) and human leukocyte antigen (HLA) did not exhibit a statistically significant relationship with DHF. This study emphasizes the relevance of TLR and CD209 in DHF susceptibility and resistance across diverse geographical locations.
Topics: Humans; Severe Dengue; Dengue Virus; Tumor Necrosis Factor-alpha; Serogroup; Case-Control Studies; Dengue
PubMed: 38368646
DOI: 10.1016/j.jiph.2024.02.001 -
PharmacoEconomics - Open Mar 2024In this ever-expanding treatment landscape, there is a lack of consolidated health-related quality of life (HRQOL) outcomes and utility reports in relapsed or refractory...
BACKGROUND
In this ever-expanding treatment landscape, there is a lack of consolidated health-related quality of life (HRQOL) outcomes and utility reports in relapsed or refractory (R/R) large B cell lymphoma (LBCL) to inform health care policy and decision-maker assessments for both old and new products. These assessments can have a direct effect on what treatment options are available to patients and physicians.
OBJECTIVE
A systematic literature review (SLR) was performed to understand the HRQOL evidence for treatments in R/R LBCL and identify associated health utility values.
METHODS
The SLR searched and screened literature published from 1 January 2003 to 2 May 2022. Studies were screened based on Population, Intervention, Comparator, Outcome, Study design criteria established a priori and were assessed by two independent reviewers; quality assessments of the evidence were performed in accordance with health technology assessment recommendations from the National Institute for Health and Care Excellence. Several types of therapies were included, such as chimeric antigen receptor (CAR) T cell products (lisocabtagene maraleucel, axicabtagene ciloleucel, tisagenlecleucel), novel therapies (selinexor, nivolumab, polatuzumab vedotin, and bendamustine), salvage therapies, and rituximab.
RESULTS
The review identified 33 unique studies reporting HRQOL, including 15 economic studies that reported health state utility values, 9 clinical trials, 7 health technology assessment reports, and 1 each of a vignette-based study and a point-in-time survey. Improvements in general and/or lymphoma-specific HRQOL measures were observed with CAR T cell therapy in both the second-line and third-line or later settings. On-treatment utility values for CAR T cell therapies ranged from 0.50 to 0.74. Values for remission/progression-free survival (0.70-0.90) and for disease progression (0.39-0.59) were similar across studies. For novel therapies, utility values were 0.83 for progression-free survival and ranged from 0.39 to 0.71 for disease progression. On-treatment utility values for salvage chemotherapy ranged from 0.63 to 0.67.
CONCLUSIONS
Overall, the evidence synthesized in this SLR provides a comprehensive understanding of the HRQOL evidence in R/R LBCL. This article identified several sources for utility values in the published literature showing variation in the HRQOL outcomes for patients across a variety of therapeutics. Treatment of R/R LBCL with CAR T cell therapies was associated with improvement in health utility values. Mixed results were found for novel therapies and salvage therapies. More data are needed as new therapies are used in this patient population to inform treatment decision-making.
PubMed: 38198111
DOI: 10.1007/s41669-023-00464-5 -
PloS One 2024Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results.... (Meta-Analysis)
Meta-Analysis
Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results. Currently, no reliable biomarkers are available to predict the survival, recurrence, and progression of meningioma patients in clinical practice. This study aims to evaluate the prognostic value of immunohistochemistry-based (IHC) biomarkers of meningioma patients. A systematic literature search was conducted up to November 2023 on PubMed, CENTRAL, CINAHL Plus, and Scopus databases. Two authors independently reviewed the identified relevant studies, extracted data, and assessed the risk of bias of the studies included. Meta-analyses were performed with the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). The risk of bias in the included studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool. A total of 100 studies with 16,745 patients were included in this review. As the promising markers to predict OS of meningioma patients, Ki-67/MIB-1 (HR = 1.03, 95%CI 1.02 to 1.05) was identified to associate with poor prognosis of the patients. Overexpression of cyclin A (HR = 4.91, 95%CI 1.38 to 17.44), topoisomerase II α (TOP2A) (HR = 4.90, 95%CI 2.96 to 8.12), p53 (HR = 2.40, 95%CI 1.73 to 3.34), vascular endothelial growth factor (VEGF) (HR = 1.61, 95%CI 1.36 to 1.90), and Ki-67 (HR = 1.33, 95%CI 1.21 to 1.46), were identified also as unfavorable prognostic biomarkers for poor RFS of meningioma patients. Conversely, positive progesterone receptor (PR) and p21 staining were associated with longer RFS and are considered biomarkers of favorable prognosis of meningioma patients (HR = 0.60, 95% CI 0.41 to 0.88 and HR = 1.89, 95%CI 1.11 to 3.20). Additionally, high expression of Ki-67 was identified as a prognosis biomarker for poor PFS of meningioma patients (HR = 1.02, 95%CI 1.00 to 1.04). Although only in single studies, KPNA2, CDK6, Cox-2, MCM7 and PCNA are proposed as additional markers with high expression that are related with poor prognosis of meningioma patients. In conclusion, the results of the meta-analysis demonstrated that PR, cyclin A, TOP2A, p21, p53, VEGF and Ki-67 are either positively or negatively associated with survival of meningioma patients and might be useful biomarkers to assess the prognosis.
Topics: Meningioma; Humans; Biomarkers, Tumor; Prognosis; Meningeal Neoplasms; DNA Topoisomerases, Type II; Ki-67 Antigen; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Immunohistochemistry; Poly-ADP-Ribose Binding Proteins
PubMed: 38758750
DOI: 10.1371/journal.pone.0303337 -
International Journal of Molecular... Sep 2023The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and... (Review)
Review
The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and CAR-T cell therapies in relapsed/refractory (R/R) haematological malignancies. A systematic literature review was performed until 21 November 2022. Inclusion criteria: cohort studies/clinical trials aimed at evaluating the efficacy and/or safety of the combination of CAR-T cell therapy with PD-1/PD-L1 inhibitors in R/R haematological malignancies, which had reported results. Those focusing only on ICI or CAR-T separately or evaluating the combination in other non-hematological solid tumours were excluded. We used a specific checklist for quality assessment of the studies, and then we extracted data on efficacy or efficiency and safety. A total of 1867 articles were identified, and 9 articles were finally included (early phase studies, with small samples of patients and acceptable quality). The main pathologies were B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin's lymphoma (B-NHL). The most studied combination was tisagenlecleucel with pembrolizumab. In terms of efficacy, there is great variability: the combination could be a promising option in B-ALL, with modest data, and in B-NHL, although hopeful responses were received, the combination does not appear better than CAR-T cell monotherapy. The safety profile could be considered comparable to that described for CAR-T cell monotherapy.
Topics: Humans; Immune Checkpoint Inhibitors; Receptors, Chimeric Antigen; Programmed Cell Death 1 Receptor; Neoplasm Recurrence, Local; Hematologic Neoplasms; Immunotherapy, Adoptive; T-Lymphocytes
PubMed: 37834228
DOI: 10.3390/ijms241914780