-
Cancer Medicine Sep 2023The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to NT. We performed a meta-analysis to estimate their predictive significance.
METHODS
A systematic literature search of PubMed, Ovid MEDLINE and EMBASE databases was performed to identify eligible studies. Studies on patients with rectal cancer undergoing NT in which the predictive significance of at least one of the immunological markers of interest was assessed by immunohistochemistry (IHC) in pretreatment biopsies were included.
RESULTS
Seventeen studies reporting sufficient data met the inclusion criteria for meta-analysis. High levels of total CD3+, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs), as well as stromal and intraepithelial CD8+ compartments, significantly predicted good pathological response to NT. Moreover, high levels of total (tumoral and immune cell expression) PD-L1 resulted associated to a good pathological response. On the contrary, high levels of intraepithelial CD4+ TILs were correlated with poor pathological response. FoxP3+ TILs, tumoral PD-L1 and CTLA-4 were not correlated to the treatment response.
CONCLUSION
This meta-analysis indicated that high-density TILs might be predictive biomarkers of pathological response in patients that underwent NT for rectal cancer.
Topics: Humans; B7-H1 Antigen; Neoadjuvant Therapy; CD8-Positive T-Lymphocytes; Biomarkers; Rectal Neoplasms; Biopsy; Lymphocytes, Tumor-Infiltrating; Prognosis
PubMed: 37537787
DOI: 10.1002/cam4.6423 -
Forensic Science, Medicine, and... Jun 2021Although many clinical reports have been published, little is known about the pathological post-mortem findings from people who have died of the novel coronavirus...
Although many clinical reports have been published, little is known about the pathological post-mortem findings from people who have died of the novel coronavirus disease. The need for postmortem information is urgent to improve patient management of mild and severe illness, and treatment strategies. The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. A systematic literature search and a critical review of the collected studies were conducted. An electronic search of PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EMBASE) from database inception to June 2020 was performed. We found 28 scientific papers; the total amount of cases is 341. The major histological feature in the lung is diffuse alveolar damage with hyaline membrane formation, alongside microthrombi in small pulmonary vessels. It appears that there is a high incidence of deep vein thrombosis and pulmonary embolism among COVID-19 decedents, suggesting endothelial involvement, but more studies are needed. A uniform COVID-19 post-mortem diagnostic protocol has not yet been developed. In a time in which international collaboration is essential, standardized diagnostic criteria are fundamental requirements.
Topics: Alveolar Epithelial Cells; Autopsy; Brain; COVID-19; Fibrin; Fibroblasts; Humans; Kidney; Leukocytes, Mononuclear; Lung; Myositis; Respiratory Mucosa; Thrombosis
PubMed: 33026628
DOI: 10.1007/s12024-020-00310-8 -
Canadian Journal of Gastroenterology &... 2022The goal of this systematic review and meta-analysis was analyzing published studies on the role of neutrophil to lymphocyte ratio (NLR) in infection and spatially... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The goal of this systematic review and meta-analysis was analyzing published studies on the role of neutrophil to lymphocyte ratio (NLR) in infection and spatially spontaneous bacterial peritonitis (SBP) among cirrhotic patients.
METHODS
PubMed, Web of Science, and Scopus were searched until May 24, 2022. The Newcastle-Ottawa scale was used for quality assessment.
RESULTS
Of 14 studies included in our study, six studies were on infection with 2786 hospitalized cirrhotic patients, of whom 934 developed an infection. Other studies were on SBP with 1573 cirrhotic patients with ascites, of whom 557 developed SBP. The pooled results showed that there was no difference in NLR levels between hospitalized cirrhotic patients who developed infection compared to those who did not (random-effects model: SMD = 0.63, 95% CI = -0.01-1.27, =0.054). However, cirrhotic patients with ascites who developed SBP had elevated levels of NLR compared to those who did not (random-effects model: SMD = 1.05, 95% CI = 0.52-1.57, < 0.001). This difference remained significant in prospective studies (SMD = 0.94, 95% CI = 0.51-1.38, < 0.001) but not in retrospective studies (SMD = 1.37, 95% CI = -0.56-3.29,=0.165), in the subgroup analysis according to the study design. The pooled sensitivity of NLR was 92.07% (95% CI = 74.85%-97.84%) and the pooled specificity was 72.58% (95% CI = 57.72%-83.69%). The pooled positive likelihood ratio, negative likelihood ratio, DOR of NLR were 3.35(95%CI = 2.06-5.46), 0.10 (95%CI = 0.03-0.38), and 30.78 (95%CI = 7.01-135.04), respectively.
CONCLUSION
Our results support NLR to be a valid biomarker that can be readily integrated into clinical settings to help in the prevention and prediction of SBP among cirrhotic patients.
Topics: Ascites; Biomarkers; Humans; Liver Cirrhosis; Lymphocytes; Neutrophils; Peritonitis; Prospective Studies; Retrospective Studies
PubMed: 36204262
DOI: 10.1155/2022/8604060 -
The Lancet. Gastroenterology &... Jul 2024Microsatellite instability (MSI) status and tumour-infiltrating lymphocytes (TIL) are established prognostic factors in colorectal cancer. Previous studies evaluating... (Meta-Analysis)
Meta-Analysis
Clinical significance of combined tumour-infiltrating lymphocytes and microsatellite instability status in colorectal cancer: a systematic review and network meta-analysis.
BACKGROUND
Microsatellite instability (MSI) status and tumour-infiltrating lymphocytes (TIL) are established prognostic factors in colorectal cancer. Previous studies evaluating the combination of TIL and MSI status identified distinct colorectal cancer subtypes with unique prognostic associations. However, these studies were often limited by sample size, particularly for MSI-high (MSI-H) tumours, and there is no comprehensive summary of the available evidence. We aimed to review the literature to compare the survival outcomes associated with the subtypes derived from the integrated MSI-TIL classification in patients with colorectal cancer.
METHODS
In this systematic review and network meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Library without language restrictions, for articles published between Jan 1, 1990, and March 13, 2024. Patient cohorts comparing different combinations of TIL (high or low) and MSI status (MSI or microsatellite stable [MSS]) in patients with surgically resected colorectal cancer were included. Studies were excluded if they focused on neoadjuvant therapy or on other immune markers such as B cells or macrophages. Methodological quality assessment was done with the Newcastle-Ottawa scale; data appraisal and extraction was done independently by two reviewers. Summary estimates were extracted from published reports. The primary outcomes were overall survival, disease-free survival, and cancer-specific survival. A frequentist network meta-analysis was done to compare hazard ratios (HRs) and 95% CI for each outcome. The MSI-TIL subgroups were prognostically ranked based on P-score, bias, magnitude, and precision of associations with each outcome. The protocol is registered with PROSPERO (CRD42023461108).
FINDINGS
Of 302 studies initially identified, 21 studies (comprising 14 028 patients) were included in the systematic review and 19 (13 029 patients) in the meta-analysis. Nine studies were identified with a low risk of bias and the remaining ten had a moderate risk of bias. The MSI-TIL-high (MSI-TIL-H) subtype exhibited longer overall survival (HR 0·45, 95% CI 0·34-0·61; I=77·7%), disease-free survival (0·43, 0·32-0·58; I=61·6%), and cancer-specific survival (0·53, 0·43-0·66; I=0%), followed by the MSS-TIL-H subtype for overall survival (HR 0·53, 0·41-0·69; I=77·7%), disease-free survival (0·52, 0·41-0·64; I=61·6%), and cancer-specific survival (0·55, 0·47-0·64; I=0%) than did patients with MSS-TIL-low tumours (MSS-TIL-L). Patients with the MSI-TIL-L subtype had similar overall survival (0·88, 0·66-1·18; I=77·7%) and disease-free survival (0·93, 0·69-1·26; I=61·6%), but a modestly longer cancer-specific survival (0·72, 0·57-0·90; I=0%) than did the MSS-TIL-L subtype. Results from the direct and indirect evidence were strongly congruous.
INTERPRETATION
The findings from this network meta-analysis suggest that better survival was only observed among patients with TIL-H colorectal cancer, regardless of MSI or MSS status. The integrated MSI-TIL classification should be further explored as a predictive tool for clinical decision-making in early-stage colorectal cancer.
FUNDING
German Research Council (HO 5117/2-2).
Topics: Humans; Microsatellite Instability; Lymphocytes, Tumor-Infiltrating; Colorectal Neoplasms; Prognosis; Network Meta-Analysis; Disease-Free Survival; Clinical Relevance
PubMed: 38734024
DOI: 10.1016/S2468-1253(24)00091-8 -
Chest Jul 2023Monocyte distribution width (MDW) is an emerging biomarker for infection. It is available easily and quickly as part of the CBC count, which is performed routinely on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Monocyte distribution width (MDW) is an emerging biomarker for infection. It is available easily and quickly as part of the CBC count, which is performed routinely on hospital admission. The increasing availability and promising results of MDW as a biomarker in sepsis has prompted an expansion of its use to other infectious diseases.
RESEARCH QUESTION
What is the diagnostic performance of MDW across multiple infectious disease outcomes and care settings?
STUDY DESIGN AND METHODS
A systematic review of the diagnostic performance of MDW across multiple infectious disease outcomes was conducted by searching PubMed, Embase, Scopus, and Web of Science through February 4, 2022. Meta-analysis was performed for outcomes with three or more reports identified (sepsis and COVID-19). Diagnostic performance measures were calculated for individual studies with pooled estimates created by linear mixed-effects models.
RESULTS
We identified 29 studies meeting inclusion criteria. Most examined sepsis (19 studies) and COVID-19 (six studies). Pooled estimates of diagnostic performance for sepsis differed by reference standard (Second vs Third International Consensus Definitions for Sepsis and Septic Shock criteria) and tube anticoagulant used and ranged from an area under the receiver operating characteristic curve (AUC) of 0.74 to 0.94, with mean sensitivity of 0.69 to 0.79 and mean specificity of 0.57 to 0.86. For COVID-19, the pooled AUC of MDW was 0.76, mean sensitivity was 0.79, and mean specificity was 0.59.
INTERPRETATION
MDW exhibited good diagnostic performance for sepsis and COVID-19. Diagnostic thresholds for sepsis should be chosen with consideration of reference standard and tube type used.
TRIAL REGISTRY
Prospero; No.: CRD42020210074; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Monocytes; COVID-19; Sepsis; Biomarkers; Communicable Diseases; COVID-19 Testing
PubMed: 36681146
DOI: 10.1016/j.chest.2022.12.049 -
Viruses Mar 2022During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4... (Review)
Review
During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), lymphocyte-activation gene-3 (LAG-3), T cell immunoglobulin and mucin domain-3 (Tim-3), CD160, 2B4 (CD244), and V-domain Ig suppressor of T cell activation (VISTA), can lead to chronic T cell exhaustion. These ICs play predominant roles in regulating the progression of HIV/SIV infection by mediating T cell responses as well as enriching latent viral reservoirs. It has been demonstrated that enhanced expression of ICs on CD4 and CD8 T cells could inhibit cell proliferation and cytokine production. Overexpression of ICs on CD4 T cells could also format and prolong HIV/SIV persistence. IC blockers have shown promising clinical results in HIV therapy, implying that targeting ICs may optimize antiretroviral therapy in the context of HIV suppression. Here, we systematically review the expression profile, biological regulation, and therapeutic efficacy of targeted immune checkpoints in HIV/SIV infection.
Topics: Animals; CD8-Positive T-Lymphocytes; Disease Progression; HIV Infections; Humans; Immunoglobulins; Lymphocyte Activation; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus
PubMed: 35336991
DOI: 10.3390/v14030581 -
Journal of Oral Pathology & Medicine :... Jan 2022Inflammation seems to play a critical role in the development and progression of different cancers. Neutrophil-to-lymphocyte ratio (NLR) is an easily measurable marker... (Meta-Analysis)
Meta-Analysis Review
Inflammation seems to play a critical role in the development and progression of different cancers. Neutrophil-to-lymphocyte ratio (NLR) is an easily measurable marker of systemic inflammation. The purpose of this systematic review and meta-analysis was to evaluate the prognostic role of the pre-treatment NLR, in terms of overall survival (OS) and disease-free survival (DFS), in patients with primary head and neck squamous cell carcinoma (HNSCC) treated by surgery alone or followed by chemo/radiotherapy. This systematic review was performed according to the guidelines reported in the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Meta-analysis of OS and DFS was performed using the inverse of variance test. Fixed-effect models were used on the basis of the presence of heterogeneity. Risk of bias assessment and trial sequential analysis (TSA) were also performed; the quality of the evidence was evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The analysis revealed that a higher value of pre-treatment NLR correlates with a statistically significant decrease of OS (HR, 1.56; 95% CI: [1.35, 1.80]; p < 0.00001) and a lower DFS (HR, 1.64; 95% CI: [1.30, 2.07]; p < 0.0001) in HNSCC patients.
Topics: Head and Neck Neoplasms; Humans; Lymphocytes; Neutrophils; Prognosis; Squamous Cell Carcinoma of Head and Neck
PubMed: 34797592
DOI: 10.1111/jop.13264 -
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 -
European Respiratory Review : An... Sep 2023Peripheral blood monocyte counts have been associated with poor outcomes in interstitial lung disease (ILD). However, studies are limited by variable biomarker... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral blood monocyte counts have been associated with poor outcomes in interstitial lung disease (ILD). However, studies are limited by variable biomarker thresholds, analytic approaches and heterogenous populations. This systematic review and meta-analysis characterised the relationship between monocytes and clinical outcomes in ILD.
METHODS
Electronic database searches were performed. Two reviewers screened abstracts and extracted data. Pooled estimates (hazard ratios (HRs)) of monocyte count thresholds were calculated for their association with mortality using ≥0.6×10 and >0.9×10 cells·L for unadjusted models and ≥0.95×10 cells·L for adjusted models, using random effects, with heterogeneity and bias assessed. Disease progression associated with monocytes >0.9×10cells·L was also calculated.
RESULTS
Of 3279 abstracts, 13 were included in the systematic review and eight in the meta-analysis. The pooled unadjusted HR for mortality for monocyte counts ≥0.6×10 cells·L was 1.71 (95% CI 1.34-2.19, p<0.001, I=0%) and for monocyte counts >0.90×10 cells·L it was 2.44 (95% CI 1.53-3.87, p=0.0002, I=52%). The pooled adjusted HR for mortality for monocyte counts ≥0.95×10 cells·L was 1.93 (95% CI 1.24-3.01, p=0.0038 I=69%). The pooled HR for disease progression associated with increased monocyte counts was 1.83 (95% CI 1.40-2.39, p<0.0001, I=28%).
CONCLUSIONS
Peripheral blood monocyte counts were associated with an increased risk of mortality and disease progression in patients with ILD.
Topics: Humans; Monocytes; Lung Diseases, Interstitial; Patients; Disease Progression
PubMed: 37673424
DOI: 10.1183/16000617.0072-2023 -
The Journal of Maternal-fetal &... Dec 2023Using straightforward and accessible haematological parameters platelet/lymphocyte ratio (PLR) to diagnose preeclampsia (PE) early and precisely remains a challenge.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Using straightforward and accessible haematological parameters platelet/lymphocyte ratio (PLR) to diagnose preeclampsia (PE) early and precisely remains a challenge. Although several clinical studies suggested that PLR is able to diagnose PE, there has been no systematic evaluation of the diagnostic utility.
OBJECTIVES
To examine the diagnostic accuracy and potential applicability of PLR in the detection of PE.
STUDY DESIGN
Seven databases were searched using a combination of PLR and PE terms, and all potentially pertinent studies were systematically searched up to March 2023. All potentially relevant studies both prospective and retrospective were reviewed. To assess the diagnostic value of PLR for PE, pooled sensitivity (Sen), specificity (Spe), diagnostic odds ratio (DOR) and area under the summary receiver operating characteristic curve (SROC-AUC) were calculated.
RESULTS
Thirteen studies were enrolled in the meta-analysis. In the second and third trimesters, the PLR suggested a diagnostic value for PE with a pooled Sen of 54.7% [95% confidence interval (CI) (51.7, 57.6)], Spe of 77.8% [95% CI (75.5, 80.0)], + LR of 2.457 [95% CI (1.897, 3.182)], -LR of 0.584 [95% CI (0.491, 0.695)], DOR of 4.434 [95% CI (3.071, 6.402)], the SROC-AUC of 0.7296 and the standard error (SE) of 0.0370.
CONCLUSION
For the diagnosis of PE, PLR has a limited sensitivity but an acceptable specificity, and showed moderate accuracy. Further using complete blood count (CBC) indicators such as PLR alone or in combination to diagnose and predict PE could reduce healthcare costs and improve maternal and child prognosis.
Topics: Child; Female; Humans; Pregnancy; Lymphocytes; Pre-Eclampsia; Prospective Studies; Retrospective Studies; ROC Curve; Sensitivity and Specificity
PubMed: 37455131
DOI: 10.1080/14767058.2023.2234540