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Journal of Hematology & Oncology Aug 2014The aberrant hemostasis is a common manifestation of cancer, and venous thromboembolism (VTE) is the second leading cause of cancer patients' mortality. Tissue factor... (Review)
Review
The aberrant hemostasis is a common manifestation of cancer, and venous thromboembolism (VTE) is the second leading cause of cancer patients' mortality. Tissue factor (TF), comprising of a 47-kDa transmembrane protein that presents in subendothelial tissues and leukocytes and a soluble isoform, have distinct roles in the initiation of extrinsic coagulation cascade and thrombosis. Laboratory and clinical evidence showed the deviant expression of TF in several cancer systems and its tumor-promoting effects. TF contributes to myeloid cell recruitment in tumor stroma, thereby remodeling of tumor microenvironment. Additionally, the number of TF-positive-microparticles (TF+MP) from tumor origins correlates with the VTE rates in cancer patients. In this review, we summarize our current understanding of the TF regulation and roles in tumor progression and clinical complications.
Topics: Animals; Blood Coagulation; Hemostasis; Humans; Neoplasms; Thromboplastin; Tumor Microenvironment; Venous Thromboembolism
PubMed: 25084809
DOI: 10.1186/s13045-014-0054-8 -
Clinical Orthopaedics and Related... May 2017In the assessment of possible periprosthetic knee infection, various imaging modalities are used without consensus regarding the most accurate technique. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In the assessment of possible periprosthetic knee infection, various imaging modalities are used without consensus regarding the most accurate technique.
QUESTIONS/PURPOSES
To perform a meta-analysis to compare the accuracy of various applied imaging modalities in the assessment of periprosthetic knee infection.
METHODS
A systematic review and meta-analysis was conducted with a comprehensive search of MEDLINE and Embase in accordance with the PRISMA and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) recommendations to identify clinical studies in which periprosthetic knee infection was investigated with different imaging modalities. The sensitivity and specificity of each imaging technique were determined and compared with the results of microbiologic and histologic analyses, intraoperative findings, and clinical followup of more than 6 months. A total of 23 studies, published between 1990 and 2015, were included for meta-analysis, representing 1027 diagnostic images of symptomatic knee prostheses. Quality of the included studies showed low concerns regarding external validity, whereas internal validity indicated more concerns regarding the risk of bias. The most important concerns were found in the lack of uniform criteria for the diagnosis of a periprosthetic infection and the flow and timing of the included studies. Differences among techniques were tested at a probability less than 0.05 level. Where there was slight overlap of confidence intervals for two means, it is possible for the point estimates to be statistically different from one another at a probability less than 0.05. The z-test was used to statistically analyze differences in these situations.
RESULTS
Bone scintigraphy was less specific than all other modalities tested (56%; 95% CI, 0.47-0.64; p < 0.001), and leukocyte scintigraphy (77%; 95% CI, 0.69-0.85) was less specific than antigranulocyte scintigraphy (95%; 95% CI, 0.88-0.98; p < 0.001) or combined leukocyte and bone marrow scintigraphy (93%; 95% CI, 0.86-0.97; p < 0.001). Fluorodeoxyglucose positron emission tomography (FDG-PET) (84%; 95% CI, 0.76-0.90) was more specific than bone scintigraphy (56%; 95% CI, 0.47-0.64; p < 0.001), and less specific than antigranulocyte scintigraphy (95%; 95% CI, 0.88-0.98; p = 0.02) and combined leukocyte and bone marrow scintigraphy (93%; 95% CI, 0.86-0.97; p < 0.001). Leukocyte scintigraphy (88%; 95% CI, 0.81-0.93; p = 0.01) and antigranulocyte scintigraphy (90%; 95% CI, 0.78-0.96; p = 0.02) were more sensitive than FGD-PET (70%; 95% CI, 0.56-0.81). However, because of broad overlapping of confidence intervals, no differences in sensitivity were observed among the other modalities, including combined bone scintigraphy (93%; 95% CI, 0.85-0.98) or combined leukocyte and bone marrow scintigraphy (80%; 95% CI, 0.66-0.91; p > 0.05 for all paired comparisons).
CONCLUSIONS
Based on current evidence, antigranulocyte scintigraphy and combined leukocyte and bone marrow scintigraphy appear to be highly specific imaging modalities in confirming periprosthetic knee infection. Bone scintigraphy was a highly sensitive imaging technique but lacks the specificity needed to differentiate among various conditions that cause painful knee prostheses. FDG-PET may not be the preferred imaging modality because it is more expensive and not more effective in confirming periprosthetic knee infection.
LEVEL OF EVIDENCE
Level III, diagnostic study.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Knee; Bone Marrow; Child; Child, Preschool; Female; Fluorodeoxyglucose F18; Granulocytes; Humans; Knee Joint; Knee Prosthesis; Leukocytes; Male; Middle Aged; Positron-Emission Tomography; Predictive Value of Tests; Prosthesis-Related Infections; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Treatment Outcome; Young Adult
PubMed: 28050818
DOI: 10.1007/s11999-016-5218-0 -
Strahlentherapie Und Onkologie : Organ... Dec 2023Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells,... (Review)
Review
OBJECTIVE
Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells, radiation therapy (RT) can alter TME composition. With this systematic review, we provide a better understanding on how RT can regulate macrophage characterization, namely the M1 antitumor and the M2 protumor polarization, with the aim of describing new effective RT models and exploration of the possibility of integrating radiation with other available therapies.
METHODS
A systematic search in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out in PubMed, Google Scholar, and Scopus. Articles from January 2000 to April 2020 which focus on the role of M1 and M2 macrophages in the response to RT were identified.
RESULTS
Of the 304 selected articles, 29 qualitative summary papers were included in our analysis (16 focusing on administration of RT and concomitant systemic molecules, and 13 reporting on RT alone). Based on dose intensity, irradiation was classified into low (low-dose irradiation, LDI; corresponding to less than 1 Gy), moderate (moderate-dose irradiation, MDI; between 1 and 10 Gy), and high (high-dose irradiation, HDI; greater than 10 Gy). While HDI seems to be responsible for induced angiogenesis and accelerated tumor growth through early M2-polarized TAM infiltration, MDI stimulates phagocytosis and local LDI may represent a valid treatment option for possible combination with cancer immunotherapeutic agents.
CONCLUSION
TAMs seem to have an ambivalent role on the efficacy of cancer treatment. Radiation therapy, which exerts its main antitumor activity via cell killing, can in turn interfere with TAM characterization through different modalities. The plasticity of TAMs makes them an attractive target for anticancer therapies and more research should be conducted to explore this potential therapeutic strategy.
Topics: Humans; Tumor-Associated Macrophages; Neoplasms; Macrophages; Tumor Microenvironment
PubMed: 37347290
DOI: 10.1007/s00066-023-02097-3 -
Clinical Endocrinology Mar 2021Neutropenia, a low absolute neutrophil count (ANC), may be a sign of new-onset hyperthyroidism. The aim of this systematic review and meta-analysis was to provide the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Neutropenia, a low absolute neutrophil count (ANC), may be a sign of new-onset hyperthyroidism. The aim of this systematic review and meta-analysis was to provide the most reliable estimates of prevalence, degree and response to treatments of neutropenia in the pure hyperthyroidism setting.
METHODS
A comprehensive literature search was performed in PubMed and Scopus databases for retrieving articles in English and non-English languages reporting ANC values/neutropenic cases at presentation and after therapy in patients with hyperthyroidism. A proportion meta-analysis was performed with DerSimonian and Laird method (random-effects model). Pooled data were presented with 95% confidence intervals (95% CI) and displayed in a forest plot. I statistic index was used to quantify the heterogeneity among the studies. Sensitivity analyses for the prevalence of neutropenia and the mean of ANC in hyperthyroid patients were performed by excluding the studies without full details. Trim and fill analysis and Egger's linear regression test were carried out to evaluate the publication bias. A two-sided P-value of <.05 was regarded as significant for all analyses. The National Heart, Lung and Blood Institute Quality Assessment Tool was used to evaluate the quality of studies included.
RESULTS
The literature search yielded 1880 studies of which 13 studies were included for systematic review and meta-analysis. Results of the meta-analysis demonstrated that the prevalence of neutropenia in newly diagnosed and untreated patients with Graves' hyperthyroidism was 10% (CI 5%-19%, I 88.6%) and summary mean ANC value in neutropenic was 1.4 ± 0.3 × 10 /L. In all neutropenic patients under ATD therapy neutropenia resolved, thus without the worsening of the baseline ANC values or the development of agranulocytosis. The sensitivity analyses showed similar results as those of the main analyses. For all outcomes, the publication bias was not statistically significant or not calculable.
CONCLUSIONS
Graves' disease per se is associated with neutropenia in about 10% of cases. Neutropenia usually appears as a mild to moderate laboratory abnormality with no detectable consequences. Subnormal/mild neutropenia should not be regarded as a contraindication to use ATDs, and clinicians should know that treating hyperthyroidism they have a significant chance to normalize ANC too.
Topics: Graves Disease; Humans; Hyperthyroidism; Neutropenia; Neutrophils; Prevalence
PubMed: 32799342
DOI: 10.1111/cen.14313 -
The Journal of Investigative Dermatology Nov 2022Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to... (Meta-Analysis)
Meta-Analysis
Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to preventing secondary complications. This systematic review, which includes 247 animal studies, shows the postburn response of 14 different immune cell types involved in immediate and long-term effects in both wound tissue and circulation. Peripheral blood neutrophil and monocyte numbers increased directly after burns, whereas thrombocyte numbers increased near the end of the first week. However, lymphocyte numbers were decreased for at least 2 weeks. In burn wound tissue, neutrophil and macrophage numbers accumulated during the first 3 weeks. Burns also altered cellular functions because we found an increased migratory potential of leukocytes, impaired antibacterial activity of neutrophils, and enhanced inflammatory mediator production by macrophages. Neutrophil surges were positively associated with burn size and were highest in rats. Altogether, this comprehensive overview of the temporal immune cell dynamics shows that unlike normal wound healing, burn injury induces a long-lasting inflammatory response. It provides a fundamental research basis to improve experimental set-ups, burn care, and outcomes.
Topics: Rats; Animals; Burns; Neutrophils; Macrophages; Anti-Bacterial Agents; Inflammation Mediators
PubMed: 35623415
DOI: 10.1016/j.jid.2022.05.004 -
Pediatric Allergy and Immunology :... Feb 2024Preschool children with wheezing disorders pose diagnostic and therapeutic challenges and consume substantial healthcare resources. Peripheral eosinophil blood count... (Meta-Analysis)
Meta-Analysis Review
Preschool children with wheezing disorders pose diagnostic and therapeutic challenges and consume substantial healthcare resources. Peripheral eosinophil blood count (EBC) has been proposed as a potential indicator for future asthma development. This review by the European Academy of Allergy and Clinical Immunology (EAACI) Preschool Wheeze Task Force aimed to provide systematic evidence for the association between increased EBC and the risk of future asthma, as well as to identify potential cutoff values. In February 2023, a search of PubMed, EMBASE, and Cochrane Library databases was conducted to identify studies comparing EBCs in preschool children with wheezing who continued to wheeze later in life and those who did not. Included observational studies focused on children aged <6 years with a wheezing disorder, assessment of their EBCs, and subsequent asthma status. No language or publication date restrictions were applied. Among the initial 3394 studies screened, 10 were included in the final analysis, involving 1225 patients. The data from these studies demonstrated that high EBC in preschool children with wheezing is associated with future asthma development, with odds ratios of 1.90 (95% CI: 0.45-7.98, p = .38), 2.87 (95% CI: 1.38-5.95, p < .05), and 3.38 (95% CI: 1.72-6.64, p < .05) for cutoff values in the <300, 300-449, and ≥450 cells/μL ranges, respectively. Defining a specific cutoff point for an elevated EBC lacks consistency, but children with EBC >300 cells/μL are at increased risk of asthma. However, further research is needed due to the limitations of the included studies. Future investigations are necessary to fully elucidate the discussed association.
Topics: Humans; Child, Preschool; Eosinophils; Respiratory Sounds; Asthma; Recurrence
PubMed: 38339981
DOI: 10.1111/pai.14078 -
Frontiers in Immunology 2023Rheumatoid arthritis (RA) is an autoimmune disease that currently has an unknown cause and pathogenesis, and is associated with many complications and a high disability...
Rheumatoid arthritis (RA) is an autoimmune disease that currently has an unknown cause and pathogenesis, and is associated with many complications and a high disability rate. The neutrophil extracellular trap network (NETs) is a newly discovered mechanism that allows neutrophils to capture and kill pathogens. Multiple studies in recent years have highlighted its relevance to the progression of rheumatoid arthritis. Despite the growing number of studies indicating the crucial role of NETs in RA, there has been no bibliometric review of research hotspots and trends in this area. In this study, we retrieved articles related to NETs in RA from the Web of Science Core Collection (WoSCC) database from 1985 to 2023 and used visualization tools such as Citespace, VOSviewer, Tableau Public, and Microsoft Office Excel 2021 to analyze the data. After screening, we included a total of 416 publications involving 2,334 researchers from 1,357 institutions in 167 countries/regions, with relevant articles published in 219 journals. The U.S., China, and Germany are the top 3 countries/regions with 124, 57, and 37 publications respectively. Mariana J. Kaplan is the most published author, and journals such as Frontiers in Immunology and International Journal of Molecular Sciences have had a significant impact on research in this field. The clinical application of PAD enzymes and their inhibitors, and the drug development of NETs as therapeutic targets for RA is a trend for future research. Our study provides a comprehensive bibliometric analysis and summary of NETs in RA publications, which will aid researchers in conducting further scientific research.
Topics: Humans; Extracellular Traps; Arthritis, Rheumatoid; Autoimmune Diseases; Neutrophils; Bibliometrics
PubMed: 37680637
DOI: 10.3389/fimmu.2023.1205445 -
PloS One 2021Drug research with animal models is expensive, time-consuming and translation to clinical trials is often poor, resulting in a desire to replace, reduce, and refine the...
Drug research with animal models is expensive, time-consuming and translation to clinical trials is often poor, resulting in a desire to replace, reduce, and refine the use of animal models. One approach to replace and reduce the use of animal models is to use in vitro cell-culture models. To study bone physiology, bone diseases and drugs, many studies have been published using osteoblast-osteoclast co-cultures. The use of osteoblast-osteoclast co-cultures is usually not clearly mentioned in the title and abstract, making it difficult to identify these studies without a systematic search and thorough review. As a result, researchers are all developing their own methods, leading to conceptually similar studies with many methodological differences and, as a consequence, incomparable results. The aim of this study was to systematically review existing osteoblast-osteoclast co-culture studies published up to 6 January 2020, and to give an overview of their methods, predetermined outcome measures (formation and resorption, and ALP and TRAP quantification as surrogate markers for formation and resorption, respectively), and other useful parameters for analysis. Information regarding these outcome measures was extracted and collected in a database, and each study was further evaluated on whether both the osteoblasts and osteoclasts were analyzed using relevant outcome measures. From these studies, additional details on methods, cells and culture conditions were extracted into a second database to allow searching on more characteristics. The two databases presented in this publication provide an unprecedented amount of information on cells, culture conditions and analytical techniques for using and studying osteoblast-osteoclast co-cultures. They allow researchers to identify publications relevant to their specific needs and allow easy validation and comparison with existing literature. Finally, we provide the information and tools necessary for others to use, manipulate and expand the databases for their needs.
Topics: Animals; Bone Resorption; Cell Differentiation; Coculture Techniques; Databases, Factual; Drug Discovery; Humans; Models, Animal; Osteoblasts; Osteoclasts; RANK Ligand
PubMed: 34735456
DOI: 10.1371/journal.pone.0257724 -
BioMed Research International 2022In light of the growing emphasis on classifying stroke patients for different levels of monitoring intensity and emergency treatments, we conducted a systematic review... (Meta-Analysis)
Meta-Analysis Review
In light of the growing emphasis on classifying stroke patients for different levels of monitoring intensity and emergency treatments, we conducted a systematic review of a wide range of clinical studies, according to the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, with no restrictions on the language or publication date, to analyze the potential of the neutrophil-to-lymphocyte ratio (NLR) as an early neurological deterioration (END) risk predictor. A comprehensive search was carried out in PubMed, Scopus, and Web of Science databases from the inception to March 13, 2022. Nine articles were included in our study. Stroke patients with END had significantly higher NLR levels than the those without END (SMD = 0.73; CI 95% = 0.42-1.05, value < 0.001). In the subgroup analysis, according to ethnicity, East Asian patients with END had elevated levels of NLR compared to those without END (SMD = 0.79; CI 95% = 0.52-1.06, value < 0.001). However, the difference in the Caucasian group was not significant (SMD = 0.60; CI 95% = -0.50-1.70, value = 0.28). In the subgroup analysis according to the type of stroke, the NLR levels in patients with hemorrhagic stroke who developed END were similar to those without END (SMD = 0.84, CI 95% = -0.10-1.77, value = 0.07). Vice versa, in the ischemic stroke group, patients with END had elevated levels of NLR compared to those without END (SMD = 0.67, CI 95% = 0.38-0.96, value < 0.001). NLR is a unique inflammatory biomarker whose increase in END suggests an immune system dysfunction in the pathogenesis of the disease.
Topics: Biomarkers; Humans; Lymphocytes; Neutrophils; Stroke
PubMed: 36033552
DOI: 10.1155/2022/8656864 -
Langenbeck's Archives of Surgery Feb 2023Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR),... (Meta-Analysis)
Meta-Analysis Review
Prognostic role of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte, and lymphocyte-to-monocyte ratio in operated rectal cancer patients: systematic review and meta-analysis.
BACKGROUND
Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been proposed as useful prognostic indexes in cancer patients. However, their role in rectal cancer is controversial.
METHODS
A comprehensive literature review was conducted including MEDLINE/Pubmed, EMBASE, SCOPUS, and the Cochrane Database of Systematic Reviews through May 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Quality was appraised with the Methodological Index for Non-Randomized Studies (MINORS) tool. Aim of the study was to summarize available literature on PLR, NLR, and LMR in patients with rectal cancer undergoing resection.
RESULTS
Forty-seven observational studies (14,205 patients) were included; there were 42 retrospective and 5 prospective cohort studies with an average MINORS score of 14.6 (range: 12-18). Worse overall survival was associated with high NLR (HR 1.81; 95%CI 1.52-2.15; p < 0.001), high PLR (HR 1.24; 95%CI 1.06-1.46; p = 0.009), and low LMR (HR 0.67; 95%CI 0.49-0.91; p = 0.01). High NLR and low LMR were also associated with disease-free-survival (HR 1.68; 95%CI 1.35-2.08; p < 0.001 and HR 0.71; 95%CI 0.58-0.87; p < 0.001, respectively).
CONCLUSIONS
NLR, PLR, and LMR are independent clinical predictors for overall survival in patients with rectal cancer treated with curative surgery. NLR and LMR are also good predictors for disease free survival. These biomarkers, which are readily available, appear optimal prognostic indexes and may help clinicians predict the prognosis of rectal cancer and develop individualized treatment strategies.
Topics: Humans; Prognosis; Neutrophils; Monocytes; Retrospective Studies; Prospective Studies; Lymphocytes; Biomarkers; Rectal Neoplasms
PubMed: 36781510
DOI: 10.1007/s00423-023-02786-8