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The American Journal of Dermatopathology Dec 2023The presence or absence of tissue eosinophilia has previously aided in the diagnosis of inflammatory skin conditions. However, recent studies have elucidated the... (Review)
Review
The presence or absence of tissue eosinophilia has previously aided in the diagnosis of inflammatory skin conditions. However, recent studies have elucidated the presence of eosinophils in traditionally eosinophil-poor inflammatory skin diseases, such as dermatomyositis (DM), psoriasis, and lichen sclerosus (LS). This systematic review of the literature explores previous studies of tissue eosinophilia in skin biopsies of dermatoses that are believed to be classically poor in eosinophil. We identified 26 studies, the majority of which were retrospective reviews. The percent of specimens with increased eosinophils in psoriasis ranged from 18%-73%, pityriasis rubra pilaris (PRP) 22%-63%, LS 29%-53%, DM 15%-44%, morphea 8%-45%, hypertrophic lichen planus (LP) 0%-21%, and oral LP 0%-4%. These reports of tissue eosinophilia in reputed eosinophil-poor dermatologic conditions present a diagnostic pitfall and suggest that tissue eosinophilia itself should not be used to rule out a diagnosis of one of these conditions.
Topics: Humans; Eosinophilia; Eosinophils; Lichen Sclerosus et Atrophicus; Pityriasis Rubra Pilaris; Psoriasis; Retrospective Studies; Skin
PubMed: 37883982
DOI: 10.1097/DAD.0000000000002550 -
Fundamental & Clinical Pharmacology Apr 2023Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of... (Meta-Analysis)
Meta-Analysis Review
Cell therapy procedure using anti-inflammatory macrophage M2 can potentially reduce Clinical Score in animals with Experimental Autoimmune Encephalomyelitis: A preclinical systematic review and meta-analysis study.
Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS). This systematic review and meta-analysis study was designed to assess the overall therapeutic effects of MP2 cell therapy on Clinical Score and motor impairment in EAE-induced animals. All experiments on MP2 cell therapy in animals with EAE were gathered (by October 2, 2022) from English (PubMed, Scopus, WoS, Science Direct, and ISC) and Persian (MagIran and SID) databases. The searching strategy was designed using "Experimental Autoimmune Encephalomyelitis," "Multiple Sclerosis," and "Macrophage M2" keywords. Following primary and secondary screenings, eligible papers were selected based on the PRISMA 2020 guideline, and the study quality was assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) checklist. The difference in means of Clinical Score (score 0-5) as the effect size (ES) was analyzed based on the random effect model (CMA software, v.2). Subgrouping (EAE phases of Onset, Peak, and Recovery) was applied, and I index was used to assess the heterogeneity index. Publication bias and sensitivity indices were also evaluated. P < 0.05 was considered significant, and the confidence interval (CI) was determined 95%. Among 22 gathered papers, medium to high quality studies were selected for meta-analysis. Difference in means, P value, and I for Onset, Peak, and Recovery phases were 0.082 (CI95%: -0.323-0.159, P value: 0.504, I : 67.961%), -0.606 (CI95%: -1.518 to -0.305, P value: 0.192, I : 96.070%), and -1.103 (CI95%: -1.390 to -0.816, P value: 0.000, I : 30.880%), respectively and Overall Effect was found -0.509 (CI95%: -0.689 to -0.328, P value < 0.001). Also, P value (two-tailed) indices for publication bias were 0.366 and 0.583 for Egger's regression intercept and Begg rank correlation, respectively. The P value for sensitivity was detected 0.003. Cell therapy procedure using MP2 can potentially alleviate the Clinical Scores Index and correct the motor defects in Recovery phase of EAE animals. In healthy mice, the brain and myelin surrounding neurons are in a healthy and physiological state (1). To evaluate MS in humans, it is necessary to model this type of disease in animals using EAE procedure through subcutaneous injection of CFA, MOG , MT, and Pert. Thus, inflammation and autoimmunity occur, which finally lead to myelin destruction and motor symptoms (2). By aspiration of progenitor cells available in bone marrow, the MP2 can be isolated and cultured. By activation of these types of cells, a rich collection of MP2 can be prepared for the cell-therapy process (3). After injection through the tail vein or intra-peritoneal procedure, these cells can be located in CNS through crossing from the BBB. They begin their anti-inflammatory activities and help repair the damaged myelin (4). Eventually, the clinical symptoms can be modified considerably, and the animal motor function improves (5). CFA, complete Freund's adjuvant; MOG , myelin oligodendrocyte glycoprotein; MT, Mycobacterium tuberculosis; Pert, pertussis; EAE, Experimental Autoimmune Encephalomyelitis; BM, bone marrow; MP2, macrophage M2; and BBB, blood brain barrier.
Topics: Humans; Mice; Animals; Encephalomyelitis, Autoimmune, Experimental; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Anti-Inflammatory Agents; Macrophages; Mice, Inbred C57BL; Peptide Fragments
PubMed: 36300567
DOI: 10.1111/fcp.12844 -
Advanced Drug Delivery Reviews Dec 2022Despite the advances in immunotherapy for cancer treatment, patients still obtain limited benefits, mostly owing to unrestrained tumour self-expansion and immune evasion... (Review)
Review
Despite the advances in immunotherapy for cancer treatment, patients still obtain limited benefits, mostly owing to unrestrained tumour self-expansion and immune evasion that exploits immunoregulatory mechanisms. Traditionally, myeloid cells have a dominantly immunosuppressive role. However, the complicated populations of the myeloid cells and their multilateral interactions with tumour/stromal/lymphoid cells and physical abnormalities in the tumour microenvironment (TME) determine their heterogeneous functions in tumour development and immune response. Tumour-associated myeloid cells (TAMCs) include monocytes, tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), dendritic cells (DCs), and granulocytes. Single-cell profiling revealed heterogeneous TAMCs composition, sub-types, and transcriptomic signatures across 15 human cancer types. We systematically reviewed the biophysical heterogeneity of TAMC composition and pro/anti-tumoral and immuno-suppressive/stimulating properties of myeloid-derived microenvironments. We also summarised comprehensive clinical strategies to overcome resistance to immunotherapy from three dimensions: targeting TAMCs, reversing physical abnormalities, utilising nanomedicines, and finally, put forward futuristic perspectives for scientific and clinical research.
Topics: Humans; Immunotherapy; Tumor Microenvironment; Myeloid-Derived Suppressor Cells; Myeloid Cells; Neoplasms
PubMed: 36273512
DOI: 10.1016/j.addr.2022.114585 -
Journal of Digestive Diseases Aug 2015We designed this systematic review and meta-analysis aiming to clarify the advantage of steroid therapy compared with non-steroid therapy for the treatment of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We designed this systematic review and meta-analysis aiming to clarify the advantage of steroid therapy compared with non-steroid therapy for the treatment of eosinophilic esophagitis (EoE).
METHODS
PubMed, EMBASE, Medline, ISI Web of Science and the Cochrane Database of Systematic Reviews were searched to identify relevant randomized controlled trials (RCTs) comparing steroid and non-steroid therapy, and retrospective and prospective trials on steroid therapy for EoE. RevMan 5.2 was used for the analysis. Weighted mean difference and 95% confidence interval (CI) were estimated and pooled using meta-analysis methods.
RESULTS
Six RCTs including 193 participants fulfilled the inclusion criteria for meta-analysis, and another two RCTs, three prospective and five retrospective trials were included in systematic review. Meta-analysis showed that topical steroids significantly decreased the mean and peak esophageal eosinophils (EOS) count compared to non-steroid therapy (MDmean = -23.41, 95% CImean -42.08--4.73, P = 0.01 and MDpeak = -51.27, 95% CIpeak -78.62--23.92, P = 0.0002). There were 14 trials showing the efficacy of steroids on decreasing the EOS count, 10 showing the amelioration of symptoms, and five showing endoscopic improvement. Only mild adverse events were reported for topical steroids.
CONCLUSIONS
Steroids are effective on decreasing the EOS count in EoE patients. Its value in ameliorating symptoms and endoscopic changes remains undetermined due to the lack of comparable criteria.
Topics: Eosinophilic Esophagitis; Eosinophils; Glucocorticoids; Humans; Leukocyte Count; Proton Pump Inhibitors
PubMed: 26058809
DOI: 10.1111/1751-2980.12265 -
Health Technology Assessment... Dec 2010Acute leukaemia is a group of rapidly progressing cancers of bone marrow and blood classified as either acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia... (Review)
Review
BACKGROUND
Acute leukaemia is a group of rapidly progressing cancers of bone marrow and blood classified as either acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL). Haemopoietic stem cell transplantation (SCT) has developed as an adjunct to or replacement for conventional chemotherapy with the aim of improving survival and quality of life.
OBJECTIVES
A systematic overview of the best available evidence on the clinical effectiveness and cost-effectiveness of SCT in the treatment of acute leukaemia.
DATA SOURCES
Clinical effectiveness: electronic databases, including MEDLINE, EMBASE and the Cochrane Library, were searched from inception to December 2008 to identify published systematic reviews and meta-analyses. Cochrane CENTRAL, MEDLINE, EMBASE and Science Citation Index (SCI) were searched from 1997 to March 2009 to identify primary studies. Cost-effectiveness: MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects (DARE) and NHS Economic Evaluation Database (NHS EED) were searched from inception to January 2009.
STUDY SELECTION
Potentially relevant papers were retrieved and independently checked against predefined criteria by two reviewers (one in the case of the cost-effectiveness review).
STUDY APPRAISAL
Included reviews and meta-analyses were critically appraised and data extracted and narratively presented. Included randomised controlled trials (RCTs) and donor versus no donor (DvND) studies were mapped to the evidence covered in existing systematic reviews and meta-analyses according to a framework of 12 decision problems (DPs): DP1 related to SCT in adults with AML in first complete remission (CR1); DP2 to adults with AML in second or subsequent remission or with refractory disease (CR2+); DP3 to children with AML in CR1; DP4 to children with AML in CR2+; DP5 to adults with ALL in CR1; DP6 to adults with ALL in CR2+; DP7 to children with ALL in CR1; DP8 to children with ALL in CR2+; DP9 to comparison of different sources of stem cells in transplantation; DP10 to different conditioning regimens; DP11 to the use of purging in autologous SCT; and DP12 to the use of T-cell depletion in allogeneic SCT.
RESULTS
Fifteen systematic reviews/meta-analyses met the inclusion criteria for the review of clinical effectiveness, thirteen of which were published from 2004 onwards. Taking into account the timing of their publications, most reviews appeared to have omitted an appreciable proportion of potentially available evidence. The best available evidence for effectiveness of allogeneic SCT using stem cells from matched sibling donors came from DvND studies: there was sufficient evidence to support the use of allogeneic SCT in DP1 (except in good-risk patients), DP3 (role of risk stratification unclear) and DP5 (role of risk stratification unclear). There was conflicting evidence in DP7 and a paucity of evidence from DvND studies for all decision problems concerning patient groups in CR2+. The best available evidence for effectiveness of autologous SCT came from RCTs: overall, evidence suggested that autologous SCT was either similar to or less effective than chemotherapy. There was a paucity of evidence from published reviews of RCTs for DPs 9-12. Nineteen studies met the inclusion criteria in the cost-effectiveness review, most reporting only cost information and only one incorporating an economic model. Although there is a wealth of information on costs and some information on cost-effectiveness of allogeneic SCT in adults with AML (DPs 1 and 2), there is very limited evidence on relative costs and cost-effectiveness for other DPs.
LIMITATIONS
Time and resources did not permit critical appraisal of the primary studies on which the reviews/meta-analyses reviewed were based; there were substantial differences in methodologies, and consequently quantitative synthesis of data was neither planned in the protocol nor carried out; some of the studies were quite old and might not reflect current practice; and a number of the studies might not be applicable to the UK.
CONCLUSIONS
Bearing in mind the limitations, existing evidence suggests that sibling donor allogeneic SCT may be more effective than chemotherapy in adult AML (except in good-risk patients) in CR1, childhood AML in CR1 and adult ALL in CR1, and that autologous SCT is equal to or less effective than chemotherapy. No firm conclusions could be drawn regarding the cost-effectiveness of SCT in the UK NHS owing to the limitations given above. Future research should include the impact of the treatments on patients' quality of life as well as information on health service use and costs associated with SCT from the perspective of the UK NHS.
Topics: Adult; Child; Cost-Benefit Analysis; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 21138675
DOI: 10.3310/hta14540 -
Cytotherapy May 2024Acute myeloid leukemia (AML) is classified as a hematologic malignancy characterized by the proliferation of immature blood cells within the bone marrow (BM), resulting... (Review)
Review
BACKGROUND AIMS
Acute myeloid leukemia (AML) is classified as a hematologic malignancy characterized by the proliferation of immature blood cells within the bone marrow (BM), resulting in an aberrant and unregulated cellular growth. The primary therapeutic modalities for AML include chemotherapy and hematopoietic stem cell transplantation. However, it is important to note that these treatments are accompanied by important adverse effects and mortality rates. Therefore, the need for more effective treatment options seems necessary, and dendritic cell (DC) vaccine therapy can be one of these options. In this study, we aim to investigate the effectiveness of DC vaccination therapy for the management of AML.
METHODS
PubMed, Scopus, ProQuest, Web of Science, and Google Scholar databases were searched for this systematic review. The articles were evaluated based on the inclusion criteria of this study and initially compared in terms of titles or abstracts. Finally, the articles related to the topic of this review were obtained in full text. The complete remission and partial remission, survival, correlative immune assays, and health-related metrics were used to evaluate this cellular immunotherapy effectiveness. The quality of the studies was assessed independently using the Cochrane risk-of-bias tools. The compiled data were input into a standard Excel spreadsheet. Each domain was evaluated as having either a "low risk," "high risk," or "unclear risk" of bias.
RESULTS
Among the 3986 studies that were determined, a total of 11 correlated trials were selected for inclusion in this systematic review. DC vaccine therapy was effective in inducing complete and partial remission, and stabilization of the disease. Additionally, it was discovered that the treatment strengthened the immune system as seen by increased levels of CD4 and CD8 T cells, Th1 cytokines, WT1-specific T cells, and activated NK cells.
CONCLUSION
We conducted a systematic review that supports the use of DC vaccine therapy as an effective treatment for AML. The therapy demonstrated potentials in achieving remission, enhancing the immune system function, and increasing overall survival. However, more studies are required to improve the methods of preparing and delivering the DC vaccine, and to confirm its long-term safety and effectiveness.
Topics: Humans; Leukemia, Myeloid, Acute; Dendritic Cells; Cancer Vaccines; Vaccination; Immunotherapy
PubMed: 38483358
DOI: 10.1016/j.jcyt.2024.02.009 -
PeerJ 2022There have been promising results published regarding the potential of stem cells in regenerative medicine. However, the vast variety of choices of techniques and the...
BACKGROUND
There have been promising results published regarding the potential of stem cells in regenerative medicine. However, the vast variety of choices of techniques and the lack of a standard approach to analyse human osteoblast and osteoclast differentiation may reduce the utility of stem cells as a tool in medical applications. Therefore, this review aims to systematically evaluate the findings based on stem cell differentiation to define a standard gene expression profile approach.
METHODS
This review was performed following the PRISMA guidelines. A systematic search of the study was conducted by retrieving articles from the electronic databases PubMed and Web of Science to identify articles focussed on gene expression and approaches for osteoblast and osteoclast differentiation.
RESULTS
Six articles were included in this review; there were original articles of human stem cell differentiation into osteoblasts and osteoclasts that involved gene expression profiling. Quantitative polymerase chain reaction (qPCR) was the most used technique for gene expression to detect differentiated human osteoblasts and osteoclasts. A total of 16 genes were found to be related to differentiating osteoblast and osteoclast differentiation.
CONCLUSION
Qualitative information of gene expression provided by qPCR could become a standard technique to analyse the differentiation of human stem cells into osteoblasts and osteoclasts rather than evaluating relative gene expression. and could be applied to detect osteoblasts and osteoclasts, respectively, while could be applied to detect both osteoblasts and osteoclasts. This review provides future researchers with a central source of relevant information on the vast variety of gene expression approaches in analysing the differentiation of human osteoblast and osteoclast cells. In addition, these findings should enable researchers to conduct accurately and efficiently studies involving isolated human stem cell differentiation into osteoblasts and osteoclasts.
Topics: Humans; Osteoclasts; Transcriptome; Osteoblasts; Cell Differentiation; Stem Cells
PubMed: 36275474
DOI: 10.7717/peerj.14174 -
Immune Cell Alterations in Psychotic Disorders: A Comprehensive Systematic Review and Meta-Analysis.Biological Psychiatry Jan 2024A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and...
BACKGROUND
A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with healthy control participants has been lacking.
METHODS
Multiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO) were searched for eligible studies up until October 18, 2022. All studies investigating circulating immune cells in the blood and CSF from patients with psychotic disorders (ICD-10: F20 and F22-29) compared with healthy control participants were included.
RESULTS
A total of 86 studies were included in the meta-analysis. In the blood, the following categories of immune cells were elevated: leukocyte count (31 studies, standardized mean difference [SMD] = 0.35; 95% CI, 0.24 to 0.46), granulocyte count (4 studies, SMD = 0.57; 95% CI, 0.12 to 1.01), neutrophil granulocyte count (21 studies, SMD = 0.32; 95% CI, 0.11 to 0.54), monocyte count (23 studies, SMD = 0.40; 95% CI, 0.23 to 0.56), and B lymphocyte count (10 studies, SMD = 0.26; 95% CI, 0.04 to 0.48). Additionally, the neutrophil/lymphocyte ratio (23 studies, SMD = 0.40; 95% CI, 0.19 to 0.60), the monocyte/lymphocyte ratio (9 studies, SMD = 0.31; 95% CI, 0.04 to 0.57), and the platelet/lymphocyte ratio (10 studies, SMD = 0.23; 95% CI, 0.03 to 0.43) were elevated. The CSF cell count showed a similar tendency but was not significantly elevated (3 studies, SMD = 0.14; 95% CI, -0.04 to 0.32).
CONCLUSIONS
The results indicate a broad activation of the immune system in psychotic disorders, with cells from both the myeloid and the lymphoid line being elevated. However, CSF analyses were lacking in most of the studies, and many studies were hampered by insufficient adjustment for confounding factors such as body mass index and smoking.
PubMed: 38185237
DOI: 10.1016/j.biopsych.2023.11.029 -
Cureus Jan 2022Chronic myeloid leukemia (CML) is a slow-growing type of cancer that originates in the blood-forming cells of the bone marrow and is caused by a chromosomal mutation... (Review)
Review
Chronic myeloid leukemia (CML) is a slow-growing type of cancer that originates in the blood-forming cells of the bone marrow and is caused by a chromosomal mutation that is thought to occur spontaneously. CML could potentially lead to the development of myeloid sarcoma (MS), which is a rare neoplasm composed of immature myeloid cells that could evolve into a tumor mass at any anatomical site other than the bone marrow. MS can develop spontaneously or as a result of another form of myeloid neoplasm. Most instances of CML precede blast phase (BP) within two to three years after the first diagnosis of CML chronic phase (CP) at the age of pre-tyrosine kinase inhibitor (TKI) treatment. MS developing in CML patients during the era of TKI treatment is infrequently mentioned in the literature, primarily in single-case studies. As a result, the prognostic influence of MS in CML patients has not been well investigated. In the age of TKI treatment, it is uncertain whether MS and medullary BP have comparable clinical and prognostic relevance. The precise diagnosis of MS is critical for effective treatment, which is frequently delayed due to a high risk of misdiagnosis. This review focuses on the relationship between the development of MS from CML, and it culminates with recommendations for future hematology practice. A literature search was conducted in multiple databases, and the studies were appraised based on the inclusion and exclusion criteria. Finally, studies to date have shown that the existence of CML and its possible progression to MS in individuals map out the numerous implications this disease has in hematology practice. Though occurrences are uncommon in general, the prognosis for patients is bleak, necessitating the exploration and implementation of diagnostic and therapy advancements. Because there is limited evidence in the literature on its existence in the medullary chronic phase and outcomes in the era of TKI, it must be carefully investigated because it might be the first symptom of progressive illness prior to hematological progression.
PubMed: 35036234
DOI: 10.7759/cureus.21077 -
Biomedicine & Pharmacotherapy =... May 2024Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues... (Review)
Review
Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability to recognize and eliminate cancer cells. This review paper explores the intricate interplay between CAR-T therapy and radiotherapy (RT), investigating their synergistic potential. Radiotherapy, a standard cancer treatment, involves using high doses of radiation to target and damage cancer cells, disrupting their ability to grow and divide. We highlight that RT modulates the TME, augments antigen presentation, and promotes immune cell infiltration, bolstering CAR-T cell-mediated tumor eradication. Molecular insights shed light on RT-induced alterations in tumor stroma, T cell recruitment promotion, and induction of immunogenic cell death. Noteworthy, strategies, such as combining hypofractionated radiotherapy with myeloid-derived suppressor cell blockade, underscore innovative approaches to enhance CAR-T cell therapy in solid tumors. Bridging indications for RT and CAR-T cells in hematological malignancies are discussed, emphasizing scenarios where RT strategically enhances CAR-T cell efficacy. The paper critically evaluates the RT as a bridge compared to traditional chemotherapy, highlighting timing and dosage considerations crucial for optimizing CAR-T therapy outcomes. In summary, the paper provides valuable insights into the intricate molecular mechanisms activated by RT and innovative strategies to improve CAR-T cell therapy, fostering a deeper understanding of their combined potential in cancer treatment.
Topics: Humans; Neoplasms; Tumor Microenvironment; Immunotherapy, Adoptive; Animals; Receptors, Chimeric Antigen; Combined Modality Therapy; Radiotherapy
PubMed: 38574625
DOI: 10.1016/j.biopha.2024.116532