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Diagnostics (Basel, Switzerland) Aug 2022Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed... (Review)
Review
Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed complex interactions between infectious agents and hosts that result in heterogeneous manifestations of sepsis. Sepsis can cause immunosuppression and increase the expression of checkpoint inhibitor molecules, including programmed death protein (PD-1) and programmed death ligand 1 (PD-L1), and thus PD-1 and PD-L1 are thought to be useful as diagnostic and prognostic tools for sepsis. PD-1 is an inhibitor of both adaptive and innate immune responses, and is expressed on activated T lymphocytes, natural killer (NK) cells, B lymphocytes, macrophages, dendritic cells (DCs), and monocytes, whereas PD-L1 is expressed on macrophages, some activated T and B cells, and mesenchymal stem cells as well as various non-hematopoietic cells. This systematic review aims to assess the PD-1 and PD-L1 protein expression levels and concentrations in septic and other infectious patients.
PubMed: 36010357
DOI: 10.3390/diagnostics12082004 -
Cureus Sep 2022Asthma is a non-communicable and long-term condition affecting children and adults. The air passages in the lungs become narrow due to inflammation and tightening of the... (Review)
Review
Asthma is a non-communicable and long-term condition affecting children and adults. The air passages in the lungs become narrow due to inflammation and tightening of the muscles around the small airways. Symptoms of asthma are intermittent and include cough, wheeze, shortness of breath, and chest tightness. Asthma is very often underdiagnosed and under-treated in many regions, especially in developing countries. While many studies show that viral infections can precipitate asthmatic attacks, very few studies have been conducted to see if history or current asthmatic attack increases the risk of viral infections. Our study aims to determine the predisposition of asthmatics to develop various viral infections and susceptibility toward certain viruses that cause upper respiratory tract infections. We performed a literature review of both published and unpublished articles. We included case reports, case series, reviews, clinical trials, cohort, and case-control studies, written only in English. Commentaries, letters to editors, and book chapters were excluded. Our initial search yielded 948 articles, of which 826 were rejected either because they were irrelevant or because they did not meet our inclusion criteria. We finally screened 122 abstracts and identified 24 relevant articles. People with a history of asthma have an abnormal innate immune response, making them potentially slower in clearing the infection and susceptible to both infections and virus-induced cell cytotoxicity. Also, in these studies, deficiencies in the interferon alpha response of peripheral blood mononuclear cells and plasmacytoid dendritic cells have been observed in asthmatics, both adults and children. Asthmatics with a viral infection usually present with an acute exacerbation of asthma, represented by dyspnea and cough, with other prodromal symptoms including vomiting and general malaise. The review includes an update on the relevance of dysregulated immune pathways in causing viral infections in asthmatic populations. It focuses on the evidence to suggest that people with asthma are at increased risk of viral infection, and viral infections in turn are known to precipitate and worsen the asthmatic status, making this a vicious cycle. The authors also suggest that further studies be undertaken to elucidate the pathophysiology and identify the critical therapeutic steps to break this vicious cycle and improve the quality of life for people with asthma.
PubMed: 36225449
DOI: 10.7759/cureus.28839 -
Journal of Magnetic Resonance Imaging :... Oct 2023Diffusion-weighted imaging has been applied to investigate alterations in multiple sclerosis (MS). In the last years, advanced diffusion models were used to identify... (Review)
Review
Diffusion-weighted imaging has been applied to investigate alterations in multiple sclerosis (MS). In the last years, advanced diffusion models were used to identify subtle changes and early lesions in MS. Among these models, neurite orientation dispersion and density imaging (NODDI) is an emerging approach, quantifying specific neurite morphology in both grey (GM) and white matter (WM) tissue and increasing the specificity of diffusion imaging. In this systematic review, we summarized the NODDI findings in MS. A search was conducted on PubMed, Scopus, and Embase, which yielded a total number of 24 eligible studies. Compared to healthy tissue, these studies identified consistent alterations in NODDI metrics involving WM (neurite density index), and GM lesions (neurite density index), or normal-appearing WM tissue (isotropic volume fraction and neurite density index). Despite some limitations, we pointed out the potential of NODDI in MS to unravel microstructural alterations. These results might pave the way to a deeper understanding of the pathophysiological mechanism of MS. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.
Topics: Humans; Neurites; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; Multiple Sclerosis; White Matter; Brain
PubMed: 37042392
DOI: 10.1002/jmri.28727 -
Therapeutic Advances in Urology Feb 2017Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied... (Review)
Review
BACKGROUND
Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC.
METHODS
We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015. One author reviewed search results for irrelevant and duplicate studies and two other authors independently extracted data from the studies. We collated study findings and calculated a weighted treatment effect across studies using Review Manager (version 5.3. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration).
RESULTS
We identified 14 controlled studies with 4013 RCC patients after excluding irrelevant and duplicate studies from 11,319 references retrieved from a literature search. Overall, five autologous tumor cell vaccines, one peptide-based vaccine, one virus-based vaccine and one dendritic cell (DC)-based vaccine were studied in nine controlled studies of active specific immunotherapies. A total of three passive immunotherapies including autologous cytokine-induced killer (CIK) cells, auto lymphocyte therapy (ALT) and autologous lymphokine-activated killer (LAK) cells were studied in four controlled studies. The clinical efficacy of tumor lysate-pulsed DCs, with CIK cells was studied in one controlled trial concurrently. The overall quality of studies was fair. Meta-analysis of seven studies showed that patients undergoing specific immunotherapy had significantly higher overall survival (OS) than those in the control group [hazard ratio (HR) = 0.72; 95% confidence interval (CI) = 0.58-0.89, = 0.003]. In addition, a meta-analysis of four studies showed that there was a significant difference in progression-free survival (PFS) between patients undergoing specific immunotherapy and patients in control groups (HR = 0.86; 95% CI = 0.73-1, = 0.05).
CONCLUSIONS
Results of this systematic review suggest that some specific immunotherapies such as Reniale, ACHN-IL-2, Newcastle disease virus (NDV) virus-infected autologous tumor cells, ALT and CIK treatment could be beneficiary for the treatment of patients with RCC.
PubMed: 28203287
DOI: 10.1177/1756287216681246 -
Frontiers in Immunology 2023Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival.
METHOD
Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356).
RESULTS
We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56-0.99; = -2.00, = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45-0.99; = -1.99, = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21-0.68; Z = -3.23; = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45-0.80; = -3.53; = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50-0.96; = -2.23; = 0.0256).
CONCLUSION
Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.
Topics: Humans; Standard of Care; Glioma; Brain Neoplasms; Progression-Free Survival; Immunotherapy
PubMed: 37483593
DOI: 10.3389/fimmu.2023.966696 -
Frontiers in Physiology 2022Intensified training coupled with sufficient recovery is required to improve athletic performance. A stress-recovery imbalance can lead to negative states of...
Intensified training coupled with sufficient recovery is required to improve athletic performance. A stress-recovery imbalance can lead to negative states of overtraining. Hormonal alterations associated with intensified training, such as blunted cortisol, may impair the immune response. Cortisol promotes the maturation and migration of dendritic cells which subsequently stimulate the T cell response. However, there are currently no clear reliable biomarkers to highlight the overtraining syndrome. This systematic review and meta-analysis examined the effect of intensified training on immune cells. Outcomes from this could provide insight into whether these markers may be used as an indicator of negative states of overtraining. SPORTDiscus, PUBMED, Academic Search Complete, Scopus and Web of Science were searched until June 2022. Included articles reported on immune biomarkers relating to lymphocytes, dendritic cells, and cytokines before and after a period of intensified training, in humans and rodents, at rest and in response to exercise. 164 full texts were screened for eligibility. Across 57 eligible studies, 16 immune biomarkers were assessed. 7 were assessed at rest and in response to a bout of exercise, and 9 assessed at rest only. Included lymphocyte markers were CD3, CD4 and CD8 T cell count, NK cell count, NK Cytolytic activity, lymphocyte proliferation and CD4/CD8 ratio. Dendritic cell markers examined were CD80, CD86, and MHC II expression. Cytokines included IL-1β, IL-2, IL-10, TNF-α and IFN-γ. A period of intensified training significantly decreased resting total lymphocyte (0.57, 95% CI 0.30) and CD8 T cell counts (0.37, 95% CI 0.04), and unstimulated plasma IL-1β levels (0.63, 95% CI 0.17). Resting dendritic cell CD86 expression significantly increased ( 2.18, 95% CI 4.07). All other biomarkers remained unchanged. Although some biomarkers alter after a period of intensified training, definitive immune biomarkers are limited. Specifically, due to low study numbers, further investigation into the dendritic cell response in human models is required.
PubMed: 36439269
DOI: 10.3389/fphys.2022.998925 -
Clinical Nutrition ESPEN Feb 2023Vitamin E has been investigated for its antitumor potential, including the ability to change cancer gene pathways as well as promote antioxidant and pro-oxidant activity. (Review)
Review
BACKGROUND
Vitamin E has been investigated for its antitumor potential, including the ability to change cancer gene pathways as well as promote antioxidant and pro-oxidant activity.
OBJECTIVE
Therefore, this systematic review aimed to evaluate antitumor and chemopreventive activity of different vitamin E isoforms (tocopherols and tocotrienols) through in vitro and in vivo studies.
METHOD
The systematic review was registered in PROSPERO (No. CRD4202126207) and the search was carried out in four electronic databases (PubMed, Science Direct, Scopus and Web of Science) in June 2021 by three independent reviewers. The search equation used was: "Supplementation" AND ("Vitamin E" OR Tocopherol OR Tocotrienol) AND "breast cancer" AND (chemotherapy OR therapy OR prevention). In vitro studies and animal models of breast cancer supplemented with tocopherol or tocotrienol vitamers, alone or in combination, were included.
RESULTS
The results revealed 8546 relevant studies that were initially identified in our search. After analysis, a total of 12 studies were eligible for this systematic review. All studies included animal models, and 5 of them also performed in vitro experiments on cancer cell lines. The studies performed supplementation with tocopherols, mixtures (tocopherols and tocotrienols) and synthetic vitamin E forms. There was an significant association of estradiol, dendritic cells and pterostilbene in combined therapy with vitamin E. Vitamin E delayed tumor development, reduced tumor size, proliferation, viability, expression of anti-apoptotic and cell proliferation genes, and upregulated pro-apoptotic genes, tumor suppressor genes and increased immune response. The effects on oxidative stress markers and antioxidant activity were conflicting among studies. Only one study with synthetic vitamin E reported cardiotoxicity, but it did not show vitamin E genotoxicity.
CONCLUSION
In conclusion, vitamin E isoforms, isolated or associated, showed antitumor and chemopreventive activity. However, due to studies heterogeneity, there is a need for further analysis to establish dose, form, supplementation time and breast cancer stage.
Topics: Animals; Vitamin E; Tocotrienols; Antioxidants; Tocopherols; Neoplasms; Vitamins
PubMed: 36657931
DOI: 10.1016/j.clnesp.2022.11.001 -
Neurological Sciences : Official... Jun 2024High-grade gliomas (HGGs) constitute the most common malignant primary brain tumor with a poor prognosis despite the standard multimodal therapy. In recent years,... (Review)
Review
High-grade gliomas (HGGs) constitute the most common malignant primary brain tumor with a poor prognosis despite the standard multimodal therapy. In recent years, immunotherapy has changed the prognosis of many cancers, increasing the hope for HGG therapy. We conducted a comprehensive search on PubMed, Scopus, Embase, and Web of Science databases to include relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Fifty-two papers were finally included (44 phase II and eight phase III clinical trials) and further divided into four different subgroups: 14 peptide vaccine trials, 15 dendritic cell vaccination (DCV) trials, six immune checkpoint inhibitor (ICI) trials, and 17 miscellaneous group trials that included both "active" and "passive" immunotherapies. In the last decade, immunotherapy created great hope to increase the survival of patients affected by HGGs; however, it has yielded mostly dismal results in the setting of phase III clinical trials. An in-depth analysis of these clinical results provides clues about common patterns that have led to failures at the clinical level and helps shape the perspective for the next generation of immunotherapies in neuro-oncology.
Topics: Humans; Glioma; Immunotherapy; Brain Neoplasms; Immune Checkpoint Inhibitors
PubMed: 38308708
DOI: 10.1007/s10072-024-07350-w -
Magnetic Resonance Imaging Dec 2023Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and... (Review)
Review
Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and inflammation, which lead to neurodegeneration and cognitive decline. Its diagnosis and monitoring are performed through conventional structural MRI, in which T2-hyperintense lesions can be identified, but this technique lacks sensitivity and specificity, mainly in detecting damage to normal appearing tissues. Models of diffusion-weighted MRI such as diffusion-tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) allow to uncover microstructural abnormalities that occur in MS, mainly in normal appearing tissues such as the normal appearing white matter (NAWM), which allows to overcome limitations of conventional MRI. DTI is the standard method used for modelling this kind of data, but it has limitations, which can be tackled by using more complex diffusion models, such as NODDI, which provides additional information on morphological properties of tissues. Although there are several studies in MS using both diffusion models, there is no formal assessment that summarizes the findings of both methods in lesioned and normal appearing tissues, and whether one is more advantageous than the other. Hence, this systematic review aims to identify what microstructural abnormalities are seen in lesions and/or NAWM in relapsing-remitting MS while using two different approaches to modelling diffusion data, namely DTI and NODDI, and if one of them is more appropriate than the other or if they are complementary to each other. The search was performed using PubMed, which was last searched on November 2022, and aimed at finding studies that either utilized both DTI and NODDI in the same dataset, or only one of the methods. Eleven articles were included in this review, which included cohorts with a relatively low sample size (total number of patients = 254, total number of healthy controls = 240), and patients with a moderate disease duration, all with relapsing-remitting MS. Overall, studies found decreased fractional anisotropy (FA), neurite density index (NDI) and orientation dispersion index (ODI), and increased mean, axial and radial diffusivities (MD, AD and RD, respectively) in lesions, when compared to contralateral NAWM and healthy controls' white matter. Compared to healthy controls' white matter, NAWM showed lower FA and NDI and higher MD, AD, RD, and ODI. Results from the included articles confirm that there is active demyelination and inflammation in both lesions and NAWM, as well as loss in neurites, and that structural damage is not confined to focal lesions, which is in concordance with histological findings and results from other imaging techniques. Furthermore, NODDI is suggested to have higher sensitivity and specificity, as seen by inspecting imaging results, compared to DTI, while still being clinically feasible. The use of biomarkers derived from such advanced diffusion models in clinical practice could imply a better understanding of treatment efficacy and disease progression, without relying on the manifestation of clinical symptoms, such as relapses.
Topics: Humans; Multiple Sclerosis; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; White Matter; Brain; Neurites; Image Processing, Computer-Assisted
PubMed: 37775062
DOI: 10.1016/j.mri.2023.09.010 -
F1000Research 2018Hidradenitis suppurativa (HS) is a chronic inflammatory disease with significant morbidity and impact on quality of life. Our understanding of the pathophysiology is...
Hidradenitis suppurativa (HS) is a chronic inflammatory disease with significant morbidity and impact on quality of life. Our understanding of the pathophysiology is incomplete, impairing efforts to develop novel therapeutic targets. Immunohistochemistry studies have produced conflicting results and no systematic evaluation of study methods and results has been undertaken to date. This systematic review aimed to collate and describe all reports of immunohistochemical staining in HS. This systematic review was registered with PROSPERO and conducted in line with the PRISMA reporting guidelines. Potential bias was assessed using the NIH Criteria and antibodies used across various studies were tabulated and compared. : A total of 22 articles were identified describing results from 494 HS patients and 168 controls. 87 unique immunohistochemical targets were identified. The overall quality of studies was sub-optimal with staining intensity confounded by active treatment. Conflicting data was identified and able to be reconciled through critical evaluation of the study methodology. : Keratinocyte hyperplasia with loss of cytokeratin markers co-localizes with inflammation comprising of dendritic Cells, T-lymphocytes and macrophages, which are known to play central roles in inflammation in HS. Primary follicular occlusion as a pathogenic paradigm and the principal driver of HS is unclear based upon the findings of this review. Inflammation as a primary driver of disease with secondary hyperkeratosis and follicular occlusion is more consistent with the current published data.
Topics: Animals; Desmocollins; Female; Hidradenitis Suppurativa; Humans; Hyperplasia; Inflammation; Keratosis; Male; Membrane Glycoproteins; Mice; Quality of Life; Ubiquitin-Protein Ligases
PubMed: 31281635
DOI: 10.12688/f1000research.17268.2