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Annals of the Rheumatic Diseases Oct 2023Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most...
The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
OBJECTIVE
Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the of diagnosis, treatment and monitoring of HLH/MAS.
METHODS
A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS.
RESULTS
The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance.
CONCLUSION
These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.
Topics: Child; Adult; Humans; United States; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Rheumatology; Consensus
PubMed: 37487610
DOI: 10.1136/ard-2023-224123 -
Arthritis & Rheumatology (Hoboken, N.J.) Oct 2023Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most...
The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS).
OBJECTIVE
Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the early stages of diagnosis, treatment and monitoring of HLH/MAS.
METHODS
A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS.
RESULTS
The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance.
CONCLUSION
These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.
Topics: Adult; Child; Humans; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Consensus; Physicians; Advisory Committees
PubMed: 37486733
DOI: 10.1002/art.42636 -
European Review For Medical and... Jul 2023Bisphosphonates, the most common anti-resorptive medications, are internalized by osteoclasts, where they inhibit the macrophage colony-stimulating factor (M-CSF)...
OBJECTIVE
Bisphosphonates, the most common anti-resorptive medications, are internalized by osteoclasts, where they inhibit the macrophage colony-stimulating factor (M-CSF) pathway, preventing their differentiation, inhibiting anchorage to the cell membrane, and inducing apoptosis. In patients undergoing oral bisphosphonate therapy, oral surgery involves a high risk of developing drug-related osteonecrosis of the jaws (BRONJ/MRONJ), among the possible complications.
MATERIALS AND METHODS
A systematic search was carried out on the PubMed, Scopus and Cochrane Library search engines, using the keywords "oral bisphosphonates AND tooth extraction", "third molar extraction AND oral bisphosphonates". In addition, we manually evaluated the articles included in references from other sources and an analysis of the Gray Literature was performed. A secondary outcome was to evaluate the assessment of pharmacological (antibiotics) use in the BRONJ/MRONJ management. The revision protocol followed the indications of the Cochrane Handbook, and was registered in the INPLASY database, while the drafting of the manuscript was based on PRISMA.
RESULTS
The results of the systematic review, after the study identification and selection process, included a total of 7 studies: 4 retrospective studies, 2 prospective studies and 1 case report. The main complication was represented by osteonecrosis of the jaws, which appears to be related to the duration of treatment with bisphosphonates; in addition, data regarding the anatomical location of post-extraction sites, the sex and age of patients, comorbidities and various systemic risk factors were extrapolated. The most frequent post-extraction complication in patients treated with oral bisphosphonates is osteonecrosis of the jaws, with a significant prevalence in the posterior region of the mandible. In some cases, delayed healing of the surgical wound was also found; moreover, the duration of exposure to oral bisphosphonates influences the onset of complications.
CONCLUSIONS
Ongoing studies continue to unravel the role of the oral environment response in alveolar bone homeostasis and how it might contribute to the induction of BRONJ/MRONJ. Approaching the problem from this perspective could provide new directions for the prevention of BRONJ/MRONJ and expand our understanding of the unique oral microenvironment.
Topics: Humans; Bone Density Conservation Agents; Prospective Studies; Retrospective Studies; Bisphosphonate-Associated Osteonecrosis of the Jaw; Diphosphonates; Osteonecrosis; Tooth Extraction
PubMed: 37458653
DOI: 10.26355/eurrev_202307_32996 -
Endocrine, Metabolic & Immune Disorders... 2024Several studies have identified CD163 as a potential mediator of diabetes mellitus through an immune-inflammation. Further study is necessary to identify its specific...
BACKGROUND
Several studies have identified CD163 as a potential mediator of diabetes mellitus through an immune-inflammation. Further study is necessary to identify its specific mechanism.
OBJECTIVES
In this study, we aimed to investigate CD163 as a potential biomarker associated with immune inflammation in diabetes mellitus through a systematic review and bioinformatics analysis.
METHODS
We searched PubMed, Web of Science, the Cochrane Library, and Embase databases with a time limit of September 2, 2022. Furthermore, we conducted a systematic search and review based on PRISMA guidelines. Additionally, diabetic gene expression microarray datasets GSE29221, GSE30528, GSE30529, and GSE20966 were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) for bioinformatics analysis. The PROSPERO number for this study is CRD420222347160.
RESULTS
Following the inclusion and exclusion criteria, seven articles included 1607 patients, comprising 912 diabetic patients and 695 non-diabetic patients. This systematic review found significantly higher levels of CD163 in diabetic patients compared to non-diabetic patients. People with diabetes had higher levels of CRP expression compared to the control group. Similarly, two of the three papers that used TNF- α as an outcome indicator showed higher expression levels in diabetic patients. Furthermore, IL-6 expression levels were higher in diabetic patients than in the control group. A total of 62 samples were analyzed by bioinformatics (33 case controls and 29 experimental groups), and 85 differential genes were identified containing CD163. According to the immune cell correlation analysis, CD163 was associated with macrophage M2, γδ T lymphocytes, macrophage M1, and other immune cells. Furthermore, to evaluate the diagnostic performance of CD163, we validated it using the GSE20966 dataset. In the validation set, CD163 showed high diagnostic accuracy.
CONCLUSION
This study suggests CD163 participates in the inflammatory immune response associated with diabetes mellitus and its complications by involving several immune cells. Furthermore, the results suggest CD163 may be a potential biomarker reflecting immune inflammation in diabetic mellitus.
Topics: Humans; Biomarkers; Computational Biology; Diabetes Mellitus; Inflammation; Macrophages
PubMed: 37455460
DOI: 10.2174/1871530323666230714162324 -
International Journal of Molecular... Jul 2023Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and... (Review)
Review
Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and potentially serving as a therapeutic agent for chronic inflammatory diseases. The aim of this review was to systematically investigate preclinical and clinical studies on maresin to inform translational research. Two independent reviewers performed comprehensive searches with the term "Maresin (NOT) Review" on PubMed. A total of 137 studies were included and categorized into 11 human organ systems. Data pertinent to clinical translation were specifically extracted, including delivery methods, optimal dose response, and specific functional efficacy. Maresins generally exhibit efficacy in treating inflammatory diseases, attenuating inflammation, protecting organs, and promoting tissue regeneration, mostly in rodent preclinical models. The nervous system has the highest number of original studies ( = 25), followed by the cardiovascular system, digestive system, and respiratory system, each having the second highest number of studies ( = 18) in the field. Most studies considered systemic delivery with an optimal dose response for mouse animal models ranging from 4 to 25 μg/kg or 2 to 200 ng via intraperitoneal or intravenous injection respectively, whereas human in vitro studies ranged between 1 and 10 nM. Although there has been no human interventional clinical trial yet, the levels of MaR1 in human tissue fluid can potentially serve as biomarkers, including salivary samples for predicting the occurrence of cardiovascular diseases and periodontal diseases; plasma and synovial fluid levels of MaR1 can be associated with treatment response and defining pathotypes of rheumatoid arthritis. Maresins exhibit great potency in resolving disease inflammation and bridging tissue regeneration in preclinical models, and future translational development is warranted.
Topics: Animals; Humans; Mice; Anti-Inflammatory Agents; Chronic Disease; Docosahexaenoic Acids; Inflammation; Macrophages
PubMed: 37446190
DOI: 10.3390/ijms241311012 -
BMC Oral Health Jul 2023The current literature suggests the significant role of foam cells in the initiation of atherosclerosis through the formation of a necrotic core in atherosclerotic...
BACKGROUND
The current literature suggests the significant role of foam cells in the initiation of atherosclerosis through the formation of a necrotic core in atherosclerotic plaques. Moreover, an important periodontal pathogen called Porphyromonas gingivalis (P. gingivalis) is indicated to play a significant role in this regard. Thus, the aim of this systematic review was to comprehensively study the pathways by which P. gingivalis as a prominent bacterial species in periodontal disease, can induce foam cells that would initiate the process of atherosclerosis formation.
METHODS
An electronic search was undertaken in three databases (Pubmed, Scopus, and Web of Science) to identify the studies published from January 2000 until March 2023. The risk of bias in each study was also assessed using the QUIN risk of bias assessment tool.
RESULTS
After the completion of the screening process, 11 in-vitro studies met the inclusion criteria and were included for further assessments. Nine of these studies represented a medium risk of bias, while the other two had a high risk of bias. All of the studies have reported that P. gingivalis can significantly induce foam cell formation by infecting the macrophages and induction of oxidized low-density lipoprotein (oxLDL) uptake. This process is activated through various mediators and pathways. The most important factors in this regard are the lipopolysaccharide of P. gingivalis and its outer membrane vesicles, as well as the changes in the expression rate of transmembrane lipid transportation channels, including transient receptor potential channel of the vanilloid subfamily 4 (TRPV4), lysosomal integral protein 2 (LIMP2), CD36, etc. The identified molecular pathways involved in this process include but are not limited to NF-κB, ERK1/2, p65.
CONCLUSION
Based on the results of this study, it can be concluded that P. gingivalis can effectively promote foam cell formation through various pathogenic elements and this bacterial species can affect the expression rate of various genes and the function of specific receptors in the cellular and lysosomal membranes. However, due to the moderate to high level of risk of bias among the studies, further studies are required in this regard.
Topics: Humans; Foam Cells; Porphyromonas gingivalis; Macrophages; Atherosclerosis; Periodontitis
PubMed: 37442956
DOI: 10.1186/s12903-023-03183-9 -
Journal of Functional Biomaterials May 2023Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes... (Review)
Review
Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes in tendon and tendon-bone healing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic and comprehensive review of the literature was performed on 21 January 2023. The electronic databases searched included Medline (through PubMed), Web of Science, Embase, Scopus, Cochrane Library and Ovid. In the end, a total of 1794 articles were systematically reviewed. Furthermore, a "snowball" search was also carried out. Finally, forty-six studies were included for analysis, with the total sample size being 1481 rats, 416 mice, 330 rabbits, 48 dogs, and 12 sheep. In these studies, exosomes promoted tendon and tendon-bone healing and displayed improved histological, biomechanical and morphological outcomes. Some studies also suggested the mechanism of exosomes in promoting tendon and tendon-bone healing, mainly through the following aspects: (1) suppressing inflammatory response and regulating macrophage polarization; (2) regulating gene expression, reshaping cell microenvironment and reconstructing extracellular matrix; (3) promoting angiogenesis. The risk of bias in the included studies was low on the whole. This systematic review provides evidence of the positive effect of exosomes on tendon and tendon-bone healing in preclinical studies. The unclear-to-low risk of bias highlights the significance of standardization of outcome reporting. It should be noted that the most suitable source, isolation methods, concentration and administration frequency of exosomes are still unknown. Additionally, few studies have used large animals as subjects. Further studies may be required on comparing the safety and efficacy of different treatment parameters in large animal models, which would be conducive to the design of clinical trials.
PubMed: 37367263
DOI: 10.3390/jfb14060299 -
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 -
Cureus Apr 2023The main risk factor for atherosclerotic cardiovascular disease is smoking. Nicotine and carbon monoxide are two dangerous substances that are found in cigarette smoke.... (Review)
Review
The main risk factor for atherosclerotic cardiovascular disease is smoking. Nicotine and carbon monoxide are two dangerous substances that are found in cigarette smoke. The increased heart rate can have an almost instantaneous impact on the heart and blood vessels. Smoking is well known to cause oxidative stress, endanger the lining of the arteries, and accelerate the accumulation of fatty plaque in the blood vessels. It raises the danger of sudden thrombotic events, inflammatory alterations, and low-density lipoprotein oxidation. The smoke's carbon monoxide decreases the blood's capacity to deliver oxygen, adding to the heart's stress. Notably, these risks increase when diabetes, hypertension, high cholesterol, and glucose intolerance are present. It has a detrimental effect on peripheral blood vessels, raising the possibility of thromboangiitis obliterans. Stroke risk is known to be increased by smoking. As compared to those who continue to smoke, those who give up smoking have a much longer life expectancy. Chronic cigarette smoking has been shown to affect the macrophages' ability to remove cholesterol. Abstinence from smoking enhances the function of high-density lipoproteins and cholesterol efflux, lowering the risk of plaque buildup. In this review, we present the most recent information regarding the causal relationship between smoking and cardiovascular health as well as the long-term advantages of quitting.
PubMed: 37234135
DOI: 10.7759/cureus.38073 -
Frontiers in Immunology 2023Kidney stone disease (KSD) is one of the earliest medical diseases known, but the mechanism of its formation and metabolic changes remain unclear. The formation of...
Kidney stone disease (KSD) is one of the earliest medical diseases known, but the mechanism of its formation and metabolic changes remain unclear. The formation of kidney stones is a extensive and complicated process, which is regulated by metabolic changes in various substances. In this manuscript, we summarized the progress of research on metabolic changes in kidney stone disease and discuss the valuable role of some new potential targets. We reviewed the influence of metabolism of some common substances on stone formation, such as the regulation of oxalate, the release of reactive oxygen species (ROS), macrophage polarization, the levels of hormones, and the alternation of other substances. New insights into changes in substance metabolism changes in kidney stone disease, as well as emerging research techniques, will provide new directions in the treatment of stones. Reviewing the great progress that has been made in this field will help to improve the understanding by urologists, nephrologists, and health care providers of the metabolic changes in kidney stone disease, and contribute to explore new metabolic targets for clinical therapy.
Topics: Humans; Kidney Calculi; Reactive Oxygen Species; Oxalates
PubMed: 37228601
DOI: 10.3389/fimmu.2023.1142207