Neutrophils Research Articles

Study on the correlation between controlling nutritional status score and clinical biochemical indicators in patients with colorectal cancer

PurposeThe controlling nutritional status (CONUT) score is an important tool for predicting the prognosis of colorectal cancer (CRC); however, its effectiveness is relatively insufficient. This study aimed to screen for more effective clinical indicators as supplements to the CONUT scoring system and improve the predictive value of CRC prognosis. Patients and methodsBetween 2014 and 2020, the clinical information of all CRC patients in our unit was retrospectively collected, and the CONUT scores were calculated based on the levels of serum albumin (ALB), lymphocytes (LC), and total cholesterol. The included patients were divided into the following three groups: normal nutrition (0–1), mild malnutrition (2–4), and moderate-to-severe malnutrition (5–12). The correlations between the CONUT score and baseline characteristics and clinical indicators were evaluated. ResultsThis study ultimately included 5014 CRC patients. The nutritional status of patients with colon cancer (CC) was worse than that of rectal cancer (RC). The nutritional status was worse in men than in women. The older the patient, the poorer the nutritional status, and the poorer the nutritional status, the longer the hospital stay. In addition, poor nutritional status in patients is indicated by higher values of neutrophils (NE), monocytes (MC), eosinophils (EOS), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), carcinoembryogenic antigen (CEA), and lower values of white blood cells (WBC), basophils (BAS), haemoglobin (HB), total protein (TP), triglycerides (TG), low density lipoprotein (LDL), aspartate transaminase (AST), and blood urea nitrogen (BUN), which was statistically significant (P < 0.05). Indicators that significantly correlated with the CONUT score reflected the immune nutritional status, including WBC (odds ratio [OR] = 0.036, P < 0.001), NE (OR = 30.815, P < 0.001), MC (OR = 41.388, P < 0.001), EOS (OR = 27.577, P < 0.001), BAS (OR = 0.006, P = 0.046), and LDL (OR = 0.319, P < 0.001). ConclusionAdditional variables such as WBC, NE, MC, EOS, BAS, and LDL may be used as supplementary indicators in the CONUT scoring system to more effectively predict the clinical prognosis of CRC patients.

Adverse effects of microparticles on transfusion of stored red blood cell concentrates

BackgroundSystemic and pulmonary coagulopathy and inflammation are important characteristics of transfusion-related acute lung injury (TRALI). Whether microparticles that accumulate in transfused red blood cell concentrates (RBCs) have proinflammatory and procoagulant potential and contribute to adverse reactions of RBC transfusions is unclear. AimTo investigate the ability of microparticles in stored RBCs to promote thrombin generation and induce human pulmonary microvascular endothelial cell (HMVEC) activation and damage. MethodsThe number and size of microparticles were determined by flow cytometric and nanoparticle tracking analyses, respectively. Thrombin generation and the intrinsic coagulation pathway were assayed by a calibrated automated thrombogram and by measuring activated partial thromboplastin time (aPTT), respectively. The expression of ICAM-1 and the release of cytokines by endothelial cells were detected by flow cytometric analyses. HMVEC damage was assessed by incubating lipopolysaccharide-activated endothelial cells with MP-primed polymorphonuclear neutrophils (PMNs). ResultsThe size of the microparticles in the RBC supernatant was approximately 100–300 nm. Microparticles promoted thrombin generation in a dose-dependent manner and the aPTT was shortened. Depleting microparticles from the supernatant of RBCs stored for 35 days by either filtration or centrifugation significantly decreased the promotion of thrombin generation. The expression of ICAM-1 on HMVECs was increased significantly by incubation with isolated microparticles. Furthermore, microparticles induced the release of interleukin-6 (IL-6) and interleukin-8 (IL-8) from HMVECs. Microparticles induced lipopolysaccharide-activated HMVEC damage by priming PMNs, but this effect was prevented by inhibiting the PMNs respiratory burst with apocynin. ConclusionMicroparticles in stored RBCs promote thrombin generation, HMVEC activation and damage which may be involved in TRALI development.

Elevated level of circulating calprotectin correlates with severity and high mortality in patients with COVID-19.

Patients with coronavirus disease-2019 (COVID-19) are characterized by hyperinflammation. Calprotectin (S100A8/S100A9) is a calcium- and zinc-binding protein mainly secreted by neutrophilic granulocytes or macrophages and has been suggested to be correlated with the severity and prognosis of COVID-19. To thoroughly evaluate the diagnostic and prognostic utility of calprotectin in patients with COVID-19 by analyzing relevant studies. PubMed, Web of Science, and Cochrane Library were comprehensively searched from inception to August 1, 2023 to retrieve studies about the application of calprotectin in COVID-19. Useful data such as the level of calprotectin in different groups and the diagnostic efficacy of this biomarker for severe COVID-19 were extracted and aggregated by using Stata 16.0 software. Fifteenstudies were brought into this meta-analysis. First, the pooled standardized mean differences (SMDs) were used to estimate the differences in the levels of circulating calprotectin between patients with severe and non-severe COVID-19. The results showed an overall estimate of 1.84 (95% confidence interval [CI]: 1.09-2.60). Diagnostic information was extracted from 11 studies, and the pooled sensitivity and specificity of calprotectin for diagnosing severe COVID-19 were 0.75 (95%CI: 0.64-0.84) and 0.88 (95%CI: 0.79-0.94), respectively. The AUC was 0.89 and the pooled DOR was 18.44 (95%CI: 9.07-37.51). Furthermore, there was a strong correlation between elevated levels of circulating calprotectin and a higher risk of mortality outcomes in COVID-19 patients (odds ratio: 8.60, 95%CI: 2.17-34.12; p < 0.1). This meta-analysis showed that calprotectin was elevated in patients with severe COVID-19, and this atypical inflammatory cytokine might serve as a useful biomarker to distinguish the severity of COVID-19 and predict the prognosis.

Влияние фоновой лимфопении на реактивность показателей неспецифического иммунитета в ответ на общее холодовое воздействие

Lymphopenia is a condition in which there are lower than normal counts of lymphocytes in the blood. Combination of lymphopenia and prolonged exposure to low temperatures leads to a reduction of adaptive resources, increasing risks of chronic inflammatory processes and secondary environmentally induced immunodeficiencies. The aim of the study was to compare characteristics of immune reactivity in response to cold exposure depending on background level of lymphocytes. Changes in hematologic and immunologic parameters in 203 participants before and immediately after short-term cold exposure were studied. Measurements included skin temperature (forehead, backside of palm), blood pressure, heart rate, leukogram, and hemogram. Levels of ferritin, lactoferrin, transferrin, interleukin-6, interleukin-1β, TNFα, erythropoietin, and irisin were determined using the enzyme immunoassay method. Apoptosis and necrosis of lymphocytes were assessed by flow cytometry analysis using AnV/PI double staining assay. Regardless of the background level of lymphocytes in peripheral blood, same-type responses to short-term cold exposure were observed in cardiovascular system as well as in irisin and ferritin levels, providing an evidence of activating thermoregulation and thermal homeostasis mechanisms. Lymphopenia is associated with a decrease in activity of nonspecific defense - in response to cold exposure there were no changes in level and functional activity of circulating neutrophil granulocytes that can increase the risks of chronicization of infectious processes in this group.

The potential effect of Garlium GEM HCTM as a tick control agent in cattle.

As resistance to chemical acaricides increases amongst tick populations, investigations of natural remedies that have acaricidal or tick-repellent effects have become essential in the search for alternatives for sustainable tick control. Garlium GEM HC (Garlium), a natural concentrated garlic product, was supplemented in-feed to beef cattle to determine if it could assist in reducing the number of attached ticks on cattle. Two grams of Garlium was supplemented daily to eight Bonsmara steers over 43 days. A second group of eight steers served as controls. All animals were infested with a similar number of Rhipicephalus appendiculatus adults and Rhipicephalus microplus larvae. Subsequently, the number of attached engorged ticks and the hatchability of the tick eggs were determined. Blood samples were collected from the steers for whole blood analyses. The results were analysed using a twosample t-test procedure. Due to large standard deviations observed, most of the tick parameters were only numerically improved. Although not significant, the number of larvae produced by female R. appendiculatus ticks per host was reduced by 23%. Estimated number of R. microplus larvae produced from ticks harvested from Garlium supplemented cattle were reduced by 42.3% (p = 0.10). No adverse effect was observed on haematocrits or haemoglobin concentrations. Garlium reduced segmented neutrophil count in the treatment group, suggesting that the immune system was less challenged. Although not statistically significant, the effect of reducing the number of larvae produced per host for the two tick species by approximately 20% and 40% respectively, may be of economic benefit to commercial cattle farmers.

6-Parts Haematology Parameters Evaluation Using Abbott Alinity H

Nowadays, there are variety of automated hematology analyzers available in the market. However, the new product of diagnostic equipment should be evaluated and validated to ensure their capability. Thorough process of testing on all new hematology analyzers must be performed to certify that reliable result will be released and for patient safety. This study was carried out to evaluate automated hematology analyzers; Abbott Alinity H, in the Hospital Universiti Sains Malaysia setting. Blood samples send for complete blood count were selected randomly (n = 50) from healthy subjects and those who have different blood disorders. Blood specimens and quality control materials were analysed on the Abbott Alinity H to evaluate the precision. For correlation, the Sysmex XN-1000 was used as the comparative method. The study showed very good correlation between Abbott Alinity H and Sysmex, XN-1000 in the parameters such as white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), mean cell volume (MCV), platelet (PLT), neutrophil (NEU), lymphocyte (LYM), monocyte (MONO), eosinophil (EOS), and basophil (BASO). For the precision, all the parameters are performed well within allowable limits of performance for Abbott Alinity H. In conclusion, the Abbott Alinity H demonstrated an acceptable performance in term of precision and the analyzer was equivalent with the Sysmex XN-1000.

Fibromyalgia: one year in review 2024.

Fibromyalgia (FM) remains a condition with a pathogenesis that is not completely understood, affecting a significant portion of the global population. This article summarises the main advances in FM during the last year. Even in 2023, research on FM was notably active. From a clinimetric perspective, studies have been conducted to evaluate the possibilities of interchanging the primary indices of disease severity, primarily for studies with substantial case numbers. Regarding FM pathogenesis, ongoing research focuses on small fiber neuropathy: some studies have documented its association with central sensitisation, while others have revealed distinct sensory profiles in patients with FM and small fiber neuropathy compared to those solely with small fiber neuropathy. Dorsal root ganglia seem to play a crucial role in the pathogenesis of FM as they host satellite glial cells, which are targeted by pain-driving immunoglobulin G. These antibodies have been identified in a subset of patients exhibiting high symptom severity. An important study conducted on animal models confirmed the role of neuroinflammation at the level of dorsal root ganglia, in this case mediated by polymorphonuclear neutrophils. Mounting evidence underscores the link between COVID-19 and the persistence of FM symptoms after recovery. In identifying potential biomarkers aiding FM diagnosis, research has also concentrated on studying the expression of specific circulating microRNAs. Recent discoveries have unveiled novel therapeutic strategies for FM, especially focused in non-pharmacological interventions. This includes a focus on non-invasive brain stimulation and exercise programs, all directed towards relieving symptoms and improving functionality in individuals affected by the condition.

How murine neutrophils are hijacked within the microenvironment of pancreatic cancer.

Discoveries made in the past decades have brought out that, in addition to their classical primary defensive functions against infections, polymorphonuclear neutrophils play key effector roles not only in chronic inflammatory and immune-mediated diseases but also in cancer. In addition, depending on their differentiation/activation status and/or on the physiological or pathological microenvironment in which they reside, neutrophils have been shown to behave as highly plastic cells, able to acquire new phenotypes/functional states. All these features are well manifested in cancer and modulated during tumor progression. Herein, we discuss intriguing data by Lai Ng's group that have shed light on the origin and development of terminally differentiated, proangiogenic, tumor-associated neutrophils, facilitating tumor growth in a murine orthotopic model of pancreatic ductal adenocarcinoma. These findings help to progress toward the ambitious goal of selectively targeting only the skewed pathological neutrophil populations present within the tumor microenvironment.

Hematological and biochemical reference values for the Brazilian Pony breed

The aim of this study was to characterize the hematological profile of the equine Brazilian Pony breed herds in northern of Rio de Janeiro state, Brazil. Blood samples were separated in categories: adult stallions, pregnant mares and non-pregnant mares. The red blood cells (RBC), packed cell volume (PCV), hemoglobin (Hgb), main corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cells (WBC) and differential count of basophils (Baso), eosinophils (Eos), band cells (Bands), segmented neutrophils (Neut), lymphocytes (Lym), monocytes (Mono), and platelets (Plat) were evaluated. The biochemical parameters of urea (Urea), alanine aminotransferase (ALP), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and creatinine (Creatinine) were measured in pregnant and non-pregnant mares. Analysis of variance was carried out with difference of hematological parameters between males and females. Also, analysis of variance was used to verify the effect of pregnancy on biochemical parameters. There was effect of sex on RBC, hemoglobin, VCM and MHCH, but PVC and MHC were not affected by sex. Higher means were observed in females. There was an effect of sex on WBC, eosinophils and neutrophils. There was effect of pregnancy on AST, but no effect on urea, GGT and Creatinine. According to the results obtained in this study, it can be concluded that the analysis of the blood count and the biochemical of the Brazilian Pony reveals specificities compared to other equine breeds. Thus, these results could be used as biomarkers for the evaluation of the Brazilian Pony breed in Rio de Janeiro.

Involvement of peptidylarginine deiminase 4 in eosinophil extracellular trap formation and contribution to citrullinated histone signal in thrombi

BackgroundExtracellular traps formed by neutrophils (NETs) and eosinophils (EETs) have been described in coronary thrombi, contributing to thrombus stability. A key mechanism during NET formation is histone modification by the enzyme PAD4. Citrullinated histones, the product of PAD4 activity, are often attributed to neutrophils. Eosinophils also express high levels of PAD4. ObjectivesWe aimed to explore the contribution of PAD4 to EET formation. MethodsWe performed immunohistological analyses on thrombi, including a large, intact, and eosinophil-containing thrombus retrieved from the right coronary artery using an aspiration catheter and stroke thrombi from thrombectomy retrieval. We studied eosinophils for their capability to form PAD4-dependent EETs in response to strong ET-inducing agonists as well as activated platelets and bacteria. ResultsHistopathology and immunofluorescence microscopy identified a coronary thrombus rich in platelets and neutrophils, with distinct areas containing von Willebrand factor and citrullinated histone H3 (H3Cit). Eosinophils were also identified in leukocyte-rich areas. The majority of the H3Cit+ signal colocalized with myeloperoxidase, but some colocalized with eosinophil peroxidase, indicating EETs. Eosinophils isolated from healthy volunteers produced H3Cit+ EETs, indicating an involvement of PAD4 activity. The selective PAD4 inhibitor GSK484 blocked this process, supporting PAD4 dependence of H3Cit+ EET release. Citrullinated histones were also present in EETs produced in response to live Staphylococci. However, limited evidence for EETs was found in mouse models of venous thrombosis or infective endocarditis. ConclusionAs in NETosis, PAD4 can catalyze the formation of EETs. Inhibition of PAD4 decreases EET formation, supporting the future utility of PAD4 inhibitors as possible antithrombotic agents.

Novel high-yield potato protease inhibitor panels block a wide array of proteases involved in viral infection and crucial tissue damage

Viruses critically rely on various proteases to ensure host cell entry and replication. In response to viral infection, the host will induce acute tissue inflammation pulled by granulocytes. Upon hyperactivation, neutrophil granulocytes may cause undue tissue damage through proteolytic degradation of the extracellular matrix. Here, we assess the potential of protease inhibitors (PI) derived from potatoes in inhibiting viral infection and reducing tissue damage. The original full spectrum of potato PI was developed into five fractions by means of chromatography and hydrolysis. Individual fractions showed varying inhibitory efficacy towards a panel of proteases including trypsin, chymotrypsin, ACE2, elastase, and cathepsins B and L. The fractions did not interfere with SARS-CoV-2 infection of Vero E6 cells in vitro. Importantly, two of the fractions fully inhibited elastin-degrading activity of complete primary human neutrophil degranulate. These data warrant further development of potato PI fractions for biomedical purposes, including tissue damage crucial to SARS-CoV-2 pathogenesis.Key messagesProtease inhibitor fractions from potato differentially inhibit a series of human proteases involved in viral replication and in tissue damage by overshoot inflammation.Protease inhibition of cell surface receptors such as ACE2 does not prevent virus infection of Vero cells in vitro.Protease inhibitors derived from potato can fully inhibit elastin-degrading primary human neutrophil proteases.Protease inhibitor fractions can be produced at high scale (hundreds of thousands of kilograms, i.e., tons) allowing economically feasible application in lower and higher income countries.

Study of the effect of a drug from the macromycetes Ganoderma lucidum on the phagocytic activity of peripheral blood neutrophils in patients with year-round allergic rhinitis

Modern complex therapy of patients with persistent (year-round, chronic) allergic rhinitis (AR), based on the use of antihistamines and intranasal glucocorticosteroids, in many cases is not effective enough, since drug therapy acts only on individual links in the pathogenesis, without preventing the progression of the allergic disease. At the same time, the quantitative and reserve capabilities of neutrophil granulocytes are depleted, which increases the level of antigenic load in patients with AR. The aim of this study is to investigate the phagocytic activity of neutrophils in patients with AR who received basic therapy and patients who received basic therapy and a course of the drug from the macromycetes Ganoderma lucidum "Astmagan". We examined 40 patients of both sexes with AR, the duration of the disease ranged from 6 months to 2 years. Patients were divided into 2 equal groups: The 1st group consisted of patients who received basic therapy (oral Loratadine and intranasal Nasonex). The 2nd group consisted of patients who received basic therapy and a course of "Astmagan". The treatment course lasted 90 days. The control group consisted of 25 healthy individuals. After the treatment, patients in both groups showed a statistically significant positive dynamics of phagocytic system activity: in group 1, the phagocytic index (FI) increased by 30 % (p=0.001), in the second group this indicator reached the normal level. Also, in patients of group 1, the phagocytic number (PN) increased by 35 % (p=0.0001), but did not reach the normal level.&#x0D; According to the results of comparative evaluation, a greater efficacy of the treatment complex with the additional use of "Astmagan" was established, which is manifested in the restoration of phagocytic activity of peripheral blood neutrophils, the effect persists for 6 months after treatment.

Neutrophil extracellular traps - a potential trigger for the development of thrombocytopenia during extracorporeal membrane oxygenation.

Neutrophil extracellular traps (NETs) have recently emerged as a potential link between inflammation, immunity, and thrombosis, as well as other coagulation disorders which present a major challenge in the context of extracorporeal membrane oxygenation (ECMO). By examining blood from ECMO patients for NETs and their precursors and correlating them with clinical and laboratory biomarkers of coagulation and inflammation, this study aims to evaluate the association between the presence of NETs in the bloodstream of ECMO patients and the development of potentially severe coagulation disorders during ECMO therapy. Therefore, blood samples were collected from healthy volunteers (n=13) and patients receiving veno-venous (VV) ECMO therapy (n=10). To identify NETs and their precursors, DNA and myeloperoxidase as well as granulocyte marker CD66b were visualized simultaneously by immunofluorescence staining in serial blood smears. Differentiation of DNA-containing objects and identification of NETs and their precursors was performed semiautomatically by a specific algorithm using the shape and size of DNA staining and the intensity of MPO and CD66b signal. Neutrophil extracellular traps and their precursors could be detected in blood smears from patients requiring VV ECMO. Compared to volunteers, ECMO patients presented significantly higher rates of NETs and NET precursors as well as an increased proportion of neutrophil granulocytes in all detected nucleated cells. A high NET rate prior to the initiation of ECMO therapy was associated with both increased IL-6 and TNF-α levels as an expression of a high cytokine burden. These patients with increased NET release also presented an earlier and significantly more pronounced decrease in platelet counts and ATIII activity following initiation of therapy compared with patients with less elevated NETs. These findings provide further indications for the development of immune-mediated acquired thrombocytopenia in ECMO patients.

The oncolytic bacteria-mediated delivery system of CCDC25 nucleic acid drug inhibits neutrophil extracellular traps induced tumor metastasis

BackgroundNeutrophil extracellular traps (NETs), antibacterial weapons of neutrophils (NEs), have been found to play a crucial role in cancer metastasis in recent years. More and more cancer research is focusing on anti-NETs. However, almost all anti-NETs treatments have limitations such as large side effects and limited efficacy. Therefore, exploring new anti-NETs therapeutic strategies is a long-term goal.ResultsThe transmembrane protein coiled-coil domain containing 25 (CCDC25) on tumor cell membranes can bind NETs-DNA with high specificity and affinity, enabling tumor cells to sense NETs and thus promote distant metastasis. We transformed shCCDC25 into VNP20009 (VNP), an oncolytic bacterium, to generate VNP-shCCDC25 and performed preclinical evaluation of the inhibitory effect of shCCDC25 on cancer metastasis in B16F10 lung metastasis and 4T1 orthotopic lung metastasis models. VNP-shCCDC25 effectively blocked the downstream prometastatic signaling pathway of CCDC25 at tumor sites and reduced the formation of NETs while recruiting more neutrophils and macrophages to the tumor core, ultimately leading to excellent metastasis inhibition in the two lung metastasis models.ConclusionThis study is a pioneer in focusing on the effect of anti-NET treatment on CCDC25. shCCDC25 is effectively delivered to tumor sites via the help of oncolytic bacteria and has broad application in the inhibition of cancer metastasis via anti-NETs.Graphical

Crosstalk between keratinocytes and neutrophils shapes skin immunity against S. aureus infection.

Staphylococcus aureus (S. aureus) infection of the skin leads to a rapid initial innate immune response with keratinocytes in the epidermis as the initial sensors. Polymorphonuclear neutrophils (PMNs) are the first innate immune cells to infiltrate infection sites where they provide an effective first-line of defense. Previous work of our group showed that in inflamed skin a crosstalk between PMNs and keratinocytes results in enhanced S. aureus skin colonization. In this work, we used an in vitro co-culture model to studied the crosstalk between primary human keratinocytes (PHKs) and PMNs in a sterile environment and upon S. aureus infection. We investigated the influence of PHKs on PMN activation by analyzing PMN lifespan, expression of degranulation markers and induction of proinflammatory cytokines. Furthermore, we analyzed the influence of PMNs on the inflammatory response of PHKs. Finally, we investigated the influence of the skin microbiome on PMN-mediated skin inflammation. We show that co-culture of PMNs with PHKs induces activation and degranulation of PMNs and significantly enhances their lifespan compared to PMN cultivation alone by an IL-8 mediated mechanism and, furthermore, primes PMNs for enhanced activity after S. aureus infection. The prolonged incubation with PMNs also induces inflammatory responses in PHKs which are further exacerbated in the presence of S. aureus and induces further PMN recruitment thus fueling skin inflammation. Interestingly, infection of PHKs with the skin commensal S. epidermidis reduces the inflammatory effects of PMNs in the skin and exhibits an anti-inflammatory effect. Our data indicate that skin infiltrating PMNs and PHKs influence each other in such a way to enhance skin inflammation and that commensal bacteria are able to reduce the inflammatory effect.

A nomogram of preoperative indicators predicting lymph vascular space invasion in cervical cancer.

To develop predictive nomograms of lymph vascular space invasion (LVSI) in patients with early-stage cervical cancer. We identified 403 patients with cervical cancer from the Affiliated Hospital of Jiangnan University from January 2015 to December 2019. Patients were divided into the training set (n = 242) and the validation set (n = 161), with patients in the training set subdivided into LVSI (+) and LVSI (-) groups according to postoperative pathology. Preoperative hematologic indexes were compared between the two subgroups. Univariate and multivariate logistic regression analyses were used to analyze the independent risk factors for LVSI, from which a nomogram was constructed using the R package. LVSI (+) was present in 94 out of 242 patients in the training set, accompanied by a significant increase in the preoperative squamous cell carcinoma antigen (SCC), white blood cells (WBC), neutrophil (NE), platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and tumor size (P < 0.05). Univariate analysis showed that SCC, WBC, NE, NLR, PLR, SII, and tumor size were correlated with LVSI (P < 0.05), and multivariate analysis showed that tumor size, SCC, WBC, and NLR were independent risk factors for LVSI (P < 0.05). A nomogram was correspondingly established with good performance in predicting LVSI [training: ROC-AUC = 0.845 (95% CI: 0.731-0.843) and external validation: ROC-AUC = 0.704 (95% CI: 0.683-0.835)] and high accuracy (training: C-index = 0.787; external validation: C-index = 0.759). The nomogram based on preoperative tumor size, SCC, WBC, and NLR had excellent accuracy and discriminative capability to assess the risk of LVSI in early-stage cervical cancer patients.

Trained Innate Immunity in Animal Models of Cardiovascular Diseases.

Acquisition of immunological memory is an important evolutionary strategy that evolved to protect the host from repetitive challenges from infectious agents. It was believed for a long time that memory formation exclusively occurs in the adaptive part of the immune system with the formation of highly specific memory T cells and B cells. In the past 10-15 years, it has become clear that innate immune cells, such as monocytes, natural killer cells, or neutrophil granulocytes, also have the ability to generate some kind of memory. After the exposure of innate immune cells to certain stimuli, these cells develop an enhanced secondary response with increased cytokine secretion even after an encounter with an unrelated stimulus. This phenomenon has been termed trained innate immunity (TI) and is associated with epigenetic modifications (histone methylation, acetylation) and metabolic alterations (elevated glycolysis, lactate production). TI has been observed in tissue-resident or circulating immune cells but also in bone marrow progenitors. Risk-factors for cardiovascular diseases (CVDs) which are associated with low-grade inflammation, such as hyperglycemia, obesity, or high salt, can also induce TI with a profound impact on the development and progression of CVDs. In this review, we briefly describe basic mechanisms of TI and summarize animal studies which specifically focus on TI in the context of CVDs.

A study of clinical and serological correlation of early myocardial injury in elderly patients infected with the Omicron variant.

Myocardial injury in elderly Omicron variant patients is a leading cause of severe disease and death. This study focuses on elucidating the clinical characteristics and potential risk factors associated with myocardial injury in elderly patients infected with the Omicron variant. Myocardial injury was defined based on elevated cardiac troponin concentrations exceeding the 99th percentile upper reference limit. Among 772 elderly Omicron-infected patients, categorized into myocardial injury (n = 263) and non-myocardial injury (n = 509) groups. The stratified log-rank statistic was used to compare the probability of patients developing intensive care. Receiver operating characteristic curves were used to determine the best cut-off values of clinical and laboratory data for predicting myocardial injury. Univariate and multivariate logistic regression was adopted to analyze the risk factors for myocardial injury. The occurrence of myocardial injury in Omicron variant-infected geriatric patients was up to 34.07% and these patients may have a higher rate of requiring intensive care (P < 0.05). By comparing myocardial injury patients with non-myocardial injury patients, notable differences were observed in age, pre-existing medical conditions (e.g., hypertension, coronary heart disease, cerebrovascular disease, arrhythmia, chronic kidney disease, and heart failure), and various laboratory biomarkers, including cycle threshold-ORF1ab gene (Ct-ORF1ab), cycle threshold-N gene (Ct-N), white blood cell count, neutrophil (NEUT) count, NEUT%, lymphocyte (LYM) count, LYM%, and D-dimer, interleukin-6, procalcitonin, C-reactive protein, serum amyloid A, total protein, lactate dehydrogenase, aspartate aminotransferase, glomerular filtration rate, blood urea nitrogen, and serum creatinine (sCr) levels (P < 0.05). Furthermore, in the multivariable logistic regression, we identified potential risk factors for myocardial injury in Omicron variant-infected elderly patients, including advanced age, pre-existing coronary artery disease, interleukin-6 > 22.69 pg/ml, procalcitonin > 0.0435 ng/ml, D-dimer > 0.615 mg/L, and sCr > 81.30 μmol/L. This study revealed the clinical characteristics and potential risk factors associated with myocardial injury that enable early diagnosis of myocardial injury in Omicron variant-infected elderly patients, providing important reference indicators for early diagnosis and timely clinical intervention.

Neutrophils in HNSCC Can Be Associated with Both a Worse or Favorable Prognosis.

The prognostic significance of tumor-infiltrating neutrophils in head and neck squamous cell carcinoma (HNSCC) is poorly understood. It is unclear how the presence of neutrophils affects prognosis due to their polarization into cytotoxic N1 or immunosuppressive N2. Therefore, we determined the number of CD66b+ neutrophil granulocytes separately in the stromal and epithelial compartments in cancer tissues from 397 patients with HNSCC. Tumor samples from six historical patient groups were processed into tissue microarrays and stained immunohistochemically. In total, 21.9% were HPV positive (p16+). Neutrophil counts were much lower in the stromal compartment (372 ± 812) than in the epithelial cancer compartment (1040 ± 1477) (p < 0.001), with large differences between groups. In three groups with high neutrophil infiltration, high rates were associated with a favorable prognosis, whereas in two groups, high rates were a negative prognostic factor. In p16- oropharyngeal and hypopharyngeal cancer high infiltration was associated with a favorable prognosis. Cancers with an exclusion of neutrophils in the epithelial compartment were associated with improved prognosis. In oropharyngeal and hypopharyngeal HPV-negative cancer high neutrophil infiltration rates were clearly associated with prolonged survival. Neutrophil granulocytes in HNSCC may contribute to a favorable or unfavorable prognosis.

Macrophage subpopulations in pediatric patients with lupus nephritis and other inflammatory diseases affecting the kidney

BackgroundMacrophages play an important role in the pathogenesis of lupus nephritis (LN), but less is known about macrophage subtypes in pediatric LN. Here we compared renal inflammation in LN with other inflammatory pediatric kidney diseases and assessed whether inflammation correlates with clinical parameters.MethodsUsing immunofluorescence microscopy, we analyzed renal biopsies from 20 pediatric patients with lupus nephritis (ISN/RPS classes II–V) and pediatric controls with other inflammatory kidney diseases for infiltration with M1-like (CD68 + /CD206 − , CD68 + /CD163 −), M2a-like (CD206 + /CD68 +), and M2c-like macrophages (CD163 + /CD68 +) as well as CD3 + T-cells, CD20 + B-cells, and MPO + neutrophilic granulocytes. In addition, the correlation of macrophage infiltration with clinical parameters at the time of renal biopsy, e.g., eGFR and serum urea, was investigated. Macrophage subpopulations were compared with data from a former study of adult LN patients.ResultsThe frequency of different macrophage subtypes in biopsies of pediatric LN was dependent on ISN/RPS class and showed the most pronounced M1-like macrophage infiltration in patients with LN class IV, whereas M2c-like macrophages were most abundant in class III and IV. Interestingly, on average, only half as many macrophages were found in renal biopsies of pediatric LN compared to adult patients with LN. The distribution of frequencies of macrophage subpopulations, however, was different for CD68 + CD206 + (M2a-like) but comparable for CD68 + CD163 − (M1-like) CD68 + CD163 + (M2c-like) cells in pediatric and adult patients. Compared to other inflammatory kidney diseases in children, fewer macrophages and other inflammatory cells were found in kidney biopsies of LN. Depending on the disease, the frequency of individual immune cell types varied, but we were unable to confirm disease-specific inflammatory signatures in our study due to the small number of pediatric cases. Worsened renal function, measured as elevated serum urea and decreased eGFR, correlated particularly strongly with the number of CD68 + /CD163 − M1-like macrophages and CD20 + B cells in pediatric inflammatory kidney disease.ConclusionAlthough M1-like macrophages play a greater role in pediatric LN patients than in adult LN patients, M2-like macrophages appear to be key players and are more abundant in other pediatric inflammatory kidney diseases compared to LN.