Higher Neutrophil Counts Research Articles

Impact of neutrophil-to-lymphocyte ratio on clinical outcomes in patients with acute or chronic coronary syndrome undergoing percutaneous coronary intervention

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as an inflammatory biomarker associated with atherosclerosis and cardiovascular events. However, its role in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. Purpose We aimed to evaluate the clinical impact of baseline NLR in patients undergoing PCI for acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). Methods We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US hospital. We excluded patients for whom NLR was not available and those who were deemed to have active hematological or infective diseases, including patients presenting with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to clinical presentation. Within each group, we estimated the risk of 12-month adverse events using the lowest NLR quartile as reference. The primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints were MACE individual components and any periprocedural or post-discharge clinically relevant bleeding. Results A total of 7,201 patients were included in the analysis; of these 3,975 (55.2%) had ACS and 3,226 (44.8%) CCS. Patients in the 4th quartile (NLR > 5.0) were more frequently male, older, and presented more often with chronic kidney disease and complex coronary artery disease. Smoking, diabetes and history of CAD, as well as triglycerides, LDL, non-HDL and total cholesterol levels were lower in the 4th NLR quartile. In patients presenting with CCS, the risk of MACE, all-cause death, MI was similar across NLR quartiles, while the risk of bleeding increased stepwise (Figure 1). In patients presenting with ACS, the 4th NLR quartile had the highest adjusted risk of MACE (HRadj 1.82, 95% CI 1.25-2.67; P=0.002), all cause death (HRadj 2.56, 95% CI 1.41-4.66; P<0.001), and bleeding (HRadj 1.82 95% CI 1.25-2.63, P<0.001) at 1 year, as compared to the lowest quartile (Table 1). Conclusions Among patients undergoing PCI, elevated NLR is strongly associated with risk of MACE and all-cause mortality in patients presenting with ACS but not in those with CCS. Conversely, the risk of bleeding was augmented with higher NLR in both ACS and CCS patients undergoing PCI. In this setting, NLR may inform risk stratification at the time of PCI.

Impact of neutrophil-to-lymphocyte ratio on clinical outcomes in patients with or without chronic kidney disease undergoing percutaneous coronary intervention

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as inexpensive inflammatory biomarker associated with worse cardiovascular outcomes. However, little is known about its role in risk stratification of patients with both chronic kidney disease (CKD) and coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Purpose We aimed to evaluate the clinical impact of baseline NLR in patients with and without CKD undergoing PCI. Methods We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US center. We excluded patients without available NLR and those who were deemed to have active hematological or infective diseases, including patients with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to presence of CKD (eGFR < 60 ml/min). Within each group, we estimated the risk of adverse events using the lowest NLR quartile as reference. The primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction, or stroke. Secondary endpoints included incidence of clinically relevant bleeding and contrast-associated acute kidney injury (CA-AKI), defined as ≥ 0.3 mg/dL or ≥ 50% serum creatinine increase from baseline. Results A total of 7,287 patients were included in the analysis; of these 2,008 (27.6%) had CKD and 5,279 (72.4%) did not. CKD patients (mean eGFR 40.8±16.1 ml/min) were older, had more comorbidities, and presented with higher hs-CRP levels and a greater estimated risk of CA-AKI. Overall, patients with elevated NLR had more severe CAD and underwent more complex PCI. In CKD patients, incidence of adverse events increased stepwise and those in the 4th NLR quartile had the highest adjusted risks of MACE (HRadj 1.86, 95% CI 1.12-3.08; P=0.012), all cause death (HRadj 2.44, 95% CI 1.18-5.05; P=0.003) and bleeding (HRadj 1.74, 95% CI 1.07-2.84; P=0.002) at 1 year, as compared to those in the lowest quartile (Table 1). In patients without CKD, MACE and all-cause death incidences were numerically higher in the 4th quartile but risk estimates were no longer statistically significant after adjustment. The overall incidence of CA-AKI was much greater in the CKD group. When compared to the lowest quartile, patients in the 4th NLR quartile showed a trend for higher risk of CA-AKI in CKD group, while they had a significant increased risk in non-CKD group (Figure 1). Conclusions Elevated NLR is strongly associated with higher risk of MACE and all-cause mortality in CKD patients. Conversely, the risk of bleeding and CA-AKI is increased with elevated NLR in both CKD and non-CKD patients. Thus, NLR may further inform risk stratification of CKD patients undergoing PCI.

Neutrophil count predicts the complete response after transarterial chemoembolization related to favorable outcome in hepatocellular carcinoma.

Systemic inflammatory markers have emerged as novel prognostic biomarkers associated with prognosis for tumors. This study aims to investigate the predictive value of systemic inflammatory markers for complete response (CR) in patients with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE). This retrospective study enrolled 575 HCC patients undergoing TACE. Survival outcomes were evaluated based on tumor response, and the analysis was conducted using a Kaplan-Meier curve. Predictive factors for achieving a CR after the initial TACE were analyzed by univariate and multivariate analyses in a Cox regression model. After the initial TACE, 246 of 575 (42.8%) patients achieved a CR. During a median of 60 months follow-up, the CR group had better overall survival than non-CR group (median: 82.3 vs. 51.6 months, P < 0.001). Pre-TACE neutrophil count was associated with tumor response (P = 0.06). Multivariate analysis showed that hepatitis B virus infection [hazard ratio (HR) = 0.585, 95% confidence interval (CI) = 0.360-0.952, P = 0.031] and pre-TACE neutrophil count (HR = 2.854, 95% CI = 1.115-7.307, P = 0.029) were independent predictive factors for CR after the initial TACE. Additionally, a high pre-TACE neutrophil count was associated with male gender (P < 0.001), large tumor size (P < 0.001), advanced Barcelona Clinic Liver Cancer stage (P = 0.003), and high protein induced by vitamin K absence or antagonist-II level (P < 0.001). Patients who achieved CR after the initial TACE showed a favorable prognosis. Pre-TACE neutrophil count was found to be an independent predictor of CR. These findings offer valuable insights for identifying patients who would derive the greatest benefit from TACE and for distinguishing those who may require alternative treatment approaches for HCC.

Neutrophil-platelet ratio as a predictor of acute kidney injury in severe COVID-19.

Acute kidney injury (AKI) is one of the most seen complications of coronavirus-2019 (COVID-19) infection. Patients with AKI caused by COVID-19 likely have higher neutrophil counts and lower platelet and lymphocyte levels. Therefore, the predictive value of many inflammation indexes calculated from the total blood count has been investigated to predict the AKI in COVID-19. According to our clinical experience, we thought that neutrophilia and thrombocytopenia may be more common in the development of AKI. For this reason, this study aimed to evaluate the predictive value of the neutrophil-to-platelet ratio (NPR) for AKI in severe COVID-19 patients. This retrospective study included 334 severe COVID-19 patients followed up in the intensive care unit (ICU). Predictive factors for AKI were analyzed. ROC curve analysis was performed to determine the inflammation indexes' cutoff values for the AKI prediction. Multivariate analyses were performed to determine correlations between the inflammation indexes and AKI. In this study, AKI was determined at the rate of 43% (n:145). Independent risk factors affecting AKI were determined to be age (HR = 1.047, 95% confidence interval [CI]: 1.021-1.072, P < .001), the need for invasive mechanical ventilation (HR = 3.003, 95% CI: 1.645-5.481, P = .001) and the need for vasopressor (HR = 8.111, 95% CI: 3.786-17.375, P < .001). The optimal cutoff values predicting AKI were determined to be 3.9 for the NPR (AUC = 0.679, 95% CI: 0.622-0.737, P < .001) with 71.7% sensitivity and 61.9% specificity, 16.1 for the neutrophil-to-lymphocyte ratio (NLR) (AUC = 0.634, 95% CI: 0.575-0.694, P < .001) with 65.5% sensitivity and 56.1% specificity, and 3872.5 × 109L for the systemic inflammatory index (SII) (AUC = 0.566, 95% CI: 0.504-0.629, P = .038) with 60% sensitivity and 55.6% specificity. In the regression model, only NPR values above the cutoff were related to AKI (HR = 3.817, 95% CI: 1.782-8.177, P = .001). The NPR has more predictive value than the NLPR, NLR, and SII in developing AKI in severe COVID-19 patients in the ICU. NPR is a new helpful index that can help clinicians predict early AKI in critical COVID-19.

Investigation of Biochemical and Inflammatory Markers in COVID-19 Patients Hospitalized in the Intensive Care Unit: An Observational Study in Northern Iran

Background: Since the first documentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there has been a notable emphasis on it in a brief period, especially as the mortality rate and confirmed cases steadily rise. The rapid and accurate laboratory identification of an ongoing COVID-19 infection is essential for efficient pandemic control. For diagnostic purposes, various testing methods have been developed to detect the severity of COVID-19. These diagnostic methods play a crucial role in identifying and managing the spread of the virus within communities worldwide. Methods: This cross-sectional observational study was conducted from February to June 2020, spanning four months. Patient clinical records and laboratory biomarkers data were collected. Results: In this study, 263 patients were involved, with an average age of 59.38 ± 15.26 years, and 51.3% of them (135 patients) were male. The typical hospital stay was 9.25 ± 6.9 days. The patients were divided into three groups: Those who survived (49.4%), those receiving treatment (4.9%), and those who did not survive (45.6%), with all treated patients surviving. An important connection was observed between serum lactate dehydrogenase (LDH), creatine phosphokinase (CPK), urea, leukocytosis, lymphopenia, high polymorphonuclear neutrophil (PMN) counts, and poor patient outcomes (P-value &lt; 0.05). Elevated aspartate transaminase (AST) levels also showed a close relationship with adverse outcomes (P-value = 0.05). Furthermore, most patients with hyponatremia, high fasting blood glucose, and elevated serum creatinine levels did not survive, despite lacking statistical significance. Conclusions: Serum biomarkers serve as prognostic indicators for the severity of COVID-19 patients. Leveraging these markers aids in promptly diagnosing patients at high mortality risk and facilitates more effective treatments in the disease's initial phases. These biomarkers can help healthcare providers identify patients at higher risk of complications and guide the implementation of targeted interventions to improve patient outcomes.

Correlation and predictive value analysis of iliac artery calcification score and restenosis of lower extremity arteries after drug-coated balloon combined with stent implantation in patients with lower extremity atherosclerotic occlusive disease

Objective: To analyze the correlation between iliac artery calcification score and restenosis of lower extremity arteries in patients with lower extremity atherosclerotic occlusive disease (LEASO) who underwent drug-coated balloon (DCB) combined with stenting, and to assess the predictive value. Methods: A total of 105 patients with LEASO at Nanjing Drum Tower Hospital, Nanjing University Medicine School, from January 2018 to June 2023 were retrospectively included, and the patients were divided into 2 groups according to whether restenosis of the original lower limb arteries had occurred during follow-up after DCB combined stent implantation: the restenosis group (n=64) and the patency group (n=41). The clinical information of the study subjects was collected through the electronic case system, and all patients underwent CTA examination of both lower limb arteries before the operation, and the calcification scores of common iliac arteries and external iliac arteries of patients' bilateral and stenotic sides were calculated according to the results of the CTA examination. The follow-up time [M (Q1, Q3)] was 9.15 (5.67, 15.60) months in the patency group and 9.20 (6.85, 19.65) months in the restenosis group. Univariate and multivariate logistic regression models were used to analyze the factors associated with restenosis after DCB combined with stent implantation in LEASO patients. The predictive value of iliac artery calcification score for postoperative restenosis was assessed using the receiver operating characteristic (ROC) curves. Results: There were 44 males and 20 females in the restenosis group, aged (73±9) years; 31 males and 10 females in the patency group, aged (73±10) years. Compared with the patency group, the restenosis group had higher neutrophil counts, platelet counts, lymphocyte counts, neutrophil-to-lymphocyte ratios (NLR), platelet-to-lymphocyte ratios (PLR), C-reactive protein, fibrinogen, stent lengths, stent numbers, common iliac artery calcification scores (bilateral and stenotic side), and external iliac artery calcification scores (bilateral and stenotic side) (all P<0.05). Multifactorial logistic regression analysis showed that higher external iliac artery calcification score on the stenotic side (OR=1.480, 95%CI: 1.130-1.939, P=0.004) was an associated factor for restenosis of the lower extremity arteries after DCB combined with stenting.ROC curve analysis showed that the cut-off value of the external iliac artery calcification score on the stenotic side was 5.5 score, the area under the curve (AUC) for predicting restenosis of lower extremity arteries after DCB combined stent implantation in LEASO patients was 0.818 (95%CI: 0.731-0.904, P<0.001), with a sensitivity of 85.4% and a specificity of 68.8%. Conclusions: An elevated calcification score of the external iliac artery on the stenotic side is a correlate of restenosis of the lower extremity arteries after DCB combined stenting in patients with LEASO. With a cut-off value of 5.5 points, its sensitivity for predicting restenosis of the lower extremity arteries after DCB combined stenting is 85.4%, and its specificity is 68.8%.

Clinical characteristics of SARS-CoV-2 Omicron pneumonia in immunocompromised and immunocompetent patients: A retrospective cohort study

ObjectivePrevious studies evaluating the differences in COVID-19 mortality rates between immunocompromised patients and other patient groups have shown conflicting findings. This research aimed to compare the mortality rates of immunocompromised and immunocompetent patients during the Omicron-dominant period of the SARS-CoV-2 pandemic, and to identify factors associated with prognosis. MethodsWe conducted a retrospective analysis of 1085 adult patients (aged ≥18 years) admitted with COVID-19 pneumonia to the China-Japan Friendship Hospital between December 1, 2022, and January 31, 2023. We assessed the prevalence of comorbidities, incidence of co-infections and nosocomial infections, and 30-day mortality. ResultsAmong the 1085 patients, 254 were immunocompromised, and 831 were immunocompetent. Immunocompromised patients had higher rates of non-invasive ventilation use (30.3 % vs. 21.1 %), invasive ventilation (12.2 % vs. 5.3 %), and 30-day mortality (19.7 % vs. 13.7 %) compared to immunocompetent patients. However, overall mortality rates did not significantly differ based on immunocompromised status. Cox regression analysis identified that elevated troponin T (≥0.15 ng/mL), respiratory failure, high lactate dehydrogenase (≥272.5 U/L), elevated D-dimer (≥1.295 mg/L), increased C-reactive protein (≥90 mg/L), elevated interleukin-6 (>11.67 ng/L), high peripheral blood neutrophil count (>9.84 × 10⁹/L), and immunocompromised status were independent predictors of poor COVID-19 prognosis. In the immunocompetent group, current smoking and a history of interstitial lung disease were related to a worse prognosis. ConclusionsCOVID-19 pneumonia due to the Omicron variant may lead to worse outcomes in immunocompromised patients. In immunocompetent patients, careful monitoring is essential for those with respiratory failure, smoking history, or interstitial lung disease to prevent adverse outcomes.

Neutrophil count as a risk factor for cardiovascular diseases: how can we manage it?

Neutrophils activation plays a pivotal role in the pathogenesis of atherosclerotic plaque formation, progression and rupture. An association between the leukocyte count and the risk of developing myocardial infarction has been well known for many years; however, only recently did Mendelian randomization studies show that a high neutrophil count is a causal risk factor for atherosclerotic cardiovascular disease. On the other hand, experimental studies show that depletion of circulating neutrophils impairs plaque development. Clopidogrel, an antiplatelet agent, is widely used in combination with aspirin to reduce the incidence of ischemic events in patients treated with coronary stenting. Chronic treatment with this drug reduces inflammatory markers and neutrophil numbers, rarely causing severe leukopenia. The purpose of this review is to present recent evidence showing the link between neutrophil number and the development of cardiovascular diseases and to discuss how the clopidogrel-induced reduction in the neutrophil count may be a beneficial off-target effect of this drug.

Immune Cell Profiles of Patients with Sickle Cell Disease during Parvovirus B19-Induced Transient Red Cell Aplasia.

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24- cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

Low concentration of serum vitamin B12 may be a strong predictor of large-artery atherosclerosis stroke: A case-control study

IntroductionIdentifying controllable risk factors for large-artery atherosclerosis (LAA) stroke is crucial due to its significant role as a leading cause of ischemic stroke. We aimed to validate the correlation of serum vitamin B12 with LAA stroke. MethodsInpatients with LAA stroke and healthy controls were retrospectively collected for a case-control study from January 2020 to May 2022. Serum vitamin B12 concentration and other blood indicators, demographic, lifestyle factors and comorbidities were investigated. Logistic regression analysis was used to identify the correlation of serum vitamin B12 concentrations with LAA stroke, meanwhile adjusted for confounding factors. ResultsPatients with LAA stroke had significantly lower serum vitamin B12 concentrations in comparison to those of controls. In the fully adjusted model, vitamin B12 (per 1 interquartile range increase, odds ratio [OR] = 0.84, 95 % confidence interval [CI]: 0.77–0.91), vitamin B12 < 200 pg/mL (OR=7.70, 95 %CI: 2.19–27.03) and vitamin B12 < 300 pg/mL (OR=4.19, 95 %CI: 1.82–9.66) were independently factors for LAA stroke. Furthermore, the optimal cut-off values for vitamin B12 to predict LAA stroke were 305.25 pg/mL (area under the curve [AUC] = 0.71) when unadjusted and 308.25 pg/mL when adjusted for age and sex (AUC=0.68). Lower vitamin B12 concentrations were significantly associated with male sex, smoking, older age, higher neutrophil count, higher creatinine, lower folate and higher total homocysteine. ConclusionResults indicate that low concentration of serum vitamin B12 may be a strong predictor for the risk of LAA stroke.

D-Dimer and procalcitonin in patients with recurrent pericarditis: a prospective study.

Recurrent pericarditis, an inflammatory syndrome with a pathogenesis not fully elucidated, often presents diagnostic challenges. This study aims to assess the correlation of D-Dimer (D-D) and procalcitonin (PCT) levels with clinical, laboratory and imaging features in recurrent idiopathic pericarditis. We analyzed 412 patients with idiopathic recurrent pericarditis from 2019 to 2023 in our referral center. D-D and PCT values were obtained from emergency room in other Italian facilities. Among the cohort, PCT levels were assessed in 50 of 412 patients (12.1%), with only 4 showing marginal elevation. D-D levels were measured in 48 of 412 patients (11.6%), with 33 of them exhibiting elevated values. None of these patients had venous thromboembolism, and elevated D-D levels were significantly associated with pleural effusion, fever, higher CRP, increased white blood cell counts, higher neutrophil counts, reduced relative lymphocyte counts. Multivariate analysis revealed fever as the sole correlate of elevated D-D. PCT elevation was infrequent and unrelated to any variables. In idiopathic recurrent pericarditis unrelated to specific conditions, we observed a close association between elevated D-D levels and non-specific inflammation markers, including fever, increased CRP, and neutrophil leukocytosis. PCT levels were typically normal or mildly elevated.

Higher Circulating Neutrophil Counts Is Associated with Increased Risk of All-Cause Mortality and Cardiovascular Disease in Patients with Diabetic Kidney Disease.

Accumulating evidence has suggested the pathogenic roles of chronic inflammation and neutrophils in diabetic kidney disease (DKD). This study investigated the relationship between neutrophils, all-cause, and cardiovascular disease (CVD) mortality in type 2 diabetes mellitus (T2DM) patients with DKD. We used data from the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2020 to investigate the relationship between circulating neutrophils counts, kidney function indices, all-cause, and CVD mortality in adult T2DM patients with DKD. Clinical predictive models and risk scores for long-term mortality were constructed. 44,332 patients [8034 with T2DM and 36,323 without T2DM] were included. Two thousand two hundred twenty patients had DKD, and 775 died (31.5% related to CVD) during a follow-up of 6.18 (range: 5.94-6.42) years. Higher neutrophil counts (Quartile 4, Q4) were associated with increased all-cause and CVD mortality [HR 1.73 (95% CI 1.34-2.25) and 1.81 (95% CI 1.14-2.89), respectively, p < 0.0001 and 0.01]. Neutrophil counts in Q4 showed a positive correlation with urine albumin-creatinine ratio (UACR) but a negative association with eGFR (p < 0.01 for all). Clinical predictive models incorporating neutrophil counts showed satisfactory performance in forecasting 5-year and 10-year CVD mortality-free survival (ROC AUC 0.824 and 0.842, respectively), and the nomogram-predicted survival demonstrated good concordance with observed survival. Higher levels of circulating neutrophil counts show a significant correlation with renal abnormalities and higher all-cause and CVD mortality in T2DM patients with DKD. The novel clinical predictive models and risk scores incorporating neutrophil counts may facilitate stratification and, hence, risk factor management in DKD patients.

Multi-omics landscapes reveal heterogeneity in long COVID patients characterized with enhanced neutrophil activity

BackgroundOmicron variant impacts populations with its rapid contagiousness, and part of patients suffered from persistent symptoms termed as long COVID. The molecular and immune mechanisms of this currently dominant global variant leading to long COVID remain unclear, due to long COVID heterogeneity across populations.MethodsWe recruited 66 participants in total, 22 out of 66 were healthy control without COVID-19 infection history, and 22 complaining about long COVID symptoms 6 months after first infection of Omicron, referred as long COVID (LC) Group. The left ones were defined as non-long COVID (NLC) Group. We profiled them via plasma neutralizing antibody titer, SARS-CoV-2 viral load, transcriptomic and proteomics screening, and machine learning.ResultsNo serum residual SARS-CoV-2 was observed in the participants 6 months post COVID-19 infection. No significant difference in neutralizing antibody titers was found between the long COVID (LC) Group and the non-long COVID (NLC) Group. Transcriptomic and proteomic profiling allow the stratification of long COVID into neutrophil function upregulated (NU-LC) and downregulated types (ND-LC). The NU-LC, identifiable through a refined set of 5 blood gene markers (ABCA13, CEACAM6, CRISP3, CTSG and BPI), displays evidence of relatively higher neutrophil counts and function of degranulation than the ND-LC at 6 months after infection, while recovered at 12 months post COVID-19.ConclusionThe transcriptomic and proteomic profiling revealed heterogeneity among long COVID patients. We discovered a subgroup of long COVID population characterized by neutrophil activation, which might associate with the development of psychiatric symptoms and indicate a higher inflammatory state. Meanwhile, a cluster of 5 genes was manually curated as the most potent discriminators of NU-LC from long COVID population. This study can serve as a foundational exploration of the heterogeneity in the pathogenesis of long COVID and assist in therapeutic targeting and detailed epidemiological investigation of long COVID.

Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma

BackgroundUnderlying immunological mechanisms in children with moderate-to-severe asthma are complex and unclear. We aimed to investigate the association between blood inflammatory parameters and asthma burden in children with moderate-to-severe asthma.MethodsBlood inflammatory parameters (eosinophil(E) and neutrophil(N) counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6–17 years) with moderate-to-severe asthma from SysPharmPediA cohort across four European countries. Based upon low(L)/high(H) blood(B) eosinophil (LBE/HBE: &lt;/≥0.3×109/L, respectively) and neutrophil counts (LBN/HBN: &lt;/≥4×109/L, respectively), mixed(HBE-HBN), eosinophilic(HBE-LBN), neutrophilic(LBE-HBN), and paucigranulocytic(LBE-LBN) phenotypes were defined. Inflammatory mediator profiles and burden of disease (asthma control status, exacerbations and school days missed in the past year) were compared between phenotypes using adjusted logistic regression models.ResultsAmong 126 included children (41% girls and mean(sd) age of 11.94(2.76)), 22%, 44%, 11%, and 23% were classified as mixed, eosinophilic, neutrophilic, and paucigranulocytic phenotypes respectively. Neutrophilic children had lowest lung function (FEV1%predicted pre-salbutamol) compared to other groups. Children with mixed asthma were most often uncontrolled and had highest asthma-related school absence in the past year. Interleukin-6(IL-6) and matrix metalloproteinase-9(MMP-9) levels were significantly higher in patients with mixed or neutrophilic asthma, while tissue inhibitor of metalloproteinase-2(TIMP-2) was lower in patients with neutrophilic asthma compared to eosinophilic or paucigranulocytic asthma. Interleukin-5(IL-5) was increased in eosinophilic group compared to neutrophilic and paucigranulocytic groups, irrespective of the chosen cut-off for eosinophilia.ConclusionDifferences in asthma burden-related clinical expression and distinct blood inflammatory mediator profiles were found between phenotypes, highlighting implications for optimizing personalized treatment and management strategies in children with moderate-to-severe asthma.

Avatrombopag as alternative therapy for severe aplastic anemia patients who are intolerant or unresponsive to eltrombopag.

Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, EPAG contains a typical biphenyl structure, which causes liver function damage. Twenty patients with SAA who were intolerant or refractory to EPAG were enrolled in a multicenter prospective registry of the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) from October 2020 to June 2023. Eight patients who were ineffective to EPAG, six with kidney impairment, and nine with abnormal liver function (two with concomitant liver and kidney impairment) were converted to avatrombopag (AVA) therapy with the median duration of AVA treatment was 6 (3-24) months. 17 cases (85%) achieved trilineage hematological response (HR): complete remission (CR) in 3 cases (15%), good partial remission (GPR) in 4 cases (20%), partial remission (PR) in 10 cases (50%), and no response (NR) in 3 cases (15%). The median time to response was 1.7 (0.5-6.9) months, with 16 cases (94%) achieving response within six months and 17 cases (100%) within 12 months. 9 cases (50%) achieved transfusion independence. AVA converted treatment was associated with higher neutrophil counts (0.8×109/L vs 2.2×109/L, p=0.0003), platelet counts (11×109/L vs 39×109/L, p=0.0008), hemoglobin count (59g/L vs 98g/L, p=0.0002), red cell count (1.06×1012/L vs 2.97×1012/L, p=0.001), and absolute reticulocyte count (31.99 ×109/L vs 67.05×109/L p=0.0004) were all significantly elevated compared with the pre-treatment level. After the conversion to AVA therapy, liver and kidney function indexes were maintained within the normal range, no AVA related grade 2 or higher adverse events occurred, and no thrombotic events occurred. The conversion to AVA was an optimal choice for patients with SAA who were EPAG intolerant or refractory. http://www.chictr.org.cn/showproj.html?proj=125480, identifier ChiCTR2100045895.

Hereditary chronic neutrophilic leukemia in a four-generation family without transformation to acute leukemia.

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) characterized by peripheral blood neutrophilia, marrow granulocyte hyperplasia, hepatosplenomegaly, and driver mutations in the colony-stimulating factor 3 receptor (CSF3R). Designation of activating CSF3R mutations as a defining genomic abnormality for CNL has led to increased recognition of the disease. However, the natural history of CNL remains poorly understood with most patients reported being of older age, lacking germline data, and having poor survival, in part due to transformation to acute leukemia. CSF3R driver mutations in most patients with CNL have been reported to be acquired, although rare cases of germline mutations have been described. Here, we report the largest pedigree to date with familial CNL, spanning four generations with affected family members ranging in age from 4 to 53 years, none of whom have transformed to acute leukemia. A heterozygous T618I CSF3R mutation was identified in peripheral blood and mesenchymal stromal cells from the proband and in all affected living family members, while the unaffected family members tested were homozygous wild type. We show that the T618I mutation also confers a survival advantage to neutrophils in an MCL1-dependent manner. Collectively, these data provide additional insights into the natural history of familial CNL arising from T618I CSF3R mutations and suggest that enhanced neutrophil survival also contributes to the high neutrophil count observed in patients with CNL.

Long-term cardiovascular inflammation and fibrosis in a murine model of vasculitis induced by Lactobacillus casei cell wall extract.

Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD. We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram. CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages. Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection.

Lab results of COVID-19 patients: Omicron vs delta variants

BACKGROUND The coronavirus disease 2019 (COVID-19) virus has been a world-known pandemic since February 2020. Multiple variances had been established; the most common variants in Israel were omicron and delta. AIM To analyze and compare laboratory values in the "omicron" and "delta" variants of the coronavirus by conducting follow-up examinations and laboratory audits on COVID-19 patients admitted to our institution. METHODS A retrospective study, two groups, 50 patients in each group. Patients examined positive for COVID-19 were divided into groups according to the common variant at the given time. We reviewed demographic data and laboratory results such as complete blood count and full chemistry, including electrolytes and coagulation parameters. RESULTS The mean age was 52%, 66.53 ± 21.7 were female. No significance was found comparing laboratory results in the following disciplines: Blood count, hemoglobin, and lymphocytes (P = 0.41, P = 0.87, P = 0.97). Omicron and delta variants have higher neutrophil counts, though they are not significantly different (P = 0.38). Coagulation tests: Activated paritial thromoplastin test and international normalized ratio (P = 0.72, P = 0.68). We found no significance of abnormality for all electrolytes. CONCLUSION The study compares laboratory results of blood tests between two variants of the COVID-19 virus – omicron and delta. We found no significance between the variants. Our results show the need for further research with larger data as well as the need to compare all COVID-19 variants.

A Higher Neutrophil Count Is Associated with Favorable Achievement of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia Who Received Second Generation Tyrosine Kinase Inhibitor as Frontline Treatment.

ABL1 tyrosine kinase inhibitor discontinuation securely became among the therapeutic goal for chronic myeloid leukemia chronic phase patients (CML-CP). To establish successful prognostic factors for treatment-free remission (TFR), it is necessary to diagnose the patients with high-risk molecular relapse, however, a biomarker for the achievement of TFR has not been completely elucidated. Recent investigations have determined that neutrophils function crucially in cancer immunology. The research was a multicenter retrospective observational study to examine the correlation between TFR and neutrophil counts before TKI discontinuation. The investigation included patients having Philadelphia chromosome-positive CML-CP who attempted the discontinuation of TKIs after a durable deep molecular response between January 2012 and July 2021 at four institutions in Japan. 118 CML-CP patients in total discontinued TKIs and an estimated 36-month TFR rate was 65.1%. 52 patients received second-generation TKIs as frontline. Higher neutrophil count (>3210/μL) at TKIs discontinuation was determined as an independent prognostic variable for TFR in patients who received second-generation TKIs as frontline [(HR, 0.235 (95%, confidence interval (CI) 0.078-0.711); p = 0.010]. The neutrophil-mediated immunomodulation can be a significant component for the effective achievement of TFR in CML supported by our clinical observation.

Hypovitaminosis D and Leukocytosis to Predict Cardiovascular Abnormalities in Children with Kawasaki Disease: Insights from a Single-Center Retrospective Observational Cohort Study.

Introduction: An aberrant immune response involving yet unidentified environmental and genetic factors plays a crucial role in triggering Kawasaki disease (KD). Aims: The aim of this study was to assess general and laboratory data at the onset of KD in a single-center cohort of children managed between 2003 and 2023 and retrospectively evaluate any potential relationship with the development of KD-related cardiovascular abnormalities (CVAs). Patients and methods: We took into account a total of 65 consecutive children with KD (42 males, median age: 22 months, age range: 2-88 months) followed at the Department of Life Sciences and Public Health in our University; demographic data, clinical signs, and laboratory variables at disease onset, before IVIG infusion, including C-reactive protein, hemoglobin, white blood cell (WBC) count, neutrophil count, platelet count, aminotransferases, natremia, albumin, total bilirubin, and 25-hydroxyvitamin D were evaluated. Results: Twenty-one children (32.3% of the whole cohort) were found to have echocardiographic evidence of CVAs. Univariate analysis showed that diagnosis of KD at <1 year or >5 years was associated with CVAs (p = 0.001 and p = 0.01, respectively); patients with CVAs had a longer fever duration and mostly presented atypical or incomplete presentations. Interestingly, all patients with CVAs had lower levels of vitamin D (less than 30 mg/dL, p = 0.0001) and both higher WBC and higher neutrophil counts than those without CVAs (p = 0.0001 and p = 0.01, respectively). Moreover, blood levels of albumin were significantly lower in KD patients with CVAs compared to those without (11/21, 52% versus 13/44, 30%, p = 0.02). Multiple logistic regression with correction for sex showed that serum vitamin D < 30 ng/mL, WBC count > 20.000/mm3, and age > 60 months at KD onset were the only independent factors statistically associated with CVAs. Conclusions: Hypovitaminosis D, WBC count over 20.000/mm3, and age above 5 years at KD onset emerged as independent factors statistically associated with the occurrence of CVAs.