Neutrophil Count Research Articles

Reevaluation of prognostic and severity indicators for COVID-19 patients in the emergency department.

This study aimed to re-evaluate whether the scoring systems, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were effective in predicting prognosis and severity of COVID-19 patients in the emergency department (ED). COVID-19 patients enrolled in this retrospective study divided into the death (DEA) and survival (SUR) groups, the severe/critical (SC) and non-severe/critical (non-SC) groups. The Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), National Early Warning Score (NEWS) and CCEDRRN COVID-19 Mortality Score were calculated. The neutrophil, lymphocyte and platelet counts were extracted from the first routine blood examination, and NLR and PLR were calculated accordingly. Receiver Operating Characteristic (ROC) curve and logistic regression were performed. All the scoring systems, as well as NLR and PLR, significantly increased in both the DEA and SC groups. The ROC curve showed that the CCEDRRN COVID-19 Mortality Score had the highest predictive value for mortality and severity (AUC 0.779, 0.850, respectively), which outperformed the APACHE II, SOFA and NEWS. NLR presented better predictive ability for severity (AUC 0.741) than death (AUC 0.702). The APACHE II, NEWS and CCEDRRN COVID-19 Mortality Score were positively correlated with both prognosis and severity, whereas NLR only with severity. The NEWS and CCEDRRN COVID-19 Mortality Score were reconfirmed for early and rapid predicting the poor prognosis and severity of COVID-19 patients in ED, especially the CCEDRRN COVID-19 Mortality Score with the highest discrimination capacity, and NLR was more appropriate for predicting the severity.

Blood neutrophils, oligoclonal bands and bridging corticosteroids as predictive factors for MOGAD course: Insights from a multicentric Portuguese cohort

BackgroundMyelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a heterogeneous entity with either a monophasic or relapsing course. Well-established predictors of relapsing disease are lacking. ObjectiveIdentifying predictors of relapsing MOGAD, particularly at disease onset. MethodsA multicentre observational retrospective study was conducted to characterise a cohort of Portuguese adult MOGAD patients. Patients were identified from participating centre databases. Clinical and demographic data were collected from medical records. Bivariate analysis was conducted to compare patients with relapsing and monophasic MOGAD. Significant variables were included in a stepwise multiple regression analysis to identify independent predictors of relapse. ResultsEighty-seven MOGAD patients from 8 public hospitals were included. Relapsing MOGAD was found in 35.6% (n=31). Mean diagnostic delay was 3.2 (±6.2) years and time to relapse was 4.4 (±6.4) years. Multiple logistic regression showed that higher neutrophil count (p<0.01), presence of oligoclonal bands (p=0.025) and no bridging corticosteroids (p=0.038) at first attack were predictive of relapsing MOGAD. ConclusionNeutrophil count and oligoclonal bands at first attack may facilitate early decision-making regarding maintenance immunotherapy. Bridging corticosteroids may also influence the course of MOGAD. Further studies with prospective design are warranted.

Clinical and Genetic Markers of Vascular Toxicity in Glioblastoma Patients: Insights from NRG Oncology RTOG-0825.

Glioblastoma (GBM) is an aggressive form of brain cancer in which treatment is associated with toxicities that can result in therapy discontinuation or death. This analysis investigated clinical and genetic markers of vascular toxicities in GBM patients during active treatment. 591 Non-Hispanic White GBM patients with clinical data were included in the analysis from NRG RTOG-0825. Genome-wide association studies (GWAS) were performed from genotyped blood samples (N=367) by occurrence of thrombosis or hypertension (grade ≥2). A clinical prediction model was produced for each vascular toxicity. Significant GWAS variants were then added to the clinical model as a single nucleotide polymorphism (SNP) -dose effect variable to produce the final genetic models. Thrombosis and hypertension were experienced by 62 (11%) and 59 (10%) patients, respectively. Patients who experienced hypertension displayed improved survival over those without hypertension (median overall survival: 25.72 vs 15.47 months, p=0.002). The genetic model of thrombosis included corticosteroid use (OR: 7.13, p=0.02), absolute neutrophil count (OR: 1.008, p=0.19), body surface area (OR: 18.87, p=0.0008), and the SNP-dose effect (3 variants; OR: 3.79, p<.0001). The genetic model of hypertension included bevacizumab use (OR: 0.97, p=0.95) and the SNP-dose effect (6 variants; OR: 4.44, p<.0001). In this study, germline variants were superior in predicting hypertension than clinical variables alone. Additionally, corticosteroid use was a considerable risk factor for thrombosis. Future investigations should confirm the hazard of corticosteroid use on thrombosis and the impact of bevacizumab in other malignancies after accounting for the genetic risk of hypertension.

Effects of Topical Polymyxin Neomycin Hydrocortison in Patients with Non-Allergic Rhinitis, a Randomized Clinical Trial

Background: Bacterial infection is involved in the pathogenesis of inflammatory non-allergic rhinitis(NAR), and a broad-spectrum antibiotic should reduce the severity of the disease by eliminating themucosal biofilm. The purpose of this study is to assess the efficacy of a topical mixture of polymyxin,neomycin, and hydrocortisone in patients with NAR. Methods: This double-blind phase 3 randomized clinical trial was conducted on 90 patients with non- allergic rhinitis (NAR) in Mashhad, Iran. The subjects experienced symptoms for more than two weeks, and the pretrial course of topical corticosteroids was ineffective. Patients were randomly assigned to treatment groups receiving polymyxin NH, hydrocortisone, or saline. The drug was administered as nasal drops three times daily for a treatment course of two weeks, and the containers were identical. The primary outcome was nasal obstruction. Results: The pretrial comparison showed no significant difference between groups in terms of clinical findings. However, after the trial, nasal obstruction, as the primary outcome, significantly decreased from 20 subjects (66%) to 7 subjects (23%) in the Polymyxin NH group, along with other secondary outcomes, including palatal itching (56% to 23%), sneezing (76% to 40%), mucosal inflammation (100% to 75%), post-nasal drip (PND) (96% to 63%), and concha swelling (96% to 73%). In the other groups, sneezing was the only significant improvement observed in the saline group. Cytology of nasal discharge showed a reduction in nasal neutrophil counts in the Polymyxin NH group (68±16.7% to 46±27.6%) compared to the hydrocortisone and saline-treated groups. Conclusion: Topical intranasal polymyxin NH is effective in treating patients with non-allergic rhinitis.

The Roles of Vitamin D Levels, Gla-Rich Protein (GRP) and Matrix Gla Protein (MGP), and Inflammatory Markers in Predicting Mortality in Intensive Care Patients: A New Biomarker Link?

Objectives: Identifying reliable biomarkers to predict mortality in critically ill patients is crucial for optimizing management in intensive care units (ICUs). Inflammatory and metabolic markers are increasingly recognized for their prognostic value. This study aims to evaluate the association of various inflammatory and metabolic markers with ICU mortality. Methods: This prospective observational study was conducted from January 2023 to January 2024 in the City Hospital’s ICU. A total of 160 critically ill patients were enrolled. Laboratory parameters, including white blood cell (WBC) count, red cell distribution width (RDW), platelet count, neutrophil count, mean platelet volume (MPV), monocyte count, lymphocyte count, procalcitonin (PCT), C-reactive protein (CRP), calcium (Ca++), and vitamin D levels, were analyzed. Additionally, ratios such as the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory index (SII), and pan-immune-inflammation value (PIV) were calculated. Plasma levels of Gla-rich protein (GRP) and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) were measured using ELISA. Results: The mean age of the patients included in the study was 60.5 ± 15.8 years. Cardiovascular disease was present in 72 patients (45%), respiratory system disease in 58 (36%), and chronic kidney disease (CKD) in 38 (24%). Additionally, 61 patients (38%) had diabetes, and 68 (42%) had hypertension. Inflammatory markers, including PLR, NLR, and PIV, were all significantly higher in non-survivors, while calcium and vitamin D levels were lower (p &lt; 0.05). Higher WBC, RDW, neutrophil count, PLR, NLR, PIV, CRP, procalcitonin, GRP, and dp-ucMGP levels were positively correlated with longer hospital stays and increased mortality. In contrast, platelet and lymphocyte counts were negatively correlated with both outcomes (p &lt; 0.05). Vitamin D levels showed an inverse relationship with both hospital stay and mortality, indicating that lower levels were associated with worse outcomes (p &lt; 0.05). In multiple logistic regression analysis, elevated WBC count (OR = 1.20, p = 0.02), RDW (OR = 1.35, p = 0.01), neutrophil count (OR = 1.25, p = 0.01), MPV (OR = 1.20, p = 0.02), PLR (OR = 1.30, p = 0.01), NLR (OR = 1.40, p = 0.001), PIV (OR = 1.50, p = 0.001), CRP (OR = 1.32, p = 0.01), procalcitonin (OR = 1.45, p = 0.001), GRP (OR = 1.40, p = 0.001), and dp-ucMGP (OR = 1.30, p = 0.001) levels were significantly associated with increased mortality. Conclusions: Inflammatory and metabolic markers, particularly NLR, PLR, PIV, GRP, and dp-ucMGP, are strong predictors of mortality in ICU patients. These markers provide valuable insights for risk stratification and early identification of high-risk patients, potentially guiding more targeted interventions to improve outcomes.

Neutrophil-Lymphocyte Ratio as Predictor of Prognosis In Patient with Heart Failure with Reduced Ejection Fraction that Treated With Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Neprilysin Inhibitor: A Prospective Cohort Study in Aceh,

Introduction: Heart failure (HF) and inflammation are related. Angiotensin Converting Enzyme Inhibitors (ACE-I) and Angiotensin Receptor Neprilysin Inhibitors (ARNI) can reduce inflammation by lowering neutrophil counts. The neutrophil-lymphocyte ratio (NLR) is a simple marker of inflammation. There is a lack of studies showing that NLR can predict prognosis in patients with HFrEF, and further investigation is needed.Objectives: Investigating whether NLR could be a prognostic indicator for mortality and rehospitalization in patients with heart failure and reduced ejection fraction receiving treatment with ACE-I or ARNI.Methods: A prospective observational cohort study with double-blind methods was conducted at Zainal Abidin General Hospital, Banda Aceh, Indonesia. Two groups, ACE-I and ARNI, each comprised 40 participants. Initially, blood sampling was performed to determine NLR. Participants were observed weekly for three months for prognosis outcomes (death and rehospitalization). After three months, the remaining participants were invited for re-evaluation of the NLR.Results: This study found that pre-treatment NLR had a hazard ratio (HR) of 1.454 (95% CI: 1.266-1.670, p &lt; 0.001). The risk ratio of abnormal pre-treatment NLR for rehospitalization was 6.56 in the ACE-I group and 8.33 in the ARNI group. Nevertheless, both ACE-I (p = 0.014) and ARNI (p = 0.032) decreased NLR levels.Conclusions: High NLR could be as a predictor of prognosis in patients with heart failure with a decrease in left ventricular ejection fraction that treated with ACE-I or ARNI, also ACE-I and ARNI could reduce NLR levels.

Abstract 4136463: Novel Systemic Inflammatory Biomarkers Can Predict Significant Coronary Disease in High Risk Patients

Background: Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Chronic inflammation is a known risk factor for atherosclerosis, plaque formation, disease progression, and plaque instability. Novel inflammatory biomarkers have been recently linked to excess risk of adverse cardiovascular events, including incident myocardial infarction. Elevated inflammatory biomarkers may help identify patients at higher risk for severe CAD. Aim: This study aimed to evaluate the use of novel systemic inflammatory markers in predicting the pretest probability of severe CAD in patients referred to diagnostic coronary angiography in a single tertiary care center. Methods: This was a prospective observational cohort study enrolling consecutive patients referred to diagnostic coronary angiography in a tertiary care center. Preprocedural laboratory results were obtained from medical charts, including complete blood counts with differentials. Three novel systemic inflammatory markers were computed using existing mathematical formulas: systemic immune-inflammation index (SII = neutrophil count*platelet/lymphocyte); systemic inflammation response index (SIRI = neutrophil*monocyte/lymphocyte); and systemic immune inflammatory response index (SIIRI = neutrophil*monocyte*platelet/lymphocyte). The primary study outcome was severe CAD defined as the presence of ≥70% stenosis in one of three main coronary arteries requiring percutaneous coronary intervention). The outcome was adjudicated by an independent reviewers blinded to computations of biomarkers. Result: The sample included 264 patients (age 59.3±10.8, 47% Females). Overall, 84 patients (32%) met the primary study outcomes. In univariate analysis, those with severe CAD had significantly higher SIRI (2.9±0.7 vs. 2.6±0.6, p = 0.001) and SIIRI (8.4±0.8 vs. 8.1±0.7, p = 0.015) compared to their counterparts. In multivariate analysis adjusted for age and sex, only SIRI was an independent predictor of severe CAD. Using SIRI &gt; 20.8 (upper quartile) was associated with nearly three-fold excess risk of severe CAD (OR = 2.72, 95% CI 1.45-5.09). Conclusion: Elevated SIRI, a marker of ongoing systemic inflammatory response, could be indicative of severe CAD. As an inexpensive biomarker based exclusively on complete blood count, SIRI can be used to prioritize patients referred for diagnostic angiography and potentially expedite treatments in those at higher risk for coronary events.

Abstract 4125093: Association of Systemic Inflammatory Index and Systemic Inflammatory Response Index with Major Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome Who Had Primary Percutaneous Coronary Intervention

Introduction: Inflammation plays an important role in the pathogenesis of coronary artery disease and Acute Coronary Syndrome (ACS). Inflammatory indicators such as neutrophil count and monocyte count potentially may predict patients’ outcomes and prognosis in ACS. White blood cells count is an affordable and accessible way to assess the systemic immune response. Considering their multidirectional effect on atherosclerosis, new inflammatory biomarkers integrating various leukocyte subgroups have been proposed to calculate the systemic inflammatory response index (SIRI) and systemic inflammatory index (SII). Aim: The aim of this study was to assess the association between the systemic inflammatory response index (SIRI) and Systemic inflammatory index (SII) at admission with major adverse cardiovascular events (MACE) 30-days after Primary Percutaneous Coronary Intervention (PPCI) among patients with Acute Coronary Syndrome (ACS) at one referral hospital in Jordan. Method: A Prospective design was used to assess and follow 150 adults presented with ACS and received PPCI at one referral hospital in Jordan. Data was collected from patients and their medical records during hospital stay using a structured data collection form. The MACE was assessed 30-days after PPCI through phone calls with patients and confirmed from medical records. Results: The study included 150 patients with ACS, 82.7% (n= 124) of them were males. The mean age of patients was 57.68 (SD= 11.19) years. Types of ACS include stable angina 5.3% (n=8), unstable angina 24% (n=36), NSTEMI 28.7% (n=43), and STEMI 24% (n=36). All patients had interventional PCI with balloon and stent insertion. The mean of SIRI was 24.45 (SD=25.49) and the mean of SII was 663.30 (SD= 403.75). Rate of MACE as composite outcome 30-days after PPCI as 24.7% (n=37). The most MACE was unplanned repeat revascularization (n=14, 38% of MACE). Significant association between SIRI and SII, and MACE was found SIRI:(Χ 2 (2)&gt; = 12.63, p = 0.001), SII:(Χ 2 (2)&gt; = 4.23, p = 0.03) . Conclusion: The SIRI and SII are inflammatory biomarkers that should be studied as potentially predictors of MACE among patients presented with ACS.

Abstract 4137907: Elevated Plasma Neopterin Levels in Patients with Takotsubo Cardiomyopathy

Background: Takotsubo cardiomyopathy (TC) is characterized by left ventricular apical ballooning and intact coronary arteries. The pathogenesis of this disorder is likely to be catecholamine-mediated myocyte damage, microvascular dysfunction and subsequent oxidative stress; however, a number of possible alternative theories have been suggested. Neopterin is produced by activated macrophages following stimulation by interferon-g produced by T-lymphocytes and is capable of enhancing the oxidative potential of reactive oxygen species. The aim of this study was to compare plasma neopterin levels between TC patients and patients with coronary artery disease. Methods: Plasma neopterin levels were measured on admission in patients with TC (n=37), stable angina pectoris (SAP, n=66), unstable angina pectoris (UAP, n=72) and acute myocardial infarction (AMI, n=67) using HPLC. A frozen myocardium specimen was obtained by biopsy from a patient with TC and stained for neopterin, macrophages, and microvessels using immunohistochemistry. Results: Plasma neopterin levels were significantly higher in TC patients compared with SAP patients ( P &lt;0.0001) or UAP patients ( P &lt;0.05), although they were not significantly different from those in AMI patients. In TC patients, plasma neopterin levels correlated positively with neutrophil count (R=0.47, P&lt;0.05) and serum C-reactive protein levels (R=0.38, P&lt;0.05). Immunohistochemical staining showed abundant neopterin-positive macrophages in the myocardium specimen from the patient with TC. Conclusions: This study demonstrates, for the first time, that plasma neopterin levels are elevated in TC patients compared with those in SAP and UAP patients. These findings suggest that neopterin may play an important role in the pathophysiology of Takotsubo cardiomyopathy.

Abstract 4136280: Inflammation and Cancer Mortality among CVD Individuals: NHANES-Continuous study

Background: Both cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. While previous research showed a relationship between CVD and cancer incidence, limited evidence is available regarding the relationship between inflammation and cancer mortality in CVD patients. Methods: A prospective cohort study using data from the continuous National Health and Nutrition Examination Survey (NHANES) (1999-2016) merged with Medicare and National Death Index (NDI) mortality data until December 31, 2018. We included CVD individuals with no history of cancer at baseline to investigate the relationship between inflammatory markers, including Neutrophil-to-Lymphocyte ratio (NLR), as the main exposure and cancer mortality as the main outcome. Results: We included 4,089 adult individuals representing 127,809,316 individuals (47% females, 72% non-Hispanic Whites, and 5% Hispanics). The risk factor analysis (Table) using the competing risk modeling showed that while inflammatory markers did not show significant associations with cancer mortality in the overall analysis, upon stratification by race/ethnicity, NH-Blacks showed higher cancer mortality with higher WBC count (aHR 5.61, 95% CI 1.66-18.91, p=0.007) and NLR (aHR 2.97, 95% CI 1.19-7.42, p=0.02), but lower cancer mortality with higher neutrophil (aHR 0.08, 95% CI 0.01-0.60, p=0.02) and lymphocyte (aHR 0.34, 95% CI 0.15-0.80, p=0.02) counts. Notably, our NH-Blacks showed lower neutrophils at baseline than others which could be explained by a phenomenon called “Benign Ethnic Neutropenia -BEN-” that still brings more complexity when interpreting NLR. Conclusions: Our study highlights the close relationship between cardiovascular health, inflammation, and cancer mortality. The findings also suggest that race/ethnicity may play a significant role in the relationship between inflammation and cancer mortality among individuals with CVD. Yet, further research is still needed to underpin the biological pathways influencing this relationship.

Abstract 4119517: Association of Systemic Inflammatory Response Syndrome with Cardiovascular Events after Mitral Transcatheter Edge-to-edge Repair

Background: Systemic inflammatory response syndrome (SIRS) following cardiovascular interventions is associated with adverse events during hospitalization and follow-up. Mitral transcatheter edge-to-edge repair (M-TEER) is increasingly utilized for treatment of mitral regurgitation (MR). Hypothesis: It is unknown whether SIRS following M-TEER may occur and be associated with adverse clinical outcomes. Goals: to investigate the frequency and impact of SIRS following M-TEER on major cardiovascular events (MACE) and MR recurrence. Methods: A total of 158 consecutive patients with severe MR undergoing M-TEER were studied. SIRS was defined by leukocytosis (≥12×10 9 /L) and fever (T≥38 °C) within 48 hours after intervention. Baseline inflammation was measured by absolute neutrophil and lymphocyte counts and neutrophil: lymphocyte ratio (NLR). The primary endpoint of MACE was the composite of non-fatal myocardial infarction (MI), non-fatal stroke, and all-cause death. Recurrent MR at follow-up was also recorded. Results: The mean patient age was 80.8±8.8 years. 44 (27.9%) developed SIRS. NLR correlated with onset of leukocytosis and fever (p=0.04). During a median follow-up of 12.5±8.2 months, the primary endpoint occurred in 27 (17.1%) patients (6 MI, 5 strokes and 16 deaths). Patients with SIRS more often had severe MR (79.5% vs. 62.7%, p=0.02) and adverse left ventricular (LV) remodeling indicated by lack of reduction in end-diastolic diameter (LVEDD) at follow-up (p=0.12 for SIRS-patients vs. p=0.0012 for non-SIRS patients). After adjustment for pertinent variables, SIRS (HR 3.24, CI 1.13-9.31, p=0.03) was independently associated with MACE. Conclusion: SIRS after M-TEER is a strong independent predictor of MACE. Closer follow-up is warranted as patients with SIRS have more severe MR and unfavorable LV remodeling at follow-up.

Case report: A follow-up report of omental packing and drug therapy for canine prostate adenocarcinoma

Canine prostate is susceptible to diseases such as cysts, abscesses, and tumors. A 15-year-old male castrated Chinese rural dog underwent staged treatment. Preliminary diagnosis is based on examination results, including clinical symptoms (tenesmus, dysuria, frequent urination, and hematuria); hematology (elevated neutrophil count); X-rays (swelling of the prostate); ultrasound examination (less uniform echo in the prostate region, no echo effect in parenchyma); biopsy smear of prostate tissue (large number of neutrophils and rod-shaped bacteria). Therefore, the dog was preliminarily diagnosed with a prostate abscess. Antibiotic therapy was used for treatment. Three days later, the symptoms of hematuria and frequent urination did not improve, and the state was poor. The owner was advised to undergo surgical treatment-omental packing. Meanwhile, bacterial culture identification, drug sensitivity test and histopathological examination were performed. Pathological diagnosis was prostate adenocarcinoma. Subsequently, antibiotic therapy with enrofloxacin and antineoplastic maintenance therapy with mitoxantrone were administered. Six months later, the dogs were followed up, and the results showed no disease in the prostate tissue and no metastatic lesions. This is the report describing the use of omental packing for the treatment of prostate adenocarcinoma in dogs. In order to provide an important theoretical basis for the treatment of prostate cancer - omental packing into veterinary routine.

Exploring optimal administration timing of pegylated recombinant human granulocyte colony-stimulating factor for chemotherapy-induced neutropenia in early breast cancer treated with pharmorubicin and endoxan: a prospective randomized controlled clinical trial.

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) is a treatment for preventing febrile neutropenia (FN) in patients with early breast cancer. However, the optimal injection timing of PEG-rhG-CSF after chemotherapy is obscure. The trial was designed to explore the best administration timing of PEG-rhG-CSF when breast cancer patients could benefit most. Patients with early breast cancer were randomly assigned to receive a preventive injection on the 7th or 3rd day following chemotherapy. The experimental group (n = 80) received PEG-rhG-CSF treatment on day 7 after chemotherapy, whereas the control group (n = 80) received it on day 3. The occurrence of grades 3-4 neutropenia and FN in the first cycle was the primary endpoint. The secondary endpoint was the frequency of PEG-rhG-CSF dose reduction. In comparison to the control group, the experimental group exhibited higher white blood cell count (WBC) and absolute neutrophil count (ANC) on the 9th and 13th days following chemotherapy (P < 0.05). Additionally, the incidence of grade 3-4 neutropenia was significantly lower in the experimental group (P = 0.038). Furthermore, a greater proportion of patients in the experimental group met the criteria for reducing the PEG-rhG-CSF dose compared to the control group (69.74% vs. 35.06%, P < 0.001). In comparison with PEG-rhG-CSF injection on day 3 after chemotherapy, the incidence of grade 3-4 myelosuppression is lower, and the safety is more manageable after the injection on day 7. This approach potentially allows for a wider adoption of PEG-rhG-CSF dose reduction, leading to a consequential decrease in overall medical costs for patients. Clinical Trials: NCT04477616. Registered July 16, 2020.

From immune response to mental health: neutrophils in schizophrenia

Schizophrenia is a multifaceted psychiatric disorder with a complex etiology that includes genetic, environmental, and immunological factors. Emerging research has increasingly focused on the role of the immune system, particularly neutrophils, in the pathogenesis of schizophrenia. Neutrophils, the most abundant type of white blood cells, are crucial in the body’s defense mechanisms against infections and in the regulation of inflammation. This review explores the evolving evidence that implicates neutrophils in schizophrenia, highlighting their potential contribution to the disorder’s onset and progression through mechanisms such as neuroinflammation and oxidative stress. Recent studies have demonstrated elevated neutrophil counts and neutrophil-to-lymphocyte ratios (NLR) in individuals with schizophrenia, correlating with the severity of psychotic symptoms and cognitive impairments. Furthermore, genetic and molecular analyses have revealed abnormalities in neutrophil function and immune-related gene expression in schizophrenia patients. These findings suggest that neutrophil dysfunction and the resulting chronic inflammation could play a significant role in the disorder’s pathophysiology, affecting neuronal function and contributing to the clinical manifestations of schizophrenia. Neutrophil-related biomarkers, such as NLR, could aid in the diagnosis and monitoring of disease progression. Additionally, targeting neutrophil activity and associated inflammatory pathways presents a promising avenue for developing new therapeutic interventions. This review underscores the need for further research to elucidate the precise mechanisms by which neutrophils influence schizophrenia and to explore potential treatments that could improve outcomes for patients.

Identifying influencing factors and constructing a prediction model for long COVID-19 in hemodialysis patients.

This study aimed to identify the potential influencing factors and construct a prediction model for long COVID in hemodialysis patients. We retrospectively reviewed 115 patients undergoing hemodialysis in a tertiary hospital between December 2022 and January 2023. Both univariate and multivariate logistic regression models were applied to identify potential influencing factors, and the prediction model was constructed using an ROC curve. Of the 115 included patients, 60 experienced long COVID, with a prevalence of 52.2%. The univariate analysis found that a three-dose COVID-19 vaccination was associated with a reduced risk of long COVID (OR: 0.10; 95%CI: 0.01-0.86; P = 0.036). However, severe COVID (OR: 9.49; 95%CI: 1.14-78.90; P = 0.037), undergoing CT examination (OR: 3.01; 95%CI: 1.34-6.78; P = 0.008), and abnormal neutrophil (OR: 5.95; 95%CI: 1.26-28.19; P = 0.025), and platelet (OR: 2.39; 95%CI: 1.11-5.13; P = 0.025) counts were associated with a higher risk of long COVID. After adjusting for potential confounding factors, undergoing CT examination (OR: 2.60; 95%CI: 1.02-6.64; P = 0.046) and having abnormal neutrophil (OR: 8.16; 95%CI: 1.57-42.38; P = 0.013) and monocyte (OR: 17.77; 95%CI: 1.30-242.29; P = 0.031) counts were associated with a higher risk of long COVID. The prediction model constructed based on these factors showed a relatively better predictive value (AUC: 0.738; 95%CI: 0.648-0.828; P < 0.001). The risk of long COVID-19 in hemodialysis patients was significantly related to undergoing CT examination and having abnormal neutrophil and monocyte counts, and the prediction model constructed using these factors showed a moderate predictive value.

NCMP-29. BRAIN LESIONS IN A TEEN WITH NEWLY DIAGNOSED T-CELL ALL AND SARS-COV-2 INFECTION

Abstract T-cell Lymphoblastic Leukemia (T-cell ALL) accounts for up to 15% of all newly diagnosed cases of acute lymphoblastic leukemia in pediatric patients (0-18 years old). Patients are at risk of opportunistic infections during induction therapy with up to 2% developing blood stream infections when their absolute neutrophil count is above 1,500. We report a case of a 15-year-old female with High-Risk T-cell ALL, CNS1 (negative CNS disease), presenting with three days of headaches, photophobia, and non-neutropenic fever. She completed induction chemotherapy one week earlier with vincristine, daunorubicin, calaspargase and a 28-day course of dexamethasone. On physical exam, she had no focal deficits or changes in sensation or strength. CBC was notable for a white blood cell count: 7500, hemoglobin: 8.6, platelets: 328,000 and ANC (Absolute Neutrophil Count): 4700. The patient was also COVID positive on admission. A contrast enhanced MRI brain demonstrated multiple diffusion restricting and peripherally enhancing lesions, concerning for intracranial abscesses. Neurosurgery performed a burr hole craniotomy and aspirated 5 mL of purulent drainage, the culture of which grew Aspergillus fumigatus complex. The patient was started empirically on Voriconazole, in addition to broad spectrum antibiotic coverage pending culture results, due to excellent CNS penetration and proven superiority to amphotericin-based therapy for invasive aspergillosis. Micafungin was added due to CT chest demonstrating nodular infiltrates, suggesting primary pulmonary aspergillosis with CNS dissemination. The patient improved symptomatically without further sequelae. Patients with COVID-19 on prolonged courses of corticosteroids are at higher risk of developing fungal co-infections regardless of neutrophil count. While pulmonary aspergillosis is the most common location of a COVID-19 aspergillus coinfection, there have been documented reports of intracranial micro-abscesses. Contrast-enhanced brain MRI should be obtained in any patient with a recent history of COVID-19 presenting with new neurological symptoms, especially in a patient with a recent history of corticosteroids.

Association of Systemic Inflammatory Response Syndrome With Cardiovascular Events After Mitral Transcatheter Edge-to-Edge Repair.

Systemic inflammatory response syndrome (SIRS) following cardiovascular interventions is associated with adverse events during hospitalization and follow-up. Mitral transcatheter edge-to-edge repair is increasingly utilized for treatment of mitral regurgitation (MR). We investigated whether SIRS following mitral transcatheter edge-to-edge repair may occur and be associated with adverse clinical outcomes. A total of 158 consecutive patients with severe MR undergoing mitral transcatheter edge-to-edge repair were studied. SIRS was defined by leukocytosis (≥12 × 109/L) and fever (≥38 °C) within 48 hours after intervention. Baseline inflammation was measured by absolute neutrophil and lymphocyte counts and neutrophil-lymphocyte ratio. The primary end point of major cardiovascular events was the composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. Recurrent MR at follow-up was also recorded. The mean patient age was 80.8±8.8 years. Forty-four (27.9%) developed SIRS. Neutrophil-lymphocyte ratio correlated with onset of leukocytosis and fever (P=0.04). During a median follow-up of 12.5 (5.4-17.4) months, the primary end point occurred in 27 (17.1%) patients (6 myocardial infarction, 5 strokes, and 16 deaths). Patients with SIRS more often had severe MR (79.5% versus 62.7%, P=0.02) at follow-up. After adjustment for pertinent variables, SIRS (HR 2.73 [95% CI, 1.08-6.86]; P=0.03) was independently associated with major cardiovascular events. SIRS after mitral transcatheter edge-to-edge repair is a strong independent predictor of major cardiovascular events. Closer follow-up is warranted because patients with SIRS have more severe MR at follow-up.

CXCR4 antagonism ameliorates leukocyte abnormalities in a preclinical model of WHIM syndrome

BackgroundWHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome is an ultra-rare, combined primary immunodeficiency and chronic neutropenic disorder characterized by a range of clinical presentations, including peripheral neutropenia, lymphopenia, and recurrent infections. WHIM syndrome is most often caused by gain-of-function mutations in the gene encoding C-X-C chemokine receptor 4 (CXCR4). As such, inhibition of CXCR4 with XOLREMDI® (mavorixafor), an orally bioavailable CXCR4 antagonist, demonstrated clinically meaningful increases in absolute neutrophil and lymphocyte counts and concomitant reduction in infections in patients with WHIM syndrome, resulting in its recent U.S. Food and Drug Administration approval. The impact of CXCR4 antagonism on other aspects of the pathobiology in WHIM syndrome, such as lymphopoiesis and leukocyte trafficking between primary and secondary lymphoid organs, is less understood.MethodsIn the current study, the effects of CXCR4 antagonism on leukocyte trafficking and distribution in primary and secondary lymphoid organs were investigated in a mouse model of WHIM syndrome carrying the heterozygous Cxcr41013 mutation. Cxcr4+/1013 and Cxcr4 wild-type mice received the orally bioavailable CXCR4 antagonist X4-185. Blood, spleen and bone marrow samples were collected for numeration, flow cytometry, and functional studies.ResultsCxcr4+/1013 mice exhibited profound peripheral blood leukopenia as seen in patients with WHIM syndrome. CXCR4 antagonism corrected circulating leukopenia and mobilized functional neutrophils without disrupting granulopoiesis in the bone marrow of Cxcr4+/1013 mice. Furthermore, Cxcr4+/1013 displayed aberrant splenic T and B-cell counts and frequency. Treatment with X4-185 normalized splenic T-cell abnormalities, correcting the reduced CD8+ T-cell numbers, restoring the CD4/CD8 T-cell ratio, and ameliorating peripheral blood T-cell lymphopenia. In addition, CXCR4 antagonism was able to correct the abnormal frequencies and numbers of splenic marginal zone and follicular B cells in Cxcr4+/1013 mice, and ultimately normalize B-cell lymphopenia in the peripheral circulation.ConclusionsOur study provides comprehensive evidence that oral dosing with a CXCR4 antagonist can effectively correct WHIM-associated neutrophil and lymphocyte abnormalities in a mouse model of WHIM syndrome. These findings extend our understanding of how targeting the dysregulated CXCR4 signaling pathway can ameliorate the pathogenesis of WHIM syndrome.

Exploring the predictive factors in the gastrointestinal involvement of patients with immunoglobulin A vasculitis

Background. Immunoglobulin A vasculitis (IgAV), the most common systemic vasculitis in children, typically presents with gastrointestinal (GI) symptoms in about half of cases. This study aimed to analyze the clinical and laboratory findings of patients with IgAV regarding GI involvement. Methods. We compared the GI involvement data of the patients diagnosed with IgAV. Results. Of the 210 patients (60.5% female and 39.5% male), 101 had GI involvement, with abdominal pain being the predominant symptom (n=98). White blood cell, neutrophil, monocyte, and platelet counts, C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) were significantly elevated in patients with GI involvement (p&lt;0.001, p&lt;0.001, p=0.01, p=0.005, p=0.002, p&lt;0.001, p=0.03, p=0.001, p&lt;0.001, p&lt;0.001, respectively). The cutoff values for SII (&gt;1035.7), SIRI (&gt;1.65), NLR (&gt;2.73), and MLR (&gt;0.28) were determined, yielding respective sensitivities of 46%, 59%, 47%, and 53%, specificities of 83.1%, 69.1%, 81.3%, and 71.9%. Corresponding areas under the curve were 0.658, 0.668, 0.649, and 0.634, respectively (all p&lt;0.001). Conclusion. Although IgAV is a self-limiting disease, GI involvement can lead to serious consequences. Systemic inflammatory indices such as SII and SIRI may be indicative in identifying patients with GI involvement.

CTNI-61. PRELIMINARY RESULTS OF A PHASE I/II TRIAL OF SELINEXOR AND TEMOZOLOMIDE IN RECURRENT GLIOBLASTOMA

Abstract BACKGROUND Selinexor (SEL) is a first-in-class XPO1 inhibitor with potent antitumor activity through the nuclear retention and reactivation of tumor suppressor proteins, reduced translation of oncogenes, and decreased expression of anti-apoptotic proteins. As a single agent, SEL has demonstrated brain penetration and clinically relevant responses in glioblastoma. We seek to enhance the effect and benefit of SEL by priming with temozolomide (TMZ). METHODS Through an NCI Project Team, we developed a multi-institutional phase I/II clinical trial which opened across the NCI Experimental Therapeutics Clinical Trial Network. Eligibility included histologically confirmed 1st recurrent MGMT promoter methylated glioblastoma. We evaluated safety, tolerability, and dose finding with an IQ 3 + 3 design of TMZ 150mg/m2 on days 1-5 of a 28-day cycle plus SEL on days 8 and 15. RESULTS From October 2022 to March 2024, we enrolled 12 patients (n=11 evaluable) into phase I of the study. Patient characteristics included 82% male, median age 62 (range 50-77), 64% white. The median number of cycles administered was 6 (range 1-12). Two dose levels (SEL 60mg and SEL 80mg) were evaluated. No dose-limiting toxicities (DLTs) were observed. The most common treatment related adverse events were nausea (58%), decreased platelet count (50%), fatigue (50%), constipation (42%), vomiting (25%), decreased lymphocyte count (25%), and decreased neutrophil count (25%). Grade 3+ treatment related adverse events included nausea, grade 3 (n=1); decreased lymphocyte count, grades 3-4 (n=2); and anorexia, grade 3 (n=1). Phase I has completed enrollment and the recommended phase II dose will be SEL 80mg. Additional results will be presented. CONCLUSION Results suggest that a sequential dosing regimen of SEL+TMZ is feasible, well-tolerated, and may minimize the cumulative toxicity of SEL. The phase II randomized portion of this trial is enrolling nationwide and will investigate efficacy and candidate molecular signatures of vulnerability (NCI #10505, NCT05432804).