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Background/aims: Necrotizing pancreatitis (NP) presents a more severe clinical trajectory and increased mortality compared to edematous pancreatitis. Prompt identification of NP is vital for patient prognosis. A risk prediction model for NP among Chinese patients has been developed and validated to aid in early detection., Methods: A retrospective analysis was performed on 218 patients with acute pancreatitis (AP) to examine the association of various clinical variables with NP. The least absolute shrinkage and selection operator (LASSO) regression was utilized to refine variables and select predictors. Subsequently, a multivariate logistic regression was employed to construct a predictive nomogram. The model's accuracy was validated using bootstrap resampling (n=500) and its calibration assessed via a calibration curve. The model's clinical utility was evaluated through decision curve analysis., Results: Of the 28 potential predictors analyzed in 218 AP patients, the incidence of NP was 25.2%. LASSO regression identified 14 variables, with procalcitonin, triglyceride, white blood cell count at 48 hours post-admission, calcium at 48 hours post-admission, and hematocrit at 48 hours post-admission emerging as independent risk factors for NP. The resulting nomogram accurately predicted NP risk with an area under the curve of 0.822, sensitivity of 82.8%, and specificity of 76.4%. The bootstrap-validated area under the curve remained at 0.822 (95% confidence interval, 0.737 to 0.892). This model exhibited excellent calibration and demonstrated greater predictive efficacy and clinical utility for NP than APACHE II, Ranson, and BISAP., Conclusions: We have developed a prediction nomogram of NP that is of great value in guiding clinical decision.

Understanding the pig immune function is crucial for disease-resistant breeding and potentially for human health research due to shared immune system features. Immune cell ratios, like monocyte/lymphocyte ratio (MLR) and neutrophil/lymphocyte ratio (NLR), offer a more comprehensive view of immune status compared to individual cell counts. However, research on pig immune cell ratios remains limited. This study investigated MLR and NLR in a Duroc × Erhualian F 2 resource population. Heritability analysis revealed high values (0.649 and 0.688 for MLR and NLR, respectively), suggesting a strong genetic component. Furthermore, we employed an ensemble-like GWAS (E-GWAS) strategy and functional annotation analysis to identify 11 MLR-associated and 6 NLR-associated candidate genes. These genes were significantly enriched in immune-related biological processes. These findings provide novel genetic markers and candidate genes associated with porcine immunity, thereby providing valuable insights for addressing biosecurity and animal welfare concerns in the pig industry.

This study aims to evaluate the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker for cardiovascular mortality among cancer patients, utilizing data from the National Health and Nutrition Examination Survey (NHANES). From the NHANES dataset (2007-2018), we analyzed 4974 cancer survivors, investigating the prognostic significance of NLR for all-cause, cardiovascular, and cancer-specific mortality. Survival outcomes were analyzed using Cox regression and Kaplan-Meier methods. Optimal NLR cutoffs were identified as 2.61 for differentiating the higher NLR group from lower NLR group. Elevated NLR levels significantly correlated with increased all-cause mortality (HR 1.11, 95% CI 1.07-1.14, P < 0.001) and cardiovascular mortality (HR 1.14, 95% CI 1.08-1.21, P < 0.001) in adjusted models. Subgroup analyses revealed that age, sex, smoking status, and hypertension significantly influence NLR's association with cardiovascular mortality. Specific cancers including breast, prostate, non-melanoma skin, colon and melanoma experience increased all-cause and cardiovascular mortality in the higher NLR group compared to lower NLR group. Elevated NLR is a significant predictor of increased mortality in cancer patients, particularly for cardiovascular outcomes. These findings support that NLR acts as a pivotal prognostic tool with significant implications for clinical practice in the realm of cardio-oncology., (© 2024. The Author(s).)

Objective: We conducted this study to summarize the results of studies reporting the role of NLR (neutrophil to lymphocyte ratio) in PSCC (penile squamous cell carcinoma)., Methods: This meta-analysis was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. A systematic search was conducted on PubMed, Scopus, and web of science up to March 10, 2023. Fourteen studies were included in the review. The NOS (Newcastle-Ottawa Scale) was used to determine the quality of the included studies. This meta-analysis was conducted on the studies reporting the relationship between NLR and survival using HR (hazard ratio) and 95% CI (confidence interval)., Results: There was a significant association between NLR levels and the prognosis, nodal stage, and anatomical tumor stage of PSCC patients. In the meta-analysis of the association of NLR with survival, NLR level was significantly associated with lower cancer-specific survival (HR = 3.51, 95% CI = 2.07-5.98, p < 0.001) and lower disease-free survival (HR = 2.88, 95% CI = 1.60-5.20, p < 0.001). However, NLR was found to have no association with the stage, grade, location, and size of the tumor., Conclusion: NLR has a significant diagnostic and prognostic value in PSCC., (© 2024. The Author(s).)

Objective: Previous studies have shown the anti-inflammatory effect of 25-hydroxyvitamin D (25(OH)D) and the crucial roles of high-sensitive C reactive protein (hsCRP) and novel inflammatory markers (red blood cell distribution width-platelet count ratio (RDWPCR), mean platelet volume-platelet count ratio (MPVPCR), neutrophil-lymphocyte ratio (NLR) and white blood cell-neutrophil ratios (WBCNR)) in several diseases, but scarce data explored the associations of 25(OH)D with hsCRP and novel inflammatory markers. This study aimed to investigate these associations in children., Design: Cross-sectional study., Setting: Children in China., Participants: 10141 children (mean age 14.6 months) were included., Primary and Secondary Outcome Measures: HsCRP, red blood cell distribution width, platelet count, mean platelet volume, neutrophil, lymphocyte and white blood cell were measured., Results: Overall, serum 25(OH)D was inversely associated with hsCRP and novel inflammatory biomarkers. In multivariable analysis, serum 25(OH)D was inversely associated with hsCRP and novel inflammatory biomarkers (Q quartile (Q) 4 vs Q1: 1129.75 vs 2090.99 for hsCRP; 4246.94 vs 6829.89 for RDWPCR; 4863.57 vs 5545.66 for MPVPCR; 4345.76 vs 6507.46 for NLR; 2418.84 vs 2868.39 for WBCNR). Similar results also were observed in stratified analyses by sex (boys and girls). Moreover, serum 25(OH)D was inversely associated with elevated inflammation levels. After adjustment for other potential covariates, inverse associations between serum 25(OH)D and elevated inflammation levels were still observed. The corresponding ORs (95% CI) were 0.05 (0.04, 0.06) for hsCRP, 0.13 (0.11, 0.15) for RDWPCR, 0.74 (0.64, 0.85) for MPVPCR, 0.11 (0.09, 0.13) for NLR and 0.57 (0.49, 0.66) for WBCNR in the fourth quartile compared with the first quartile, respectively., Conclusions: Generally, the graded and inverse associations of serum 25(OH)D with hsCRP and four novel inflammatory markers (RDWPCR, MPVPCR, NLR and WBCNR) were observed. The present study provided further support for the anti-inflammatory effects of 25(OH)D., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Decades of research in exercise immunology have demonstrated the profound impact of exercise on the immune response, influencing an individual's disease susceptibility. Accurate prediction of white blood cells (WBCs) count during exercise can help to design effective training programs to maintain optimal the immune system function and prevent its suppression. In this regard, this study aimed to develop an easy-to-use and efficient modelling tool for predicting WBCs count during exercise. To achieve this goal, the predictive power of a range of machine-learning algorithms, including six standalone models (M5 prime (M5P), random forest (RF), alternating model trees (AMT), reduced error pruning tree (REPT), locally weighted learning (LWL), and support vector regression (SVR)) were assessed along with six types of hybrid models trained with a bagging (BA) algorithm (BA-M5P, BA-RF, BA-AMT, BA-REPT, BA-LWL, and BA- SVR). A comprehensive database was constructed from 200 eligible people. The models employed post-exercise training WBCs counts as the output parameter and seven WBCs-influencing factors, including intensity and duration of exercise, pre-exercise training WBCs counts, age, body fat percentage, maximal aerobic capacity, and muscle mass as input parameters. Comparing the prediction results of the models to the observed WBCs using standard statistics indicated that the BA-M5P model had the greatest potential to produce a robust prediction of the number of lymphocytes, neutrophils, monocytes, and WBC compared to other models. Moreover, pre-exercise training WBCs counts, intensity and duration of exercise and body fat percentage were the most important features in predicting WBCs counts. These findings hold significant implications for the advancement of exercise immunology and the promotion of public health., (© 2024. The Author(s).)

Importance: Absolute neutrophil counts (ANCs) are used to determine cancer clinical trial (CCT) eligibility and systemic anticancer therapy (SACT) dose modifications. Duffy null-associated ANC (DANC) is a nonpathologic phenotype associated with lower ANC and most frequently seen in individuals with African and Middle Eastern ancestry. It is unclear whether CCTs exclude or SACT regimens modify doses for individuals with ANC within the DANC reference range., Objective: To investigate CCT exclusions and SACT dose modifications for ANC within the DANC reference range., Design, Setting, and Participants: This cross-sectional study of contemporary CCTs and SACT regimens included adult, interventional, phase 3 CCTs for the 5 most prevalent cancers in the US and United Kingdom (prostate, breast, melanoma, colorectal, and lung cancers) testing SACTs with start dates between November 1, 2021, and November 1, 2023, and that were registered on ClinicalTrials.gov. Preferred curative-intent SACT regimens were listed in National Comprehensive Cancer Network guidelines., Exposure: Cancer clinical trial exclusions and SACT regimen modifications., Main Outcome and Measures: Proportions of CCTs that exclude and SACT regimens that modify doses for individuals with an ANC within the DANC reference range., Results: For CCTs, 289 of 382 trials (75.7%) were eligible, of which 221 (76.5% [95% CI, 71.1%-81.2%]) excluded patients with ANC values within the DANC reference range. Colorectal CCTs had the highest (38 of 44 [86.4% (95% CI, 72.6%-94.8%)]) and prostate CCTs had the lowest (11 of 23 [47.8% (95% CI, 26.8%-69.4%)]) proportions of exclusions. Of CCTs testing cytotoxic chemotherapy, 116 of 142 (81.7% [95% CI, 74.3%-87.7%]) had exclusions; 93 of 123 (75.6% [95% CI, 67.0%-82.9%]) CCTs testing targeted therapies alone and 12 of 24 (50.0% [95% CI, 29.1%-70.9%]) testing hormonal therapies alone had exclusions. Among the 113 US- and UK-based trials, exclusions were present in 89 (78.8% [95% CI, 70.1%-85.9%]). Of 71 SACT regimens, 38 (53.5% [95% CI, 41.3%-65.5%]) included dose modifications for ANC values within the DANC reference range. Lung cancer regimens had the highest (23 of 31 [74.2% (95% CI, 55.4%-88.1%)]) and prostate cancer had the lowest (0 of 12 [0 (95% CI, 0%-26.4%)]) proportions of modifications. Regimens including chemotherapy had modifications in 32 of 44 (72.7% [95% CI, 57.2%-85.0%]); 11 of 20 (55.0% [95% CI, 31.5%-76.9%]) of targeted therapy regimens and 0 of 16 (0% [95% CI, 0%-20.6%]) of hormonal therapy regimens had modifications. Among regimens including chemotherapy and/or targeted therapy, modifications were present in 38 of 55 (69.1% [95% CI, 49.7%-73.2%])., Conclusions and Relevance: In this cross-sectional study, substantial proportions of CCTs excluded and SACT regimens modified doses for patients with ANCs in the DANC reference range. These practices structurally discriminate against patients of African and Middle Eastern ancestry. While determining optimal SACT dose modifications requires further study, CCT exclusion criteria should be revised.

Introduction: Patients with leukaemia are exposed to infections as long as they are neutropenic. During this period, anorectal pathologies are among the common foci of infection with high mortality. In this study, we aim to investigate the factors that may have a predictive effect on early diagnosis and rapid intervention in perianal complications occurring in neutropenic patients diagnosed with leukaemia., Materials and Methods: A total of 90 patients with acute leukaemia, including 45 patients with anorectal pathology and 45 patients without anorectal pathology, were analysed. Demographics, blood group, BMI, haemogram and biochemical parameters at the time of diagnosis, and types of perianal pathology were recorded., Results: In the group of patients with anorectal pathology, WBC, lymphocytes, monocytes, and LDH were significantly (p<0.05) higher, and platelets, MPV, and PCT were significantly (p<0.05) lower. The multivariate model showed significant-independent (p<0.05) efficacy of WBC and MPV values in differentiating patients with and without anorectal pathology. A significant efficacy was observed at the WBC cut-off of 17000 [area under the curve 0.656 (0.542-0.770)] and the MPV cut-off of 10 [area under the curve 0.667 (0.554-0.780)] in differentiating patients with and without anorectal pathology., Discussion: Anorectal pathologies are common foci of infection in patients with acute leukaemia. Having predictive parameters that may help for early intervention will help the clinician. This is the first study in the literature to compare a control group with a group with anorectal pathologies in leukaemia patients providing a cut-off for WBC., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Background: Aortic dissection (AD) is a serious cardiovascular condition associated with high mortality rates. The systemic inflammatory response can influence the prognosis of AD, and in this context, the neutrophil-to-lymphocyte ratio (NLR) emerges as a simple and rapid inflammatory biomarker., Methods: This retrospective cohort study included 103 patients diagnosed with AD and treated in the emergency department between 2018 and 2023. Patient demographics, clinical features, and laboratory results were evaluated. Multivariate logistic regression analysis was performed to adjust for potential confounders such as age, mean systolic blood pressure, oxygen saturation, hemoglobin, lactate values, and the presence of coronary artery disease. The ability of NLR to predict mortality was analyzed using receiver operating characteristic (ROC) analysis., Results: The study population was divided into two groups: non-survivors (68% mortality rate) and survivors (32% survival rate). The non-survivor group had significantly higher NLR values compared to the survivor group (median NLR 7.66 vs. 2.5, p<0.001). Multivariate logistic regression analysis identified NLR as an independent predictor of in-hospital mortality (adjusted odds ratio [OR] 2.33, 95% confidence interval [CI] 1.42-3.82, p<0.001). ROC analysis for NLR demonstrated high discriminative power with an area under the ROC curve (AUROC) of 0.851 (95% CI 0.768-0.914). The determined cut-off point was >5.08 with a sensitivity of 77.14% and specificity of 81.82%., Conclusion: The findings indicate that high NLR is strongly associated with increased mortality risk in patients with AD and can be used in emergency clinical settings to predict mortality.

Hyperleukocytosis in pediatric acute myeloid leukemia (AML) is associated with severe complications and an inferior outcome. We report results on patients with hyperleukocytosis included in the NOPHO-DBH AML 2012 study. We recommended immediate initiation of full-dose chemotherapy (etoposide monotherapy for 5 days as part of the first course), avoiding leukapheresis and prephase chemotherapy. Of 714 patients included in the NOPHO-DBH AML 2012 study, 122 (17.1%) had hyperleukocytosis, and 111 were treated according to the recommendations with etoposide upfront without preceding leukapheresis or prephase chemotherapy. The first dose was applied the same day as the AML diagnosis or the day after in 94%. Etoposide was administered via peripheral veins in 37% of patients without major complications. After initiation of etoposide the white blood cell counts on days 2-5 were 69%, 36%, 17% and 8%, respectively, of the pre-treatment level. On day 3, 81% of patients had a white blood cell count <100 x109/L. Five-year event-free and overall survival rates for all patients with hyperleukocytosis were 52.9% (95% confidence interval [95% CI]: 44.4-63.0) and 74.1% (95% CI: 66.4-82.6), compared to 64.9% (95% CI: 60.9-69.1) and 78.9% (95% CI: 75.4-82.4) for patients without hyperleukocytosis (P<0.001 for event-free survival, P=0.1 overall survival). Six-week early mortality was 4.1% for all patients with hyperleukocytosis (2.7% for the 111 patients treated with etoposide upfront). We conclude that management of hyperleukocytosis in pediatric AML with immediate etoposide monotherapy without leukapheresis or prephase chemotherapy is feasible, safe and effective. The reduction in white blood cell count during the first days is comparable to the reported results of leukapheresis, and outcomes seem at least equivalent to therapies including leukapheresis. Based on our results, we advocate abandoning leukapheresis for hyperleukocytosis in pediatric AML. Instead, it is crucial to start induction chemotherapy as early as possible.

Background: Aortic stenosis has recently been characterised as having an inflammatory aetiology, beyond the traditional degenerative model. Recruitment of monocytes has been associated with inflammation contributing to progression of calcific aortic-valve disease. Prior research has demonstrated that pre-procedure inflammatory biomarkers do not consistently discriminate poorer outcomes in those with aortic stenosis. It remains, however, unclear if postprocedure inflammatory biomarkers, which are influenced by intraprocedural pro-inflammatory insults, can predict major adverse cardiovascular events (MACE) post transcatheter aortic valve implantation (TAVI)., Method: All patients with postprocedure monocyte levels undergoing transcatheter aortic valve implantation at The Alfred Hospital, Melbourne, Australia (2008-2019) were included. The highest monocyte count from postprocedure days 1 to 3 was used. Patients were divided into "high" or "low" postprocedure monocyte count groups using the Youden Index. The incidence of 30-day MACE a composite of stroke, acute myocardial infarction, and death) was then compared., Results: In total, 472 patients were included (54% men, median age 84 years). Fourteen (14) patients (3%) suffered a 30-day MACE. Those with high postprocedure monocyte count were more likely to: be hypertensive (p=0.049); have a higher Society of Thoracic Surgeons risk score (p=0.032); and, undergo non-transfemoral access (p=0.018). A high (≥0.975) postprocedure monocyte count was significantly associated with 30-day MACE (odds ratio [OR] 1.16 for each 0.1 increase in monocyte, p=0.025). This association remained present on multivariable analysis adjusted for age, sex, Society of Thoracic Surgeons risk score, and self-expanding valve prosthesis type (OR 1.17, p=0.028)., Conclusions: The association between postprocedure monocytosis and 30-day MACE suggests that minimising peri-procedural inflammatory insults may improve outcomes. This inexpensive and readily available biomarker may also aid in tailored risk stratification for patients., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic severe cutaneous adverse reaction that may be potentially life-threatening. Recently, a simple scoring system for the early screening of DRESS patients was derived by combining hsCRP levels, the eosinophil count, and the total body surface area (CET score). The objectives of this study were validating the CET score, and calculating its lead time advantage and cost-benefits compared to RegiSCAR scoring., Methods: This is a prospective observational case-control study, where 110 consecutive patients diagnosed with drug-induced maculopapular exanthema (MPE) were recruited during the 18 months of the study period. Patients were classified as cases (DRESS) and controls (MPE) using RegiSCAR score cut-off 2 (possible DRESS). They were also simultaneously screened using the CET score, based on which patients were classified as positive or negative. They were subsequently followed up on Day 15 for a second comparison and assessment of lead time and at 3 and 6 weeks to evaluate clinical response., Results: Seventy cases and 40 controls were recruited. At a cut-off of >2.12, the CET score had a sensitivity of 94.3%, a specificity of 60%, a positive predictive value (PPV) of 80.5%, and a negative predictive value (PPV) of 85.7%. The median delay in diagnosing DRESS using RegiSCAR was around 14.5 hours. There was a median cost benefit of 12.1 USD in favor of the CET score., Conclusions: The CET score had good diagnostic performance in screening DRESS patients with a lead time of 14.5 hours and fewer costs incurred., (© 2024 the International Society of Dermatology.)

Objective: The aim of this study is to investigate the dynamic changes and interrelationships between leukocyte components and inflammatory markers in the early stages and sepsis stage in severe burns, and explore their potential clinical significance., Methods: This is a 5-year retrospective cohort study involving 107 patients with severe burns (the total body surface area of burn (TBSA) > 50%), in which, neutrophil count, lymphocyte count, monocyte count, the ratio of the product of monocyte and lymphocyte count to neutrophil count (MLPN), procalcitonin (PCT), C-reactive protein (CRP), capillary leakage index (CLI) and creatinine (Scr) were investigated., Results: Within one week after injury, the leukocyte components and MLPN showed a V-shaped change, with a peak immediately after injury and a trough on the 4th or 5th day after injury, while CRP showed a continuous upward trend, and the leukocyte compositions of all patients were negatively correlated with CRP values. The counts of leukocytes components and CRP values in deceased patients were higher than those in surviving patients within 2 days after injury. In the resorption stage, although no significant difference in lymphocyte and monocyte counts between surviving and deceased patients was found, the monocyte and lymphocyte counts in deceased patients were lower than those in surviving patients on the 5th to 7th day after injury, while neutrophils counts and CRP values remained higher than those in surviving patients. And the dynamic changes of MLPN were consistent with those of leukocyte compositions and opposite to those of PCT values. Moreover, MLPN were negatively correlated with CRP, CLI, and Scr values in the early stage of severe burns. In sepsis stage, as the condition worsened, the values of CRP, PCT and neutrophil counts continuously increased with varying degree, while lymphocyte and monocyte counts, and MLPN showed continuously decrease, but rebounded to increase before death. And the occurrence of the trough of monocyte counts was earlier than that of lymphocyte counts, a negative correlation between neutrophil counts and PCT values was found., Conclusion: The results of this study revealed the dynamic interrelationships between leucocyte components and inflammatory indicators in the early stages and sepsis stage in severe burns, reflecting the different weightings of inflammatory responses and immune dysfunction in different disease stages and its correlation with outcomes, which providing useful clinical information for dynamic immunomodulatory therapy. Moreover, dynamic monitoring of MLPN value can provide timely information for clinical evaluation., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of in, (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Most physicians in general, and family physicians in particular, are familiar with certain parameters when ordering a hematological study, such as hemoglobin (including hematocrit and its features), leukocytes (including lymphocytes) and platelets. Nevertheless, there are two values that we use to overlook which are eosinophils and basophils. Specifically, eosinophils have a tendency to increase with allergic pathology. This article focuses on this type of cells, helping to interpret the values obtained and highlighting their importance in two of the most frequent respiratory pathologies in primary care: asthma and COPD. In addition to observing how the increase or normality of these parameters condition the diagnosis, phenotype and even the treatment., (Copyright © 2024 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) is characterized by low-grade chronic inflammation. Circulating neutrophils regroup 2 subtypes termed high- and low-density neutrophils (HDNs and LDNs). LDNs represent less than 2% of total neutrophil under physiological conditions, but their counts increase in multiple pathologies, releasing more inflammatory cytokines and neutrophil extracellular traps (NETs). The aims of this study were to assess the differential count and role of HDNs, LDNs, and NETs-related activities in patients with heart failure (HF)., Methods: HDNs and LDNs were isolated from human blood by density gradient and purified by fluorescence-activated cell sorting (FACS) and their counts obtained by flow cytometry. Formation of NETs (NETosis) was quantified by confocal microscopy. Circulating inflammatory and NETosis biomarkers were measured by enzyme-linked immunosorbent assay (ELISA). Neutrophil adhesion onto human extracellular matrix (hECM) was assessed by optical microscopy., Results: A total of 140 individuals were enrolled, including 33 healthy volunteers (HVs), 41 HFrEF (19 stable patients and 22 presenting acute decompensated HF [ADHF]), and 66 patients with HFpEF (36 stable patients and 30 presenting HF decompensation). HDNs and LDNs counts were significantly increased up to 39% and 2740%, respectively, in patients with HF compared with HVs. In patients with HF, the correlations among LDNs counts and circulating inflammatory (CRP, IL-6 and -8), troponin T, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and NETosis components were significant. In vitro, LDNs expressed more citrullinated histone H3 (H3Cit) and NETs and were more proadhesive, with ADHFpEF patients presenting the highest proinflammatory profile., Conclusions: Patients with HFpEF present higher levels of circulating LDNs- and NETs-related activities, which are the highest in the context of acute HF decompensation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain., Objective: We sought to determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma., Methods: EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during 3 years of observation in 480 participants in the Severe Asthma Research Program 3., Results: Over 3 years, EPX levels in patients with asthma were higher than normal in 27% to 31% of serum samples and 36% to 53% of sputum samples. Eosinophils and EPX correlated better in blood than in sputum (r s values of 0.74 and 0.43, respectively), and high sputum EPX levels occurred in 27% of participants with blood eosinophil counts less than 150 cells/μL and 42% of participants with blood eosinophil counts between 150 and 299 cells/μL. Patients with persistently high sputum EPX values for 3 years were characterized by severe airflow obstruction, frequent exacerbations, and high mucus plug scores. In 59 patients with asthma who started mepolizumab during observation, serum EPX levels normalized in 96% but sputum EPX normalized in only 49%. Lung function remained abnormal even when sputum EPX normalized., Conclusions: Serum EPX is a valid protein biomarker of systemic eosinophilic inflammation in asthma, and sputum EPX levels are a more sensitive biomarker of airway eosinophilic inflammation than sputum eosinophil counts. Eosinophil measures in blood frequently miss airway eosinophilic inflammation, and mepolizumab frequently fails to normalize airway eosinophilic inflammation even though it invariably normalizes systemic eosinophilic inflammation., Competing Interests: Disclosure statement The study was supported by grants from the National Institutes of Health (grant nos. U10 HL109172, U10 HL109168, U10 HL109152, U10 HL109257, U10 HL109146, U10 HL109164, and U10 HL109086). The following companies provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up: AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi–Genzyme–Regeneron, and Teva. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative. Disclosure of potential conflict of interest: M. Tang has participated in advisory boards with Sanofi. M. W. Johansson has received grants from Hoffmann-La Roche. N. N. Jarjour has received consulting fees from GlaxoSmithKline. L. C. Denlinger has received grants from the American Lung Association-Airway Clinical Research Centers (ALA-ACRC); has received consulting fees from OM Pharma; and has received study drugs for the PrecISE trial from GlaxoSmithKline, Laurel, Sun Pharma, Vifor/OM Pharma Vitaeris/CSL Behring, and Vitaflo. M. C. Peters is an employee and has stock in Gilead Sciences. M. Castro has received grants from the ALA-ACRC, Patient-Centered Outcomes Research Institute (PCORI), AstraZeneca, Gala Therapeutics, Genentech, GlaxoSmithKline, Novartis, Pulmatrix, Sanofi-Aventis, Shinogi, and Theravance; has received consulting fees from Genentech, Teva, Sanofi-Aventis, Merck, Novartis, Arrowhead Pharmaceuticals, Allakos, Amgen, OM Pharma, Pfizer, Pioneering Medicines, and GlaxoSmithKline; has received honoraria for presentations from Amgen, AstraZeneca, Genentech, Regeneron, Sanofi-Aventis, and Teva; and has stock in Aer Therapeutics. K. Sumino has participated in advisory boards with AstraZeneca. B. D. Levy has received grants from Pleris Pharmaceuticals; has received consulting fees from AstraZeneca, Gossamer Bio, Novartis, and Thetis Pharmaceuticals; and has stock ownership in Entrinsic Health and Nocion Therapeutics. E. Israel has received grants from AstraZeneca, Avillion, Gossamer Bio, and PCORI; has received royalties from UpToDate—Wolters Kluwer; has received consulting fees from AB Science, Allergy and Asthma Network, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Avillion, GlaxoSmithKline, Merck, National Heart, Lung, and Blood Institute, Pneuma Respiratory, PPS Health, Regeneron, Sanofi-Genzyme, Teva, and Cowen; has received honoraria for presentations to Westchester Medical Center; has received payment for expert testimony to Cambridge Medical Experts, Danager Lagnese, and SettlePou; has participated in an advisory board with Novartis; is an unpaid member of the coordinating committee for the National Asthma Education and Prevention Program; has stock in Vorso; and has received equipment and study drugs from Circassia, Genentech, Teva, Sun Pharma, Laurel Pharmaceuticals, Om Pharma, Nestle, CSL Behring, and Sanofi-Regeneron. W. Phipatanakul has received grants from Sanofi, Regeneron, GlaxoSmithKline, Genentech, and Novartis; has received consulting fees from Sanofi, Regeneron, GlaxoSmithKline, Genentech, Novartis, and AstraZeneca; and has received support for attending meetings/travel from Sanofi and Regeneron. S. E. Wenzel has received grants from Regeneron; has received consulting fees from Sanofi and Novartis; and has stock in Aer Therapeutics. P. G. Woodruff has received consulting fees from Roche, Sanofi, Regeneron, and AstraZeneca. J. V. Fahy has received consulting fees and has stock from Suzhou Connect Biopharmaceuticals, Ltd, and Aer Therapeutics; and has been issued two patents. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to evaluate the predictive value of neutrophil-lymphocyte ratio (NLR) in determining infection after orthopedic surgery. Methods: A comprehensive search was conducted in PubMed, EBASE, CNKI, and Wanfang databases to identify relevant studies. The quality of the included studies was assessed using QUADAS-2. Data extraction was performed to calculate sensitivity, specificity, and other indicators. Bivariate mixed-effects meta-analysis was conducted using Stata software. The sources of heterogeneity were evaluated, and a summary receiver operating characteristic curve was generated. Results: A total of 16 literatures comprising 18 studies involving 3737 patients were included in this analysis. NLR demonstrated moderate sensitivity (0.77) and specificity (0.69) in diagnosing orthopedic post-operative infection, with an area under the curve of 0.80 and diagnostic odds ratio of 7.76. Significant heterogeneity was observed among the studies, primarily due to variations in surgical type, infection type, blood test timing, and NLR cutoff value. Fagan nomogram indicated that NLR could increase the positive posterior probability to 72% and decrease the negative posterior probability to 25%. The pooled effect of the likelihood ratio dot plot for diagnosis fell in the lower right quadrant. Deek funnel plot suggested no publication bias in this study. Conclusion: NLR holds certain value in diagnosing infection after orthopedic surgery and can provide additional information to assess the risk of infection. However, its predictive performance is influenced by various factors, and it cannot be used as a sole criterion for confirming the diagnosis. Prospective studies should be conducted in the future to optimize the diagnostic threshold and explore its combination with other indicators.

Aims: We aimed to examine the role of circulating immature granulocytes (IGs) in assessing Diabetic Nephropathy (DN) mainly and also associations of other leukocyte parameters with DN., Methods: In this retrospective cross-sectional study, a total of 164 Diabetes Mellitus patients were grouped as normoalbuminuric and microalbuminuric according to urinary albumin excretion in the course of admission. Neutrophil-lymphocyte ratio (NLR), IG count (IG#) and IG percentage (IG%) levels were compared between the groups. The value of IG# and IG% levels in detecting microalbuminuria was analyzed with the Receiver operating characteristic (ROC) curve., Results: NLR was remarkably higher in the microalbuminuric group (p = 0.036). Correlation results in the microalbuminuric group were as follows: A feeble positive correlation between neutrophil count (NEU#) and serum creatinine and albumin-to- creatinine ratio (ACR) (p = 0.036, r = 0.261; p = 0.005, r = 0.347, respectively), a feeble positive correlation between lymphocyte count (LYM#) and estimated glomerular filtration rate (p = 0.021, r = 0.285). Correlation results in the normooalbuminuric group were as follows: A feeble positive correlation between NEU# and ACR (p = 0.043, r = 0.204), a feeble negative correlation between LYM# and serum creatinine (p = 0.042, r = -0.205), a poor positive correlation between IG# and ACR and HBA1C% (p = 0.048, r = 0.199; p = 0.004, r = 0.290, respectively), a positive poor correlation between IG% and HBA1C% (p = 0.019, r = 0.235). Area under the ROC curve values for IG# and IG% were not statistically noteworthy in detecting microalbuminuria (p = 0.430; p = 0.510, respectively)., Conclusions: IG# and IG% values are insufficient to predict immediate microalbuminuria, but could be considered a weak biomarker for renal damage in normoalbuminuric (<30 mg/g) diabetic patients. Further researches are needed for the use of leukocyte parameters in evaluating DN., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background : A number of acute ischemic stroke (AIS) cases may be misdiagnosed as transient ischemic attack (TIA), due to no infarct on initial computed tomography scan and/or mild deficits upon presentation. Several studies have found that the neutrophil-lymphocyte ratio (NLR) is an accurate differential diagnostic biomarker for AIS versus TIA; however, no study has evaluated the use of the NLR in differentiating CT negative AIS from TIA. Furthermore, the systemic immune-inflammation index (SII) is a relatively novel immune biomarker that has been shown to be positively correlated with AIS severity, poor functional outcomes and mortality. The purpose of this study is to determine if NLR or SII can be used as a diagnostic biomarker for the differential diagnosis of mild AIS with a negative CT upon admission and TIA. Methods : We performed a retrospective medical record review of patients diagnosed with either AIS or TIA. We collected peripheral white blood cell counts within 24 h of symptom onset and calculated the NLR and SII. Logistic regression was utilized to determine if NLR or SII are significant predictors of CT negative mild AIS. Results: CT negative mild AIS patients were 2 times as likely to have an NLR ≥ 2.71 compared to TIA patients, and CT negative mild AIS patients were 2.1 times as likely to have an SII ≥ 595 compared to TIA patients. Conclusion : NLR and SII are easily obtained biomarkers that can be used in early clinical decision making in cases of mild AIS with negative CT scan upon admission.

Neutropenia, a common side effect of chemotherapy for ovarian cancer, was observed in a 47-year-old female patient undergoing a six-cycle chemotherapy regimen. She experienced recurrent neutropenia and leukopenia but refused granulocyte colony-stimulating factor (G-CSF) due to severe bone pain and high costs. Moxibustion combined with guasha therapy (MGT) was administered each time neutropenia occurred. The treatment involved guasha therapy on the bladder meridian (BL) and the governor vessel (GV), followed by moxibustion at Zhongwan (CV 12), Guanyuan (CV 4), and Shenzhu (GV 12) points over 2-3 days. This approach led to the recovery of neutrophil and leukocyte counts, enabling the patient to complete six chemotherapy cycles without G-CSF. These findings suggest that MGT may enhance neutrophil and leukocyte counts in patients with chemotherapy-induced myelosuppression, presenting a potential alternative for those intolerant to G-CSF. However, further high-quality research is needed to confirm its efficacy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The present systematic review was performed to identify risk factors associated with life-threatening complications of head and neck space infections (LCHNSI) within the included studies and assess the magnitude of their impact on patients., Methods: We systematically searched PubMed, Web of Science, EmBase, Scopus and CNKI for articles that reported risk factors associated with life-threatening complications of head and neck space infections from inception to 14 December 2023. Only factors reported in at least three papers were considered in the meta-analysis. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using fixed effects model and random effects model. The between-study heterogeneity of effect size was quantified using the Q statistic and I 2 . In addition, subgroup analysis stratified by study characteristics and sensitivity analysis were performed to explore the potential sources of heterogeneity and the stability of the results., Results: The review included a total of 29 studies. The results revealed that the risk factors which associated with LCHNSI were included diabetes mellitus (OR = 3.31, 95 % CI: 2.49-4.40), total leukocyte count(≥15 × 10 9 /L) (OR = 1.21, 95 %CI: 1.04-1.42), multiple space involvement (OR = 4.32, 95 %CI: 3.47-5.38), combined systemic diseases (OR = 9.94, 95 %CI: 6.30-15.67), advanced age(≥60) (OR = 3.90, 95 %CI: 2.80-5.44), dyspnoea (OR = 23.39, 95 %CI: 12.41-44.10), high temperature(≥39°C) (OR = 3.23, 95 %CI: 2.02-5.17), retropharyngeal space involvement (OR = 3.62, 95 %CI: 2.06-6.35), parapharyngeal space involvement (OR = 4.62, 95 %CI: 2.27-9.42)., Conclusions: According to the current analysis, diabetes mellitus, total leukocyte count(≥15 × 10 9 /L), combined systemic diseases, multiple space involvement, advanced age(≥60), dyspnoea, high temperature (≥39 °C), retropharyngeal space involvement, parapharyngeal space involvement were the risk factors for LCHNSI. To mitigate the incidence of LCHNSI, clinical staff should carefully manage these risk factors, ensure prompt diagnosis, and implement timely preventive measures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven esophageal disorder. Connective tissue disorders (CTDs) and esophageal connective tissue alterations are associated with EoE. Therefore, angiotensin II type 1 receptor blockade with losartan, an accepted CTD treatment, is a potential EoE treatment., Objective: We evaluated losartan's effects on esophageal pathology, symptoms, and safety in patients with EoE with and without a CTD in an open-label, non-placebo controlled multisite study., Methods: Fifteen participants with EoE, aged 5 to 23 years, underwent treatment with per-protocol titrated doses of losartan in an open-label, 16-week pilot trial. Losartan was added to standard of care therapy and 14 patients completed the study. Eosinophil counts served as the primary end point, whereas we also assessed the EoE Histology Scoring System, Endoscopic Reference Scores, EoE Diagnostic Panel, and patient-reported outcomes., Results: Esophageal eosinophilia was not reduced after losartan. The peak eosinophil count was not reduced for the proximal (median [interquartile range]: -3 [-22 to 3]; P = .49) and distal esophagus (median [interquartile range]: -18 [-39 to -1]; P = .23). There were no differences in losartan response in EoE with or without CTD (n = 7 and 8, respectively). Regardless, in a small subset of four participants esophageal eosinophilia was resolved with a concomitant reduction in EoE Histology Scoring System score and Endoscopic Reference Score. Across all subjects, the Pediatric EoE Symptom Score, Pediatric Quality of Life Inventory EoE Module, and EoE Diagnostic Panel improved after losartan (P < .05)., Conclusions: Losartan treatment was associated with improved patient-reported outcome scores and EoE Diagnostic Panel biomarkers although without a reduction in esophageal eosinophilia overall. A subset of patients demonstrated improved histopathologic and endoscopic features that could not be tied to a specific feature predicting response to treatment., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Aims: High platelet-derived thrombogenicity during the acute phase of ST-segment elevation myocardial infarction (STEMI) is associated with poor outcomes; however, the associated factors remain unclear. This study aimed to examine whether acute inflammatory response after STEMI affects platelet-derived thrombogenicity., Methods: This retrospective observational single-center study included 150 patients with STEMI who were assessed for platelet-derived thrombogenicity during the acute phase. Platelet-derived thrombogenicity was assessed using the area under the flow-pressure curve for platelet chip (PL-AUC), which was measured using the total thrombus-formation analysis system (T-TAS). The peak leukocyte count was evaluated as an acute inflammatory response after STEMI. The patients were divided into two groups: the highest quartile of the peak leukocyte count and the other three quartiles combined., Results: Patients with a high peak leukocyte count (＞15,222/mm 3 ; n=37) had a higher PL-AUC upon admission (420 [386-457] vs. 385 [292-428], p=0.0018), higher PL-AUC during primary percutaneous coronary intervention (PPCI) (155 [76-229] vs. 96 [29-170], p=0.0065), a higher peak creatine kinase level (4200±2486 vs. 2373±1997, p＜0.0001), and higher PL-AUC 2 weeks after STEMI (119 [61-197] vs. 88 [46-122], p=0.048) than those with a low peak leukocyte count (≤ 15,222/mm 3 ; n=113). The peak leukocyte count after STEMI positively correlated with PL-AUC during primary PPCI (r=0.37, p＜0.0001). A multivariable regression analysis showed the peak leukocyte count to be an independent factor for PL-AUC during PPCI (β=0.26, p=0.0065)., Conclusions: An elevated leukocyte count is associated with high T-TAS-based platelet-derived thrombogenicity during the acute phase of STEMI.

Background: A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with healthy control participants has been lacking., Methods: Multiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO) were searched for eligible studies up until October 18, 2022. All studies investigating circulating immune cells in the blood and CSF from patients with psychotic disorders (ICD-10: F20 and F22-29) compared with healthy control participants were included., Results: A total of 86 studies were included in the meta-analysis. In the blood, the following categories of immune cells were elevated: leukocyte count (31 studies, standardized mean difference [SMD] = 0.35; 95% CI, 0.24 to 0.46), granulocyte count (4 studies, SMD = 0.57; 95% CI, 0.12 to 1.01), neutrophil granulocyte count (21 studies, SMD = 0.32; 95% CI, 0.11 to 0.54), monocyte count (23 studies, SMD = 0.40; 95% CI, 0.23 to 0.56), and B lymphocyte count (10 studies, SMD = 0.26; 95% CI, 0.04 to 0.48). Additionally, the neutrophil/lymphocyte ratio (23 studies, SMD = 0.40; 95% CI, 0.19 to 0.60), the monocyte/lymphocyte ratio (9 studies, SMD = 0.31; 95% CI, 0.04 to 0.57), and the platelet/lymphocyte ratio (10 studies, SMD = 0.23; 95% CI, 0.03 to 0.43) were elevated. The CSF cell count showed a similar tendency but was not significantly elevated (3 studies, SMD = 0.14; 95% CI, -0.04 to 0.32)., Conclusions: The results indicate a broad activation of the immune system in psychotic disorders, with cells from both the myeloid and the lymphoid line being elevated. However, CSF analyses were lacking in most of the studies, and many studies were hampered by insufficient adjustment for confounding factors such as body mass index and smoking., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Aim: Eosinophils are normal residents of the gastrointestinal tract (GIT). They are noted in small numbers with significant variation between anatomic locations. An idiopathic increase of eosinophils is known as eosinophilic gastrointestinal disease (EGID). EGIDs are a heterologous group of disorders that produce a range of enteric and colonic syndromes. Their incidence has been increasing worldwide. Our study aimed to quantify eosinophils in each segment of the GIT in surgical specimens with normal histology to facilitate the histological diagnosis of EGID. Similarly, we aimed to describe the effect of race and gender on gastrointestinal eosinophil numbers., Methods: A retrospective, quantitative comparative study was performed. We assessed 360 surgical specimens with normal histology from the lower gastrointestinal tract of African and Caucasian adults from the Free State Province, South Africa. The number of eosinophils per mm² was counted., Results: Overall, comparable eosinophil values were noted for both males and females, and African and Caucasian South Africans. However, Caucasians recorded a higher concentration of eosinophils in the appendix and the left colon. Eosinophils were most numerous in the lamina propria, with only small numbers present in the epithelium. Our results show that the South African population has similar eosinophil distribution trends to international studies. However, South Africans had far fewer eosinophils than Japanese and North American adults in each segment., Conclusions: Specific eosinophil reference ranges were formulated to quantify reference ranges of eosinophils in the lower GIT, allowing for the accurate diagnosis of EGIDs in our population in future., (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Objective: To investigate the association between African ancestry and neutrophil counts among children living with HIV (CLWH). We also examined whether medications, clinical conditions, hospitalization, or HIV virologic control were associated with low neutrophil counts or African ancestry., Design: We conducted a secondary analysis of the Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) Study, a multicenter prospective cohort study of CLWH across 8 Canadian pediatric HIV care centers., Methods: We classified CLWH according to African ancestry, defined as "African," "Caribbean," or "Black" maternal race. Longitudinal laboratory data (white blood cells, neutrophils, lymphocytes, viral load, and CD4 count) and clinical data (hospitalizations, AIDS-defining conditions, and treatments) were abstracted from medical records., Results: Among 217 CLWH (median age 14, 55% female), 145 were of African ancestry and 72 were of non-African ancestry. African ancestry was associated with lower neutrophil counts, white blood cell counts, and neutrophil-lymphocyte ratios. Neutrophil count <1.5 × 109/L was detected in 60% of CLWH of African ancestry, compared with 31% of CLWH of non-African ancestry (P < 0.0001), representing a 2.0-fold higher relative frequency (95% CI: 1.4-2.9). Neutrophil count was on average 0.74 × 109/L (95% CI: 0.45 to 1.0) lower in CLWH of African ancestry (P < 0.0001). Neither neutrophil count<1.5 × 109/L nor African ancestry was associated with medications, hospitalizations, AIDS-defining conditions, or markers of virologic control (viral load, sustained viral suppression, and lifetime nadir CD4)., Conclusions: In CLWH, African ancestry is associated with lower neutrophil counts, without clinical consequences. A flexible evaluation of neutrophil counts in CLWH of African ancestry may avoid unnecessary interventions., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Left ventricular aneurysm (LVA) is an important complication of acute myocardial infarction. This study aimed to investigate the potential predictive value of the monocyte count to high-density lipoprotein cholesterol ratio (MHR) and a composite risk score in determining the formation of LVA in patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention., Methods: We recruited 1005 consecutive patients with STEMI. Multivariable logistic regression analysis was conducted identify the independent risk factors for LVA formation. Predictive power of MHR and composite risk score for LVA formation were assessed using receiver operating characteristic curve analysis., Results: The MHR was significantly higher among patients with LVA compared to those without LVA [6.6 (3.8-10.8) vs. 4.6 (3.3-6.3), P  < 0.001]. Univariable logistic regression analysis revealed that MHR (OR = 3.866, 95% CI = 2.677-5.582, P  < 0.001) was associated with the risk of LVA formation. The predictive value of MHR remained significant even after multivariate logistic regression analysis [odds ratio (OR) = 4.801, 95% confidence interval (CI) = 2.672-8.629, P  < 0.001]. The discriminant power of MHR for LVA is 0.712, which is superior to both monocyte ( C statistic = 0.553) and high-density lipoprotein cholesterol ( C statistic = 0.654). The composite risk score including MHR, gender, LVEF, hemoglobin, lymphocyte and left anterior descending artery as the culprit vessel could significantly increase the predictive ability ( C statistic = 0.920)., Conclusion: A higher MHR could effectively identify individuals at high risk of LVA formation, especially when combined with gender, LVEF, hemoglobin, lymphocyte and left anterior descending artery as the culprit vessel., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Thrombosis in myeloproliferative neoplasms (MPNs) is an important clinical problem, and risk-stratified management is essential. To identify the clinical characteristics of thrombosis in patients with MPNs, a nationwide multi-institutional retrospective analysis (JSH-MPN-R18) was conducted. The aim of the present study was to perform a sub-analysis of JSH-MPN-R18 findings to clarify the predictive parameters for thrombosis among complete blood count (CBC) results. Among the patients enrolled in JSH-MPN-R18, those with essential thrombocythemia (ET; n = 1152) and polycythemia vera (PV; n = 456) were investigated. We analyzed and compared CBC parameters between patients with and those without any thrombotic events using Welch's T-test. Statistical analyses were performed using the R statistical software. Thrombotic events were observed in 74 patients with ET. In multivariate analysis, only the neutrophil ratio was slightly but significantly higher for ET patients with thrombosis than for those without (p < 0.05). Of note, the absolute neutrophil count (aNeu) was considered a useful predictive tool for thrombosis among patients classified as low-risk according to the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia. Among PV patients, those with thrombosis showed significantly higher hematocrit and aNeu than did those without thrombosis. As a thrombosis-associated factor, the neutrophil ratio was slightly but significantly elevated in patients with ET. This myeloid skew might reflect a higher value of JAK2 V617F allelic frequency in patients with ET with thrombosis; this was not clarified in JSH-MPN-R18. Further accumulation of evidence, including genetic information for JAK2 and other passenger mutations, is warranted., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Backgrounds: Septic arthritis is a dangerous disease that occurs when microorganisms enter synovial fluid. It needs fast and accurate management; otherwise, it can harm the patient's life. Currently, the tests measure WBC and PMN in SF, so we hypothesized to use a proxy that is easier and faster to measure. Leukocyte esterase is an enzyme secreted by neutrophils that can be found in the synovial fluid of SA patients. In this study, we tried to investigate the sensitivity and specificity of leukocyte esterase in diagnosing septic arthritis., Methods: We obtained synovial fluid samples from forty-six patients suspected of having septic arthritis and fifty-eight healthy individuals and measured the WBCs, ESR, CRP, PMN, glucose, and protein of SF in 2021. We also used the leukocyte esterase dipstick test to investigate the level of LE in synovial fluid for one minute., Results: Based on clinical and paraclinical criteria, sixteen out of the forty-six patients were diagnosed with SA. When (++) was considered positive, the sensitivity and specificity of the LE dipstick test for the diagnosis of SA were 93.7% (95% CI: 81.8-100%) and 60% (95% CI: 42.4-77.5%, P = 0.000), respectively. When both (+) and (++) were considered positive, they were 100% and 43.3% (95% CI: 25.6-61.0% P = 0.000), respectively. All the patients in the control group had negative cultures and LE test readings (specificity = 100%)., Conclusion: The LE dipstick test can be a valuable diagnostic tool in the initial diagnosis of SA since it is affordable, fast, and reliable., (© 2024. The Author(s).)

Objectives: To summarize the clinical characteristics, outcomes and identify risk factors of Acinetobacter baumannii (AB) meningitis in children., Methods: This was a single-center, retrospective study. Children hospitalized between January 2016 and December 2021 who were diagnosed with AB meningitis were included. The clinical characteristics and outcomes were reviewed. Risk factors were determined using univariate analyses (chi-square and Mann-Whitney U tests)., Results: Seventeen patients were included; 15 cases were secondary to neurosurgery, and two were neonates with primary bacterial meningitis. Common symptoms included fever, convulsions and nervous system abnormalities. Cerebrospinal fluid (CSF) tests typically showed increased white blood cell counts dominated by neutrophils, reduced glucose levels and elevated protein levels. Ten patients were successfully treated (successful treatment [ST] group); seven had failed treatment (failed treatment [FT] group). Univariate analyses revealed that mechanical ventilation, routine white cell counts in the peripheral blood, procalcitonin, protein in the CSF, septic shock and carbapenem-resistant AB (CRAB) differed significantly between the groups., Conclusion: AB meningitis in children has a high mortality rate. FT was associated with mechanical ventilation, septic shock, CRAB, lower peripheral leukocyte counts, higher protein levels in the CSF and procalcitonin. Larger studies are needed to identify independent risk factors for adverse outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Ye, Fu, Wu, Xu, Ye, Han, Wang and Yu.)

Eosinophils have the potential to exhibit both anti-tumor properties and tumor-promoting effects. However, the impact of eosinophil levels in the bloodstream on tumorigenesis risk remains inadequately explored. Furthermore, investigations regarding the association between drugs regulating eosinophils and cancer risk are currently absent. In this study, we conducted a Mendelian randomization (MR) analysis utilizing eosinophil count and eosinophil percentage as exposures. In both cohorts, a significant association was observed between eosinophil count and the risk of colorectal cancer and skin malignancies. However, upon conducting a sensitivity analysis, heterogeneity was detected specifically in relation to skin malignancies. Subsequent reverse Mendelian randomization analysis did not indicate any evidence of reverse causality. Furthermore, the multivariate Mendelian randomization analysis results suggested that eosinophils act as a mediating factor in reducing the risk of colorectal cancer and skin malignancies in individuals with asthma. And the use of drugs that modulate eosinophilia may increase the risk of colorectal cancer. It is evident that the statistical evidence supporting a negative correlation between eosinophils count and the susceptibility to colorectal cancer is particularly robust. And, it is plausible to suggest that pharmaceutical interventions aimed at modulating eosinophilia may potentially heighten the risk of colorectal cancer. Hence, it is imperative to exercise caution and remain mindful of the potential risk of colorectal cancer when employing these medications.

To determine the clinical indicators predictive of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children and develop a robust predictive model to aid in early identification and management. A retrospective cohort study was conducted on 338 children diagnosed with RMPP out of a total of 1500 cases of Mycoplasma pneumoniae at a single tertiary hospital from May 2021 to November 2023. Clinical and demographic data analyzed included age, gender, parents' educational level, household income, body mass index, allergic constitution, and laboratory findings such as white blood cell count, neutrophil and lymphocyte counts, platelet count, and levels of C-reactive protein (CRP), D-dimer, and procalcitonin. Univariate and multivariate logistic regression analyses were performed to identify significant predictors of RMPP, and a predictive model was developed. Among the RMPP cohort, 52.4% were female, with a mean age of 6.07 ± 2.78 years. Multivariate analysis identified several significant predictors of poor prognosis, including higher body mass index, longer duration of fever, elevated white blood cell count, neutrophil count, C-reactive protein levels, and increased neutrophil to lymphocyte ratio and platelet to lymphocyte ratio. The model demonstrated outstanding diagnostic performance, with an area under the receiver operating characteristic curve of 0.963 (95% confidence interval: 0.946-0.981). Our study identifies key clinical indicators with significant diagnostic accuracy for predicting RMPP in children. The predictive model established offers a valuable tool for clinicians, potentially improving RMPP outcomes through timely intervention., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

While previous observational studies have suggested a link between leukocyte counts and vascular dementia (VD), the causal relationship between leukocyte counts and various subtypes of VD remains elusive. This study aimed to investigate the causal relationship between five types of leukocyte counts and VD, with the goal of improving prevention and treatment strategies. In this study, leukocyte counts were used as the exposure variable, with genome-wide association study (GWAS) data sourced from both the UK Biobank and the Blood Cell Consortium. Additionally, GWAS data for five subtypes of vascular dementia were obtained from the FinnGen database. We conducted rigorous statistical analysis and visualization using Mendelian randomization (MR) to elucidate the potential causal relationship between leukocyte counts and vascular dementia. This study, utilizing MR analysis with data from the UK Biobank and Blood Cell Consortium, identified significant causal associations between increased lymphocyte counts and VD. Specifically, lymphocyte counts were found to be causally related to multiple and mixed VD subtypes. Sensitivity analyses, including MR-Egger regression and MR-PRESSO tests, confirmed the robustness of these findings, with no evidence of reverse causality or significant horizontal pleiotropy detected. The results underscore a potential inflammatory or immunological mechanism in the pathogenesis of VD, highlighting lymphocytes as a key component in their etiology. This investigation establishes a robust association between elevated lymphocyte and leukocyte counts and an increased risk of VD, emphasizing the roles of inflammation, immune activation, and hematological factors in disease pathogenesis., (© 2024. The Author(s).)

Purpose: Investigate the clinical characteristics of splenomegaly secondary to acute pancreatitis (SSAP) and construct a nomogram prediction model based on Lasso-Logistic regression., Methods: A retrospective case-control study was conducted to analyze the laboratory parameters and computed tomography (CT) imaging of acute pancreatitis (AP) patients recruited at Xuanwu Hospital from December 2014 to December 2021. Lasso regression was used to identify risk factors, and a novel nomogram was developed. The performance of the nomogram in discrimination, calibration, and clinical usefulness was evaluated through internal validation., Results: The prevalence of SSAP was 9.2% (88/950), with the first detection occurring 65(30, 125) days after AP onset. Compared with the control group, the SSAP group exhibited a higher frequency of persistent respiratory failure, persistent renal failure, infected pancreatic necrosis, and severe AP, along with an increased need for surgery and longer hospital stay (P < 0.05 for all). There were 185 and 79 patients in the training and internal validation cohorts, respectively. Variables screened by Lasso regression, including platelet count, white blood cell (WBC) count, local complications, and modified CT severity index (mCTSI), were incorporated into the Logistic model. Multivariate analysis showed that WBC count ≦9.71 × 10 9 /L, platelet count ≦140 × 10 9 /L, mCTSI ≧8, and the presence of local complications were independently associated with the occurrence of SSAP. The area under the receiver operating characteristic curve was 0.790. The Hosmer-Lemeshow test showed that the model had good fitness (P = 0.954). Additionally, the nomogram performed well in the internal validation cohorts., Conclusions: SSAP is relatively common, and patients with this condition often have a worse clinical prognosis. Patients with low WBC and platelet counts, high mCTSI, and local complications in the early stages of the illness are at a higher risk for SSAP. A simple nomogram tool can be helpful for early prediction of SSAP., (© 2024. The Author(s).)

Background: An increasing body of research implicates inflammatory processes, including alterations in the neutrophil-lymphocyte ratio (NLR), in the pathophysiology of psychiatric illness. The deer mouse (Peromyscus maniculatus bairdii) is commonly studied for its naturalistic expression of compulsive-like behaviour. Towards future efforts to gain an understanding of how innate and adaptive immune processes might be involved in this model, we aimed to study the effects of pegfilgrastim, a pegylated recombinant human granulocyte colony-stimulating factor (g-CSF) analogue, on the NLR of both male and female deer mice., Methods: Briefly, 54 deer mice (equally distributed between sexes) were exposed to a single injection with either control or pegfilgrastim (0.1 or 1 mg/kg) (n = 18 per group). Six mice of each group (three per sex) were euthanized on days two, four and seven post-administration, their blood collected and the NLR calculated. Data were analysed by means of ordinary three-way ANOVA, followed by Bonferroni post-hoc testing., Results: Irrespective of dose, pegfilgrastim resulted in higher NLR values in mice of both sexes at days four and seven of testing. However, female mice exposed to the higher dose, presented with significantly higher NLR values irrespective of time, compared to male mice exposed to the same., Conclusion: The data generated from this work highlight important dose- and sex-specific aspects of pegfilgrastim with female mice showing heighted elevation of the NLR in response to high-dose pegfilgrastim administration only. Since the innate immune components of male and female deer mice is differentially sensitive to g-CSF stimulation, our results provide a useful basis for further study of sex-specific immunological processes in deer mice., (© 2024. The Author(s).)

Background: Neutrophils are key contributors to chronic airway inflammation in cystic fibrosis (CF) lung disease, although airway and blood-based neutrophil markers are seldom used. The neutrophil-to-lymphocyte ratio (NLR) is an accessible biomarker, the clinical utility of which has not been adequately studied., Objective: This study aimed to investigate the characteristics of the NLR in children with CF and its correlations with acute pulmonary exacerbations and spirometry., Design: A previous study had collected clinical data from children with CF for a 3-year period between 2016 and 2021. Retrospectively, NLR values were categorised according to patients' clinical status during blood sample collection as 'stable', 'acute pulmonary exacerbation' or 'elective admission for chronic clinical concern'., Main Outcome Measures: Demographic characteristics associated with the NLR; changes in NLR values in relation to clinical status; relationship between NLR and lung function., Results: 141 children with CF were included. NLR values during clinical stability were higher in females and increased with age. For children admitted for intravenous antibiotics, NLR values significantly increased from clinical stability (median (IQR)=1.13 (0.75-1.51)) to acute pulmonary exacerbations (median (IQR)=1.50 (0.96-2.65), p=0.001), but similar changes were not observed in elective admissions. The NLR was not associated with lung function., Conclusions: The NLR demonstrated associations with clinical status in children with CF with significant elevations during acute pulmonary exacerbations. While its utility as a single-marker measure is limited, monitoring the NLR over time may help identify periods of increased inflammation., Competing Interests: Competing interests: Editorial support was provided by ArticulateScience LLC. CE reports not related to this work educational activities for Vertex, Chiesi. JCD has undertaken Clinical trial leadership and/ or Advisory Board and speaking roles for Vertex Pharmaceuticals, Boehringer-Ingelheim, Eloxx, Algipharma, AbbVie, Arcturus, Enterprise Therapeutics, Recode, LifeArc, Genentech and Tavanta. She has received grant funding for research from UK Cystic Fibrosis Trust, Cystic Fibrosis Foundation, Cystic Fibrosis Ireland, EPSRC, NIHR. She is the president elect for the European Cystic Fibrosis Society. All other authors reported no conflicts of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Target values for 25-hydroxy vitamin D and 1,25(OH) 2 D or 1,25-dihydroxy vitamin D remain a topic of debate among clinicians. We analysed data collected from December 2012 to April 2020 from two cohorts. Cohort A, comprising 455,062 subjects, was used to investigate the relationship between inflammatory indicators (white blood cell [WBC] count and C-reactive protein [CRP]) and 25(OH)D/1,25(OH) 2 D. Cohort B, including 47,778 subjects, was used to investigate the connection between 25(OH)D/1,25(OH) 2 D and mineral metabolism markers (phosphate, calcium, and intact parathyroid hormone [iPTH]). Quadratic models fit best for all tested correlations, revealing U-shaped relationships between inflammatory indicators and 25(OH)D and 1,25(OH) 2 D. Minimal CRP and WBC counts were observed at 1,25(OH) 2 D levels of 60 pg/mL and at 25(OH)D levels of 32 ng/mL, as well as of 42 ng/mL, respectively. iPTH correlated inversely with both 1,25(OH) 2 D and 25(OH)D, while phosphate as well as calcium levels positively correlated with both vitamin D forms. Calcium-phosphate product increased sharply when 25(OH)D was more than 50 ng/mL, indicating a possible risk for vascular calcification. Multiple regression analyses confirmed that these correlations were independent of confounders. This study suggests target values for 25(OH)D between 30-50 ng/mL and for 1,25(OH) 2 D between 50-70 pg/mL, based particularly on their associations with inflammation but also with mineral metabolism markers. These findings contribute to the ongoing discussion around ideal levels of vitamin D but require support from independent studies with data on clinical endpoints.

Background: Polycyclic aromatic hydrocarbons (PAHs) and metals were associated with decreased lung function, but co-exposure effects and underlying mechanism remained unknown., Methods: Among 1,123 adults from National Health and Nutrition Examination Survey 2011-2012, 10 urinary PAHs, 11 urinary metals, and peripheral white blood cell (WBC) count were determined, and 5 lung function indices were measured. Least absolute shrinkage and selection operator, Bayesian kernel machine regression, and quantile-based g-computation were used to estimate co-exposure effects on lung function. Mediation analysis was used to explore mediating role of WBC., Results: These models demonstrated that PAHs and metals were significantly associated with lung function impairment. Bayesian kernel machine regression models showed that comparing to all chemicals fixed at median level, forced expiratory volume in 1 s (FEV 1 )/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25 and 75% decreased by 1.31% (95% CI: 0.72%, 1.91%), 231.62 (43.45, 419.78) mL/s, and 131.64 (37.54, 225.74) mL/s respectively, when all chemicals were at 75th percentile. In the quantile-based g-computation, each quartile increase in mixture was associated with 104.35 (95% CI: 40.67, 168.02) mL, 1.16% (2.11%, 22.40%), 294.90 (78.37, 511.43) mL/s, 168.44 (41.66, 295.22) mL/s decrease in the FEV 1 , FEV 1 /forced vital capacity, peak expiratory flow, and forced expiratory flow between 25% and 75%, respectively. 2-Hydroxyphenanthrene, 3-Hydroxyfluorene, and cadmium were leading contributors to the above associations. WBC mediated 8.22%-23.90% of association between PAHs and lung function., Conclusions: Co-exposure of PAHs and metals impairs lung function, and WBC could partially mediate this relationship. Our findings elucidate co-exposure effects of environmental mixtures on respiratory health and underlying mechanisms, suggesting that focusing on highly prioritized toxicants would effectively attenuate adverse effects., (© 2024. The Author(s).)

Background and Purpose: Ischemic stroke is a leading cause of mortality and disability globally, necessitating accurate prediction of intra-hospital mortality (IHM) for improved patient care. This study aimed to develop a practical nomogram for personalized IHM risk prediction in ischemic stroke patients., Methods: A retrospective study of 422 ischemic stroke patients (April 2020 - December 2021) from Chongqing Medical University's First Affiliated Hospital was conducted, with patients divided into training (n=295) and validation (n=127) groups. Data on demographics, comorbidities, stroke risk factors, and lab results were collected. Stroke severity was assessed using NIHSS, and stroke types were classified by TOAST criteria. Least absolute shrinkage and selection operator (LASSO) regression was employed for predictor selection and nomogram construction, with evaluation through ROC curves, calibration curves, and decision curve analysis., Results: LASSO regression and multivariate logistic regression identified four independent IHM predictors: age, admission NIHSS score, chronic obstructive pulmonary disease (COPD) diagnosis, and white blood cell count (WBC). A highly accurate nomogram based on these variables exhibited excellent predictive performance, with AUCs of 0.958 (training) and 0.962 (validation), sensitivities of 93.2% and 95.7%, and specificities of 93.1% and 90.9%, respectively. Calibration curves and decision curve analysis validated its clinical applicability., Conclusion: Age, admission NIHSS score, COPD history, and WBC were identified as independent IHM predictors in ischemic stroke patients. The developed nomogram demonstrated high predictive accuracy and practical utility for mortality risk estimation. External validation and prospective studies are warranted for further confirmation of its clinical efficacy., Competing Interests: The authors declared that they have no competing interests in this work., (© 2024 Zhou et al.)

Shunt infection is one of the most common complications of conventional hydrocephalus treatment. The route of invasion of a pathogen can modify the immune response of the CNS. The aim of the study is to analyze the immune response to shunt infection caused by S. epidermidis in children with hydrocephalus. The immune response to the pathogen will be analyzed on the basis of, inter alia, simple laboratory test results, such as changes in the pattern of white blood cells, including neutrophils, monocytes, and lymphocytes. The entire study analyzes changes in general parameters of the cerebrospinal fluid (pleocytosis, protein level, glucose level) and in levels of selected interleukins (IL-6, CXCL8 / IL-8, CCL3 / MIP-1a) in the cerebrospinal fluid. The clinical material analyzed in the study was collected in 2010-2014. The study group consisted of 30 patients, who were admitted to the hospital due to their first-ever episode of valve dysfunction caused by S. epidermidis infection. The control group consisted of 30 children who also suffered from congenital hydrocephalus but had not been operated on before. The most pronounced response to CSF infection in the study group was a significant increase in the counts of all investigated WBC lines in the samples collected immediately after the patients' admission to the ward. The earliest aberration of the CSF was a significant increase in protein level. An infection of a ventriculoperitoneal shunt caused by S. epidermidis evokes a very early peripheral blood response. In children affected by a ventriculoperitoneal valve infection, the humoral immune response detected in the cerebrospinal fluid precedes the increase in the level of pleocytosis. The highest level of cytokines in the cerebrospinal fluid is achieved when the pathogens are cleared. Phagocytes, and, in particular, monocytes, play an important role in the normalization of the cerebrospinal fluid parameters after the elimination of S. epidermidis. The local immune response of the central nervous system plays an important role in extinguishment of the inflammatory process., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Polis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Observational studies have shown a strong association between circulating white blood cell counts (WBC) and inflammatory skin diseases such as acne and psoriasis. However, the causal nature of this relationship is unclear. We performed a two-way two-sample Mendelian randomization (MR) analysis to investigate potential causal relationships between leukocytes and inflammatory skin diseases. The circulating white blood cell count, basophil cell count, leukocyte cell count, lymphocyte cell count, eosinophil cell count, and neutrophil cell count data were obtained from the Blood Cell Consortium (BCX). The data for inflammatory skin disorders, including acne, atopic dermatitis (AD), hidradenitis suppurativa (HS), psoriasis, and seborrheic dermatitis (SD), were obtained from the FinnGen Consortium R10. The primary analysis utilized inverse variance weighting (IVW) along with additional methods such as MR-Egger, weighted mode, and weighted median estimator. To assess heterogeneity among instrument variables, Cochran's Q test was employed, while MR-Egger intercept and MR-PRESSO were used to test for horizontal pleiotropy. IVW demonstrated that an elevated monocyte count was significantly associated with a decreased risk of psoriasis (OR = 0.897, 95% CI: 0.841-0.957, P = 0.001, FDR = 0.016). Additionally, an increased eosinophil count was causally associated with a higher risk of AD (OR = 1.188, 95% CI: 1.093-1.293, P = 0.000, FDR = 0.002). No inverse causal relationship between inflammatory skin disease and circulating white blood cell count was found. In conclusion, this study provides evidence that increased monocyte count is associated with a reduced risk of psoriasis and that there is a causal relationship between increased eosinophil counts and an increased risk of AD. These findings help us understand the potential causal role of specific white blood cell counts in the development of inflammatory skin diseases., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Aim to investigate the prognostic value of neutrophil to lymphocyte ratio (NLR) at the time of diagnosis, which is an inexpensive and easily accessible parameter, compared to factors known as prognostic value (such as R-IPI and NCCN-IPI) in patients with diffuse large B-cell lymphoma (DLBCL)., Aim: Prognostic value of NLR at diagnosis in DLBCL., Methods: A hundred (100) newly diagnosed DLBCL patients were included. The correlations between the NLR with clinical characteristics, treatment response, and survival were analyzed. The NLR cut-off value was taken at 3.5 accordıng to the receiver operating characteristic curve., Results: There were 53 patients with an NLR of 3.5 and 47 patients with an NLR < 3.5. Patients with NLR ≥ 3.5 had a complete response (CR) rate of 66.0% (n = 31/47), and patients with NLR < 3.5 had a CR rate of 98.1% (n = 51/52). The median progression-free survival (PFS) was 132.5 months (95%CI 103.1-162.0). PFS in the NLR ≥ 3.5 group (36 months) was significantly (P < 0.000) shorter than in the NLR < 3.5 group (185 months). The median overall survival (OS) for NLR ≥ 3.5 and NLR < 3.5 was 79.2 months (95% CI 51.6-106.8) and 197.8 months (95% CI 173.2-222.5), respectively. NLR ≥ 3.5 was associated with worse OS than NLR < 3.5 (P = 0.000). The high value of NLR (≥3.5) had lower treatment response rates, higher relapse, and death rates., Conclusion: High NLR was associated with poor treatment response, PFS, and OS. NLR can be used as a cost-effective and easy-to-interpret prognostic marker in DLBCL patients., (Copyright © 2024 Copyright: © 2024 Nigerian Journal of Clinical Practice.)