Cell Neutrophil Count Research Articles

Post-exchange neutrophil count, but not post-hematocrit, predicts endogenous erythropoiesis in patients with sickle cell disease undergoing chronic red cell exchange.

With chronic transfusion in sickle cell disease (SCD), equipoise exists regarding whether increasing the post-procedure hematocrit (Hct) suppresses endogenous erythropoiesis. Reticulocytosis predicts SCD morbidity and mortality, so this study's objective was to clarify the role of the post-procedure Hct in suppressing reticulocytosis and to identify other potential red cell exchange (RCE) parameters predictive of reticulocytosis. This retrospective analysis of 17 patients who underwent chronic RCE at a single institution between 2014 and 2022 examined both standard red cell exchanges (SRCE) and exchanges preceded by isovolemic hemodilution (IVH-RCE). Post-procedure parameters with biologic plausibility to influence the subsequent procedure's absolute reticulocyte count (sPre-ARC) were examined using regression modeling. Neither post-hematocrit, nor post-hemoglobin (Hb), nor ΔHb/day was associated with sPre-ARC or the change in HbS% per day (ΔHbS%/day). Concurrent Hb was predictive for SRCE but not IVH-RCE, where ARC trended lower than with SRCE. Male gender and post-procedure neutrophil and white cell counts were predictors of sPre-ARC, consistent with their associations with SCD morbidity and mortality. IVH-RCE had a stronger correlation than standard RCE between pre-Hct and neutrophil or white cell depletion. Although targeting a post-procedure Hct maintains a higher subsequent pre-procedure Hb and a lower sPre-HbS%, it does not lead to sustained suppression of reticulocytosis as measured by the sPre-ARC or the ΔHbS%/day. IVH-RCE or the addition of hydroxyurea could be considered in those patients with high reticulocyte, white blood cell, or neutrophil counts.

Effect of inflammatory factors on myocardial infarction

BackgroundCohort studies have increasingly shown associations between inflammatory markers and myocardial infarction (MI); however, the specific causal relationships between inflammatory markers and the development of MI remain unclear.Methods and resultsBy utilizing publicly accessible genome-wide association studies, we performed a two-sample Mendelian randomization (MR) analysis to explore the causal associations between inflammatory markers and myocardial infarction (MI). A random-effects inverse-variance weighted method was used to calculate effect estimates. The study included a total of 395,795 European participants for MI analysis and various sample sizes for inflammatory factors, ranging from 3,301 to 563,946 participants.Neutrophil count was found to increase the risk of MI (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.00–1.17; p = 0.04). C-reactive protein levels correlated positively with MI. No associations were observed with IL-1 beta, IL-6, IL-18, procalcitonin, TNF-α, total white cell count, or neutrophil percentage of white cells. Neutrophil count and C-reactive protein were inversely associated with lactate dehydrogenase: neutrophil cell count (OR 0.95; 95% CI, 0.93–0.98; p < 0.01) and C-reactive protein (OR 0.96; 95% CI, 0.92–1.00; p = 0.02). No associations of MI with myoglobin, troponin I, and creatine kinase-MB levels were found.ConclusionsThis two-sample MR analysis revealed a causal positive association of MI with neutrophil count, C-reactive protein level, and the myocardial injury marker lactate dehydrogenase. These results indicate that monitoring C-reactive protein and neutrophil counts may be useful in management of MI patients.

Clinical variability of equine asthma phenotypes and analysis of diagnostic steps in phenotype differentiation

BackgroundEquine asthma is a common, non-infectious, chronic lung disease that affects up to 80% of the horse population. Strict phenotyping and identification of subclinically asthmatic horses can be challenging. The aim of this study was to describe equine asthma phenotypes (mild, moderate, and severe asthma) defined by BALF cytology and occurrence of clinical signs in a population of privately owned horses and to identify the variables and examination steps with best discriminative potential. The standardised examination protocol included clinical examinations, blood work, airway endoscopy with bronchoalveolar lavage fluid analysis, arterial blood gas analysis and radiography under clinical conditions performed by one veterinarian.ResultsOut of 26 horses, four were diagnosed with mild (subclinical), seven with moderate, and seven with severe asthma based on clinical examination and BALF cytology. Eight horses served as controls. Cough with history of coughing was the strongest variable in phenotype differentiation. Factor analysis revealed an increasing clinical variability with disease severity and an overlapping of clinical presentations between phenotypes. Elevated mast cell (4/4 horses) and neutrophil counts (3/4 horses) in bronchoalveolar lavage cytology differentiated mild asthmatic horses from healthy horses. Moderate and severe asthmatic horses were characterised by clinical signs and neutrophil counts.ConclusionsThe results indicate that medical history, clinical examination and bronchoalveolar lavage cytology are minimum indispensable steps to diagnose equine asthma and that phenotypes are clinically overlapping. A differentiation of three phenotypes without neutrophil and mast cell counts in bronchoalveolar lavage cytology is not sufficient for clinical diagnostics. A comparably exact diagnosis cannot be achieved by relying on alternative examinations used in this study. Screenings of inconspicuous horses with bronchoalveolar lavage can aid in diagnosing subclinically affected animals, however, group size was small, the procedure is invasive and clinical relevance of slightly elevated cells in bronchoalveolar lavage remains unclear. Clinical relevance could not be clarified in this study, since follow-up examinations or lung function testing were not performed.

EFFECT OF GALAM LEAF EXTRACT AND TRI-CALCIUM SILICATE CEMENT ON NEUTROPHIL CELLS IN WISTAR RAT PULP

Background: Pulp capping is a method of sealing the pulp chamber in teeth with cavities that extend to the pulp. Direct pulp capping involves applying a material directly onto the exposed pulp tissue. Tri-calcium silicate cement (Ca3SiO5) is commonly used due to its nanoparticle mineral composition, but it can cause continued inflammation. Galam leaf (Melaleuca cajuputi) is known for its anti-inflammatory properties, owing to secondary metabolites like alkaloids, flavonoids, polyphenols, and saponins, potentially compensating for the drawbacks of tri-calcium silicate cement. Purpose: To determine the effect of combining Galam leaf extract (Melaleuca cajuputi subsp. Cumingiana (Turz) Barlow) with tri-calcium silicate cement as a direct pulp capping material on neutrophil cell count in the pulp of Wistar rats (Rattus norvegicus). Methods: This pure experimental study used a posttest-only control design. Thirty-six Wistar rats were divided into nine groups: one received a combination of 100% Galam leaf extract and tri-calcium silicate cement; one positive control group received tri-calcium silicate cement alone; and one negative control group received direct placement with glass ionomer cement (GIC). The neutrophil cell count was assessed on days 1, 2, and 3. Results: Two-way ANOVA results indicated a significant effect based on treatment and time (p &lt; 0.05). Further analysis with the Post Hoc Bonferroni test (p &lt; 0.05) revealed differences in neutrophil cell counts across nearly all groups on days 1, 2, and 3. Conclusion: The combination of 100% Galam leaf extract and tri-calcium silicate cement significantly reduced neutrophil cell counts compared to both positive and negative control groups on days 1, 2, and 3, indicating anti-inflammatory effect.

P102 PH-SENSOR GPR68 PLAYS A ROLE IN THE CARDIOPROTECTIVE EFFECTS OF A HIGH FIBRE DIET

Background/Objective: Dietary fibre lowers blood pressure (BP) via short-chain fatty acids, acidic metabolites released from fibre fermentation by the bacteria in the large intestine. This acidic microenvironment may activate pH-sensing receptor GPR68, expressed primarily on immune cells, which play a crucial role in BP regulation. Here, we aimed to investigate whether GPR68 confers the cardioprotective effects of a high-fibre diet in hypertension by regulating inflammatory responses. Methods: 6–8-week-old male wildtype (WT) and GPR68-deficient (Gpr68-/-) fed a control or high-fibre diet underwent subcutaneous implantation of minipumps containing Angiotensin II (0.75 mg/kg body weight/day, 4 weeks, n=8/group). BP was measured weekly by tail-cuff. Morphometric, histological, and flow cytometric analyses were performed following the 4-week protocol. Results: High-fibre-fed WT mice exhibited blunted elevations in systolic BP (week 4; p=0.0508) and lower cardiac interstitial collagen deposition (p=0.0495) compared to WT mice fed a control diet. However, high fibre did not lower BP (week 4; control vs high-fibre, p=0.689) or cardiac collagen deposition (p=0.842) in Gpr68-/- mice. High-fibre-fed WT mice exhibited improved aortic elastin content compared to control-fed WT mice (p=0.0503), whereas this remained negligible in Gpr68-/- mice (p=0.885). Flow cytometric analysis revealed that high fibre decreased aortic macrophage (p=0.0072) and neutrophil cell counts (p=0.0273) in mice, irrespective of genotype. High fibre also decreased overall renal immune cell counts (p=0.0213) and dendritic cells (p=0.0488) in mice, irrespective of genotype. Finally, high fibre-fed mice had overall decreased circulating immune cell counts (p=0.0264), specifically CD8+ T cells (p=0.0235), and γδ T cells (p=0.0264). Conclusions: High fibre intervention on Angiotensin II-treated GPR68-deficient mice did not lower their BP or cardiac fibrosis. All angiotensin II-treated mice fed a high-fibre diet exhibited prominent changes in various immune cell populations, irrespective of genotype. Nonetheless, this study provides novel insight that GPR68 is involved in the cardioprotective effects of a high-fibre diet. This is most likely via in an immune-independent manner, warranting further investigations into its underlying mechanisms of action.

Relationship between circulating white blood cell count and inflammatory skin disease: a bidirectional mendelian randomization study.

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.

Hematological Markers as Predictors of ICU Admission in COVID-19 Patients: A Case-Control Study From a Tertiary Hospital.

COVID-19 illness severity ranges from mild- to life-threatening cases necessitating critical care. Rapid prediction of disease severity and the need for critical care support in COVID-19 patients remain essential, not only for current management but also for preparedness in future pandemics. This study aimed to assess hematological parameters as predictors of intensive care unit (ICU) admission and survival in COVID-19 patients, providing insights applicable to a broad range of infectious diseases. A case-control study was conducted at Hospital Raja Perempuan Zainab II, a tertiary referral hospital in Kelantan, Malaysia, from March 2020 to August 2021. Demographics, clinical, and laboratory data were retrieved from patients' medical records. Statistical analyses, including the Chi-square (χ2) test, independent t-tests, and simple and multiple logistic regressions, were used to analyze the data. A receiver operating characteristic (ROC) curve analysis was conducted to assess the accuracy of the predictors. The median age was 51 years, with females comprising 56.7% (n=148) and males 43.3% (n=113). A total of 88.5% of patients were admitted to non-ICU wards, with a mortality rate of 5.7%. Significant differences were observed in the distribution of hematological parameters between ICU-admitted and non-admitted patients. Neutrophil (OR: 23.96, 95% CI: 7.296-78.675) and white blood cell (WBC) count (OR: 36.677, 95% CI: 2.086-644.889) were the most significant predictors for ICU admission and survival, respectively. WBC and neutrophil counts exhibited high predictive value for ICU admission, while WBC, neutrophil, lymphocyte, and immature granulocyte (IG) counts were significant predictors of survival status among COVID-19 patients. These findings underscore the continued relevance of hematological markers in managing severe respiratory infections and improving critical care triage, with implications for current and future healthcare challenges.

#758 NGAL dipstick for peritonitis: bridging the gap between rapid assessment and clinical efficiency in peritoneal dialysis

Abstract Background and Aims Neutrophil gelatinase-associated lipocalin (NGAL) is a versatile protein known for its multifunctional roles, extending beyond its conventional use as a biomarker. It actively participates in crucial biological processes such as inflammation, proliferation, and migration. This study seeks to evaluate NGALds, a recently developed dipstick test, in comparison to the established laboratory method (NGALlab) for the early detection of peritonitis related to peritoneal dialysis (PD). The focus of the investigation lies in analyzing peritoneal fluid to develop a rapid and effective diagnostic tool, aiming to enhance the management of peritonitis. Method A retrospective analysis was undertaken to validate diagnostic accuracy, utilizing parallel samples obtained from peritoneal effluents. Samples were obtained from both PD stable patients undergoing routine analysis and from PD patients with suspected or confirmed peritonitis. The assessment of NGALds involved a direct comparison with the established NGALlab. Peritoneal NGALlab quantification was conducted using the BioPorto test, employing a particle-enhanced turbidimetric immunoassay. The NGALds, a rapid semi-quantitative assay, utilized colorimetric test strips and an antibody sandwich lateral flow dipstick test. The greatest value of NGAL detected by dipstick is 600 μg/L. Statistical analyses, including Spearman rank correlation coefficients (Rs), were performed with SPSS Statistics 26.0 software. Additionally, ROC analysis was carried out using white cell count and percentage of Neutrophils in peritoneal fluids as the gold standard. Results Among the 301 peritoneal effluent samples analyzed, 156 were diagnosed with suspected peritonitis using NGALlab and ISPD criteria. Each sample underwent analyses with both NGALlab and NGALds. As depicted in Fig. 1, NGALds exhibited a robust correlation with NGALlab categories (Rs = 0.876, P &amp;lt; 0.001), accurately identifying 96% (150 out of 156) of peritonitis cases. Discrepancies between NGALlab and NGALds were most evident when NGAL values exceeded the 600 μg/L threshold. Nevertheless, these variations did not impact clinical significance, as both methods consistently diagnosed elevated NGAL values indicative of peritonitis. After ROC analysis, which yielded an AUC of 0.82 (p &amp;lt; 0.001) (Fig. 2), the Youden Index was employed to identify a threshold value of 100 μg/L for the diagnosis of suspected peritonitis. Importantly, the application of this threshold to NGALds demonstrated a positive predictive value of 0.64 and a negative predictive value of 0.87. Conclusion In conclusion, our study reinforces the significant correlation between NGAL values obtained through the laboratory standard (NGALlab) and the novel NGAL dipstick test (NGALds). Notably, NGALds exhibited high efficacy, accurately identifying 96% of peritonitis cases diagnosed by NGALlab. This robust performance positions the NGAL dipstick as a valuable and accessible alternative for rapid assessment in patients exhibiting symptoms indicative of peritonitis. The user-friendly attributes of NGALds not only make it a practical diagnostic tool but also a patient-centric one. Furthermore, the high negative predictive value provides confidence in considering NGALds as a frontline diagnostic tool for suspected peritonitis. The ease of use and prompt results open a promising avenue for improving clinical workflows, offering an opportunity for expedited and efficient peritonitis diagnosis. For instance, NGALds could find utility in centres where NGAL is unavailable in the laboratory or at the patient's home.

Filgrastim Use in the Treatment of Azathioprine-Induced Myelosuppression Toxicity After Prescription Error in the Feline.

Only one report on the successful use of filgrastim (granulocyte colony-stimulating factor) in cats for severe neutropenia following azathioprine toxicity exists. Here, we report on a case in which a cat was prescribed methimazole but the medication was filled incorrectly with azathioprine tablets and the prescription label indicated a methimazole dosing regimen that was administered for three days before recognition of the error. On presentation, the cat's physical examinations were consistent with previous examinations before ingestion of azathioprine. A complete blood cell count revealed neutropenia and leukopenia. The cat later developed hyporexia, dehydration, and vomiting. Treatment included antinausea and appetite stimulant medications, filgrastim, and antibiotics. Filgrastim given as subcutaneous injections over the course of treatment increased neutrophil cell counts after suppression. The cat made a full recovery after responding to the treatment protocol. Based on the perceived response to filgrastim in this single feline case report, its use can be considered for the treatment of azathioprine-induced neutropenia in cats.

The role of Neutrophil counts, infections and Smoking in mediating the Effect of Bronchiectasis on Chronic Obstructive Pulmonary Disease: a mendelian randomization study.

The causality of the relationship between bronchiectasis and chronic obstructive pulmonary disease (COPD) remains unclear. This study aims to investigate the potential causal relationship between them, with a specific focus on the role of airway inflammation, infections, smoking as the mediators in the development of COPD. We conducted a two-sample Mendelian randomization (MR) analysis to assess: (1) the causal impact of bronchiectasis on COPD, sex, smoking status, infections, eosinophil and neutrophil counts, as well as the causal impact of COPD on bronchiectasis; (2) the causal effect of smoking status, infections and neutrophil counts on COPD; and (3) the extent to which the smoking status, infections and neutrophil counts might mediate any influence of bronchiectasis on the development of COPD. COPD was associated with a higher risk of bronchiectasis (OR 1.28 [95% CI 1.05, 1.56]). Bronchiectasis was associated with a higher risk of COPD (OR 1.08 [95% CI 1.04, 1.13]), higher levels of neutrophil (OR 1.01 [95% CI 1.00, 1.01]), higher risk of respiratory infections (OR 1.04 [95% CI 1.02, 1.06]) and lower risk of smoking. The causal associations of higher neutrophil cells, respiratory infections and smoking with higher COPD risk remained after performing sensitivity analyses that considered different models of horizontal pleiotropy, with OR 1.17, 1.69 and 95.13, respectively. The bronchiectasis-COPD effect was 0.99, 0.85 and 122.79 with genetic adjustment for neutrophils, respiratory infections and smoking. COPD and bronchiectasis are mutually causal. And increased neutrophil cell count and respiratory infections appears to mediate much of the effect of bronchiectasis on COPD.

The Potential of Fish Protein Hydrolysate Supplementation in Nile Tilapia Diets: Effects on Growth and Health Performance, Disease Resistance, and Farm Economic Analysis.

Fish protein hydrolysate (FPH) has shown immense potential as a dietary protein supplement and immunostimulant in aquaculture, especially in Nile tilapia production. Four isoproteic diets (30% crude protein) were prepared by including FPH at varying percentages (0%, 0.5%, 1%, and 2%). Nile tilapia fed with FPH diets for 90 days, and their growth performance, feed utilization, blood biochemistry, liver and gut morphology, and resistance against Streptococcus iniae were investigated. The findings revealed that diets physical attributes such as pellet durability index and water stability were remarkably (p < 0.05) varied between experimental diet groups. Furthermore, the test diets were more palatable when FPH was included at 1% and 2%. Fish that were fed with a 2% FPH-treated diet had significantly (p < 0.05) greater growth indices than other treatments. Additionally, their feed utilization was significantly (p < 0.05) improved. The experimental diets and intestinal total bacteria count (TBC) exhibited a rising trend with FPH levels, where the 2% FPH-treated diet recorded the highest TBC. Neutrophil (109/L), lymphocyte (109/L), eosinophil (109/L), and red blood cell(1012/L) counts were significantly (p < 0.05) higher in the 2% FPH-treated group, while the white blood cell (109/L), and basophil (109/L) counts were not influenced by the FPH inclusion. Moreover, the FPH-treated groups displayed lower creatinine, bilirubin, and urea levels than the control. The histological examination demonstrated that themid-intestine of 2% FPH-fed Nile tilapia had an unbroken epithelial wall, more villi with frequent distribution of goblet cells, wider tunica muscularis, and stronger stratum compactum bonding than other treatments. Additionally, this group exhibited more nuclei and erythrocytes and less vacuolar cytoplasm in liver than their counterparts. Nile tilapia that were given a diet containing 2% FPH had significantly (p < 0.05) higher resistance (83.33%) to S. iniae during the bacterial challenge test. A significant (p < 0.05) enhancement in farm economic efficiency was observed in the higher inclusion of FPH in diets. In summary, 2% FPH supplementation in Nile tilapia diets improved their growth performance, feed utilization, health status, disease resistance, and farm economic efficiency.

Immune stimulatory effect of Nigella sativa in healthy animal models: A systematic review and meta-analysis

The immune-modulatory effects of black seeds (Nigella sativa seeds, NSS) are well documented, but the overall in vivo impact of this important natural medicinal product on immune system function has yet to be established. Here we systematically reviewed and meta-analyzed the effects of NSS on humoral [serum titers of immunoglobulins including IgG, IgM, anti-Newcastle virus disease (anti-NDV), and sheep red blood cell antigen (anti-SRBC)] and cellular immunity [total white blood cell (WBC) count and percentages of monocytes, lymphocytes, basophils, neutrophils, and eosinophils] in healthy animals. The PubMed, ScienceDirect, Web of Science, and Scopus databases were searched according to predefined eligibility criteria. Meta-analyses were performed to estimate the final effect size using RevMan software. Seventeen animal studies were eligible for analysis. For humoral immunity, the overall pooled effect size (ES) of NSS on serum titers of IgM and anti-NVD antibodies was not significantly different [mean difference (MD) 75.27, 95% CI: −44.76 to 195.30, p = 0.22 (I2 = 89%, p = 0.003), and −0.01, 95% CI: −0.27 to 0.25, p = 0.94 (I2 = 74%, p = 0.02), respectively]. However, NSS significantly increased serum titers of IgG and anti-SRBC antibodies [MD 3.30, 95% CI: 2.27 to 4.32, p = 0.00001 (I2 = 0%, p = 0.97), and 1.15, 95% CI: 0.74 to 1.56, p = 0.00001 (I2 = 0%, p = 0.43), respectively]. For cellular immunity, the ES of NSS on WBCs, monocytes, and lymphocytes were not significantly different [MD 0.29, 95% CI: −0.55 to 1.13, p = 0.50, (I2 = 14%, p = 0.32), - 0.01, 95% CI: −0.45 to 0.44, p = 0.97 (I2 = 0%, p = 0.77), and 4.73, 95% CI: −7.13 to 16.59, p = 0.43, (I2 = 99%, p = 0.00001), respectively]. In conclusion, black seeds enhance humoral immunity in healthy animals but do not affect cellular immunity.

Advanced gastrointestinal stromal tumor: reliable classification of imatinib plasma trough concentration via machine learning

AimPatients with advanced gastrointestinal stromal tumors (GISTs) exhibiting an imatinib plasma trough concentration (IM Cmin) under 1100 ng/ml may show a reduced drug response rate, leading to the suggestion of monitoring for IM Cmin. Consequently, the objective of this research was to create a customized IM Cmin classification model for patients with advanced GISTs from China.MethodsInitial data and laboratory indicators from patients with advanced GISTs were gathered, and the above information was segmented into a training set, validation set, and testing set in a 6:2:2 ratio. Key variables associated with IM Cmin were identified to construct the classification model using the least absolute shrinkage and selection operator (LASSO) regression and forward stepwise binary logistic regression. Within the training and validation sets, nine ML classification models were constructed via the resampling method and underwent comparison through the Brier scores, the areas under the receiver-operating characteristic curve (AUROC), the decision curve, and the precision-recall (AUPR) curve to determine the most suitable model for this dataset. Two methods of internal validation were used to assess the most suitable model's classification performance: tenfold cross-validation and random split-sample validation (test set), and the value of the test set AUROC was used to evaluate the model's classification performance.ResultsSix key variables (gender, daily IM dose, metastatic site, red blood cell count, platelet count, and percentage of neutrophils) were ultimately selected to construct the classification model. In the validation set, it is found by comparison that the Extreme Gradient Boosting (XGBoost) model has the largest AUROC, the lowest Brier score, the largest area under the decision curve, and the largest AUPR value. Furthermore, as evaluated via internal verification, it also performed well in the test set (AUROC = 0.725).ConclusionFor patients with advanced GISTs who receive IM, initial data and laboratory indicators could be used to accurately estimate whether the IM Cmin is below 1100 ng/ml. The XGBoost model may stand a chance to assist clinicians in directing the administration of IM.

Measurement of the Neutrophils Count and Oxidative Burst in Neutrophils of Patients with Sanjad Sakati Syndrome.

Sanjad Sakati Syndrome (SSS) is categorized as a neuroendocrine-related disease due to disorders of the nervous and hormonal systems. Since hormonal changes in these patients may affect the nature and function of the immune system. Thus, in this study, cell count and phagocytotic function of neutrophils were evaluated which may be influenced by changes in the hormonal rate and growth factors. In this study, the neutrophil count value and the oxidative burst were evaluated in six patients diagnosed with SSS and six healthy individuals. There was a significant reduction in the neutrophil count observed in SSS patients compared to healthy controls (37.41±7.93 percent vs. 66.5±6.8 percent). However, there was no significant difference in neutrophil oxidative index between patients with SSS and control subjects (172.33±55.08 vs. 217.00±77.38). We concluded that in patients with SSS, the phagocytic activity of neutrophils was not affected by hormonal changes, while the number of neutrophils and neutrophil-to-lymphocyte ratio (NLR) index were decreased.

Clinical Characteristics, Treatment, and Outcomes of Veterans with Cerebrospinal Fluid Culture Positive for Gram-Negative Rod Bacteria: A Retrospective Analysis over 18 Years in 125 Veterans Health Administration Hospitals.

Optimal management for patients with bacterial ventriculitis/meningitis due to Gram-negative rods (GNRs) has yet to be well investigated. We assessed the clinical characteristics, treatment, and outcomes of patients with a positive cerebrospinal fluid (CSF) culture for GNRs. We conducted a retrospective cohort study of all patients with a positive CSF culture within the Veterans Health Administration (VHA) system during 2003-2020. Clinical and microbiological characteristics between the true meningitis and contamination groups were compared. Of the 5919 patients with positive CSF cultures among 125 nationwide VHA acute-care hospitals, 297 (5.0%) were positive for GNRs. Among 262 patients analyzed, 156 (59.5%) were assessed as patients with true meningitis, and 106 (40.5%) were assessed as patients with contaminated CSF cultures. Patients with true meningitis had a significantly higher CSF protein (median 168 vs 57mg/dL, p < 0.001), CSF white blood cell count (median 525 vs 3/µL, p = 0.008) and percentage of neutrophils in CSF (median 88 vs 4%, p < 0.001). Enterobacterales were more common in the true meningitis group, while unidentified GNR or polymicrobial CSF cultures were more common in the contamination group. The all-cause 90-day mortality was 25.0% (39/156) in patients with true meningitis and 10.4% (11/106) in those with contaminated CSF cultures. None of the 11 patients with contaminated CSF cultures who died were considered due to missed meningitis. More than 40% of patients with a positive CSF culture with GNR did not receive treatment without negative consequences. Careful clinical judgment is required to decide whether to treat such patients.

Relationship between airway inflammation, small airway dysfunction, and frequency of acute exacerbations in patients with chronic obstructive pulmonary disease

ContextRecurrent exacerbations in COPD patients are associated with accelerated reduction in lung function. Airway inflammation and small airway dysfunction were recognized for a long time as an essential feature of COPD.AimTo study the relationship between neutrophilic airway inflammation, small airway dysfunction, and frequency of acute exacerbations in COPD patients.Settings and designThis was a cross-sectional study.Patients and methodsThirty COPD patients were enrolled and classified into two groups: infrequent exacerbators (IFE) “who developed ≤ 1 exacerbation per year” and frequent exacerbators (FE) “who developed ≥ 2 exacerbations per year” in the last year prior to this study. All patients included in the study underwent clinical evaluation, and assessment of small airway dysfunction by pulmonary function testing (MEF 25–75, RV/TLC, and DLCO) and paired inspiratory and expiratory HRCT-chest to measure the mean lung density (MLD) as well as assessment of neutrophilic airway inflammation by taking BAL via bronchoscopy and examined for differential cell count.ResultsThe small airway dysfunction is more severe in the case of the FE COPD group as there were statistically significant differences between FE and IFE COPD groups in %MEF 25–75 and RV/TLC (p = 0.038 and p = 0.030, respectively). The mean value of the BAL neutrophil % was higher in FE than in IFE COPD patients but without a significant statistical difference (p = 0.513). There were statistically significant negative correlations between %FEV1 (p = 0.026), %FVC (p = 0.020), and %MEF25–75 (p = 0.005) and MLD(E/I) in all studied COPD patients.ConclusionCOPD patients associated with small airway dysfunction and increased BAL neutrophil cell count are more prone to frequent exacerbations.Trial registrationClinicalTrials.gov NCT06040931. Registered 18 Sept 2023—Retrospectively registered.

Study of long-term effects of pelvic radiotherapy on the function of bone marrow in recurrent cervical cancer patients.

Purpose: To study the effects of prior pelvic radiotherapy on bone marrow suppression in recurrent cervical cancer patients during chemotherapy. Methods and materials: The cases of 129 patients with recurrent cervical cancer were reviewed, of which 77 patients had pelvic radiotherapy history and another 52 patients with no pelvic radiotherapy history were used as control group. All patients received a chemotherapy regimen of paclitaxel combined with carboplatin (TC) per 21 days for 5-6 times. Hematologic toxicity, including count of red blood cell, white blood cell and neutrophil cell and platelet, was defined by using Common Terminology Criteria for Adverse Events (version 4.0). The relationship between age, body mass index, disease free survival, pathological types, FIGO stages, radiotherapy methods and the degree of bone marrow suppression during chemotherapy was statistically analyzed, respectively, for all recurrent cervical cancer patients. Results: Among 77 patients with previous radiotherapy history, 73 recurrent patients (94.8%) had bone marrow suppression followed by chemotherapy. Recurrent cervical cancer patients without prior radiotherapy (n=52) showed a lower risk of bone marrow suppression followed by chemotherapy (n=39, 75.0%, P < 0.05). The probability of severe bone marrow suppression (grade III-IV) after chemotherapy in recurrent cervical patients with or without history of radiotherapy was 41.6% and 13.5%, respectively (P < 0.05). In univariate analysis, radiotherapy methods were associated with the incidence of grade III-IV bone marrow suppression in recurrent cervical cancer patients (P=0.005). In multivariate analysis, radiotherapy methods and extended-field radiotherapy were the risk factor of grade III-IV bone marrow suppression (χ2=16.975, P=0.001). No significant differences in the counts of white blood cell, hemoglobin and platelet were observed before chemotherapy at relapse between patients with and without prior radiotherapy. Reduction of white blood cell counts, absolute value of neutrophil cell and platelet counts composited majority type of grade III and IV bone marrow suppression. Conclusions: The prior pelvic radiotherapy significantly increased the incidence of bone marrow suppression during chemotherapy in recurrent cervical cancer patients. When treating recurrent cervical cancer patients with chemotherapy who had prior radiotherapy, especially for those experienced external beam radiation therapy, essential attention and timely intervention are recommended to ensure completion of chemotherapy and clinical efficacy.

Breastfeeding and Neonatal Age Influence Neutrophil-Driven Ontogeny of Blood Cell Populations in the First Week of Human Life.

The first few days of life are characterized by rapid external and internal changes that require substantial immune system adaptations. Despite growing evidence of the impact of this period on lifelong immune health, this period remains largely uncharted. To identify factors that may impact the trajectory of immune development, we conducted stringently standardized, high-throughput phenotyping of peripheral white blood cell (WBC) populations from 796 newborns across two distinct cohorts (The Gambia, West Africa; Papua New Guinea, Melanesia) in the framework of a Human Immunology Project Consortium (HIPC) study. Samples were collected twice from each newborn during the first week of life, first at Day of Life 0 (at birth) and then subsequently at Day of Life 1, 3, or 7 depending on the randomization group the newborn belongs to. The subsequent analysis was conducted at an unprecedented level of detail using flow cytometry and an unbiased automated gating algorithm. The results showed that WBC composition in peripheral blood changes along patterns highly conserved across populations and environments. Changes across days of life were most pronounced in the innate myeloid compartment. Breastfeeding, and at a smaller scale neonatal vaccination, were associated with changes in peripheral blood neutrophil and monocyte cell counts. Our results suggest a common trajectory of immune development in newborns and possible association with timing of breastfeeding initiation, which may contribute to immune-mediated protection from infection in early life. These data begin to outline a specific window of opportunity for interventions that could deliberately direct WBC composition, and with that, immune trajectory and thus ontogeny in early life. This trial is registered with NCT03246230.

Causal associations of white blood cell count and sudden sensorineural hearing loss: a bidirectional and multivariable Mendelian randomization study.

Numerous compelling observational studies have demonstrated a plausible correlation between the white blood cell count and the susceptibility to sudden sensorineural hearing loss (SSNHL). Nevertheless, the exact causal relationship between these two factors remains ambiguous. The objective of our study was to assess the causal impact of white blood cell count on sudden sensorineural hearing loss through the implementation of a bidirectional and multivariable Mendelian randomization (MR) methodology. Genetic data pertaining to white blood cell count were acquired from the Blood Cell Consortium, encompassing a total of 563,946 subjects. Concurrently, summary data on sudden sensorineural hearing loss were sourced from a Genome-Wide Association Study (GWAS), involving 196,592 participants, comprising 1,491 cases and 195,101 controls. The primary method employed for MR analysis was the Inverse Variance Weighted method (IVW), while sensitivity analysis utilized the Weighted Median method, MR-Egger method, and MR-PRESSO method. In IVW method, genetically predicted elevated lymphocyte cell count demonstrates an effective reduction in the risk of sudden sensorineural hearing loss (odds ratio = 0.747, 95% CI = 0.565-0.987, p = 0.04). These findings remain consistent in multivariate MR analysis, even after adjusting for monocyte cell count and neutrophil cell count levels (odds ratio = 0.929, 95% CI = 0.867-0.995, p = 0.036). However, there is no discernible evidence supporting a direct causal relationship between monocyte cell count and neutrophil cell count levels and the occurrence of SSNHL. Within the normal range, higher lymphocyte cell count levels exhibit a potential protective effect against SSNHL. Meanwhile, no direct causal relationship are identified between monocyte cell count and neutrophil cell count levels and the risk of SSNHL.

The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study.

Studies have suggested that the progress of most kidney diseases from occurrence to course and subsequent related complications are closely related to inflammatory reaction. Increased common leukocytes count in the family (neutrophils, eosinophils, basophils, lymphocytes, etc.) are also involved in the tissue damage of kidney diseases. However, these studies are only traditional observational studies, which cannot prove whether there is a causal relationship between these four kinds of leukocytes count and kidney diseases. We aim to explore the causal relationship between these four kinds of leukocytes count and kidney diseases by Mendelian randomization (MR). Large sample size of the genome-wide association database of four cell traits (neutrophil, basophil, lymphocyte, and eosinophil cell counts) in the leukocyte family were used as exposure variables. The outcome variables were various renal diseases (including chronic renal failure, acute renal failure, hypertensive heart or/and kidney disease, hypertensive renal disease, disorders resulting from impaired renal tubular function, and type 1 diabetes with renal complications). The covariates used in multivariable MR are also four cell traits related to blood cells (neutrophil, basophil, lymphocyte, and eosinophil cell counts). Instrumental variables and single nucleotide polymorphic loci were identified (P < 5 × 10-8. Linkage disequilibrium R2 < 0.001). The causal relationships were studied by inverse variance weighted (IVW), weighted median, and MR-Egger regression. Sensitivity analysis was also performed. In our study, IVW analysis results showed that increased neutrophil cell count was a risk factor for chronic renal failure (OR = 2.0245861, 95% CI = 1.1231207-3.649606, P = 0.01896524), increased basophil cell count was a risk factor for chronic renal failure (OR = 3.975935, 95% CI = 1.4871198-10.62998, P = 0.005942755). Basophil cell count was not a risk factor for acute renal failure (OR = 1.160434, 95% CI = 0.9455132-1.424207, P = 0.15448828). Increased basophil cell count was a protective factor for hypertensive heart and/or renal disease (OR = 0.7716065, 95% CI = 0.6484979-0.9180856, P = 0.003458707). Increased basophil cell count was a risk factor for disorders resulting from impaired renal tubular function (OR = 1.648131, 95% CI = 1.010116-2.689133, P = 0.04546835). Increased lymphocyte cell count was a risk factor for hypertensive renal disease (OR = 1.372961, 95% CI = 1.0189772-1.849915, P = 0.03719874). Increased eosinophil cell count was a risk factor for type 1 diabetes with renal complications (OR = 1.516454, 95% CI = 1.1826453-1.944482, P = 0.001028964). Macrophage inflammatory protein 1b levels was a protective factor for renal failure (OR = 0.9381862, 95% CI = 0.8860402-0.9934013, P = 0.02874872). After multivariable MR was used to correct covariates (neutrophil, basophil, and lymphocyte cell counts), the correlation effect between increased eosinophil cell counts and type 1 diabetes with renal complications was still statistically significant (P = 0.02201152). After adjusting covariates (neutrophil, basophil, and eosinophil cell counts) with multivariable MR, the correlation effect between increased lymphocyte cell counts and hypertensive renal disease was still statistically significant (P = 0.02050226). This study shows that increased basophils can increase the relative risk of chronic renal failure and renal tubular dysfunction, and reduce the risk of hypertensive heart disease and/or hypertensive nephropathy, while increased basophil cell count will not increase the relative risk of acute renal failure, increased neutrophil cell count can increase the risk of chronic renal failure, increased lymphocyte cell count can increase the relative risk of hypertensive nephropathy, and increased eosinophil cell count can increase the relative risk of type 1 diabetes with renal complications. Macrophage inflammatory protein 1b levels was a protective factor for renal failure.