BACKGROUND: Human aging and white blood cell (WBC) count are complex traits influenced by multiple genetic factors. Predictors of chronological age have been developed using epigenetic clocks. However, the bidirectional causal effects between epigenetic clocks and WBC count have not been fully examined.
METHODS: This study employed Mendelian randomization (MR) to analyze summary statistics from four epigenetic clocks involving 34,710 participants, alongside data from the Blood Cell Consortium encompassing 563,946 individuals. We primarily explored bidirectional causal relationships using the random-effects inverse-variance weighted method, supplemented by additional MR methods for comprehensive analysis. Additionally, multivariate MR was applied to investigate independent effects of WBC count on epigenetic age acceleration.
RESULTS: In the two-sample univariate MR (UVMR) analysis, we observed that a decrease in lymphocyte count markedly accelerated aging according to the PhenoAge, GrimAge, and HannumAge metrics (all P < 0.01, β < 0), though it did not affect Intrinsic Epigenetic Age Acceleration (IEAA). Conversely, an increase in neutrophil count significantly elevated PhenoAge levels (β: 0.38; 95% CI 0.14, 0.61; P = 1.65E-03 < 0.01). Reverse MR revealed no significant causal impacts of epigenetic clocks on overall WBC counts. Furthermore, in multivariate MR, the impact of lymphocyte counts on epigenetic aging metrics remained statistically significant. We also identified a marked causal association between neutrophil counts and PhenoAge, GrimAge, and HannumAge, with respective results showing strong associations (PhenoAge β: 0.78; 95% CI 0.47, 1.09; P = 8.26E-07; GrimAge β: 0.55; 95% CI 0.31, 0.79; P = 5.50E-06; HannumAge β: 0.42; 95% CI 0.18, 0.67; P = 6.30E-04). Likewise, eosinophil cell count demonstrated significant association with HannumAge (β: 0.33; 95% CI 0.13, 0.53; P = 1.43E-03 < 0.01).
CONCLUSIONS: These findings demonstrated that within WBCs, lymphocyte and neutrophil counts exert irreversible and independent causal effects on the acceleration of PhenoAge, GrimAge, and HannumAge. Our findings highlight the critical role of WBCs in influencing epigenetic clocks and underscore the importance of considering immune parameters when interpreting epigenetic age.

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

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 (FEV1)/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 FEV1, FEV1/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.

UNASSIGNED: White blood cell (WBC) counts has been identified as a prognostic biomarker which frequently predict adverse outcomes and mortality risk in various conditions. However, evidence for the association between WBC counts and short-term outcomes after intracranial tumor resection remains limited. This study aimed to explore associations between preoperative WBC counts and thirty-day surgical mortality after craniotomy in adult intracranial tumor patients.
UNASSIGNED: This retrospective cohort study performed secondary analysis of 18,049 intracranial tumor craniotomy patients from the ACS NSQIP database (2012-2015). The major exposure and outcome were preoperative WBC counts and thirty-day surgical mortality, respectively. Cox regression modeling assessed the linear association between them. Non-linear associations between them were evaluated by conducting smooth curve fitting using an additive Cox proportional hazard model in conjunction with segmented linear regression modeling. Subgroup analysis and interaction testing assessed effect modification. Sensitivity analysis evaluated result robustness.
UNASSIGNED: The total thirty-day surgical mortality after craniotomy was 2.49% (450/18,049). The mean of preoperative WBC counts was 9.501 ± 4.402 × 10^9/L. Fully adjusted model shows that elevated preoperative WBC counts was independently associated with increased thirty-day surgical mortality (HR = 1.057, 95%CI: 1.040, 1.076). Further analysis revealed a non-linear association between them: below a WBC threshold of 13.6 × 10^9/L, higher WBC counts elevated thirty-day mortality (HR = 1.117; 95%CI: 1.077, 1.158), while risk plateaued and no significant mortality rise occurred above this level (HR = 1.015, 95%CI: 0.982, 1.050). Steroid usage status has a significant effect modification on the WBC-mortality association (P for interaction = 0.002). The non-linear WBC-mortality association was only present for non-steroid users (HR = 1.158, 95%CI: 1.108, 1.210) but not steroid users (HR = 1.009, 95%CI: 0.966, 1.055). The sensitivity analysis confirmed the result robustness.
UNASSIGNED: Elevated preoperative WBC counts were independently and non-linearly associated with an increased risk of thirty-day surgical mortality in adult non-steroid use patients undergoing craniotomy for intracranial tumors. As a convenient predictor, preoperative WBC data allows improved risk profiling and personalized management in adult intracranial tumor patients.

UNASSIGNED: Mobilization of certain immune cells may improve the ability of the immune system to combat tumor cells, but the effect of acute exercise on mobilizing immune cells has been sparsely investigated in cancer patients. Therefore, we examined how acute exercise influences circulating immune cells in breast cancer patients.
UNASSIGNED: Nineteen newly diagnosed breast cancer patients aged 36-68 performed 30 minutes of moderate-intensity exercise with a cycle ergometer. Blood samples were collected at various time points: at rest, at 15 (E15) and 30 minutes (E30) after onset of the exercise, and at 30 and 60 minutes post-exercise. We analyzed several immune cell subsets using flow cytometry.
UNASSIGNED: Acute exercise increased the number of total leukocytes, neutrophils, lymphocytes, monocytes, basophils, total T-cells, CD4+ T-cells, T helper (Th) 2-cells, Th 17-cells, CD8+ T-cells, CD4-CD8- T-cells, CD56+ natural killer (NK) cells, and CD14-CD16+ monocytes. Many of the changes were transient. Proportions of NK-cells and CD8+ T-cells increased, while the proportion of myeloid derived suppressor cells (MDSCs) reduced, and proportion of regulatory T-cells remained unchanged by exercise. Several associations were detected between cell mobilizations and disease state. For instance, tumor size correlated negatively with NK cell mobilization at E15, and progesterone receptor positivity correlated negatively with CD8+ T-cell mobilization.
UNASSIGNED: The findings show that the proportions of CD8+ T-cells and NK cells increased and the proportion of MDSCs proportion decreased in breast cancer patients after 30-minute exercise, suggesting a change in the profile of circulating immune cells towards more cytotoxic/anti-tumorigenic. The mobilization of some immune cells also appears to be related to the disease state.

UNASSIGNED: Inflammation is integral to diabetes pathogenesis. The novel hematological inflammatory biomarker, platelet to white blood cell ratio (PWR), is linked with various conditions such as chronic kidney disease and stroke. However, the association of this novel clinical indicator with diabetes still remains unclear, which is investigated in this study.
UNASSIGNED: A total of 10,973 Chinese participants were included and grouped according to the tertiles of PWR (T1, T2, and T3 groups). Diagnosis of prediabetes and diabetes adhered to American Diabetes Association criteria. Binary logistic regression was adopted to assess the relationship between PWR and both diabetes and prediabetes. The dose-response relationship of PWR and diabetes was examined using restricted cubic spline regression. Subgroup and interaction analyses were conducted to investigate potential covariate interactions.
UNASSIGNED: Individuals with higher PWR had better lifestyles and lipid profiles (all P < 0.05). After adjusting for all the covariates, the T2 group had a 0.83-fold (95% CI: 0.73-0.93, P < 0.01) risk of diabetes and that for the T3 group was 0.68-fold (95% CI: 0.60-0.78. P < 0.001). Dose-response analysis identified non-linear PWR-diabetes associations in the general population and females (both P < 0.05), but absent in males. Participants with prediabetes in the T2 and T3 groups had lower risks of diabetes (OR = 0.80 for the T2 group, P < 0.001 and 0.68 for the T3 group, P < 0.001) in the full models. All the sensitivity analysis support consistent conclusions.
UNASSIGNED: An increase in PWR significantly correlates with reduced diabetes risks. A non-linear PWR-diabetes relationship exists in the general population and females, but not in males. The correlation between PWR and diabetes indicates that PWR holds potentials in early identification and prevention of diabetes.

UNASSIGNED: In recent years, diseases caused by abnormal immune-inflammatory responses have become increasingly severe. Dietary intervention involving omega-3 polyunsaturated fatty acids (ω-3 PUFAs) has emerged as a potential treatment. However, research investigating the relationship between ω-3, ω-6 PUFAs, and ω-6 to ω-3 ratio with inflammatory biomarkers remains controversial.
UNASSIGNED: To investigate the correlation between the intake of ω-3 and ω-6 PUFAs and the ratio of ω-6: ω-3 with biomarkers of inflammation, the National Health and Nutrition Examination Survey (NHANES) data (1999 to 2020) was utilized. The systemic immune-inflammation index (SII), platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and white blood cell (WBC) were selected as study subjects. Dietary data for ω-3 and ω-6 PUFAs were collected via two 24-h dietary recall interviews. SII index and other indicators were obtained from the blood routine data. The multiple linear regression and restricted cubic spline models were utilized to evaluate the association of ω-3, ω-6 PUFAs intake, and ω-6: ω-3 ratio to SII and secondary measures.
UNASSIGNED: This study involved a total of 43,155 American adults. ω-3 and ω-6 PUFAs exhibited negative correlations with SII, PLR, NLR, and WBC. The correlation between ω-6: ω-3 ratio and SII, PLR, NLR, and WBC was not significant. Furthermore, the dose-response relationship showed that the relationship between the intake of ω-3 and ω-6 PUFAs and SII was an \"L\" pattern.
UNASSIGNED: Intake of dietary ω-3 and ω-6 PUFAs reduces the levels of several inflammatory biomarkers in the body and exerts immunomodulatory effects.

UNASSIGNED: Methicillin-resistant Staphylococcus aureus (MRSA) enteritis is a condition in which MRSA grows abnormally in the intestine after administration of antimicrobial agents, resulting in enteritis. Patients with MRSA detected in stool culture tests are often diagnosed with MSRA enteritis. However, uncertainty remains in the diagnostic criteria; therefore, we conducted epidemiological studies to define these cases.
UNASSIGNED: Patients who tested positive for MRSA by stool culture using selective media 48 h after admission to Kochi Medical School Hospital between April 1, 2012, and December 31, 2022, and did not meet the exclusion criteria were included. We defined MRSA enteritis (Group A) as cases that were responsive to treatment with vancomycin hydrochloride powder, had a Bristol Stool Scale of ≥ 5, and a stool frequency of at least three times per day; all others were MRSA carriers (Group B). Multivariate analysis was performed to risk factors associated with MRSA enteritis.
UNASSIGNED: Groups A and B included 18 (25.4%) and 53 (74.6%) patients, respectively. Multivariate logistic regression analysis showed that a white blood cell count of > 10000/µL (odds ratio [OR], 5.50; 95% confidence interval [CI], 1.12-26.9), MRSA count of ≥ 2+ in stool cultures (OR, 8.91; 95% CI, 1.79-44.3), and meropenem administration within 1 month of stool specimen submission (OR, 7.47; 95% CI, 1.66-33.6) were risk factors of MRSA enteritis.
UNASSIGNED: The case definitions reviewed for MRSA enteritis may be useful as diagnostic criteria.

Acute compartment syndrome (ACS) is a severe orthopedic issue that, if left untreated, can result in lasting nerve and muscle damage or even necessitate amputation. The association between admission laboratory blood test indicators and the occurrence of ACS in patients with tibial diaphysis fractures is currently a subject of debate. The objective of this research was to identify the contributing factors for ACS in individuals suffering from tibial diaphysis fractures. In this retrospective study, we collected data on a total of 705 individuals from our hospital, comprising 86 ACS patients and 619 non-ACS patients with tibial diaphysis fractures. These participants were categorized into two distinct groups: the ACS group and the non-ACS group. Despite the inherent limitations associated with retrospective analyses, such as potential biases in data collection and interpretation, we conducted a comprehensive analysis of demographics, comorbidities, and admission lab results. Our analytical approach included univariate analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis techniques, aiming to mitigate these limitations and provide robust findings. The statistical analysis revealed several predictors of ACS, including gender (p = 0.011, OR = 3.200), crush injuries (p = 0.004, OR = 4.622), lactic dehydrogenase (LDH) levels (p < 0.001, OR = 1.003), and white blood cell (WBC) count (p < 0.001, OR = 1.246). Interestingly, the study also found that certain factors, such as falls on the same level (p = 0.007, OR = 0.334) and cholinesterase (CHE) levels (p < 0.001, OR = 0.721), seem to provide a degree of protection against ACS. In order to better predict ACS, the ROC curve analysis was employed, which determined threshold values for LDH and WBC. The established cut-off points were set at 266.26 U/L for LDH and 11.7 × 109 cells per liter for WBC, respectively. Our research has successfully pinpointed gender, crush injuries, LDH levels, and white blood cell (WBC) count as crucial risk factors for the development of ACS in patients experiencing tibial diaphysis fractures. Furthermore, by establishing the cut-off values for LDH and WBC, we have facilitated a more personalized assessment of ACS risk, enabling clinical doctors to implement targeted early interventions and optimize patient outcomes.

White blood cells, also called leukocytes, are hematopoietic cells of the immune system that are involved in protecting the body against both infectious diseases and foreign materials. The abnormal development and uncontrolled proliferation of these cells can lead to devastating cancers. Their timely recognition in the peripheral blood is critical to diagnosis and treatment. In this study, we developed a microscopic imaging system for improving the visualization of white blood cells on Wright\'s stained blood smear slides, with two different setups: polarized light imaging and polarized hyperspectral imaging. Based on the polarized light imaging setup, we collected the RGB images of Stokes vector parameters (S0, S1, S2, and S3) of five types of white blood cells (neutrophil, eosinophil, basophil, lymphocyte, and monocyte), and calculated the Stokes vector derived parameters: the degree of polarization (DOP), the degree of linear polarization (DOLP), and the degree of circular polarization (DOCP)). We also calculated Stokes vector data based on the polarized hyperspectral imaging setup. The preliminary results demonstrate that Stokes vector derived parameters (DOP, DOLP, and DOCP) could improve the visualization of granules in granulocytes (neutrophils, eosinophils, and basophils). Furthermore, Stokes vector derived parameters (DOP, DOLP, and DOCP) could improve the visualization of surface structures (protein patterns) of lymphocytes enabling subclassification of lymphocyte subpopulations. Finally, S2, S3, and DOCP could enhance the morphologic visualization of monocyte nucleus. We also demonstrated that the polarized hyperspectral imaging setup could provide complementary spectral information to the spatial information on different Stokes vector parameters of white blood cells. This work demonstrates that polarized light imaging & polarized hyperspectral imaging has the potential to become a strong imaging tool in the diagnosis of disorders arising from white blood cells.