Higher Total White Blood Cell Research Articles

Leukopenia that successfully treated by Ustekinumab in patient with psoriatic arthritis

Introduction:Psoriatic Arthritis (PsA) is an immune-mediated disease. The effectiveness of biologics has changed therapeutic strategies for psoriasis. We report a case of leukopenia in a patient with psoriatic arthritis (PsA) who was treated with Ustekinumab. Case presentation: A 36- year- old Syrian female presented for a follow up concerning treatment of psoriatic arthritis. She was diagnosed with psoriatic arthritis according to the CASPAR criteria. She was treated with Methotrexate, then Sulfasalazine. On presentation, the physical examination revealed tender in metacarpals, proximal interphalengal joints and distal interphalengal joints of both hands. Laboratory analysis showed: white blood cells (WBC) :3500 /mm3, (Neut:23% n = 40-65%, Lymp:65% n= 25-40%), erythrocyte sedimentation rate (ESR): 40 mm/h1, and C-reactive protein (CRP): 9.3 mg/L . Given the patient’s ongoing disease activity, and the presence of leukopenia, we started with Ustekinumab 45 mg subcutaneous. After the third dose of Ustekinumab, evaluation showed improvement in her peripheral arthritis and normal laboratory findings. Discussion: Patients with psoriasis had higher total white blood cell and neutrophil. Ustekinumab has good efficacy against disease activity as well as a favourable safety profile. In literature, we found a case of myelodysplastic syndrome associated with inflammatory bowel disease treated with Ustekinumab. Another case of constitutional neutropenia and psoriasis vulgaris treated with Ustekinumab. Conclusion: This is the first case of leukopenia associated with PsA successfully treated with Ustekinumab. UST treatment might be recommended for leukopenia associated with PsA, but further researches are recommended.

Clinical characteristics and related factors analysis of adrenal crisis occurred in children with primary nephrotic syndrome

Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P>0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month,U=25.50, P=0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U=27.00,P=0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L,t=-6.22,P<0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×109 vs. (11±5)×109/L,t=4.26,P=0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19,t=2.56,P=0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0,P=0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.

Cobalt Iron Oxide (CoFe2O4) Nanoparticles Induced Toxicity in Rabbits.

The market for nanoparticles has grown significantly over the past few decades due to a number of unique qualities, including antibacterial capabilities. It is still unclear how nanoparticle toxicity works. In order to ascertain the toxicity of synthetic cobalt iron oxide (CoFe2O4) nanoparticles (CIONPs) in rabbits, this study was carried out. Sixteen rabbits in total were purchased from the neighborhood market and divided into two groups (A and B), each of which contained eight rabbits. The CIONPs were synthesized by the co-precipitation method. Crystallinity and phase identification were confirmed by X-ray diffraction (XRD). The average size of the nanoparticles (13.2 nm) was calculated by Scherrer formula (Dhkl = 0.9 λ/β cos θ) and confirmed by TEM images. The saturation magnetization, 50.1 emug-1, was measured by vibrating sample magnetometer (VSM). CIONPs were investigated as contrast agents (CA) for magnetic resonance images (MRI). The relaxivity (r = 1/T) of the MRI was also investigated at a field strength of 0.35 T (Tesla), and the ratio r2/r1 for the CIONPs contrast agent was 6.63. The CIONPs were administrated intravenously into the rabbits through the ear vein. Blood was collected at days 5 and 10 post-exposure for hematological and serum biochemistry analyses. The intensities of the signal experienced by CA with CIONPs were 1427 for the liver and 1702 for the spleen. The treated group showed significantly lower hematological parameters, but significantly higher total white blood cell counts and neutrophils. The results of the serum biochemistry analyses showed significantly higher and lower quantities of different serum biochemical parameters in the treated rabbits at day 10 of the trial. At the microscopic level, different histological ailments were observed in the visceral organs of treated rabbits, including the liver, kidneys, spleen, heart, and brain. In conclusion, the results revealed that cobalt iron oxide (CoFe2O4) nanoparticles induced toxicity via alterations in multiple tissues of rabbits.

Elucidating the effects of acute and chronic exposure to 2,4-Dichlorophenoxyacetic acid on fathead minnow (Pimephales promelas) innate immunity

Aquatic herbicides, such as 2,4-dichlorophenoxyacetic acid (2,4-D) formulations, are commonly used for invasive species management throughout the United States. Ecologically relevant concentrations of 2,4-D can impair essential behaviors, reduce survival, and act as an endocrine disruptor; however, there is limited knowledge of its effects on the health of non-target organisms. Here, we investigate the acute and chronic exposure impacts of 2,4-D on adult male and female fathead minnow (Pimephales promelas) innate immune function. We exposed both adult male and female fathead minnows to three different ecologically relevant concentrations of 2,4-D (0.00, 0.40, and 4.00 mg/L) and took blood samples at three acute time points (6, 24, and 96 h) and one chronic time point (30 days). We found that male fatheads had higher total white blood cell concentrations when exposed to 2,4-D at the acute time points. For the females, only proportions of specific cell types were altered when exposed to 2,4-D at the acute time points. However, we did not observe any significant impacts of chronic exposure to 2,4-D on any innate immune responses for either males or females. Overall, this study is the first step in answering an important question for game fisheries and management agencies while providing insight to future studies that investigate the impacts of herbicide exposure to freshwater fish health and immunity.

Baseline host determinants of robust human HIV-1 vaccine-induced immune responses: A meta-analysis of 26 vaccine regimens.

SummaryBackgroundThe identification of baseline host determinants that associate with robust HIV-1 vaccine-induced immune responses could aid HIV-1 vaccine development. We aimed to assess both the collective and relative performance of baseline characteristics in classifying individual participants in nine different Phase 1-2 HIV-1 vaccine clinical trials (26 vaccine regimens, conducted in Africa and in the Americas) as High HIV-1 vaccine responders.MethodsThis was a meta-analysis of individual participant data, with studies chosen based on participant-level (vs. study-level summary) data availability within the HIV-1 Vaccine Trials Network. We assessed the performance of 25 baseline characteristics (demographics, safety haematological measurements, vital signs, assay background measurements) and estimated the relative importance of each characteristic in classifying 831 participants as High (defined as within the top 25th percentile among positive responders or above the assay upper limit of quantification) versus Non-High responders. Immune response outcomes included HIV-1-specific serum IgG binding antibodies and Env-specific CD4+ T-cell responses assessed two weeks post-last dose, all measured at central HVTN laboratories. Three variable importance approaches based on SuperLearner ensemble machine learning were considered.FindingsOverall, 30.1%, 50.5%, 36.2%, and 13.9% of participants were categorized as High responders for gp120 IgG, gp140 IgG, gp41 IgG, and Env-specific CD4+ T-cell vaccine-induced responses, respectively. When including all baseline characteristics, moderate performance was achieved for the classification of High responder status for the binding antibody responses, with cross-validated areas under the ROC curve (CV-AUC) of 0.72 (95% CI: 0.68, 0.76) for gp120 IgG, 0.73 (0.69, 0.76) for gp140 IgG, and 0.67 (95% CI: 0.63, 0.72) for gp41 IgG. In contrast, the collection of all baseline characteristics yielded little improvement over chance for predicting High Env-specific CD4+ T-cell responses [CV-AUC: 0.53 (0.48, 0.58)]. While estimated variable importance patterns differed across the three approaches, female sex assigned at birth, lower height, and higher total white blood cell count emerged as significant predictors of High responder status across multiple immune response outcomes using Approach 1. Of these three baseline variables, total white blood cell count ranked highly across all three approaches for predicting vaccine-induced gp41 and gp140 High responder status.InterpretationThe identified features should be studied further in pursuit of intervention strategies to improve vaccine responses and may be adjusted for in analyses of immune response data to enhance statistical power.FundingNational Institute of Allergy and Infectious Diseases (UM1AI068635 to YH, UM1AI068614 to GDT, UM1AI068618 to MJM, and UM1 AI069511 to MCK), the Duke CFAR P30 AI064518 to GDT, and National Institute of Dental and Craniofacial Research (R01DE027245 to JJK). This work was also supported by the Bill and Melinda Gates Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding sources.

Haematology and serum biochemistry parameters in chemically immobilized Manipur’s Brow Antlered Deer or Sangai

Haematology and serum biochemistry parameters were determined for apparently healthy Manipur’s Brow Antlered Deer (4) or Sangai (Rucervus eldii eldii) maintained at the Conservation Breeding Centre, Langol, Manipur under semi-captive conditions. Venous blood samples were collected from the animals via the jugular vein puncture following immobilization using drug mixture of medetomidine and ketamine. Results were determined for haematological and serum biochemical parameters for the species and because of limited published information available results were compared with values obtained from captive reared Thamin (Rucervus eldii thamin) and captive/free ranging Red deer (Cervus elaphus elaphus). Higher total white blood cell, absolute lymphocyte and eosinophil, total bilirubin, lactate dehydrogenase were recorded in Manipur’s Brow antler deer than Red deer, while serum biochemical parameters such as sodium, alanine aminotransferase, alkaline phosphatase and sodium were higher while creatinine, albumin, triglycerides and cholesterol were lower than Thamin deer. The values reported here can be used as a starting point for establishing blood parameters for clinically healthy adult Manipur’s Brow Antlered Deer in India. To our knowledge, this is the first report of base-line blood values for the Manipur’s Brow Antlered Deer.

Janus kinase 2 (JAK2V617F) mutations in patients with splanchnic vein thrombosis, a single centre experience

JAK2V617F mutation is recurrent in polycythaemia vera and essential thrombocythaemia, which are myeloproliferative neoplasms (MPNs) frequently associated with arterial and venous thromboembolism. It also reported as a marker for occult MPN in patients with splanchnic venous thrombosis. We evaluate frequency of JAK2V617F and CALR mutations in patients’ samples presenting with splanchnic vein thrombosis that are sent to Clinical Referral Haematology Laboratory, Hospital Ampang, the tertiary referral laboratory offering both tests within Ministry of Health Malaysia. We retrospectively investigated JAK2V617F mutations samples from years 2016–2020 with presenting history of splanchnic vein thrombosis confirmed by ultrasound or computed tomography (CT) imaging. JAK2V617F mutation analysis was done by amplification refractory mutation system (ARMS) PCR and CALR mutation analysis by high resolution melting (HRM). There was a total of 93 patients (47 men and 46 women) during 2016 and 2020. 16 patients were found to have the JAK2V617 mutation, and the remaining were negative for JAK2V617F and CALR mutation. Of note, we found that patients with JAK2 V617F mutation presented with higher total white blood cell count and platelet count than those without mutation (p<0.05). Despite thrombosis being a common manifestation of MPN, the role of screening JAK2V617F mutations in all patients presenting with splanchnic vein thrombosis without other features of MPN is unclear. However, the significance of this mutation screening provides an accurate diagnosis and further understanding of the role of JAK2V617F mutation in thrombosis has a great potential for future development of therapeutics intervention.

Higher total white blood cell and neutrophil counts are associated with an increased risk of fatal stroke occurrence: the Guangzhou biobank cohort study

BackgroundChronic inflammatory diseases are linked to an increased risk of stroke events. The white blood cell (WBC) count is a common marker of the inflammatory response. However, it is unclear whether the WBC count, its subpopulations and their dynamic changes are related to the risk of fatal stroke in relatively healthy elderly population.MethodsIn total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 11.5 (standard deviation = 2.3) years. After review of available records, 503 stroke deaths (ischaemic 227, haemorrhagic 172 and unclassified 104) were recorded. Cox proportional hazards regression was used to assess the associations between the WBC count, its subpopulations and their dynamic changes (two-phase examination from baseline to the 1st follow-up) and the risk of fatal all stroke, fatal ischaemic stroke and fatal haemorrhagic stroke.Results(i) Regarding the WBC count in relation to the risk of fatal stroke, restricted cubic splines showed an atypically U-curved association between the WBC count and the risk of fatal all stroke occurrence. Compared with those in the lowest WBC count quartile (< 5.3*10^9/L), the participants with the highest WBC count (> 7.2*10^9/L) had a 53 and 67% increased risk for fatal all stroke (adjusted hazard ratio [aHR] = 1.53, 95% confidence interval (CI) 1.16–2.02, P = 0.003) and fatal haemorrhagic stroke (aHR = 1.67, 95% CI 1.10–2.67, P = 0.03), respectively; compared with those in the lowest quartile (< 3.0*10^9/L), the participants with the highest NEUT count (> 4.5*10^9/L) had a 45 and 65% increased risk for fatal all stroke (aHR = 1.45, 95% CI 1.10–1.89, P = 0.008) and fatal ischaemic stroke (aHR = 1.65, 95%CI 1.10–2.47 P = 0.02), respectively. With the additional adjustment for C-reactive protein, the same results as those for all stroke and ischaemic stroke, but not haemorrhagic stroke, were obtained for the WBC count (4 ~ 10*10^9/L) and the NEUT count (the NEUT counts in the top 1% and bottom 1% at baseline were excluded). (ii) Regarding dynamic changes in the WBC count in relation to the risk of fatal stroke, compared with the stable group (− 25% ~ 25%, dynamic changes from two phases of examination (baseline, from September 1st, 2003 to February 28th, 2008; 1st follow-up, from March 31st 2008 to December 31st 2012)), the groups with a 25% increase in the WBC count and NEUT count respectively had a 60% (aHR = 1.60, 95% CI 1.07–2.40, P = 0.02) and 45% (aHR = 1.45, 95% CI1.02–2.05, P = 0.04) increased risk of fatal all stroke occurrence.ConclusionsThe WBC count, especially the NEUT count, was associated with an increased risk of fatal all stroke occurrence. Longitudinal changes in the WBC count and NEUT count increase in excess of 25% were also associated with an increased risk of fatal all stroke occurrence in the elderly population.

Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and other hematological parameters in psoriasis patients

BackgroundPsoriasis is a chronic immune‐mediated skin disorder. Systemic inflammation plays an important role in the pathogenesis of psoriasis.MethodsA total of 477 patients with psoriasis vulgaris (PsV, n = 347), generalized pustular psoriasis (GPP, n = 37), erythrodermic psoriasis (PsE, n = 45), arthritic psoriasis (PsA, n = 25) and mixed psoriasis (n = 23), and 954 healthy control subjects were included in the study. Demographic, clinical, and laboratory information were collected and compared between subgroups.ResultsCompared with the healthy control group, patients with psoriasis had higher total white blood cell (WBC), neutrophil, platelet counts, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR), but lower hemoglobin (Hb) levels, lymphocyte and red blood cell (RBC) counts. NLR values in the PsV group were significantly lower than those in the GPP, PsE, and PsA groups, with GPP group being the highest. PLR values in the PsV group were significantly lower than those in the GPP, PsE, and PsA groups. There was no significant correlation between the psoriasis area severity index (PASI) score and either the NLR or PLR in the PsV group.ConclusionsElevated NLR and PLR were associated with psoriasis and differed between subtypes, suggesting that they could be used as markers of systemic inflammation in psoriasis patients.

Transcriptional profiling of leukocytes in critically ill COVID19 patients: implications for interferon response and coagulation

BackgroundCOVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and differentially expressed genes as well as significantly enriched gene sets were identified.ResultsWe enrolled seven COVID19 + (PCR positive, 2 SARS-CoV-2 genes) and seven age- and sex-matched COVID19- (PCR negative) control ICU patients. Cohorts were well-balanced with the exception that COVID19− patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19 + patients were more likely to suffer bilateral pneumonia. The mortality rate for this cohort of COVID19 + ICU patients was 29%. As indicated by both single-gene based and gene set (GSEA) approaches, the major disease-specific transcriptional responses of leukocytes in critically ill COVID19 + ICU patients were: (i) a robust overrepresentation of interferon-related gene expression; (ii) a marked decrease in the transcriptional level of genes contributing to general protein synthesis and bioenergy metabolism; and (iii) the dysregulated expression of genes associated with coagulation, platelet function, complement activation, and tumour necrosis factor/interleukin 6 signalling.ConclusionsOur findings demonstrate that critically ill COVID19 + patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19− patients, providing guidance for future targeted studies exploring novel prognostic and therapeutic aspects of COVID19.

Venous Thromboembolism (VTE) in Sickle Cell Disease (SCD) Is Associated with Neutrophilia

Introduction Venous thromboembolic events (VTE) are a frequent complication of patients with sickle cell disease (SCD). The estimated incidence of thrombosis is 25% and is associated with increased morbidity and mortality. Recent studies have implicated leukocytes and their subsets in development and propagation of VTE in malignancies and inflammatory diseases. However the role of leukocytes have not been elucidated in SCD. We conducted a retrospective study to precisely study the association of leukocytes and their subsets in VTE. Methods We accessed the medical records of patients with SCD who presented to University Hospitals Seidman Cancer Center from 2004 to 2018. Information collected included demographic characteristics, comorbidities, laboratory parameters as well as treatment details. Patient records were reviewed for VTE with radiographic confirmation. Cases were defined as patients with SCD with diagnosed VTE and controls were SCD patients without VTE. Cases and controls were matched for age, gender, red blood cell (RBC) genotype and treatment. We included twice as many controls as cases for the study. Inclusion criteria were age greater than 18 years and were followed up at the outpatient sickle cell clinic. Patients were excluded if they had infection, thrombophilia, neoplasm, pregnancy or arterial thrombosis. For cases, lab parameters at the time of the VTE were recorded. Since most patients with VTE were diagnosed during an admission, lab parameters for controls were also recorded during an admission for pain crises. For both cases and controls, steady state lab data 3 months prior to their admission was also recorded and compared. Data was analyzed using STATA SE 15 version. Mann-Whitney U test was used to analyze continuous variables and Fischer's exact test was used to analyze discrete variables. P-values less than 0.05 were considered significant. Results A total of 263 records were reviewed of which 97 patients were eligible for the study. There were 35 patients with VTE and 62 patients without VTE. Baseline characteristics are presented in Table 1. Compared to controls, patients with VTE had more comorbidities such as avascular necrosis (AVN; p = 0.0038), pulmonary hypertension or albuminuria (pHTN; p= 0.032), higher body mass index (BMI) (p = 0.038) and had more hospitalizations (p &amp;lt; 0.001). Due to small number of patients, the comorbidities were analyzed as a group across all genotypes. A complete list of comparison of comorbidities is summarized in Table 2. When compared to controls, patients with VTE as a group had higher total white blood cell count (WBC) and neutrophil count (p=0.0032 and p = 0.0006 respectively) at the time of event. When RBC genotype was taken into account, patients with SC and SS genotype had a significantly elevated neutrophil count whereas only patients with SS genotype had a higher WBC count compared to controls (Please refer to Table 3). When compared to controls, cases as a group also had WBC and neutrophil count 3 months prior to the event (p=0.025 and p=0.020 respectively). Patients with SS and SC patients had a significantly higher WBC count 3 months prior compared to their non VTE counterparts (Please refer to Table 4) No other comorbidity or lab parameter was found to be significantly different between cases and controls. A multivariate analysis could not be performed due to small study numbers. Conclusion Our study is the first to show that VTE in SCD was associated with higher neutrophil counts 3 months prior to the event suggesting that patients with baseline or steady state leukocytosis and neutrophilia are at increased risk of thrombosis. Larger studies are needed to confirm this association. In addition, patients with VTE also had higher incidence of comorbidities such as AVN, pHTN or albuminuria and increased hospitalizations. Given the small number of patient, a multivariate analysis was not possible. While the association between pHTN and VTE is well documented; the association of AVN and higher BMI with VTE described here is novel and needs further exploration with larger studies. Disclosures Little: Hemex Health, Inc.: Patents &amp; Royalties; GBT: Research Funding.

Neutrophil Extracellular Traps (NETs) Are a Subset of Smudge Cells Identifiable By Peripheral Smear Autoanalyzers

Background. Neutrophil Extracellular Traps (NETs) are composed of extracellular decondensed chromatin networks that play an important role in immune and inflammatory response regulation. Simple and reliable identification of NETs has been challenging. Automated analyzers such as the CellaVision® Hematology Autoanalyzer identify a subset of cell-derived entities as smudge cells. We hypothesize that, in addition to the typical degenerated lymphocytes (DLs) forming smudge cells, a proportion of smudge cells as identified by the Autoanalyzer are actually NETs. Since patients with high numbers of NETs have increased and specific morbidities, accurate and rapid identification of NETs may be clinically useful. Methods. To test our hypothesis, we analyzed peripheral blood smears from samples processed by the CellaVision® Hematology Autoanalyzer. To differentiate NETs from DLs we used morphologic characteristics, immunohistochemistry, and flow cytometry. After immunohistochemistry and flow cytometry informed our morphologic classification of NETs and DLs, we relied solely on morphology. Smears with &gt;20% smudge cells were classified as the study group; the control group had &lt; 5% smudge cells. Medical chart review was performed by investigators blinded to sample group designation. Data obtained from chart review included patient demographics; presence of bacterial and/or viral infection occurring &lt;1 week of sample collection; myeloproliferative and lymphoproliferative disorders (LPD); solid organ malignancy and/or transplant; sickle cell disease; chronic kidney (CKD) and liver diseases; autoimmune disorders; HIV; thrombotic events. We reviewed the same sample laboratory data for hemoglobin, platelet counts, and white blood cell (WBC) counts. Statistical analyses were performed using two-sided t-test with α =0.05 for continuous variables, chi-square for categorical variables with samples size &gt;10 and Fisher's exact tests for categorical variables with sample size &lt;10. Results. 155 samples were used in the analysis: 96 in the study group, 59 in the control group. Cell-derived entities staining strongly with myeloperoxidase (MPO), neutrophil elastase (NE), and leukocyte alkaline phosphatase (LAP) were classified as NETs. On flow cytometry, these NETs are at least twice as large as WBCs, display extracellular DNA (as identified by Sytox dye) and stain positively for MPO [Figure 1]. On Wright-Giemsa stain, these appeared morphologically as cell remnants with decondensed nuclei, no intact cytoplasm, dispersed granules, and polarized chromatin projections that resemble spider webs [Figure 2]. Of 96 patient samples with &gt;20% smudge cells, morphologic analyses designated 88 as NETs and only 8 as DLs. Comparing patients with &gt;20% to &lt;5% total smudge cells, the former had a higher incidence of bacterial infections (p=0.0091), as well as higher WBC, lymphocyte, monocyte counts and hemoglobin (p=0.014, 0.009, 0.004, 0.01 respectively) [Table 1]. High percentage of smudge cells correlated with a higher percentage of bacterial infection when compared to those with fewer smudge cells despite a non-significant difference in total neutrophil counts. Only 3 of the 36 patients with documented bacterial infection in the &gt;20% smudge cell group had a neutrophils &gt;8.5 x109/L. Of 13 infants &lt;1yr of age with &gt;20%smudge cells, 5 had a bacterial infection with normal neutrophil counts. When the smudge cells were separated according to their category, NETs vs DLs, the DL group was older, had more LPD, higher total WBC, lymphocyte and monocyte counts (p=0.000044, 0.00036, 0.018, 0.022, 0.033) [Table 2]. Slides with mostly NETs had higher LAP scores than those classified as mostly DLs (172 +30.5 vs 103.3 +30.8, p=0.0087). Conclusions: NETosis is a relatively newly discovered tool in the neutrophil's arsenal. This study is the first to identify NETs on peripheral smear evaluations as performed by a routine Hematology Autoanalyzer and to differentiate them from DLs using a reliable set of morphologic characteristics, immunohistochemical stains, and flow cytometry probes. This study also supports data that associate NETs with bacterial infections. This could be clinically useful in diagnosis of infection in the absence of leukocytosis. Disclosures Billett: Albert Einstein College of Medicine: Patents &amp; Royalties: Patent application pending for NETs AI software. Kushnir:Janssen Pharmaceuticals: Research Funding. Reyes Gil:Albert Einstein College of Medicine: Patents &amp; Royalties: Patent application pending for NETs AI software.

The association of plasma lipids with white blood cell counts: Results from the Multi-Ethnic Study of Atherosclerosis

Previous studies have demonstrated that elevated cholesterol results in increased white blood cell counts in mouse models. However, there is insufficient evidence to support this in humans. The objective of the study was to investigate the relationship of plasma lipids with white blood cell counts (basophils, eosinophils, monocytes, neutrophils and lymphocytes) in the Multi-Ethnic Study of Atherosclerosis. The analysis included 2873 Multi-Ethnic Study of Atherosclerosis participants witha complete white blood count and differential analysis. The cross-sectional association of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels with different white blood cell counts was analyzed by multivariable linear regression. After adjusting for sociodemographic and confounding factors including red blood cell counts, platelet counts, use of lipid-lowering medication, cardiovascular disease risk factors and other lipid measures, and multiple testing correction, a one-standard deviation increment in total cholesterol and low-density lipoprotein cholesterol was associated with 2.8% and 2.3% lower total white blood cell counts, 3.7% and 3.0% lower monocyte counts, and 3.4% and 2.7% lower neutrophil counts (all P<.01). The same increment in logarithm-transformed triglyceride levels was associated with 2.3% higher total white blood cell counts and 4.5% higher lymphocyte counts (both P<.001). Similar results were obtained after excluding participants taking lipid-lowering medication. A one-standard deviation increase in high-density lipoprotein cholesterol was associated with a 1.5% lower white blood cell count (P=.018) but was not significantly associated with changes in any individual cell type. While significant associations were observed between plasma lipid levels and white blood cell populations, the heterogeneous and modest nature of these relationships makes it hard to support the hypothesis that lipids are in the causal pathway for leukogenesis in humans.

C-Reactive Protein Is Elevated Only in High Creatine Kinase Responders to Muscle Damaging Exercise.

The purpose of this study was to investigate if exertional rhabdomyolysis induced by an acute bout of plyometric exercise in untrained individuals was associated with histological characteristics of skeletal muscle, creatine kinase (CK) polymorphism or secondary damage. Twenty-six healthy male untrained individuals completed a bout of plyometric exercise (10 sets of 10 maximal squat jumps, with each standardized to achieve at least 95% of individual maximal jump height). Blood samples were taken, and perceived pain was scored immediately before the exercise intervention and 6 h, 1, 2, and 3 days post-intervention. Muscle biopsies were collected 9 or 4 days before (baseline) and 3 days after plyometric jumps. Subjects were divided into two groups, high (n = 10) and low responders (n = 16), based on a cut-off limit for exertional rhabdomyolysis of peak CK activity ≥ 1000 U/L in any post-exercise blood sample. Perceived pain was more severe assessed in squat than standing position. Low responders perceived more pain at 6 h and 1 day, while high responders perceived more pain than low responders on days three and four after exercise; structural (dystrophin staining) and ultra-structural (transmission electron microscopy) analysis of muscle fibers revealed no baseline pathology; damage was evident in all individuals in both groups, with no difference between high and low responders in either damage or fiber type proportion. High responders had significantly higher total white blood cell and neutrophil counts 6 h and significantly higher C-reactive protein (CRP) 6 h and days one and two after exercise compared to low responders. High responders had significantly greater muscle myeloperoxidase (MPO) levels in baseline and 3 day post-exercise biopsies compared to baseline of low responders. MLCK C49T single polymorphism was present in 26% of volunteers, whose CK responses were not higher than those with MLCK CC or CT genotype. In conclusion, perceived pain is more effectively assessed with potentially affected muscle under eccentric strain, even if static. High CK responders also have pronounced CRP responses to unaccustomed plyometric exercise intervention. Exertional rhabdomyolysis after unaccustomed eccentric exercise may be related to underlying inability to resolve intramuscular MPO.

Diagnostic Value of Parameters Related to White Blood Cell Counts for Troponin I Elevation in CO Poisoning.

To assess myocardial injury related to acute carbon monoxide (CO) poisoning, serial troponin I is measured in patients not presenting with troponin I elevation. This retrospective study investigated whether parameters related to white blood cell (WBC) counts (total and differential WBC counts, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio) improved predictive accuracy for troponin I elevation (> 0.04ng/ml) in patients not presenting with evidence of myocardial injury. Serial parameters, troponin I values, and clinical courses were collected in 241 patients. Troponin I was elevated in 33 (13.7%) patients after hospitalization. The median lag times to troponin I elevation in patients with undetectable and detectable troponin I (0.015ng/ml ≤ troponin I ≤ 0.04ng/ml) at presentation were 5.9h and 3.0h, respectively. Patients with troponin I elevation after presentation had higher total WBC and neutrophil counts and NLRs and a lower lymphocyte count during the first 4h after presentation than patients without troponin I elevation during hospitalization. Total WBC count, neutrophil count, and log NLR at presentation were selected as independent predictive factors for troponin I elevation after presentation. However, only the neutrophil count and log NLR at presentation improved the predictive accuracy in combination with clinical parameters compared with that achieved with a predictive model including only clinical parameters. The optimal cut-off neutrophil count and NLR were 5.21 × 103/uL and 4.02, respectively. The total neutrophil count and NLR, which are widely available and inexpensive parameters obtained in the emergency department (ED), are promising screening tools for predicting the risk of troponin I elevation in patients without evidence of myocardial injury-related acute CO poisoning at presentation.

Heightened Immune System Function in Polar Bears Using Terrestrial Habitats.

Climate change is altering the distribution of some wildlife species while warming temperatures are facilitating the northward expansion of pathogens, potentially increasing disease risk. Melting of Arctic sea ice is increasingly causing polar bears (Ursus maritimus) of the southern Beaufort Sea (SBS) to spend summer on land, where they may encounter novel pathogens. Here, we tested whether SBS polar bears on shore during summer exhibited greater immune system activity than bears remaining on the sea ice. In addition, we tested whether the type of immune response correlated with body condition, because adaptive responses (slowly developing defenses against specific pathogens) often require less energy than innate responses (rapid defenses not based on pathogen identity). After accounting for body condition, we found that polar bears on shore exhibited higher total white blood cell counts, neutrophils, and monocytes than bears on the ice, suggesting more infections. Lymphocytes, eosinophils, basophils, and globulins did not differ. C-reactive protein, an indicator of inflammation, also did not differ between habitats. Body condition was associated with variables indicative of both innate and adaptive immunity, suggesting that neither response was uniquely limited by energy resources. Our data indicate that as more polar bears spend longer periods of time on shore, they may experience more infections. We encourage continued health monitoring of this species and studies of the long-term fitness consequences from disease.

Hematologic Values of Healthy and Sick Free-ranging Lesser Flamingos ( Phoeniconaias minor) in Kenya.

We determined hematologic parameters of five healthy and nine sick free-ranging Lesser Flamingos ( Phoeniconaias minor) from Lake Nakuru, Kenya. Heterophilia and lymphopenia were evident in sick birds, with up to 7.5-fold higher heterophil-to-lymphocyte ratio in sick birds compared to healthy birds. Leucopenia was present in a few sick birds. A higher than normal packed cell volume was observed in birds that had evidence of acute disease, whereas a lower than normal packed cell volume was seen in birds with evidence of prolonged sickness. Healthy birds had higher total white blood cell counts and lymphocyte counts and lower heterophil counts than zoo flamingos. Most sick birds were diagnosed with septicemia, occasionally with fibrinous exudation into the coelomic cavities. One bird had mycobacterial granulomas, one had a corynebacterium-associated wing abscess, and one had a wing fracture. We provide hematologic data for free-ranging Lesser Flamingos and compare the parameters of sick and healthy birds.

Neutrophil-lymphocyte Ratio and C-reactive Protein Level in Patients with Major Depressive Disorder Before and After Pharmacotherapy

Neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP) level are useful biomarkers of inflammation. This study aimed to assess NLR and CRP level in patients with major depressive disorder before and after pharmacotherapy to determine whether NLR or CRP could be used as biomarkers of severity of major depression and whether there was any sex difference. Patients with major depression who received no pharmacotherapy 1 month prior to the study were included. Their haemoglobin, total white blood cell count, neutrophil and lymphocyte counts, NLR, and CRP levels were evaluated at baseline and 12 weeks post pharmacotherapy, as were the Montgomery Asberg Rating Scale for Depression, the Scale for Impact of Suicidality Management and Assessment and Planning of Care (SIS-MAP), and the Clinical Global Impression Scale - Severity. 24 male and 26 female patients were included. At 12 weeks after pharmacotherapy, males had a higher haemoglobin level (p = 0.025), higher total white blood cell count (p = 0.018), and lower percentage of neutrophils (p = 0.019) than females. There was no sex difference in NLR or CRP. From baseline to 12 weeks, males had no significant change in any blood parameter, but females had a significantly greater increase in the percentage of neutrophils (p = 0.0001) and decrease in the percentage of lymphocytes (p = 0.012), resulting in a significantly increased NLR (p = 0.001). Both males and females had significant improvement on all 3 scales (p < 0.001). At 12 weeks, in males, the increase in NLR positively correlated with CRP as well as the Montgomery-Asberg Depression Rating Scale and the SIS-MAP, but not the Clinical Global Impression-Severity Scale. In females, the increase in NLR did not correlate with CRP or any of the scales. In female patients, the NLR increased in response to antidepressant therapy while CRP remained unchanged. This indicated that inflammation has a role in the pathogenesis of major depression.

Immune parameters in different age classes of captive male Steller's eiders (Polysticta stelleri)

The immune system is important for host defense against antigens, but little is known about Steller's eider (Polysticta stelleri) immunology. This study compared hematological parameters, serum protein levels, lymphocyte proliferation, heat shock protein levels and oxidative damage in four different age classes of captive male Steller's eiders. The hatch year cohort had significantly higher total white blood cell and lymphocyte counts. The second year cohort had significantly higher albumin, alpha globulins and lymphocyte proliferation, and significantly lower beta globulin levels. The 9 year old males had a significantly higher IgY:IgY(ΔFc) ratio. The oldest eiders in the study, 14 + year old males, had significantly higher serum IgY, pre-albumin and glutathione reductase activity, and the lowest lymphocyte proliferation. This study provided a baseline of immune parameters in captive male Steller's eiders, and the results suggested the parameters were influenced by age-related changes.

Evaluation of the expression of CD200 and CD56 in CD34-positive adult acute myeloid leukemia and its effect on the response to induction of chemotherapy

Background: Acute myeloid leukemia (AML) is characterized by an excess number of myeloid cells in the marrow with maturation arrest and infiltration of bone marrow (BM) and other tissues by myeloblasts, resulting in BM failure. Objectives: The main goal of the present study is to investigate CD200 and CD56 aberrant expression in CD34-positive blasts, in newly diagnosed adult AML patients and their relation with the clinical and hematological parameters, as well as to identify their prognostic significance after induction therapy. Materials and Methods: This was a prospective cross-sectional study on thirty patients with newly diagnosed AML, who were tested for the expression of CD200, CD56 using multicolor flow cytometry and re-evaluated after induction therapy regimen. Results: CD200 and CD56 were aberrantly expressed in 53.3% and 20.0%, respectively, while coexpression of both markers was observed in 13.3%. Interestingly, both markers were expressed more in monocytic subtypes. Significantly, the induction failure in CD200 + patients was 75%, while it was 66.7% in CD56+ patients. Conclusion: The findings of this research provide insights that CD200 and CD56 were closely related to bad prognostic parameters, including high total white blood cell count, low platelet's counts, and low response to induction therapy.