Increase In White Blood Cell Count Research Articles

Postoperative systemic inflammatory response syndrome predicts increased mortality in patients after elective craniotomy.

Patients undergoing craniotomy are at high risk of perioperative morbidity and mortality due to excessive inflammatory responses. The purpose of the present study is to evaluate the prognostic utility of postoperative systemic inflammatory response syndrome (SIRS) in patients undergoing craniotomy. We performed a retrospective cohort study of patients who underwent craniotomy between January 2011 and March 2021. SIRS was diagnosed based on two or more criteria (hypo-/hyperthermia, tachypnea, leukopenia/leukocytosis, tachycardia). We used univariate and multivariate analysis for the development of SIRS with postoperative 30-day mortality. Of 12,887 patients who underwent craniotomy, more than half of the patients (n = 6,725; 52.2%) developed SIRS within the first 7 days after surgery, and 157 (1.22%) patients died within 30 days after surgery. In multivariable analyses, SIRS (OR, 1.57; 95% CI, 1.12-2.21) was associated with 30-day mortality. Early SIRS was not predictive of 30-day mortality, whereas delayed SIRS was predictive of 30-day mortality. Abnormal white blood cell (WBC) counts contributed the most to the SIRS score, followed by abnormal body temperature, respiratory rate, and heart rate. Postoperative SIRS commonly occurs after craniotomy and is an independent predictor of postoperative 30-day mortality. This association was seen only in delayed SIRS but not early SIRS. Moreover, increased WBC counts contributed the most to the SIRS score.

Association between white blood cell count and adverse pregnancy outcomes: a retrospective cohort study from a tertiary hospital in China

ObjectivesThis study aimed to clarify the relationship between white blood cell (WBC) and adverse pregnancy outcomes.DesignA total of 25 270 pregnant women underwent peripheral blood white blood cell count tests...

Inflammation mediates the effect of adiposity and lipid metabolism indicators on the embryogenesis of PCOS women undergoing in vitro fertilization/intracytoplasmic sperm injection.

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine and metabolic disease affecting women of reproductive age. The low-grade chronic inflammation in PCOS is considered to be associated with obesity and dyslipidemia. We aim to investigate the potential mediating role of white blood cell (WBC) count, a representative inflammatory marker, in the effect of adiposity and lipid metabolism indicators on IVF/ICSI outcomes in PCOS women. We conducted a retrospective cohort study of 1,534 PCOS women who underwent their first IVF/ICSI cycles with autologous oocytes at a reproductive center from January 2018 to December 2020. The associations between PCOS women's adiposity and lipid metabolism indicators and WBC count and IVF/ICSI outcomes were examined using multivariable generalized linear models. Mediation analyses were conducted to evaluate the possible mediating role of WBC count. We found significant dose-dependent correlations between adiposity and lipid metabolism indicators and IVF/ICSI outcomes (i.e., hormone levels on the ovulatory triggering day, oocyte development outcomes, fertilization, early embryo development outcomes, and pregnancy outcomes) (all p < 0.05), as well as between adiposity and lipid metabolism indicators and WBC count (all p < 0.001). Increasing WBC count was associated with adverse oocyte and embryonic development outcomes (all p < 0.05). Mediation analyses suggested that increasing serum TG and LDL-C levels and decreasing serum HDL-C level were significantly associated with reduced high-quality Day 3 embryo count in PCOS women, with 21.51%, 9.75%, and 14.10% mediated by WBC count, respectively (all p < 0.05). We observed significant associations between lipid metabolism indicators and high-quality Day 3 embryo count in PCOS women, partially mediated by inflammation-related mechanisms, suggesting the potential intervention target for improving embryo quality in PCOS women.

Elevation in white blood cell count and development of hyper LDL cholesterolemia

To investigate the relationship between white blood cell (WBC) count and incidence of hyper-low-density lipoprotein (LDL) cholesterolemia in a population-based longitudinal study. This is a retrospective study using data of annual health check-ups for residents of Iki City, Japan. A total of 3312 residents (≥ 30 years) without hyper-LDL cholesterolemia at baseline were included in this analysis. Primary outcome was incidence of hyper-LDL cholesterolemia (LDL cholesterol levels ≥ 3.62 mmol/L and/or use of lipid lowering drugs). During follow-up (average 4.6 years), 698 participants development of hyper-LDL cholesterolemia (incidence 46.8 per 1000 person-years). Higher incidence of hyper-LDL cholesterolemia was observed among participants with higher leukocyte count (1st quartile group: 38.5, 2nd quartile group: 47.7, 3rd quartile group: 47.3, and 4th quartile group: 52.4 per 1,000 person-years, P = 0.012 for trend). Statistically significant relation was observed even after adjustment for age, gender, smoking, alcohol intake, leisure-time exercise, obesity, hypertension and diabetes: hazard ratio 1.24 (95% confidence interval 0.99 to 1.54) for 2nd quartile group, 1.29 (1.03–1.62) for 3rd quartile group and 1.39 (1.10–1.75) for 4th quartile group, compared with 1st quartile group (P for trend = 0.006). Increased WBC count was related to incidence of hyper-LDL cholesterolemia in general Japanese population.

White Blood Cell Count Predicts Mortality in Patients with Spontaneous Intracerebral Hemorrhage.

The association between white blood cell (WBC) counts and mortality in patients with intracerebral hemorrhage (ICH) has not been established. The aim of this study is to determine whether higher WBC is associated with mortality at 90days. A retrospective observational study was conducted at two medical hospitals in China. Baseline WBC count on admission served as the primary predictor variable. Longitudinal WBC counts within the first week after admission were collected to assess the effects of WBC trajectory and the median and maximum WBC counts on outcomes following ICH. Associations of WBC count with outcomes were evaluated in multivariable regression analyses. We identified 3613 patients with ICH who met the inclusion criteria. After adjusting primary confounding variables, patients with increased WBC count had a significantly higher risk of 90-day mortality (p < 0.001 for trend). In the receiver operating characteristic analyses, the capacity for all-cause mortality prediction by WBC count on admission (area under the ROC curve (AUC) = 0.65) was superior to other important inflammatory markers, includingneutrophil(AUC = 0.64) , lymphocyte(AUC = 0.57), albumin(AUC = 0.57), and platelet count(AUC = 0.53), p < 0.001for WBC vs.neutrophil, and the median WBC count (AUC = 0.66) within the first week after admission was a better marker than admission WBC count (p = 0.02). In patients with ICH, WBC count on admission was associated with all-cause mortality at 90days. Additionally, the median and maximum WBC counts within the first week after admission showed better predictive ability for the 90-day mortality compared with the WBC count on admission.

White blood cell count affects fetal fraction and test failure rates in noninvasive prenatal screening.

To investigate the effects of white blood cell (WBC) count on fetal fraction (FF), which is an essential quality control for obtaining reliable results, and on the rate of screen failures in noninvasive prenatal screening (NIPS). Noninvasive prenatal screening, serum lipid and liver enzyme level measurements, and WBC count were performed for 4,281 pregnancies with male fetuses. After adjusting for confounders, including the maternal characteristics and alanine aminotransferase (ALT) levels, the effect of WBC count on FF and test failure rate was measured by linear and logistic regression analyses. Fetal fraction was negatively associated with BMI, ALT, IVF conceptions, and WBC count and positively correlated with gestational age in the multivariate linear regression model. Moreover, WBC count was the most important factor affecting FF after BMI according to the standardization coefficient analysis. In the 4,281 pregnancy samples with male fetuses, FF decreased with WBC count from 11.45% at ≤8 to 9.02% at >12, and FF markedly decreased to 7.40% in pregnancies with a higher WBC count (>12) and higher BMI (≥25 kg/m2). Meanwhile, the test failure rates were significantly higher in the WBC count > 12 group (4.29%) than in the WBC count ≤ 8 group (0.89%). Notably, when the BMI of pregnancies with a WBC count of >12 was >25, the rate reached 7.53%. Subsequently, multivariate logistic regression analysis further confirmed that an increased BMI and WBC count were independently and significantly associated with the test failure rates. An increased WBC count was associated with lower FF and higher test failure rates, suggesting that these important factors should be carefully considered during genetic counseling in pregnant women who decide to undergo blood collection or resampling.

Significant impact of body mass index on the relationship between increased white blood cell count and new-onset diabetes.

An elevated white blood cell (WBC) count has been linked to incident diabetes. WBC count has been positively associated with body mass index (BMI), and elevated BMI has been reported to be a strong predictor of future diabetes. Hence, the association of increased WBC count with the subsequent development of diabetes may be mediated by increased BMI. This study was designed to address this issue. We selected subjects from the 104,451 participants enrolled from 2012 to 2018 in the Taiwan Biobank. We only included those with complete data at baseline and follow-up and those without diabetes at baseline. Finally, 24,514 participants were enrolled in this study. During an average 3.88 years of follow-up, 248 (1.0%) of the participants had new-onset diabetes. After adjusting for demographic, clinical, and biochemical parameters, increased WBC count was associated with new-onset diabetes in all of these participants (p ≤ 0.024). After further adjustment for BMI, the association became insignificant (p = 0.096). In addition, subgroup analysis of 23,430 subjects with a normal WBC count (range: 3500-10500/µl) demonstrated that increased WBC count was significantly associated with new-onset diabetes after adjusting for demographic, clinical, and biochemical parameters (p ≤ 0.016). After further adjustment for BMI, this association was attenuated (p = 0.050). In conclusion, our results showed that BMI had a significant impact on the relationship between increased WBC count and new-onset diabetes in all study participants, and BMI also attenuated the association in those with a normal WBC count. Hence, the association between increased WBC count and the future development of diabetes may be mediated by BMI.

Using cinnamon (Cinnamomum zeylanicum) and turmeric (Curcuma longa L) powders as an antibiotic growth promoter substitutions in broiler chicken’s diets

In the current study supplementations of cinnamon (Cinnamomum zeylanicum) powder (CNP) and turmeric (Curcuma longa L) powder (TP) as an antibiotic growth promoter substitutions on growth performance, intestinal microbiota and hematological profile of broiler chickens have been investigated. A total of 240, one day old as-hatched broiler chickens (ROSS 308) were randomly assigned into five treatments with four replicates per treatment and 10 chickens per replicate. Treatment groups were C: control (fed basal diet); CNP1: 0.5% CNP; CNP2: 1.0% CNP; TP1: 0.5% TP; TP2: 1.0% TP and 500 mg oxytetracycline (OTC)/kg of diet. Body weight gain (BWG), feed intake, and feed conversion ratio (FCR) were improved (p < 0.05) by CNP and TP while OTC improved BWG and FCR. Ileal and cecal Lactobacillus and total aerobes were significantly improved while coliforms and Escherichia coli were decreased by CNP, TP, and OTC. The percentage of packed cell volume (%PCV), hemoglobin (Hb), red blood cell (RBC) count, and white blood cell (WBC) count was increased by CNP and TP while OTC decreased %PCV, Hb, RBC, and increased WBC count. In conclusion, the results showed that OTC can be safely replaced by CNP and TP at 1.0% dose rate in broiler chicken’s diets.

Neuropsychological Features in Patients with General Paresis of the Insane at an Early Stage.

BACKGROUND This study aimed to explore the features of cognitive impairment in patients with neurosyphilis at the early stage of mild cognitive impairment (MCI). MATERIAL AND METHODS A total of 18 patients with asymptomatic neurosyphilis (ANS), 19 patients with neurosyphilis at the MCI stage (neurosyphilis-MCI), and 15 patients with neurosyphilis at the dementia stage (neurosyphilis-dementia) were enrolled. Cognitive function was evaluated using comprehensive rating scales. Tests of syphilis in blood and cerebrospinal fluid (CSF) were conducted, and white blood cell (WBC) counts and protein levels in CSF were measured. RESULTS Overall cognitive function and individual cognitive domains, including memory, language, visuospatial skill, and attention/executive function, were all significantly impaired in the neurosyphilis-MCI group compared with the ANS group, and were further impaired in the neurosyphilis-dementia group. Although there was no difference in serum rapid plasma regain (RPR) titer among the 3 groups, the number of patients with serum RPR titer ≥1: 32 in the neurosyphilis-MCI group was much higher than that in the ANS group. CSF RPR positive rate in the neurosyphilis-MCI group was significantly higher than that in the ANS group. The WBC count, protein level, and the rate of elevated protein level or increased WBC count in CSF did not differ among the 3 groups. CONCLUSIONS The feature of cognitive impairment of neurosyphilis-MCI patients displayed multiple-domain amnestic MCI. Perhaps there were extensive brain areas involved at the early stage, and a continuous neuroinflammatory process was through the different stages of neurosyphilis. Early diagnosis and treatment are very important for preventing the progression of general paresis of the insane.

Association of the MACROD2 rs6110695 A>G polymorphism with an increasing WBC count in a Korean population.

IntroductionWe aimed to find a novel candidate gene related to the white blood cell (WBC) count in a Korean population. Since WBC count has been reported to have a relation to the risk of chronic diseases according to previous literature, WBC level prediction can be helpful for managing future risk of chronic disease development. In this aspect, a gene newly found in the present study is expected to be utilized as a tool for judging an individual's WBC level.MethodsBased on the 153 study participants' genotype data produced by the Korean Chip. The mono‐adenosine diphosphate ribosylhydrolase 2 (MACROD2) rs6110695 A>G polymorphism had a significant strong association with WBC count, thus, the MACROD2 gene emerged as a novel candidate gene for WBC count. To verify the effects of the single‐nucleotide polymorphisms on WBC count, the participants were grouped according to the rs6110695 AA and AG genotypes.ResultsWBC to apolipoprotein A‐I ratio, WBC count, granulocyte to lymphocyte ratio, monocyte to platelet ratio, and interferon‐γ level were significantly higher in the AG genotype group than in the AA genotype group. Through the receiver operating characteristic curve analysis, the rs6110695 AA and AG genotypes were discriminated by the optimal WBC count cutoff value of 5.450. As expected, the results in the participants having a WBC count over 5.450 were similar to the AG genotype group.ConclusionsWe revealed that the MACROD2 rs6110695 AG genotype has an association with increasing WBC count. Since, as previous literature described, WBC count is one of the main risk factors for chronic diseases, WBC count measurement in individuals with the rs6110695 AG genotype that was found in the present study may help manage future chronic disease risk.

Hematological biomarkers of systemic inflammation in genuine (physiologic and pathologic) halitosis

Halitosis is an unpleasant odor discharged through the oral cavity with a prevalence as high as 30%–50% of the general population. Conventional diagnostic methods have been focused on mouth air analysis measuring the amount of sulfur compounds which does not directly reflect the cause of halitosis. Also, the possible role of halitosis as an indicator of general health status has been steadily suggested and inflammation has been constantly associated with aversive body odor. Therefore, this study aimed to search for inter-relationships between hematologic indicators, clinical characteristics, and halitosis measurement that can predict the presence of pathologic halitosis and its intensity. Furthermore, the tentative relationship between halitosis and the presence of systemic inflammation was investigated. A total of 125 patients were divided into 103 patients in the genuine halitosis group (value ⩾80 ppb) and 22 patients in the pseudo halitosis group (value <80 ppb) based on portable sulfide monitor measurements. Clinical examination and hematological indices including inflammatory prognostic factors and halitosis measurements including organoleptic testing, portable sulfide monitor, and gas chromatography were evaluated. The genuine halitosis group showed a significantly higher white blood cell (WBC) count (p< 0.01) compared to the pseudo halitosis group. Erythrocyte sedimentation rate (ESR, β = 0.341, p < 0.05) values and duration of halitosis (β= 0.353, p < 0.05) showed a significant association with halitosis intensity and neutrophil to lymphocyte ratio (NLR) values (β = 3.859, p < 0.05) were significantly related to genuine halitosis diagnosis. A new WBC cut-off value of 5575 μl−1 showed near to fair discriminative power in predicting genuine halitosis (area under the curve 0.661, p < 0.05). The results of this study showing an increased WBC count in genuine halitosis and its strong association with hematologic indices of subclinical inflammation including ESR and NLR suggest inflammatory hematologic markers as potential diagnostic tools in the diagnosis of genuine halitosis.

Clinical and Paraclinical Predictive Factors for In-hospital Mortality in Adult Patients with COVID-19: A Cross-sectional Study in Iran

Background: COVID-19, a type of coronavirus emerged in Wuhan, China in December 2019, causing an epidemic of pneumonia with unknown reasons. Objective: This study aimed to investigate the factors affecting in-hospital mortality of patients with COVID-19 hospitalized in one of the main hospitals in central Iran. Methods: This retrospective cross-sectional study (February-May 2020) was conducted on patients with a confirmed diagnosis of COVID-19 admitted to Yazd Shahid Sadoughi Hospital in Iran. The patients with uncompleted or missed medical files were excluded from the study. Data were extract-ed from the patients' medical files and then analyzed. The patients were categorized as survivors and non-survivors groups, and they were compared. Results: Total 573 patients were enrolled and 356 (62.2%) were male. The mean±SD of age was 56.29±17.53 years, and 93 (16.23%) died. All the complications were more in non-survivors. Inten-sive care unit (ICU) admission was in 20.5% of the patients, which was more in non-survivors (P&lt;0.001). The results of multivariate logistic regression test showed that pleural effusion in lung computed tomography (CT) scan (OR=0.055, P=0.019), white blood cell (WBC) (OR=1.418, P=0.022), serum albumin (OR=0.009, P&lt;0.001), non-invasive mechanical ventilation (OR=34.351, P&lt;0.001), and acute respiratory distress syndrome (ARDS) (OR=66.039, P=0.003) were the predic-tive factors for in-hospital mortality. Conclusion: In-hospital mortality with COVID-19 was about 16%. Plural effusion in lung CT scan, increased WBC count, lower mount of serum albumin, non-invasive mechanical ventilation, and ARDS were obtained as the predictive factors for in-hospital mortality.

Topical hemostatic application on staple line in laparoscopic sleeve gastrectomy: a single-surgeon experience.

Laparoscopic sleeve gastrectomy (LSG) is a common bariatric procedure with low complication rates. Several hemostatic agents have been used to reduce staple line bleeding, but its impact is unclear. The primary endpoint of this study was to compare the early (30-day) complications comparing oxidized regenerated cellulose (ORC) and fibrin sealant (FS) application on the staple line. The secondary endpoints were to compare the need for postoperative blood transfusion, postoperative blood work values of hemoglobin (Hb), white blood cell (WBC), C-reactive protein (CRP), drain output volume and hospital length of stay (LOS). A retrospective analysis of all patients who underwent LSG between January and October 2021 was performed. Subjects were divided into two groups according to the use of ORC versus FS on the staple line. Early postoperative complications, Hb level, WBC count, and drain output volume were compared between groups. A total number of 77 patients were included: 27 in the ORC-group and 50 in the FS-group. No major complication was recorded in both groups. There was no significant difference in the need for blood transfusion, Hb value, and drain output volume on postoperative day (POD) 1 and 2. There was a significantly higher WBC count in the ORC-group on POD 1 and 2. There was no difference in hospital LOS between the groups. The use of FS and ORC was associated with a comparable low rate of bleeding. ORC causes an increased WBC count postoperatively, but this showed no clinical relevance.

Prognostic Factors for Contralateral Recurrence of Upper Tract Urothelial Carcinoma after Nephroureterectomy: A Large Multiregional Study.

Simple SummaryRecurrence of cancer on the opposite side after the removal of primary upper tract urothelial carcinoma (UTUC) is uncommon, but the risk of subsequent deterioration of kidney function may be severe and result in the need for permanent dialysis. There is a clear correlation between inflammation and tumor development in patients with cancer. As the presence of white blood cells (WBC) in urine is an indicator of local inflammation and a biomarker for bladder recurrence of UTUC, we hypothesized that systemic inflammation is involved in the occurrence of contralateral lesions. We proved that elevated serum WBC, late chronic kidney disease, and multiple tumors are independent prognostic factors for contralateral recurrence. Moreover, in a subgroup analysis, the importance of chronic kidney disease in contralateral recurrence was demonstrated for the first time in a non-Asian population. It is recommended that high-risk patients be closely followed up to monitor the opposite upper urinary tract.This study aimed to examine the prognostic significance of preoperative inflammation-associated blood cell markers in the metachronous contralateral recurrence of upper tract urothelial carcinoma (UTUC). Patients with nonmetastatic UTUC treated in Taiwan and the U.S. between 1990 and 2017 were included. The Kaplan–Meier method was used to calculate the contralateral recurrence rate, and multivariate logistic regression was performed to study the association of blood cell markers and clinicopathological characteristics with contralateral recurrence. Overall, a total of 1039 patients were included in this study, 52 of whom (5.0%) developed metachronous recurrence of the contralateral side. Kaplan–Meier analysis indicated that a history of bladder cancer (p = 0.006), multiple tumors (p = 0.016), advanced chronic kidney disease (CKD; p < 0.001), elevated serum white blood cell (WBC) count (p < 0.001), and decreased hemoglobin levels (p = 0.001) significantly reduced the contralateral recurrence-free survival. Multivariate analysis showed that multiple tumors (hazard ratio (HR), 1.87; p = 0.030), advanced CKD (HR, 2.63; p = 0.002) and increased WBC count (HR, 2.60; p = 0.001) were independent risk factors for higher contralateral recurrence rate. Notably, advanced CKD was a significant factor regardless of the patient’s region. In summary, multiple tumors, advanced CKD and elevated serum WBC count are independent predictors of contralateral recurrence in patients with UTUC. It is recommended that patients with these adverse characteristics be closely followed up to monitor the opposite upper urinary tract.

Temporal Evolution of White Blood Cell Count and Differential: Reliable and Early Detection Markers for Surgical Site Infection Following Spinal Posterior Decompression Surgery.

Introduction For early detection of surgical site infection (SSI) following spinal decompression surgery, we compared temporal changes in the values of laboratory markers that are not affected by operative parameters. Methods The study included 302 patients, which were divided into an SSI group (patients who developed deep SSI) and a non-SSI group for analysis. We reviewed data on C-reactive protein level, total white blood cell (WBC) count, and WBC differential percentage and count before spinal decompression, on postoperative day 1, and on postoperative day 4. We identified laboratory markers that are not affected by operative parameters (operating time, intraoperative blood loss, and number of operative segments). Laboratory markers with a significant difference observed between the peak or nadir value and the value in the subsequent survey day were considered as an indicator of SSI. We examined the utility of each indicator by calculating sensitivity and specificity. Furthermore, we investigated the utility of the combination of all five indicators (wherein the recognition of one marker was considered positive). Results Temporal changes in five laboratory markers were considered indicators of SSI. The changes from postoperative day 1 to postoperative day 4 were as follows: (1) increased WBC count (42% sensitivity, 88% specificity), (2) increased neutrophil percentage (25% sensitivity, 96% specificity), (3) increased neutrophil count (25% sensitivity, 94% specificity), (4) decreased lymphocyte percentage (25% sensitivity, 95% specificity), and (5) decreased lymphocyte count (25% sensitivity, 85% specificity). The combination of these five markers showed a 50% sensitivity, 81% specificity, and 0.65 AUC. Conclusions Five markers were found to be reliable indicators of SSI following spinal decompression surgery because they were not affected by operative parameters. The combination of all five indicators had moderate sensitivity and high specificity. Therefore, this may be reliable and useful for the early detection of SSI.

Clinical and biological features of mantle cell lymphoma patients with co-expression of CD10 and BCL-6: a retrospective study.

BackgroundMantle cell lymphoma (MCL) with co-expression of CD10 and BCL-6 was scarcely reported, and its biological features were largely remained unknown. Thus, this study aimed to describe the clinical and biological features, as well as outcome of MCL patients with co-expression of CD10 and BCL-6.MethodsA total of 104 cases of MCL who were admitted to our hospital between January 2011 and October 2018 were recruited. Those patients were diagnosed according to the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues, in compliance with the results of cytomorphology and immunohistochemical analysis. Patients were followed up through telephone interviews, medical records. Differences in age, gender, leukocyte count, lactate dehydrogenase (LDH) level, beta-2 microglobulin (β2-MG) level and results of immunohistochemistry were analyzed. Then the event-free survival (EFS) rate and overall survival (OS) rate were performed by the Kaplan-Meier method and log-rank test.ResultsThe results showed that, in total, 5 patients had superficial lymph node enlargement, 2 patients suffered from abdominal discomfort, and 1 patient’s red blood cell (RBC) count was abnormal at the time of diagnosis. All patients were in stage IV, 75% had bone marrow involvement, and 75% and 100% of patients had elevated levels of LDH and β2-MG, respectively. Three classic genes and five variants were involved in the 8 patients. MCL patients with the co-expression of CD10 and BCL-6 had higher Ki-67 index, white blood cell (WBC) count, LDH level, and β2-MG level than those of without co-expression of CD10 and BCL-6 (P=0.025, 0.038, 0.015, and 0.021, respectively). Besides, MCL patients with CD10 and BCL-6 co-expression had shorter OS and EFS (χ2=6.401 and 5.975; P=0.011 and 0.015, respectively), indicating patients’ susceptibility to get complex karyotype and TP53 abnormality.ConclusionsMCL patients with co-expression of CD10 and BCL-6 were more likely to have bone marrow involvement, higher Ki-67 index, increased WBC count, and elevated levels of LDH and β2-MG at the time of diagnosis, then might has complex cytogenetic and poor prognosis.

Defective Notch Activation in Mesenchymal Cells Contributes to Myeloproliferative Neoplasm in Aged Mice

Increasing evidence supports important roles of the bone marrow (BM) microenvironment in the development of hematological malignancies. Recently, the non-cell autonomous role of Notch signaling has emerged as one of the key regulators of normal and malignant hematopoiesis. By using a Mx1 - Cre -mediated Rbpj gene deletion in mice (Mx1 - Cre ; R bpjf/f) as a genetic model of Notch loss-of function, we have previously discovered that loss of Rbpj in microenvironment leads to a myeloproliferative neoplasm (MPN)-like disease, which is driven by increased miR-155 expression, NF-kB activation, and inflammatory cytokine production (Wang et al . Cell Stem Cell, 2014). The Mx1 promoter is active in hematopoietic cells as well as in non-hematopoietic cells. In vitro analysis of the impact of Mx1 - Cre -induced R bpj gene deletion on BM endothelial cells (EC), mesenchymal stem cells (MSC), bone cells, andhematopoietic cells showed a greater increase of miR-155 expression in EC and MSC compared to other cell types, leading to higher production of inflammatory cytokines, in particular G-CSF and TNF-a. Comparative in vivo studies showed that EC-specific R bpj knockout mice (Tie2 - CreER ;Rbpjf/f) developed an inflammation and MPN-like disease like Mx1 - Cre ; R bpjf/f mice. However, the disease affected 80% of Tie2 - CreER ;Rbpjf/f mice (compared to 100% of Mx1 - Cre ; R bpjf/f), took longer time to develop (8-12 months vs. 4 months), and was less aggressive than in Mx1 - Cre ; R bpjf/f mice.To further dissect the individual contribution of different stromal cell types to the regulation of myelopoiesis, we used an Osterix (Osx)-Cre -mediated loss-of-function approach to inactivate Rbpj in mesenchymal cells in vivo . We found that the impact of Osx -driven Notch loss-of-function in mice is age-dependent. 5-month-old Osx-Cre ; Rbpjf/f mice showed no abnormal hematologic features compared to controls, as they exhibited similar numbers and percentages of white blood cells (WBC), lymphocytes, neutrophils, red blood cells, and platelets, and comparable percentages of Gr-1+CD11b+ granulocytes, B220+ B cells, and CD3+ T cells in their BMs and spleens. Age-dependent myeloid skewing was shown in wild-type (WT) control mice, but interestingly, was more accentuated in Osx-Cre ; Rbpjf/f mice. Osx-Cre ; Rbpjf/f mice between 11 and 18 months of age showed significantly increased WBC counts in their blood due to increases in neutrophils, lymphocytes and monocytes, but exhibited similar percentages of hematopoietic populations in their BMs and spleens. However, 2 out of 7 mice in the oldest cohort between 17 and 18 months of age showed significant hematological differences in terms of numbers and percentages of hematopoietic cells in their blood, BMs and spleens compared to age-matched controls. Detailed analysis of individual mice revealed that the 2 mutant mice showed an MPN-like disease with circulating myeloid progenitors, splenomegaly and increased granulocyte-macrophage progenitors (GMP) in the BM. In summary, the deletion of Rb pj induced a MPN-like disease in 15% of Osx-Cre ; Rbpjf/f mice and was age-dependent.Cytokine analysis revealed an overall increase of inflammatory cytokines in WT mice during aging; G-GSF and GM-CSF were detected only in the blood of aged (11- to 18-month-old) mice but not young (5-month-old), and C5/C5a was 14-fold increased. Interestingly, in the young Osx-Cre ; Rbpjf/f mice, the levels of many cytokines, such as TIMP-1, IL-16, TNF-a, M-CSF, C5/C5a, IP-10/CXCL10, and CCL2/MCP-1, were already more elevated (1.5- to 20-fold) than in age-matched controls. Importantly, the Osx-Cre ; Rbpjf/f mice that developed MPN showed specific increases of CXCL13/BCA-1, IL-1RA, IL-16, and TIMP-1, which were approximately 2- to 5-fold higher than in age-matched WT control and non-MPN mutant mice, indicating that these cytokines are strongly associated with the MPN phenotype. These data suggest that changes in the BM niche and inflammatory cytokines due to loss of Notch signaling in mesenchymal cells may cooperate with the physiological increase of inflammation occurring during aging in the development of MPN. Collectively, these observations show that loss of Notch signaling leads to different levels of inflammation and has a different biological impact depending on the specific niche cell type. DisclosuresNo relevant conflicts of interest to declare.

Backtracing persistent biomarker shifts to the age of onset: A novel procedure applied to men’s and women’s white blood cell counts in post-traumatic stress disorder

• Some biomarkers in mental disorders retain shifted levels long time after the onset. • A backtrace procedure for persistent shifts in cross-sectional data is presented. • It is demonstrated on leukocyte counts in post-traumatic stress disorder. • Neutrophil, lymphocyte and eosinophil counts showed the most impressive results. • The procedure opens new avenues for biomarker research in large epidemiological studies. Traumatic experiences tend to be preserved in altered biomarker profiles. These profiles can be traced back from cross-sectional data regarding the age of exposure. Consequently, the change across developmental stages, e.g. from childhood to adulthood, can also be reconstructed. This study introduces a backtrace procedure that is illustrated using white blood cell (WBC) counts in full / partial post-traumatic stress disorder (PTSD). The procedure was applied separately on men's and women's data to provide a replication of the analysis based on different subsamples. The analysis was carried out with data from the CoLaus|PsyCoLaus study (N = 5111, 2370 men and 2741 women, age range 35–88 years). It was restricted to traumatic experiences that occurred until the age of 35, i.e., the lower age limit of the sample. The WBC counts from up to two assessments were standardized, pooled and assigned to the reported age of trauma exposure. This resulted in age series for each marker, whereas the reference values were based on subjects who did not experience any trauma exposure. The backtrace procedure ascertained the peaks and troughs of the age series and determined the best-fitting critical age range surrounding each peak or trough based on the best p-value from simple t-tests. In CoLaus|PsyCoLaus, 750 participants reported trauma exposure until the age of 35, and 86 (out of 329) men and 187 (out of 421) women thereof were coded with a full or partial PTSD. Full / partial PTSD after trauma exposure in childhood was characterized by increased WBC counts (lymphocytes, eosinophils – in women also neutrophils). This pattern was partly retained during adolescence, in men due to eosinophils counts and in women due to lymphocyte counts. For exposure in young adulthood, the deviations were in the negative direction – in men with decreased basophils, in women with decreased lymphocytes and monocytes. Summarizing, the backtrace approach revealed WBC profiles in PTSD that were specific to particular developmental age stages. The strongest persistent upregulation of the immune system related to trauma exposure was traceable to childhood / early adolescence both in men and in women. Further research will show which biomarkers are similarly suitable for backtracing as WBC counts. As in PTSD, the backtrace approach could also be applied to identifying persistent biomarker profiles in other mental disorders, as well as autoimmune and other chronic diseases.

Severe extensive community acquired aspergillus infection in a full\u2010term infant accompanied with increases in white blood cell counts and C-reactive protein: a case report

BackgroundAspergillus infection is more common among premature infants in neonatal intensive care units, who have decreased qualitative immune defenses and need various invasive treatment procedures. It is rare in normal full-term neonates, especially in newborn babies from the community. Moreover, the white blood cell (WBC) count and C-reactive protein (CRP) level may be normal or slightly changed in fungal infections, but the neonate reported in this study had significant increases in WBC and CRP. To the best of our knowledge, this is the first report on a full-term neonate from the community with aspergillus infection accompanied by significant increases in WBC and CRP levels.Case presentationA 28-day-old infant, who received empirical antibiotic treatment for 10 days because of neonatal pneumonia, was referred to our neonatal department from the local hospital. The infant had persistent infection and multiple organ failure syndromes. Bronchoscopy and deep sputum smear were performed to identify the pathogen, which confirmed aspergillus infection in the sputum. Fluconazole was immediately administered, but the baby died after three days. Thereafter, an autopsy was performed with parental consent. There were multiple necrotic areas in the lungs and liver, and pathological examination revealed aspergillus.ConclusionsThe present case emphasized that community-sourced aspergillus infection can exist in full-term neonates, with significantly increased WBC count and CRP level. Advanced antibiotics were not effective in this case, and fungal infections should have been considered earlier.

Association of PML-RARα Fusion mRNA Type With Pretreatment Hematologic Characteristics But Not Treatment Outcome in Acute Promyelocytic Leukemia: An Intergroup Molecular Study

AbstractIn each case of acute promyelocytic leukemia (APL) one of three PML-RARα mRNA types is produced, depending on the break/fusion site in the PML gene that is linked to a common RARα gene segment: a short (S)-form type, PML exon 3 RARα exon 3; a long (L)-form type, PML exon 6 RARα exon 3; or a variable (V)-form type, variably deleted PML exon 6 RARα exon 3. We evaluated whether PML-RARα mRNA type is associated with distinct pretreatment clinical characteristics and therapeutic outcome in previously untreated adult APL patients registered to protocol INT 0129 by the Eastern Cooperative Oncology Group, the Southwest Oncology Group, and the Cancer and Leukemia Group B. Of 279 clinically eligible cases, 230 were molecularly evaluable, and of these, 111 were randomized to receive remission induction therapy with all-trans retinoic acid (ATRA) and 119 with conventional chemotherapy. Nine cases not excluded by central pathology review were PML-RARα negative, and notably, none of five of these cases treated with ATRA achieved complete remission (CR). Among 221 PML-RARα–positive cases, there were 82 S-form cases (37%), 121 L-form cases (55%), and 18 V-form cases (8%). Before any antileukemic therapy, the S-form type, compared with the L-form type, was associated with higher values for the white blood cell (WBC) count (median 2,500/μL v 1,600/μL; P = .009), the percentage of blood blasts plus promyelocytes (median 29% v 8.5%; P = .03), and the absolute blood blasts plus promyelocytes (884/μL v 126/μL; P = .019). Also, an increased percentage of S-form versus L-form cases had the M3 variant phenotype, 24% v 12% (P = .036). There were no differences between S-form and L-form cases in either CR rate (79% v 69%; P = .14) or disease free survival distribution (multivariate analysis adjusting for the association of S-form type and higher WBC count; P = .40). We conclude that the S-form type is associated with previously-identified adverse risk WBC parameters but that the identification of the S-form or L-form type of PML-RARα mRNA, per se, does not predict clinical outcome or add to the value of an increased WBC count as a negative prognostic indicator in APL patients.