Peripheral White Blood Cell Count Research Articles

Vascular Graft Infections, Mycotic Aneurysms, and Endovascular Infections: A Scientific Statement From the American Heart Association.

### Background The use of synthetic material for reconstructive vascular surgery was first reported during the early 1950s. Infection involving vascular graft prostheses is an infrequent but devastating complication of reconstructive vascular graft surgery and is associated with a high morbidity and, in some situations, mortality. Improvements in surgical techniques and graft design, including the use of native venous or arterial tissue, have reduced the frequency of infection and severity of complications from vascular graft infection (VGI). However, these advances have also led to more frequent vascular graft procedures occurring in a patient population with multiple underlying comorbidities that would have previously disqualified them as candidates for vascular reconstructive surgery. Underlying comorbidities, such as diabetes mellitus or immune compromise, increase the risk of infection and serious infection-related complications. The major complications of VGI include sepsis, amputation, disruption of infected anastomotic suture line with rupture or pseudoaneurysm formation, embolization of infected thrombi, reinfection of reconstructed vascular grafts, enteric fistulae to the small or large bowel, bacteremic spread of infection to other sites, and death. VGIs can be categorized broadly into those that occur in an extracavitary location, primarily in the groin or lower extremities, or in an intracavitary location, primarily within the abdomen or less commonly within the thorax. ### Frequency The frequency of VGI depends on the anatomic location of the graft. The infection rate is 1.5% to 2% for most extracavitary grafts and as high as 6% with vascular grafts in the groin.1–9 For intracavitary grafts, the infection rate is ≈1% to 5%.1–6 Graft infection is most common after emergency procedures and after reoperation.1–4,10 Aortic graft erosion or fistulous communication into the duodenum or other areas of the bowel reportedly occurs in 1% to 2% of patients after aortic reconstruction.11, …

Effects of occupational exposure to carbon black on peripheral white blood cell counts and lymphocyte subsets.

The International Agency for Research on Cancer has classified carbon black (CB) as a possible (Group 2B) human carcinogen. Given that most CB manufacturing processes result in the emission of various types of chemicals, it is uncertain if the adverse health effects that have been observed in CB-exposed workers are related to CB specifically or are due to other exposures. To address this issue, we conducted a cross-sectional molecular epidemiology study in China of 106 male factory workers who were occupationally exposed to pure CB and 112 unexposed male workers frequency-matched by age and smoking status from the same geographic region. Repeated personal exposure measurements were taken in workers before biological sample collection. Peripheral blood from all workers was used for the complete blood cell count and lymphocyte subsets analysis. Compared to unexposed workers, eosinophil counts in workers exposed to CB were increased by 30.8% (P = 0.07) after adjusting for potential confounders. When stratified by smoking status, statistically significant differences in eosinophils between CB exposed and unexposed workers were only present among never smokers (P = 0.040). Smoking is associated with alterations in various cell counts; however, no significant interaction between CB exposure and smoking status for any cell counts was observed. Given that inflammation, characterized in part by elevated eosinophils in peripheral blood, may be associated with increased cancer risk, our findings provide new biologic insights into the potential relationship between CB exposure and lung carcinogenesis. Environ. Mol. Mutagen. 57:589-604, 2016. © 2016 Wiley Periodicals, Inc.

Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway.

It has been reported that amyloid precursor protein(APP) promotes cell proliferation and metastasis in various types of solid cancers. In our previous study, we showed that APP is highly expressed and regulates leukemia cell migration in AML1‑ETO-positive(AE) leukemia. Whether APP is involved in the regulation of AE leukemia cell proliferation or apoptosis is unclear. In the present study we focused on the correlation of APP with c-KIT mutation/overexpression and cell proliferation and apoptosis in AE leukemia. APP and c-KIT expression detected by quantitative real-time(qPCR) method, and c-KIT mutations screened using PCR in bone marrow cells from 65 patients with AE leukemia before their first chemotherapy, were simultaneously assessed. Furthermore, the Kasumi-1 cell line was chosen as the cell model, and the APP gene was knocked down using siRNA technology. The correlation of cell cycle distribution and apoptosis and c-Kit expression with APP expression levels, as well as the regulation of the PI3K/AKT signaling pathway by APP were analyzed in the Kasumi-1 cell line. The results showed that peripheral white blood cell counts (P=0.008) and bone marrow cellularity (P=0.031), but not bone marrow blasts, were correlated with APP expression. Moreover, the patients with APP high expression had a significantly higher incidence of c-KIT mutations (P<0.001) and increased levels of c-KIT expression (P=0.001) and poorer disease outcome. In the Kasumi-1 cell line, as compared with the wild-type and negative control cells, cell apoptosis, both early (P<0.001) and late (P<0.001), was significantly increased when the APP gene was knocked down, concomitant with reduced levels of anti-apoptotic protein Bcl-2 and increased levels of caspase-3and-9, however, no apparent change was observed in the cell cycle distribution (P>0.05). Moreover, the knockdown of APP markedly decreased c-KIT expression at both the transcription (as evidenced by qPCR analysis) and translation (as confirmed by CD117 assay and western blot analysis) levels, as well as p-AKT and its downstream targets including NF-κB, p53 and Bcl-2. In conclusion, APP may cooperate with c-KIT mutation/overexpression in the regulation of cell apoptosis but not proliferation in AE leukemia via the PI3K/AKT signaling pathway.

Correlation between fecal calprotectin levels, disease severity and the hypervirulent ribotype 027 strain in patients with Clostridium difficile infection.

BackgroundClostridium difficile is the most common infectious etiology of nosocomial diarrhea. Fecal calprotectin (fc) is a sensitive marker of intestinal inflammation, found to be associated with enteric bacterial infections and inflammatory bowel disease.MethodsWe evaluated fc levels using a Chemiluminescent immunoassay method, in hospitalized patients with C. difficile infection (CDI) diagnosed by molecular stool examination and assessed correlation with virulent ribotype 027 strain infection, antibiotic susceptibility by gradient Etest strip performed on C. difficile colonies and clinical and laboratory measures of disease severity. Statistical analysis was performed for correlation of fc levels with clinical and laboratory parameters, disease severity and patient outcomes.ResultsOverall 29 patients with CDI were admitted at the Poria medical center in northern Israel, during June 2014-May 2015. Resistance to metronidazole was found in 3 (10.3 %) isolates and to vancomycin in 5 (17.2 %) isolates. Regarding patient outcomes, within 30 days of CDI diagnosis, recurrence of disease occurred in 10 (34.5 %) patients and 2 patients (6.9 %) died. Seven (24.1 %) isolates were C. difficile ribotype 027. Mean fc level was 331.4 μg/g (21–932). Higher fc levels were found in patients with C. difficile ribotype 027 (p < 0.0005). Fc levels were also correlated with elevated peripheral blood white cell count (p = 0.0007). A trend for higher fc levels was found in patients with a higher clostridium severity score index (p = 0.0633). No correlation was found between fecal calprotectin levels and age, sex, functional status, community versus hospital acquired CDI, antibiotic susceptibility, fever, and creatinine levels.ConclusionsOur study highlights the fact that fc has a potential role as a biomarker of disease severity and binary toxin producing ribotype associated disease.

Long-term safety of umbilical cord mesenchymal stem cells transplantation for systemic lupus erythematosus: a 6-year follow-up study.

The aim of this study is to assess the long-term safety of allogeneic umbilical cord mesenchymal stem cells (UC MSCs) transplantation for patients with refractory systemic lupus erythematosus (SLE). Nine SLE patients, who were refractory to steroid and immunosuppressive drugs treatment and underwent MSCs transplantation in 2009, were enrolled. One million allogeneic UC MSCs per kilogram of body weight were infused intravenously at days 0 and 7. The possible adverse events, including immediately after MSCs infusions, as well as the long-term safety profiles were observed. Blood and urine routine test, liver function, electrocardiogram, chest radiography and serum levels of tumor markers, including alpha fetal protein (AFP), cancer embryo antigen (CEA), carbohydrate antigen 155 (CA155) and CA199, were assayed before and 1, 2, 4 and 6 years after MSCs transplantation. All the patients completed two times of MSCs infusions. One patient had mild dizzy and warm sensation 5min after MSCs infusion, and the symptoms disappeared quickly. No other adverse event, including fluster, headache, nausea or vomit, was observed. There was no change in peripheral white blood cell count, red blood cell count and platelet number in these patients after followed up for 6years. Liver functional analysis showed that serum alanine aminotransferase, glutamic-oxalacetic transaminase, total bilirubin and direct bilirubin remained in normal range after MSCs infusions. No newly onset abnormality was detected on electrocardiogram and chest radiography. Moreover, we found no rise of serum tumor markers, including AFP, CEA, CA125 and CA199, before and 6years after MSCs infusions. Our long-term observational study demonstrated a good safety profile of allogeneic UC MSCs in SLE patients.

CEBPA mutations in patients with de novo acute myeloid leukemia: data analysis in a Chinese population.

BackgroundThis study was aimed to explore the clinical characteristics and prognoses of acute myeloid leukemia (AML) patients with CEBPA mutations.Patients and methodsThree hundred and forty-five patients with de novo AML were retrospectively analyzed with regard to CEBPA mutations, clinical characteristics, therapeutic responses, and long-term outcomes.ResultsCEBPA mutations were detected in 59 patients (17.10%), with 47 cases harboring double mutations and 12 cases harboring single mutations. In those with a normal karyotype (NK), 44 cases (25.29%) were detected with CEBPA mutations. The following characteristics were observed in CEBPA-mutated patients: most (66.10%) of them were M1 or M2; they presented with higher peripheral white blood cell counts (23.71 [12.6, 60.02] ×109/L versus 7.34 [2.38, 26.63] ×109/L; u=4.944, P<0.001) and higher hemoglobin levels (89.64±23.05 g/L versus 75.65±23.65 g/L; t=4.156, P<0.001) than those observed in patients without the mutation; and the expression of CD7 and HLA-DR was higher, whereas that of CD34 and CD56 was lower in patients with the mutation than in those without the mutation. Compared with those without the mutation, patients with CEBPA mutations had a superior complete remission rate (75.0% versus 56.54%; χ2=6.185, P=0.013) and superior overall survival (P=0.034).ConclusionThe frequency of CEBPA mutations may be higher in Chinese patients with AML than has been reported in populations of western countries, and the presence of CEBPA mutations is an indication of favorable prognoses for these patients.

Analysis of the Physiological Variation in Neutrophil CD64 Expression during the Early Neonatal Period.

Background Several biomarkers for the diagnosis of sepsis are elevated during the early neonatal period due to physiological variations. The aim of this study was to investigate the physiological variation in neutrophil CD64 (nCD64) expression during the early neonatal period and the change in nCD64 expression in neonates with noninfectious diseases. Methods Of 71 neonates enrolled in this prospective study, 5 and 51 were diagnosed as having bacteremia and noninfectious diseases, respectively. Fifteen healthy neonates were enrolled as normal controls. Peripheral white blood cell counts, serum C-reactive protein and procalcitonin levels, and nCD64 expression were examined at birth and on the first and fifth day of life in neonates with noninfectious diseases and healthy neonates. In neonates with bacteremia, these markers were measured at onset. Results nCD64 expression was significantly higher in neonates with bacteremia (median, 1,992) than in those with noninfectious diseases (1,823, p < 0.001) and healthy neonates (1,848, p = 0.002). Unlike other biomarkers, no differences in nCD64 expression were observed on the same days between neonates with noninfectious diseases and healthy neonates. Conclusion nCD64 expression may be a useful marker for the diagnosis of bacterial infection in the early neonatal period, because it does not show any physiological variations.

Bone marrow donor‐related variables associated with harvest outcome in HLA‐haploidentical transplantation with postinfusion cyclophosphamide

Several transplantation outcomes have been shown to be associated with the infused bone marrow cell dose/kg of the recipient's body weight. The donor bone marrow density is directly related to the infused cell dose. The aim of the present study was to identify donor-related variables that are associated with high donor bone marrow density. We retrospectively analysed the predictive factors of high marrow density in 65 consecutive HLA-haploidentical bone marrow donors harvested at our centre between 2009 and 2013. Body mass index (BMI) and peripheral white blood cell (WBC) count were directly associated with bone marrow density (regression coefficient β = 5·33 and β = 2·93, respectively; P < 0·01). The likelihood of obtaining a collection with a high density was first predicted using BMI (BMI ≥30, mean density = 25·8 TNC/ml × 10(6) ). Second, donors with a BMI <30 were split into two groups according to peripheral WBC count (WBC <8 × 10(3) /mm(3) : mean density = 18·4 TNC/ml × 10(6) ; WBC ≥8 × 10(3) /mm(3) : mean density = 23·1 TNC/ml × 10(6) ). We also observed that the density of the first collected bag directly correlated with the overall density (R(2) = 0·69, P < 0·01). The donor-related features BMI and WBC count affect the cell quantity obtainable with the harvest and should be taken into account when choosing the donor.

50 Years Ago in TheJournal ofPediatrics: The Peripheral White Blood Count in Respirovirus Infection

Portnoy B, Hanes B, Salvatore, MA, Eckert HL. J Pediatr 1966;68:181-8 Portnoy et al documented the peripheral white blood cell (WBC) counts in hundreds of hospitalized children with respiratory tract viruses, comparing children who were symptomatically and asymptomatically infected. The median WBC counts were significantly different: 14 465/mm3 in the symptomatic group vs 9000 in the asymptomatic group, but with large overlap. The hypotheses driving this investigation were not clearly stated by the investigators, but in the Discussion they speculated that the higher WBC counts in the symptomatic children may have been due in part to coincident infection by bacteria. The accurate identification of bacterial superinfection in viral respiratory tract illness remains a vexing problem. Influenza has a well-documented incidence of bacterial superinfection, most commonly with Streptococcus pneumoniae, particularly in fatal cases. Indeed, the name “Haemophilus influenzae” was derived from its original isolation from the lungs of persons suffering from severe influenza in the late 19th century. The frequency of bacterial superinfection in other viral respiratory tract infection is not well established. Respiratory viruses alter upper airway defenses, upregulate bacterial adhesion factors on epithelial cells, and disrupt elements of innate immunity in the lungs, so it is remarkable that even with influenza, the marked majority of lower respiratory tract infection in children is purely viral. The dilemma, then, has been to identify the few who are truly coinfected with bacteria, especially in severe disease, allowing the clinician to intelligently use or safely withhold antibiotics. Readily assessable variables such as fever, WBC count (as suggested by the data in Portnoy et al), and the acute phase reactant C-reactive protein insufficiently discriminate viral and bacterial disease in the individual child. Procalcitonin, a sensitive and specific acute phase reactant in detecting bacterial disease, was inadequate as a stand-alone test in identifying bacterial coinfection during the H1N1 influenza pandemic, although persistently low procalcitonin measurements may allow discontinuation of antibiotics once started. In the future, viral and bacterial or mixed viral/bacterial pneumonias may prove to have unequivocally distinct and measurable cytokine signatures, but for now the perfect test to identify bacterial superinfection in viral respiratory tract disease remains elusive, and the clinician must use multiple clues in assessing the need for, and duration of, antibiotics.

Development of a preliminary diagnostic measure for bovine leukosis in dairy cows using peripheral white blood cell and lymphocyte counts.

Analysis of the association between antibodies against bovine leukemia virus (BLV), BLV proviral load, and white blood cell (WBC) and lymphocyte counts was performed with 774 dairy cows. The average age, WBC counts and lymphoid cell counts tended to be higher in BLV antibody-positive cows than in antibody-negative cows. There was a similar trend in levels of proviral DNA. We analyzed age, WBC counts and lymphocyte counts by principal component analyses to create a distribution chart of the principle component scores. Using the chart, we categorized cows into four quadrants based on additional information, such as the presence of antibody and the levels of proviral DNA. Antibody-positive cows and cows with high BLV proviral load were found mostly in one quadrant of the chart, indicating that it is possible to predict the risk of infection without any knowledge on antibody status by using information, such as WBC counts as a biomarker. When only antibody-positive cows were included in the analysis, a characteristic distribution of different levels of proviral DNA was seen in the quadrants, suggesting that it is possible to estimate the extent of bovine leukosis infection by using this analysis. For this analysis and categorization of the cows into quadrants, we computed a mathematical formulation using discriminant analysis based on age and WBC and lymphocyte counts. This mathematical formulation for the hematological preliminary diagnosis of the disease is recommended as a screening tool to monitor bovine leukosis.

The modulating effects of propofol and its lipid carrier on canine neutrophil functions.

Propofol (2,6-diisopropylphenol), being used as an intravenous sedative and anesthetic agent, influences not only upon nervous system but also for host inflammatory response through modulating neutrophil functions. This study is designed to evaluate the modulating effects of propofol and its lipid carrier administration at clinically relevant rate on canine neutrophil functions. Clinically healthy beagle dogs were received propofol (8.8 mg/kg) from cephalic vein and maintained with propofol dropping infusion (26.4 mg/kg/hr). Blood samples were collected from the dogs before infusion and 30 min after the start of propofol administration, and neutrophil functions were evaluated. The dogs were also administered lipid carrier, and neutrophil functions were evaluated in the same manner as propofol administration. Peripheral white blood cell and neutrophil counts decreased after the propofol or lipid carrier administration. The administration of propofol or lipid carrier significantly reduced neutrophil adherence ability. The superoxide production of neutrophils was measured by luminol-dependent chemiluminescence response using with opsonized zymosan. Peak height of neutrophil chemiluminescence curve was reduced by propofol and lipid carrier administration, on the contrary, peak time of neutrophil chemiluminescence curve was delayed. Administration of propofol or lipid carrier also reduced neutrophil adherence ability to nylon fibers. In the present study, we showed the modulating effects of propofol and its lipid carrier on canine neutrophil functions. However, there was no significant difference in the modulating effects between propofol group and lipid carrier group. Therefore, the modulating effects observed here were deeply concerned in lipid carrier administration.

Therapeutic Leukapheresis for the Management of Hyperleukocytosis: Ten-year Experience in a Tertiary Care Hospital

This article is available from http://www.labmedonline.org 2016, Laboratory Medicine Online This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Hyperleukocytosis is a medical emergency that is characterized by increased blood viscosity and predisposition to various neurological, pulmonary, and gastrointestinal complications. In addition, patients are at risk of the tumor lysis syndrome because of the increased tumor burden. Therapeutic leukapheresis is an important treatment for these emergent states. In this study, we retrospectively analyzed therapeutic leukapheresis procedures that were performed in our institution during the last 10 yr. Methods: We retrospectively analyzed therapeutic leukapheresis procedures conducted from July 2005 to March 2015 at a tertiary care hospital. We present our observations, especially the procedural characteristics and hematological parameters before and after the aforementioned procedures. Results: Seventy-two patients underwent a total of 146 therapeutic leukapheresis procedures. The average presenting white blood cell (WBC) count was 268×10/μL, and ranged from 54×10/μL to 673×10/μL. After an average of two sessions, a statistically significant drop in the WBC counts was observed. The average WBC removal rates during the initial and entire therapeutic leukapheresis procedures of each patient were 33% and 46%, respectively. The platelet count and hemoglobin concentration were significantly reduced. Conclusions: Therapeutic leukapheresis significantly reduces peripheral WBC counts and is a safe and effective procedure for the treatment of hyperleukocytosis.

White blood cell count and clinical outcomes after intracerebral hemorrhage: The INTERACT2 trial

BackgroundIncreased inflammatory reaction can aggravate brain injury after acute intracerebral hemorrhage, but the clinical effect of such response is not fully understood. The aim of this study was to determine associations of peripheral white blood cell (WBC) count on clinical outcome among participants of the INTERACT2 study. MethodsINTERACT2 was a randomized controlled trial of early intensive (target systolic level<140mmHg) compared to guideline-recommended (target systolic level<180mmHg) blood pressure (BP) lowering in 2839 patients with acute ICH (<6h) and elevated systolic BP (150–220mmHg). Blood samples were collected on admission and WBC count was measured at local laboratories. The primary outcome was death or major disability, defined by scores 3–6 on the modified Rankin Scale at 90days. Secondary outcome was death at 90days. Associations of baseline WBC count and outcomes were evaluated in logistic regression models. INTERACT2 is registered with http://www.clinicaltrials.govNCT00716079. ResultsThere were 2630 participants with relevant data who were classified into quartiles of WBC counts (≤6.22, 6.24–7.89, 7.90–10.17, and ≥10.20×109/L, respectively). Increased WBC count was associated with younger age, elevated body temperature, increased glucose level, stroke severity, larger baseline hematoma volume, and intraventricular extension. Risks of death or major disability at 90days increased progressively with higher WBC count: frequencies of 49.9%, 52.0%, 52.3% and 58.1% for quartile groups, respectively (P=0.004 for trend). However, after adjustment for baseline clinical and imaging variables including age, sex, region, lipid lowering therapy, body temperature, glucose, systolic BP, heart rate, high NIHSS scores, volume and location of hematoma, intraventricular extension, time from onset to CT scan, and randomized treatment, the association between WBC count and primary outcome was no longer significant (P=0.426 for trend). Patients with increased WBC count had significantly higher risk of death (P=0.0003 for trend), but again the association was no longer significant after adjustment for baseline clinical and imaging variables. ConclusionsElevated WBC count on admission is not an independent prognostic variable in patients with acute ICH.

Dynamic changes and influencing factors of leukocyte and platelet count in preterm infants

Objective To investigate the dynamic changes and influencing factors of peripheral blood white blood cells (WBC), differential counts (DCs) and platelet (PLT) count in preterm infants to understand the changing characteristics of these blood parameters in preterm infants of different postnatal age, gestational age, and birth weight. Methods Totally 2 849 preterm infants admitted to the Department of Neonatology of Northwest Women's and Children's Hospital from November 30, 2011 to November 30, 2014 were retrospectively analyzed except for those diagnosed with infectious diseases, hematological system diseases, or immunologic diseases. All of the subjects were divided into seven groups based on their postnatal age, three groups based on gestational age and three groups based on birth weight, or male and female groups, respectively. Peripheral blood samples were obtained for determination of WBC, DCs and PLT. Statistical analysis was performed with one-way analysis of variance, t-test and Spearman linear correlation analysis. Results WBC, neutrophil (Ne), lymphocyte (Ly), monocyte (Mo), eosinophil (Eo), basophil (Ba) and PLT counts were significantly different among the seven groups of preterm babies of different postnatal age (F=172.00, 364.90, 34.88, 14.22, 80.82, 168.10 and 86.64, respectively, all P 2- ≤5 [(10.62±4.68)×109/L], further gradual decrease thereafter, and then being stable in day >14-≤21 and >21-≤30 [(10.54±3.09)×109/L and (10.27±3.70)×109/L, respectively]. PLT counts showed no significant change within one day after birth and in day >1-≤2 [(240.56±63.54)×109/L and (240.85±71.47)×109/L, respectively], then began to increase in day >2-≤5 [(249.21±80.55)×109/L], peaked in day >7-≤14 [(339.11±121.84)×109/L], and decreased gently and became stable finally. The changing trends of Ne and Ly were cross and inverted in day > 5-≤7. WBC, Ne, Ly, Mo, Eo, Ba and PLT counts of the preterm infants were all correlated with the postnatal age shown by Spearman linear correlation analysis (r=-0.46, -0.60, 0.18, -0.07, 0.33, -0.47 and 0.29, respectively, all P<0.01). With the increase of gestational age, WBC, Ne, Mo, and PLT counts increased, but Ly and Eo counts decreased. And all of the above showed significant difference (F=81.00, 124.49, 13.34, 18.35, 5.35 and 4.11, respectively, all P<0.05). While, the WBC, Ne, Mo, Ba and PLT counts showed positive relationship with the increase of birth weight (F=122.12, 133.09, 39.38, 13.77 and 21.24, respectively, all P<0.05). WBC, Ne and PLT counts of female infants were higher than those of male babies (t=16.35, 16.72 and 13.19, respectively, all P<0.05). Conclusions The peripheral WBC, DCs and PLT counts of preterm infants change dynamically with postnatal age with the remarkable variations on day >2-≤5 after birth and stable after 14 days of age. WBC, DCs and PLT counts might all be influenced by gestational age, birth weight and gender to some extend. Key words: Leukocyte count; Platelet count; Infant, premature

Moderate Exercise Training Attenuates Inflammation in Transgenic Sickle Cell Mice

Sickle cell disease (SCD) is a monogenic disorder characterized by severe systemic and vascular inflammation. There is strong evidence that moderate exercise training reduces inflammation in healthy people as well as in multiple diseases conditions. The aim of this study was to characterize the effects of moderate exercise training in a humanized transgenic mouse model of SCD (Townes) in mice expressing exclusively human sickle hemoglobin (SS). The SS mice display many of the features of human SCD including systemic inflammation and chronic anemia. We designed a treadmill training protocol of 1hr/day, 5 days a week for 8 weeks. Prior to the training, the maximal oxygen uptake (V̇O2max) was assessed by an exhaustive incremental exercise. SS mice (n=22) had lower V̇O2max (mean ± SEM: 7,068 ml/kg/hr ± 133 vs. 8,407 ml/kg/hr ± 224.5, p<0.0001) and lower maximal speed (14.3 m/min ± 0.7 vs. 29.3 m/min ± 1.7, p<0.0001) than control AA mice expressing exclusively normal human hemoglobin (n=12). Together these results indicate SS mice have an inherently reduced aerobic exercise capacity; nonetheless, they tolerated a training regimen at 60% of V̇O2max. After eight weeks of training, SS mice had a lower hematocrit (20.3% ± 0.8% vs. 24.4% ± 1.8%, p=0.04; n=8) than untrained SS littermates that were exposed to all other experimental conditions except training. There were only moderate changes in red blood cell count (Trained: 4.8.106/µL ± 0.2, Untrained: 5.7.106/µL ± 0.5, p>0.05) or total hemoglobin (Trained: 5.6 g/dL ± 0.2 vs 6.3 g/dL ± 0.4, p>0.05) between the two groups suggesting the low hematocrit in the trained mice was probably due to increased plasma volume, which is a normal physiological response to exercise training. The spleen/body mass ratio was significantly lower in the trained SS mice compared to the untrained littermates (5.7 mg/g body weight ± 0.3 vs. 7.0 mg/g body weight ± 0.9, p=0.04). Importantly, the spleen was less congested in the trained SS mice, and the magnitude of congestion in all animals (trained and untrained) correlated very strongly with the relative spleen mass (r=0.7, p=0.009). Exercise training significantly increased the percent of oxyhemoglobin in the venous blood of SS mice (Trained: 39% ± 4.3, Untrained: 22.3 ± 4.1, p=0.016). And, there was a corresponding decrease in the percent carboxyhemoglobin (Trained: 2.3% ± 0.7, Untrained 6.2% ± 0.5, p=0.001). These data suggest moderate exercise training may reduce the proportion HbS that is deoxygenated in the venous circulation. In addition, exercise training significantly reduced the peripheral blood white cell count in the SS mice (Training: 14.7.103/µL ± 0.9, Untrained: 21.6.103/µL ± 3.1, p=0.03); this change was reflected by a corresponding lower lymphocyte count in the trained mice (12.103/µL ± 0.8 vs. 17.3.103/µL ± 2.3, p=0.028). Finally, running decreased the liver expression of heme oxygenase-1 (HO-1) mRNA (p=0.04) and the plasma concentration of macrophage inflammatory protein-1β (MIP-1β, p=0.03). Interestingly, HO-1 is implicated in metabolic inflammation and MIP-1β promotes endothelial adhesion of CD8+ T cell through a VCAM-1 dependent pathway. Together with the reductions in leukocyte counts, we suggest that moderate exercise training may reduce sequestration of sickle erythrocytes/congestion, resting blood deoxygenation and inflammation in SCD. DisclosuresNo relevant conflicts of interest to declare.

Clinical Significance of Soluble Interleukin-2 Receptor in Patients with Acute Leukemia

Objective: Investigate the expression level and clinical significance of serum soluble interleukin-2 receptor (sIL-2R, sCD25) in patients with acute leukemia.Methods: Serum sCD25 level were measured using enzyme linked immunosorbent assays (ELISA) in 97 acute leukemia patients and 10 healthy contrlols. Clinical and laboratory features, including bone marrow cellularity, white blood cell count (WBC), platelets (PLT), lactate dehydrogenase (LDH), serum ferritin (SF), erythrocyte sedimentation rate (ESR), as well as overall survival (OS) data were collected.Results: (1) Serum sCD25 level of the newly diagnosed leukemia group was significantly higher than that of the control group (P<0.0001). (2) Among the newly diagnosed AML patients, serum sCD25 level of the M3 group was significantly lower than that of the M2 or non-M2/M3 group (P<0.05). In addition, serum sCD25 level of the low/intermediate risk (AML) or standard risk (ALL) group was lower than that of the high risk group (P<0.05). (3) Serum sCD25 level of the complete remission (CR) group was significantly lower than that of the newly diagnosed group (P<0.002). However, no significant decrease was found in serum sCD25 level of the relapsed/refractory group compared to that of the newly diagnosed group. (4) Serum sCD25 level in newly diagnosed patients was positively correlated with peripheral WBC, LDH and SF. (5) Furthermore, although OS of the low sCD25 level group (sCD25<2000pg/ml) was not significantly different compared to the intermediate sCD25 level group (2000≤sCD25≤4000pg/ml) (P =0.532), both that of the low or intermediate sCD25 level group were significantly superior to that of the high sCD25 level group (sCD25>4000pg/ml) (P<0.05).Conclusion: Serum sCD25 levels have important clinical significance in evaluating disease activity, treatment outcomes and prognosis in patients with acute leukemia. DisclosuresNo relevant conflicts of interest to declare.

Leukapheresis Reduces 4-Week Mortality in Leukemia Patient with Hyperleukocytosis-a Retrospective Study from a Tertiary Center

Background: Hyperleukocytosis is complication of leukemia and is defined as peripheral white blood cell (WBC) count greater than 100, 000/mm^3. The high WBC count can increase blood viscosity and lead to leukostatsis, which is a medical emergency most commonly seen in acute leukemias. The use of Leukapheresis, is controversial and there are few guidelines. We performed a retrospective review of outcomes in patients with hyperleukocytosis who received leukapheresis in Houston Methodist Hospital between 2006 and 2015.Methods: The patient data was queried from METEOR (Methodist Environment for Translational Enhancement and Outcomes Research), a clinical data warehouse and analytics environment that integrates existing business data warehouse with internal and external research databases and national registries to support clinical research and outcome studies for improving patient care cost-effectively. METEOR data warehouse contains records dating back to January 1, 2006 with over 1 million unique patients and over 4 million unique patient encounters. We queried for the diagnosis of leukemia and those that received at least one course of leukapheresis and also obtained baseline demographics, and overall outcomes.Results: We reviewed 5585 of whom 42 patients who meet the criteria-patients, 29 of them have diagnosis of AML, 6 with CLL, 4 with ALL, and 3 with CML. The baseline demographics included 29 males and 13 females, whose median age was 52.5; 19 were Caucasians while 10 were African Americans, 5 Hispanic, 5 Asian and 3 reportedly as others.As shown in Table 1, the population is divided into 3 groups according to WBC before leukapheresis. Group 1 has 7 patients with WBC <100,000, median of 80.460. Group 2 has 17 patients with WBC range from 100,000 to 200,000, median of 150,740. Group 3 has 18 patients with WBC above 200,000, median of 252,200.In group 1, the average leukostatsis symptom grade is 1.43, average % decrease of WBC is 34.54%, ( blast-84%). In group 2, the average leukostatsis symptom grade is 1.88, average % decrease of WBC is 48.25%, ( blast- 69%). In group 3, the average leukostatsis symptom grade is 1.06, average % decrease of WBC is 42.81%, (blast-59.5%).In terms of complications, in group 1, 42.86% presented with acute kidney injury (AKI), 28.57% with tumor lysis syndrome, 28.57% with disseminated intravascular coagulation (DIC), 28.57% with sepsis, 14.29% with pneumonia, 42.86% with respiratory failure, 14.29% and with acute coronary syndrome (ACS). In group 2, 17.65% presented with AKI, 47.06% with TLS, 47.06 % with DIC, 23.53% with sepsis, 11.76% with pneumonia, 41.18% with respiratory failure, and 5.88% with acute coronary syndrome. In group 3 11.10 % presented with acute kidney injury, 44.44% with TLS, 38.89 % with DIC, 22.22% with sepsis, 11.11% with pneumonia, 27.78 % with respiratory failure, and 5.56 % with ACS. The 4 weeks mortality rate are 42.86% for group 1, 29.41% for group 2, and 22.22% for group 3.Conclusions: We have validated the Hyperleukocytosis grading schema and usefulness of leukapheresis. Our data indicates comparable mortality in pts with WBC between 100 -200,000 and > 200,000. Further statistical review of this data set will be presented at the ASH Meeting, Orlando 2015Table 1Group 1Group 2Group 3WBC range<100,000100,000 to 200,000>200,000Number of patients71718Average leukostasis symptom grade1.431.881.06% Lymphoid leukemia14.29%17.65%33.33%Median WBC before leukapheresis80,460150,740252,200Average % decrease of WBC34.54%48.25%42.81%Median % of blast before leukapheresis84%69%59.5%Average % change in %blast5.35%11.23%-6.55%Average Creatinine after Leukapheresis2.391.471.38Average uric acid after leukapheresis8.776.526.75Average Fibrinogen after leukapheresis424.25336.78300.56% Acute kidney injury42.86%17.65%11.10%% Tumor lysis syndrome28.57%47.06%44.44%% DIC28.57%47.06%38.89%% Sepsis28.57%23.53%22.22%% Pneumonia14.29%11.76%11.11%% Respiratory failure42.86%41.18%27.78%% Acute Coronary Syndrome14.29%5.88%5.56%% 4 weeks Mortality42.86%29.41%22.22%

The clinical features of respiratory infections caused by the Streptococcus anginosus group.

BackgroundThe Streptococcus anginosus group (SAG) play important roles in respiratory infections. It is ordinarily difficult to distinguish them from contaminations as the causative pathogens of respiratory infections because they are often cultured in respiratory specimens. Therefore, it is important to understand the clinical characteristics and laboratory findings of respiratory infections caused by the SAG members. The aim of this study is to clarify the role of the SAG bacteria in respiratory infections.MethodsA total of 30 patients who were diagnosed with respiratory infections which were caused by the SAG bacteria between January 2005 and February 2015 were retrospectively evaluated.ResultsRespiratory infections caused by the SAG were mostly seen in male patients with comorbid diseases and were typically complicated with pleural effusion. Pleural effusion was observed in 22 (73.3%) patients. Empyema was observed in half of the 22 patients with pleural effusion. S. intermedius, S. constellatus and S. anginosus were detected in 16 (53.3 %), 11 (36.7 %) and 3 (10.0 %) patients, respectively. Six patients had mixed-infections. The duration from the onset of symptoms to the hospital visit was significantly longer in “lung abscess” patients than in “pneumonia” patients among the 24 patients with single infections, but not among the six patients with mixed-infection. The peripheral white blood cell counts of the “pneumonia” patients were higher than those of the “lung abscess” patients and S. intermedius was identified significantly more frequently in patients with pulmonary and pleural infections (pneumonia and lung abscess) than in patients with bacterial pleurisy only. In addition, the patients in whom S. intermedius was cultured were significantly older than those in whom S. constellatus was cultured.ConclusionsRespiratory infections caused by the SAG bacteria tended to be observed more frequently in male patients with comorbid diseases and to more frequently involve purulent formation. In addition, S. intermedius was mainly identified in elderly patients with having pulmonary infection complicated with pleural effusion, and the aspiration of oral secretions may be a risk factor in the formation of empyema thoracis associated with pneumonia due to S. intermedius.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-015-0128-6) contains supplementary material, which is available to authorized users.

IDH1 Gene Mutation and Its Clinical Significance in patients with Acute Myeloid Leukemia

To evaluate the incidence rate of IDH1 in acute myeloid leukemia and analyze its effect on clinical characteristics and prognosis. Mononuclear cells in bone marrow samples were collected from 192 adult patients with newly diagnosed AML. Polymerase chain reaction (PCR) and direct sequencing were used to amplify exon 4 of IDH1 gene, the gene sequencing was used to analyze the gene mutations, at same time, the detection of NPM1, FLT3-TKD, FLT3-ITD, C-KIT, CEPBA, TET2 and JAK2V617F and MLL mutations were carried out, the follow-up was used to determine its therapeutic efficacy and outcomes of patients. The clinical and laboratory data of these cases were collected, and their clinical characteristics and prognosis were then analyzed. Among the 192 AML patients, 13 cases were detected with IDH1 gene mutation, the mutation rate was 6.77% [95% CI (5.70%-13.38%)]. The sequencing chart of IDH1 gene showed double peaks, the mutations were heterozygous, out of them c.G395A (p.R132H) was found in 8 cases, c.C394T was found in 4 cases (p.R132C), c.C394A (p.R132S) was found in 1 cases, R132H and R132C are common, 13 cases showed missense mutation. The median age in mutation group was 52 years old, the median age in unnutration group was 40 years, there was significant difference between them (P = 0.010). Mutation rate of IDH1 gene in M1 and M2 was significantly higher than that in other FAB subtypes. There were no significant difference in sex, newly diagnosed peripheral white blood cell count, hemoglobin, platelet count, peripheral blood and bone marrow original cell proportion of primitive cells between them. Mutation of IDH1 gene had certain correlation with NPM1 gene mutation, but no correlation with FLT3-TKD, FLT3-ITD, C-KIT, TET2 and JAK2V617F and MLL natations was found. In addition, the IDH1 mutation easily occurred in patients with normal karyotype or in patients with middle prognostic risk karyotype, IDH1 mutation occurred in 11 cases with normal karyotype, the mutation rate was 10.28%, IDH1 mutation were observed in 2 cases with abnormal karyotype, the mutation rate was 3.50%, there was significant difference. In AML patients with middle prognostic risk karyotype. The complete remission (CR) and the 3 year survival (OS) rate of IDH1 mut patients were less than that in IDH1 wt, there was significant difference (P < 0.05). The IDH1 mutation more easily occurr in older AML patients and mutations effect of IDH1 on clinical characteristics may represent a molecular marker for poor prognosis in AML.

Janus Kinase Inhibitor Tofacitinib Shows Potent Efficacy in a Mouse Model of Autoimmune Lymphoproliferative Syndrome (ALPS).

Autoimmune lymphoproliferative syndrome (ALPS) is a non-malignant genetic disorder of lymphocyte homeostasis with defective Fas-mediated apoptosis. Current therapies for ALPS primarily target autoimmune manifestations with non-specific immune suppressants with variable success thus highlighting the need for better therapeutics for this disorder. The spectrum of clinical manifestations of ALPS is mirrored by MRL/lpr mice that carry a loss of function mutation in the Fas gene and have proven to be a valuable model in predicting the efficacy of several therapeutics that are front-line modalities for the treatment of ALPS. We evaluated the potential efficacy of tofacitinib, an orally active, pan-JAK inhibitor currently approved for rheumatoid arthritis as a single agent modality against ALPS using MRL/lpr mice. We demonstrate that a 42-day course of tofacitinib therapy leads to a lasting reversal of lymphadenopathy and autoimmune manifestations in the treated MRL/lpr mice, Specifically, in treated mice the peripheral blood white blood cell counts were reversed to near normal levels with almost a 50 % reduction in the TCRαβ(+)CD4(-)CD8(-)T lymphocyte numbers that coincided with a parallel increase in CD8(+) T cells without a demonstrable effect on CD4(+) lymphocytes including FoxP3(+) regulatory T cells. The elevated plasma IgG and IgA levels were also drastically lowered along with a significant reduction in plasmablasts and plasmacytes in the spleen. On the basis of these results, it is likely that tofacitinib would prove to be a potent single agent therapeutic modality capable of ameliorating both offending lymphadenopathy as well as autoimmunity in ALPS patients.