Higher Leukocyte Counts Research Articles

Determinants of Mortality in Necrotizing Soft Tissue Infections.

BackgroundNecrotizing soft tissue infections (NSTI) are frequently encountered, with a high mortality despite advances in health care.Material and MethodsPatients presenting with NSTI were prospectively followed up in an attempt to identify factors that were significantly associated with mortality.ResultsThere were a total of 86 patients [65 males (75.6%) and 21 females (24.4%)] with an overall mortality of 33.7% (29 patients). The average age was 50.37 years and trauma was the commonest aetiology (34 patients, 66.7%). The average duration of symptoms prior to presentation was 10.56 days; the lower limb was most commonly involved (62 patients, 72.09%). Fifty nine patients had comorbidities (commonest being diabetes mellitus in 41). Age above 50 years, symptoms for more than 8.5 days, involved surface area more than 15.5%, of the total body surface, on-admission pulse rate more than 99 beats/minute, systolic blood pressure less than 103 mm Hg, Glasgow scale less than 12, need for inotropes, low hemoglobin, high leukocyte counts, uraemia, deranged coagulation, low serum albumin, and high levels of lactic acid were significant for mortality. On multivariate analysis, only age above 50 years, presence of acidosis and low serum albumin significantly affected survival.ConclusionNSTI carry high mortality. The identification of potential risk factors associated with mortality might help in guiding and optimizing the management of patients who present with NSTI.

Thromboelastometry in patients with advanced chronic liver disease stratified by severity of portal hypertension

BackgroundRotational thromboelastometry (ROTEM) has been studied in patients with advanced chronic liver disease (ACLD) without considering the impact of portal hypertension. We evaluated the influence of the hepatic venous pressure gradient (HVPG) on ROTEM results in patients with ACLD.MethodsCross-sectional study; ACLD patients undergoing HVPG measurement within the prospective Vienna Cirrhosis Study (NCT03267615) underwent concomitant ROTEM testing.ResultsAmong 159 patients (68% male; Child–Pugh-A: 53%, Child–Pugh-B: 34%, Child–Pugh-C: 13%), 21 patients (13%) had a HVPG between 6 and 10 mmHg, 84 patients (53%) between 10 and 19 mmHg, and 54 patients (34%) ≥ 20 mmHg. Child–Pugh-C patients (vs. Child–Pugh-A and vs. Child–Pugh-B patients, respectively) showed longer clot formation time (CFT: median 187 s vs. 122 s vs. 122 s, p = 0.007) and lower maximum clot firmness (MCF: median: 45 mm vs. 56 mm vs. 56 mm, p = 0.002) in extrinsic thromboelastometry (EXTEM), while platelet counts were similar across Child–Pugh stages. In the overall cohort, ROTEM parameters did not differ by severity of portal hypertension. However, among compensated Child–Pugh-A patients, MCF decreased with increasing portal pressure, i.e. in higher HVPG strata (HVPG 9–10 mmHg: median MCF: 59 mm vs. HVPG 10–19 mmHg: 56 mm vs HVPG ≥ 20 mmHg: 54 mm, p = 0.023). Furthermore, patients with short CFT and high MCF in EXTEM had higher levels of lipopolysaccharide-binding protein, C-reactive protein, and procalcitonin, as well as higher leukocyte counts (all p < 0.05).ConclusionsPortal hypertension seems to impact ROTEM results only in compensated Child–Pugh-A patients. Bacterial translocation and systemic inflammation may trigger a procoagulant state in patients with ACLD.

The effectiveness of tetragonola honey combinations Aff.biroi and royal jelly as immunomodulators : immunomodulators modelling in facing the plague of COVID-19

COVID-19 epidemic caused serious concern around the world. Innate and adaptive immunity prevents occurring acute infection. Immunomodulatory activity tests and increased leucocyte cells in rat have been carried out using honey (H) and royal jelly (RJ). This study aims to prove the combination of honey and royal jelly in increasing the leucocyte profile in male Sprague Dawley rats. This study used 28 rats divided into 7 groups, namely the negative control and positive, single dose group H and single dose RJ and the combination dose 1, dose 2, and dose 3, then on day the 8th and 11th rats were injected intraperitoneally with 2% sheep red blood cell antigen as much as 0.5 ml. Leucocyte profile were carried out on the 8th and 15th days. The results showed significant difference on leukocyte count (p = 0.000), but there was a decrease in the normal range on day 15th. The highest leucocyte count was showed on the honey and the combination 3 group. Leukocyte differential showed no significant difference (p&gt; 0.05). The honey group and the dose combination 3 showed an increase in the number of segment neutrophils. The difference in lymphocyte reduction was seen between the honey and royal jelly group, with the dose combination 3, respectively. There are significant differences in granulocyte cells enhancement between the honey group and the dose combination 3. We concluded that single dose honey can be an immunomodulatory. Dose combination 3 can be an alternative for further research for immunomodulatory supplement product.

Outcomes and Laboratory and Clinical Findings of Asthma and Allergic Patients Admitted With Covid-19 in a Spanish University Hospital.

Individual susceptibility and clinical outcome of Covid-19 are variable and mortality is also very variable across countries, being particularly high in Spain. Comorbidities might increase the risk for less favourable outcomes, but it has been reported that patients with antecedents of asthma or allergic diseases were under-represented among hospitalized Covid-19 patients. Aiming to compare the clinical evolution of patients with antecedents of asthma or allergic diseases and patients without these antecedents, we analyzed a series of 113 consecutive patients with Covid-19 in a regional hospital in Spain. We collected and analyzed the putative effect of the 16 most common co-morbidities, previous treatment with 33 drug classes, symptoms, radiological, and laboratory findings at admission and drug therapy after admission. Predictors of long hospital stays were older age (P = 0.002), low oxygen saturation (P = 0.001) and bilateral radiological findings at admission (P = 0.023). Predictors of Intensive Care Unit (ICU) admission were the previous use of calcium-channel blockers (P = 0.005), proton pump inhibitors (P = 0.017), low oxygen saturation (P = 0.002), high leukocyte count (P = 0.011), and high D-dimer values (P = 0.005). Predictors of mortality were older age (P = 0.001), antecedents of cerebrovascular disorders (P = 0.034), previous use of oral anticoagulants (P = 0.009) or selective serotonin reuptake inhibitors (P = 0.003), and increased levels of interleukin-6 (P = 0.001). Patients with antecedents of allergic diseases were about ten years younger (P = 0.003) and had fewer comorbidities (P = 0.026) than the rest of the patients. In conclusion, antecedents of allergic diseases might influence hospitalization risk in relatively young patients.

Recurrent genetic abnormalities detected by FISH in adult B ALL and association with hematological parameters.

BackgroundRecurrent genetic abnormalities influence prognosis in B lymphoblastic leukemia. BCR‐ABL rearrangement is associated with higher leukocyte counts and older age at presentation. Among adults, BCR ‐ABL ‐ is the commonest recurrent abnormality whereas, IgH rearrangements are rare.AimAim of this study was to identify common recurrent genetic abnormalities in adult B ALL and study their association with hematological findings.MethodsBone marrow and peripheral blood from patients with B acute lymphoblastic leukemia were analyzed for complete blood counts, bone marrow morphology and cytogenetic abnormalities. The study group was divided into smaller groups based on cytogenetic abnormalities. Hematological parameters and presence of recurrent genetic abnormalities was compared across age groups and gender by non parametric tests.Results BCR‐ABL positive group had a higher leukocyte count than BCR‐ABL negative group. Among groups 1 to 5, group 1 with gains of chromosomes was associated with leucopenia and higher age at presentation. BCR‐ABL is commonest recurrent abnormality followed by IgH rearrangements.ConclusionPatients with gains of chromosomes alone have low total leukocyte counts at presentation.

The Outcome of Acute Lymphoblastic Leukemia in 109 Adult Iraqi Patients.

While many studies addressed the outcome of adult ALL in developed Western countries, there is paucity of such prospective studies from developing Mediterranean ones. This is a prospective cohort study conducted at Hiwa Cancer Hospital in Sulaimani city and Nanakali Hospital in Erbil city-Kurdistan Iraq from March 2012 to August 2017. The main characteristics of adult ALL patients, type of therapy and risk factors were analyzed to assess their impact on treatment outcome and survival status. A total of 109 adult ALL patients were included with a median age of 24years and male to female ratio of 1.7:1. B-ALL accounted for 76.1% of the cases, while the rest were T-ALL. BCR-ABL rearrangement was encountered in 12% of B-ALL. Complete remission (CR) rate was 81.7%, the overall 5year survival (OS) was 38%, Relapse Free 5year Survival (RFS) was 49%. Younger adults (< 35years) had significantly higher CR rates and OS compared to the older group (P < 0.001 each). On the other hand, gender, high leucocyte count ≥ 50×109/L, immunophenotype (including B and T ALL subtypes), and clinical risk status did not predict a poor outcome. Multivariate analysis revealed that only age < 35years and BCR-ABL rearrangement were significantly associated with better OS. Despite some limitations, the outcomes of Iraqi adult ALL is comparable to those reported in Western developed countries, with particularly favorable outcomes in younger patients. The need to improve outcome in adult ALL remains an important priority in our country as it is throughout the world.

MPN-364: The Clinical Significance of JAK2V617F Mutational Status on Phenotypic Features in Philadelphia-Negative Chronic Myeloproliferative Neoplasms

Context: The JAK2V617F mutation is present in the majority of patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The impact of this mutation on disease phenotype in the aforementioned diseases is still a matter of discussion. This study aims to determine differences in clinical presentation and disease outcome among PV, ET, and PMF patients with and without the JAK2V617F mutation. Objective: A total of 410 consecutive Philadelphia-negative MPN patients, 170 with ET, 135 with PV, and 105 with PMF under follow-up between 1995 and 2020 were included in this study. Methods: Two hundred twenty-eight patients (118 ET, 84 PMF, 26 PV) were genotyped for the JAK2V617F mutation with the JAK2 MutaScreen assay (Ipsogen, Luminy Biotech, Marseille, France). In 182 patients (109 PV, 52 ET, 21 PMF), JAK2V617F mutation was detected by LightCycler techniques, which is genotype assessment based on melting curve analysis. Results: In our study, the JAK2V617 mutation-positive PV group consisted of a significantly lower number of male patients (p=0.008). JAK2V617F mutation-positive PV patients had significantly higher leukocyte and platelet counts and lower Hgb levels (p=0.001; p=0.001 and p=0.018, respectively). Rates of total thrombosis and arterial thrombosis were significantly higher in JAK2V617F mutation-positive PV compared to JAK2V617F mutation-negative PV (42.7%, 20%; respectively; p=0.035 and 26.4%, 8%; respectively; p=0.042). In our study, JAK2V617F mutation-positive ET patients had significantly higher Hgb and Htc levels and lower platelet counts at initial diagnosis (p=0.001; p=0.001 and p=0.001, respectively). The JAK2V617 mutation-negative PMF group consisted of a significantly higher number of female patients (p=0.001). In PMF patients, the presence of JAK2V617F mutation was significantly associated with increased spleen size (p=0.042) and higher leukocyte count (p=0.019). There was a trend toward higher incidence of venous thrombosis in JAK2V617F mutation-positive PMF compared to JAK2V617F mutation-negative PMF (10%; 0; respectively; p=0.051) patients. Conclusion: We conclude that JAK2V617F-mutated ET patients express a PV-like phenotype, JAK2V617F mutation in PMF patients is associated with a more pronounced myeloproliferative phenotype and higher incidence of venous thrombosis, and JAK2V617F-mutated PV patients express a higher rate of total thrombosis and arterial thrombosis.

First Report of Tsukamurella conjunctivitidis CAPD-related Peritonitis

First Report of Tsukamurella conjunctivitidis CAPD-related Peritonitis

Relationship of JAK2 (V617F) Allelic Burden with Clinico- Haematological Manifestations of Philadelphia-Negative Myeloproliferative Neoplasms.

JAK2 (V617F) allelic burden is the main genetic driver behind and a potential differentiator between individual myeloproliferative neoplasm (MPN) subtypes. This study aimed to explore the relationship between JAK2 (V617F) allelic burden, MPN subtypes and their clinico-haematological manifestations in a Singapore-based cohort. Analysis was performed on a retrospectively collected dataset of 128 patients diagnosed with JAK2 (V617F) positive Philadelphia-negative MPNs between 2016 to 2017 in Singapore. Genomic analysis was conducted on blood samples via DNA extraction and Droplet Digital Polymerase Chain Reaction (ddPCR). The mean age was 62.4 (SD=14.1). 85 out of the 128 (66.4%) patients were male. There was a statistically significant difference in allelic burdens between the different MPN disease subtypes χ2(3) = 9.064, p=0.028, with essential thrombocytosis (ET) patients having the lowest mean JAK2 percentage allelic burden (26.5%). Patients with an allelic burden >50% had higher leukocyte counts (MWU 1016.5, p=0.001), haemoglobin levels (MWU 1287.0, p=0.045), lactate dehydrogenase levels (MWU 611.5, p=0.001), and lower platelet levels (MWU 1164.0, p=0.008). Subgroup analysis revealed none of these correlations was significant in the ET subgroup. The results are largely in concordance with previous research in Asian cohorts demonstrating the association between allelic burden and clinico-haematological manifestations of MPN. However, in the ET subgroup, the JAK2 (V617F) allelic burden do not correlate positively for haematological parameters which is only seen in Asian patients.

MPN-376: The Clinical Impact of the Burden of JAK2V617F Mutated Allele in Philadelphia-Negative Chronic Myeloproliferative Neoplasms

Context: Several studies reported the impact of JAK2V617F allele burden on phenotypic properties and clinical course in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs). We aimed to analyze the association of mutated JAK2V617F allele burden with clinical phenotype and laboratory characteristics in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. Objective: A total of 202 consecutive Philadelphia-negative MPN patients, 118 with ET and 84 with PMF, were included in this study. Methods: We used a real-time, semi-quantitative polymerase chain reaction (PCR) with JAK2 MutaScreen assay (Ipsogen, Luminy Biotech, Marseille, France) to screen JAK2V617 mutations and mutant allele burden. Results: According to the JAK2V617F status, ET patients were stratified into three groups: JAK2V617F mutation-negative (n=54) and JAK2V617F-positive with mutant allele burden in the lower quartile (n=59) and upper quartile (n=5) ranges. ET patients with upper quartile JAK2V617F allele burden had significantly lower Hgb levels (p=0.001), lower Htc levels (p=0.001), and higher LDH levels (p=0.008) as compared to the other two groups. Also, ET patients with upper quartile JAK2V617F allele burden had significantly increased spleen size and higher bleeding complications (p=0.034; 0.002; respectively). We observed significant association between ET patients with high JAK2V617F allele burden and higher death rates (p=0.007). There was a trend towards higher incidence of venous thrombosis in ET patients with upper quartile JAK2V617F allele burden (p=0.057). According to JAK2V617F status, PMF patients were stratified into three groups: JAK2V617F mutation-negative (n=25) and JAK2V617F-positive with mutant allele burden in the lower quartile (n=41) and upper quartile (n=18) ranges. Comparison across all three groups revealed significant associations between upper quartile allele burden and higher leukocyte counts (p=0.001). Also, PMF patients with upper quartile JAK2V617F allele burden had significantly increased spleen size compared to the other two groups (p=0.018). We observed significant association between PMF patients with low JAK2V617F allele burden and higher incidence of venous thrombosis (p=0.035). Conclusion: Our study reported that presence of higher V617F allele burden in ET is associated with defined haematological and clinical markers indicative of a more aggressive behavior while, in PMF, low allele burden was found to be associated with higher incidence of venous thrombosis.

Risk Factors for Rebleeding after Emergency Endoscopic Treatment of Dieulafoy Lesion.

Background and Objective: Dieulafoy lesion is a rare, but life-threatening, cause of gastrointestinal hemorrhage, and endoscopic therapy is the preferred first-line treatment. The present study aims to analyze the risk factors for rebleeding after endoscopic hemostasis of gastroduodenal Dieulafoy lesion. Methods. A retrospective review of patients with Dieulafoy lesion who developed acute gastrointestinal bleeding and were treated primarily with endoscopic therapy from September 2014 to April 2019 was conducted. Results. A total of 133 patients with Dieulafoy lesion were included in the present study. The mean age of these patients was 56.05 ± 16.58 years, and 115 patients were male. Among these 133 patients, 26 patients developed rebleeding within 30 days of endoscopic therapy. The 30-day rebleeding rate for pure injection therapy (epinephrine, cyanoacrylate, or lauromacrogol injection alone), nonpure injection therapy (argon plasma coagulation, band ligation, and hemoclip application alone), and combination therapy (combination of any >2 methods) was 45.2%, 12.8%, and 11%, respectively. In the univariable analysis, endoscopic treatment, prothrombin time, gender, Rockall score, and leukocyte count were the risk factors for rebleeding. In the multivariable analysis, pure injection endoscopic treatment, white blood cells (>10 × 109/L), and prothrombin time >12 seconds were the independent risk factors for rebleeding. Conclusion. Patients who undergo pure injection endoscopic treatment and have a high leukocyte count (>10 × 109/L) or elevated prothrombin time (>12 seconds) have an increased risk of rebleeding within 30 days after endoscopic treatment for gastroduodenal Dieulafoy lesion. Combined endoscopic treatment is the most effective therapy to prevent rebleeding in gastroduodenal Dieulafoy lesion.

High Clostridium difficile Infection among HIV-Infected Children with Diarrhea in a Tertiary Hospital in Mwanza, Tanzania.

Clostridium difficile causes a million of illnesses each year worldwide and can affect people of all ages. Limited data exist on the prevalence of C. difficile infections (CDI) among children below five years of age in developing countries. This study is aimed at determining the prevalence, associated factors, and outcome of the Clostridium difficile infection among children with diarrhea attending a tertiary hospital in Mwanza, Tanzania. Stool samples were collected and cultured anaerobically to isolate Clostridium difficile, followed by C. difficile toxin A and B assay and ribotyping. A total of 301 children with diarrhea were enrolled. A total of 22 (7.31%, 95% CI: 0.89-0.95) nonrepetitive stool samples were positive for Clostridium difficile. Eighteen (81%) of C. difficile isolates were toxigenic, and 16 (72.7%) had unknown ribotypes. Independent predictors of positive C. difficile were as follows: positive HIV status, hospital stay of more than four days, high stool leukocyte count, and watery stool. Clostridium difficile-positive children had significantly higher median duration of the diarrhea than those without C. difficile. Clinicians should consider C. difficile as a possible cause of diarrhea in children living in developing countries and institute appropriate management to prevent associated morbidities and mortalities. Furthermore, there is a need of joint effort to improve C. difficile diagnosis and surveillance in developing countries to establish the unknown epidemiology of CDI in these countries.

Image Guided Percutaneous Drainage of Intra-Abdominal Collections

Background: Intra-abdominal collections and abscesses are commonly encountered in surgical practice. They contribute to significant morbidity and mortality, hence, need to be addressed expeditiously. Percutaneous catheter drainage (PCD) is an important treatment modality that is now in vogue. Aim: This study was carried out to assess the outcomes of image guided PCD of intra-abdominal collections/ abscesses. Materials and Methods: This prospective study was carried out at a tertiary centre on patients who underwent image guided drainage of intra-abdominal collections/ abscesses from Jul 2014 to Dec 2016. Data was collected by following up the patients both clinically and radiologically. Results: 31 patients underwent PCD. Procedure was successful in 77.4%. Complete resolution was observed in all post-operative collections. Collections resolved after a single drainage procedure in 71% while the remaining 29% required multiple drainage procedures. Liver abscesses were the commonest, with multiple foci. Organisms were isolated in 13%, Escherichia coli being the commonest isolate. Higher leucocyte counts, lower levels of drain amylase and shorter duration of antibiotics were significantly associated with the success of the procedure. There were no complications other than an isolated case of biliary fistula following drainage of liver abscess. Ultrasonography was found to be at par with CT scan for PCD. Conclusion: Image guided PCD is a safe and efficacious procedure for the treatment of intra-abdominal collections and abscesses. It has a high success rate, especially in postoperative collections. The procedure has low morbidity and low complication rates. High leucocyte count, short duration of antibiotic exposure and low levels of drain fluid amylase are independent predictors of favourable outcome after percutaneous drainage.

3148 – SRSF2P95H AND TET2 LOSS CO-OPERATE TO PROMOTE CHRONIC MYELOMONOCYTIC LEUKAEMIA IN VIVO

Sequencing of >3000 MDS and related myeloid neoplasms has provided a detailed picture of the genetic landscape of these cancers. Most harbour mutations in two pathways: the RNA spliceosome (eg. SRSF2, SF3B1, U2AF1) and epigenetic regulators (eg. DMNT3, TET2). Co-mutation of SRSF2 and TET2 are profoundly enriched in MDS and MDS/MPN (p=2.63 × 10-14; q=1.21 × 10-12). In CMML and the related chronic neutrophilic leukaemia and atypical chronic myeloid leukaemia, there is a positive association between mutation of SRSF2 and TET2 (p=0.002). This association is strongest in CMML (p=0.004), where SRSF2 mutations occur in ∼50% of patients and TET2 mutations in ∼60%. SRSF2/TET2 co-mutation influences clinical presentation, with co-mutated CMML having higher leukocyte counts yet less pronounced monocytosis compared to those with wild-type SRSF2/TET2. Based on the human clinical genetics, we crossed the conditional Srsf2P95H/+ mutants with Tet2fl/fl mice to establish animals where we could mutate both concomitantly. At 52 weeks post gene mutation there is a hypocellular bone marrow with increased myeloid bias at the expense of B lymphoid and erythroid lineages in the Srsf2/Tet2 double mutants. Under conditions of native haematopoiesis with aging, a distinct myeloid bias and monocytosis develop in the Srsf2/Tet2 mutants which is not seen in either single mutant or controls. The compound Srsf2/Tet2 mutants display increased granulocytic and monocytic proliferation (myelo-monocytic hyperplasia) with increased immature promonocytes and monoblasts (∼10-15% total nucleated cells) and evidence of binucleate promonocytes. These are features of CMML (CMML-2). Upon secondary transplant, recipients developed leukocytosis, monocytosis and splenomegaly. This demonstrates that our model is able to reproduce SRSF2/TET2 co-operativity in vivo, yielding a disease with core characteristics of CMML, unlike single Srsf2 or Tet2 mutation.

Severe, Reversible Acute Lung Injury During Autologous Hematopoietic Stem Cell Mobilization After Filgrastim in a Child With Neuroblastoma: A Case Report

Peripheral blood hematopoietic stem cell mobilization is widely performed in a variety of clinical facilities and is believed to be a safe outpatient procedure. In this report, we describe a child with neuroblastoma who developed an extremely severe acute lung injury after granulocyte colony-stimulating factor was used for peripheral hematopoietic stem cell mobilization.A 3-year-old boy with a medical history of patent foramen ovale and secundum atrial septal defect was diagnosed with an MYCN-amplified neuroblastoma and treated with chemotherapy. During stem cell mobilization with filgrastim, the boy was in very good clinical condition, with a peripheral white blood cell (WBC) count of 57.17 K/μL, but he suddenly deteriorated, and nausea, seizures, and nystagmus were observed. The patient developed dyspnea with hemoptysis, and lung computed tomography showed bilateral asymmetrical pulmonary opacification demonstrating an anteroposterior density gradient. Because of rapidly progressing circulatory and respiratory failure, the child was hospitalized in the intensive care unit. Corticosteroid therapy, broad-spectrum antibiotic therapy, and cardiovascular support with mechanical ventilation were immediately instituted, and the child recovered without sequelae.The presented case emphasizes that life-threatening complications can occur during granulocyte colony-stimulating factor administration, and patient surveillance is warranted, especially if high leukocyte counts are observed or the patient exhibits cardiopulmonary signs.

Association Between Random Glucose Level and Leukocytes Count in Female Cancer Patients.

Leukocytosis is common among patients suffering from cancer when leukocytes count exceeds 11,000 cells per mm3. This is a usual immune response toward infection and foreign elements. This leads to the release of inflammatory mediators at the targeted site. Studies have found leukocytes count increase in diabetes mellitus patients. Random glucose level indicates the patient is at risk of developing diabetes mellitus. In this study, the association between random glucose level and leukocytes count in female cancer patients is evaluated. About 210 cancer patients included in this study and the results have indicated a positive association between high glucose level and high leukocyte count. This indicates poor prognosis of the patients as high glucose levels increase tumor cell proliferation and high leukocytes count can induce inflammation leading to the progression of cancer and increase mortality rate.

Peripheral Blood Leukocytes and Platelets Serve as Prognostic Factors in Breast Cancer.

Background: Tumor-infiltrating lymphocytes have been reported to be associated with response to neoadjuvant chemotherapy and survival in breast cancer (BC) patients. However, little is known about the value of peripheral blood parameter in predicting the prognosis in BC. Methods: In this study, parameters of complete blood count from 417 BC patients with a median 7.6-year follow-up after surgery were collected and correlated with patient survival. Results: It was found that leukocyte counts were positively correlated with disease-free survival (DFS, p = 0.016) and overall survival (OS, p = 0.014), whereas platelet counts were negatively correlated with DFS (p = 0.003) and OS (p = 0.082) in BC. Leukocyte and platelet counts were independent prognostic factors for the BC patient survival. Besides, the prognostic value of leukocyte and platelet counts was further evaluated in the BC patients with different molecular subtypes. Together, BC patients with high leukocyte counts and low platelet counts had better DFS (p = 0.001) and OS (p = 0.017) than the other patients. Conclusion: Parameters of complete blood count could be acquired easily and serve as cost-effective prognostic biomarkers in BC.

NTAL is associated with treatment outcome, cell proliferation and differentiation in acute promyelocytic leukemia

Non-T cell activation linker (NTAL) is a lipid raft-membrane protein expressed by normal and leukemic cells and involved in cell signaling. In acute promyelocytic leukemia (APL), NTAL depletion from lipid rafts decreases cell viability through regulation of the Akt/PI3K pathway. The role of NTAL in APL cell processes, and its association with clinical outcome, has not, however, been established. Here, we show that reduced levels of NTAL were associated with increased all-trans retinoic acid (ATRA)-induced differentiation, generation of reactive oxygen species, and mitochondrial dysfunction. Additionally, NTAL-knockdown (NTAL-KD) in APL cell lines led to activation of Ras, inhibition of Akt/mTOR pathways, and increased expression of autophagy markers, leading to an increased apoptosis rate following arsenic trioxide treatment. Furthermore, NTAL-KD in NB4 cells decreased the tumor burden in (NOD scid gamma) NSG mice, suggesting its implication in tumor growth. A retrospective analysis of NTAL expression in a cohort of patients treated with ATRA and anthracyclines, revealed that NTAL overexpression was associated with a high leukocyte count (P = 0.007) and was independently associated with shorter overall survival (Hazard Ratio: 3.6; 95% Confidence Interval: 1.17–11.28; P = 0.026). Taken together, our data highlights the importance of NTAL in APL cell survival and response to treatment.

Increased systemic inflammation and altered distribution of T-cell subsets in postmenopausal women.

AimTo investigate markers of systemic inflammation in pre- and postmenopausal women and identify possible predictors of systemic inflammation with menopause.MethodsCross-sectional study of 69 healthy women between 45- and 60 years. Blood samples were collected to assess leukocyte subsets and plasma cytokines. MRI and DXA scans were performed to assess body composition. Through uni- and multivariate analyses, follicle-stimulating hormone (FSH), visceral fat mass and age were evaluated as predictors of systemic inflammation in relation to menopause.ResultsPostmenopausal women tended to have higher leukocyte counts (5.4 x109 vs. 4.9 x109 cells/l, p = 0.05) reflected in increased total lymphocytes (1.8 x109 vs. 1.6 x109 cells/l, p = 0.01) and monocytes (0.5 x109 vs. 0.4 x109 cells/l, p = 0.02), compared to premenopausal women. Increased visceral fat mass was a strong predictor of high leukocyte subsets. Postmenopausal women had higher plasma TNF-α (2.24 vs. 1.91 pg/ml, p = 0.01) and IL-6 (0.45 vs. 0.33 pg/ml, p = 0.004) compared to premenopausal women and high FSH was a significant predictor of increased plasma TNF-α, IL-1β and IL-6. Menopause was further associated with increased T-cells (1,336 vs. 1,128 cells/μl, p = 0.04) reflected in significantly higher counts of exhausted-, senescent-, and memory CD4+ T-cell subsets.ConclusionsMenopause is associated with increased systemic inflammation as well as exhausted- and senescent T-cells. We suggest, that both increased visceral fat mass and declining sex hormone levels might contribute to postmenopausal systemic inflammation and calls for further large-scale studies to confirm these findings.

Leucocyte Subsets Effectively Predict the Clinical Outcome of Patients With COVID-19 Pneumonia: A Retrospective Case-Control Study.

Background: The clinical characteristics of coronavirus disease 2019 (COVID-19) have been well-studied, while effective predictors for clinical outcome and research on underlying mechanisms are scarce.Methods: Hospitalized COVID-19 pneumonia patients with definitive clinical outcome (cured or died) were retrospectively studied. The diagnostic performance of the leucocyte subsets and other parameters were compared using the area under the receiver operating characteristic curve (AUC). Further, the correlations between leucocyte subsets and inflammation-related factors associated with clinical outcome were subsequently investigated.Results: Among 95 subjects included, 56 patients were cured, and 39 died. Older age, elevated aspartate aminotransferase, total bilirubin, serum lactate dehydrogenase, blood urea nitrogen, prothrombin time, D-dimer, Procalcitonin, and C-reactive protein levels, decreased albumin, elevated serum cytokines (IL2R, IL6, IL8, IL10, and TNF-α) levels, and a decreased lymphocyte count indicated poor outcome in patients with COVID-19 pneumonia. Lymphocyte subset (lymphocytes, T cells, helper T cells, suppressor T cells, natural killer cells, T cells+B cells+NK cells) counts were positively associated with clinical outcome (AUC: 0.777; AUC: 0.925; AUC: 0.900; AUC: 0.902; AUC: 0.877; AUC: 0.918, resp.). The neutrophil-to-lymphocyte ratio (NLR), neutrophil to T lymphocyte count ratio (NTR), neutrophil percentage to T lymphocyte ratio (NpTR) effectively predicted mortality (AUC: 0.900; AUC: 0.905; AUC: 0.932, resp.). Binary logistic regression showed that NpTR was an independent prognostic factor for mortality. Serum IL6 levels were positively correlated with leucocyte count, neutrophil count, and eosinophil count and negatively correlated with lymphocyte count.Conclusion: These results indicate that leucocyte subsets predict the clinical outcome of patients with COVID-19 pneumonia with high efficiency. Non-self-limiting inflammatory response is involved in the development of fatal pneumonia.