Peripheral Neutrophil Counts Research Articles

PF807 TREATMENT OF SEVERE INFECTIONS IN NEUTROPENIC PATIENTS WITH GRANULOCYTE TRANSFUSIONS: A SINGLE CENTRE EXPERIENCE IN 57 PATIENTS TREATED WITH 603 TRANSFUSIONS

Background:Life threathening infections among neutropenic patients treated with intensive chemotherapy or haematopoetic stem cell transplantation (HSCT) are frequent cause of morbidity and mortality. In the past decade granulocyte transfusions (GT) from donors stimulated with G‐CSF were increasingly used as a therapeutic modality and as preventive measure of such infections.Aims:To evaluate the efficacy and safety of GT and to evaluate possible correlation between the increase of the neutrophil count in peripheral blood and the neutrophil concentration in a single transfusion.Methods:We retrospectively analysed data of severly neutropenic patients that presented with severe infections and were treated with GT between 2012 and 2019. Primary end point was patients survival from infections. Secondary endpoints included the increase in neutrophil count in peripheral blood after one GT and to establish a cut off value for the neutrophil count in single apheresis product that is still clinically effective.Results:We included 57 patients, Female/Male ratio was 39%/61%, mean age 52y, and together received 603 GT. The majority (n = 47,82%) had acute leukemia and all of them were treated with intensive chemotherapy or underwent HSCT. They were all severely neutropenic (mean value of neutrophils at GT onset was 0,22x109/L) and had life threatening infection (mean CRP = 202) that wasn’t managable despite wide spectrum of antimicrobal and antifungal drugs. Some of them (n = 16,28%) had pulmonary infiltrates that were highly suspicious for invasive fungal infection. Patients received median of 8 GT with mean volume of 361 ml. Average time of treatment was 16 days. Mean neutrophil count per apheresis was 4,84x1010(135,5x109/L). We analysed the increment of neutrophils after 24 h and the average increase was 0,79x109/L(peak 14,50x109/L). The only GT toxicity we observed was respiratory distress in one patient (n = 1, 1,8 %). Overall mortality related to infections was 36,7% (n = 18). Among later, 6 patients (10,5%), achieved transient infection improvement on their clinical course but at the end died due to progression of haematological malignancy.Summary/Conclusion:The use of GT in neutropenic patients is safe with good survival rate and may reduce mortality rate due to severe infections. The results are consistent with previous literature data. As depicted on the graph (Graph 1), we couldn’t confirm the correlation between the increase of peripheral blood neutrophil count and the neutrophil concentration in a single aphaeresis unit. Consequentially, we couldn’t establish clear numeric cut value for clinical effectiveness of GT. This is likely due to the fact that it is hard to evaluate the dynamic of increase in neutrophils. Namely increases were higher towards the end of GT treatment, being associated with reestablished bone marrow regeneration. In some cases no increase was observed due to engraftment failure in HSTC recipients or because of hematologic malignancy progression. We also have to take in to consideration the ability of the transfused neutrophils to migrate to the site of inflamation and consequently, despite high apheresis concentration of neutrophils, disproportional values in peripheral blood. Although GT may offer effective and possible life saving therapeutic modality, it is difficult to confirm it's effectiveness, because of nonuniform patients population and lack of control group.image

PF808 COMPARISON BETWEEN COBE SPECTRA® AND SPECTRA OPTIA® APHERESIS SYSTEMS FOR HEMATOPOIETIC PROGENITOR CELLS (HPC) COLLECTION IN HEALTHY DONORS: SINGLE CENTRE EXPERIENCE

Background: Life threathening infections among neutropenic patients treated with intensive chemotherapy or haematopoetic stem cell transplantation (HSCT) are frequent cause of morbidity and mortality. In the past decade granulocyte transfusions (GT) from donors stimulated with G-CSF were increasingly used as a therapeutic modality and as preventive measure of such infections. Aims: To evaluate the efficacy and safety of GT and to evaluate possible correlation between the increase of the neutrophil count in peripheral blood and the neutrophil concentration in a single transfusion. Methods: We retrospectively analysed data of severly neutropenic patients that presented with severe infections and were treated with GT between 2012 and 2019. Primary end point was patients survival from infections. Secondary endpoints included the increase in neutrophil count in peripheral blood after one GT and to establish a cut off value for the neutrophil count in single apheresis product that is still clinically effective. Results: We included 57 patients, Female/Male ratio was 39%/61%, mean age 52y, and together received 603 GT. The majority (n = 47,82%) had acute leukemia and all of them were treated with intensive chemotherapy or underwent HSCT. They were all severely neutropenic (mean value of neutrophils at GT onset was 0,22x109/L) and had life threatening infection (mean CRP = 202) that wasn’t managable despite wide spectrum of antimicrobal and antifungal drugs. Some of them (n = 16,28%) had pulmonary infiltrates that were highly suspicious for invasive fungal infection. Patients received median of 8 GT with mean volume of 361 ml. Average time of treatment was 16 days. Mean neutrophil count per apheresis was 4,84x1010(135,5x109/L). We analysed the increment of neutrophils after 24 h and the average increase was 0,79x109/L(peak 14,50x109/L). The only GT toxicity we observed was respiratory distress in one patient (n = 1, 1,8 %). Overall mortality related to infections was 36,7% (n = 18). Among later, 6 patients (10,5%), achieved transient infection improvement on their clinical course but at the end died due to progression of haematological malignancy.Summary/Conclusion: The use of GT in neutropenic patients is safe with good survival rate and may reduce mortality rate due to severe infections. The results are consistent with previous literature data. As depicted on the graph (Graph 1), we couldn’t confirm the correlation between the increase of peripheral blood neutrophil count and the neutrophil concentration in a single aphaeresis unit. Consequentially, we couldn’t establish clear numeric cut value for clinical effectiveness of GT. This is likely due to the fact that it is hard to evaluate the dynamic of increase in neutrophils. Namely increases were higher towards the end of GT treatment, being associated with reestablished bone marrow regeneration. In some cases no increase was observed due to engraftment failure in HSTC recipients or because of hematologic malignancy progression. We also have to take in to consideration the ability of the transfused neutrophils to migrate to the site of inflamation and consequently, despite high apheresis concentration of neutrophils, disproportional values in peripheral blood. Although GT may offer effective and possible life saving therapeutic modality, it is difficult to confirm it's effectiveness, because of nonuniform patients population and lack of control group.

Association of relative neutrophilia with a distinct immunoinhibitory milieu in non-small cell lung cancer.

e14047 Background: Elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with poor prognosis in non-small cell lung cancer (NSCLC); the biological underpinnings of this observation have not been fully elucidated. We examined the relationships between peripheral neutrophil counts (PMN), NLR, circulating cytokines and angiogenic factors (CAF), and tumor microenvironment (TME) features in NSCLC. Methods: 150 patients with resectable NSCLC were enrolled in an immunoprofiling project. A panel of 43 CAFs was used to analyze preoperative plasma samples. Chemotherapy-naïve patients with CAF and a complete blood count ≤30 days preoperatively were included (n = 66; Table). For a subset, transcriptional signatures (MCP-counter, n = 50) and flow cytometry (n = 19) were used to identify TME phenotypes. Results: Increased PMNs were associated with increased pro-inflammatory CAF such as IL-1b (r = 0.392) and IL-6 (r = 0.339), as well as Th17/Tc17 associated CAF IL-17A (r = 0.320) and TNF-a (r = 0.368). Elevated NLR was inversely correlated with the lymphocyte activation marker soluble CD27 (r = -0.320, p = 0.009). This negative association was mirrored in the TME, as tumor neutrophil signatures were inversely correlated with a local IFN-g gene signature (r = -0.626, p < 0.001). Interestingly, a Th17/Tc17 peripheral signature (elevated IL-17A) was associated with an enrichment of CD8+TIM3+ cells (r = 0.623, p = 0.042) in the tumor. While this requires confirmation in a larger cohort, this correlation provides a potential rationale for targeting TIM3 in this population. Upon analysis of clinical characteristics, peripheral PMNs and NLR were higher among patients with squamous histology (PMN p = 0.009; NLR p = 0.034) and positively correlated with tumor size (PMN r = 0.344, p = 0.004; NLR r = 0.363, p = 0.003). Conclusions: A relative neutrophilia in NSCLC patients is associated with an inflammatory milieu suggestive of a Th17/Tc17 presence and decreased lymphocyte activation that is reflected within the TME. Further investigation is needed to define the role of NLR as a predictive biomarker and to identify whether neutrophils or Th17/Tc17 T cells could serve as a therapeutic target to improve immunotherapy response in NSCLC.[Table: see text]

Systemic immune-inflammation index to predict prognosis of elderly patients with newly diagnosed solid tumors.

e14517 Background: Cancer in the elderly has become a common problem due in part to the increase in life expectancy. Compared to younger counterparts, the biological characteristics of tumors and their responsiveness to therapy may differ in elderly patients, and the elderly also can have a decreased tolerance to anticancer therapy. In addition, there is less evidence from clinical trials to guide physicians in treating aged patients with solid tumors. It would be highly useful to have a simple and powerful indicator of their prognosis. In this paper we evaluated the predictive value of the Systemic Immune-inflammation Index, SII, in determining the one-year survival in elderly patients with newly diagnosed solid tumors. Methods: Data from 118 patients, 70 to 89 years of age with newly diagnosed solid tumors in 2014 were retrospectively analyzed. The patients were divided into two groups according to age: (1) 70-75 years of age and (2) over 75 years of age. We calculated SII from the equation, SII = P x N/L, where P, N and L are the preoperative peripheral blood platelet, neutrophil and lymphocyte counts per liter respectively. The optimum cutoff point for SII for a favorable prognosis was determined to be 390×109 cells/L. For evaluation of SII as a prognostic indicator, the patients were divided into high SII ( > 390×109 cells /L) and low SII (≤ 390×109 cells/L) groups. Individual values were used to determine the relationship between SII and one-year survival in the two age groups. Results: A high SII > 390×109 cells/L was correlated with poor one-year survival (χ² = 7.658, P = 0.006). Patients with low SII had improved survival. Conclusions: SII was a robust indicator of one-year survival in elderly patients with newly diagnosed solid tumors. Patients in the high SII group showed poor prognosis compared to patients with a low SII score. [Table: see text]

Disease severity and blood cytokine concentrations in dogs with natural Babesia rossi infection.

Babesia rossi causes severe disease in dogs. Here, we describe the association between serum cytokine concentrations and disease severity. Seventeen controls and 55 PCR confirmed Brossi-infected dogs were included. Diseased dogs were subdivided into 23 critically ill and 32 relatively well cases. Serum concentrations of 11 cytokines and biochemical markers of disease severity were determined. Significant differences were detected for IL-6, IL-8, IL-10, MCP-1 and TNF-α between the groups. Generally, the more complicated the disease, the more pro-inflammatory the cytokine milieu. IL-8 showed a reverse trend and was negatively correlated with disease severity. IL-6, MCP-1 and TNF-α were also significantly higher in the dogs that died (n=9) compared to the dogs that survived (n=46). IL-8 showed the opposite. MCP-1 and TNF-α were negatively correlated with biochemical markers of severity. Glucose was negatively correlated with IL-6. Cortisol, peripheral parasite density and band neutrophil count were positively correlated, whilst thyroid hormone was negatively correlated with IL-6, MCP-1 and TNF-α. As in malaria and sepsis, Brossi infection induces a pro-inflammatory cytokine storm that correlates with disease severity and adverse outcome. The multiplicity of cytokines involved argues for redundancy in the system once the disease is established.

High Systemic Immune-Inflammation Index is an Adverse Prognostic Factor for Patients With Gastroesophageal Adenocarcinoma.

The aim of this study was to determine the clinical role of the systemic immune-inflammation index in patients with resectable adenocarcinoma of the gastroesophageal junction treated with or without neoadjuvant therapy. Adenocarcinoma of the gastroesophageal junction is an aggressive disease, with less than 20% of overall patients surviving more than 5 years after diagnosis, while currently available clinical staging for esophageal cancer is lacking necessary accuracy. The systemic immune-inflammation index (SII) based on peripheral neutrophil, lymphocyte, and platelet counts has shown a prognostic impact in various malignancies. Data of consecutive patients undergoing esophagectomy (n = 320, 1992 to 2016) were abstracted. The cut point for high and low SII before neoadjuvant treatment and before surgery was calculated for illustration of the Kaplan-Meier curves. SII was used for the correlation with patients' clinicopathological characteristics as a continuous variable. Survival was analyzed with Cox proportional hazards models using clinical or pathological staging, adjusting for other known survival predictors. In both neoadjuvantly treated and primarily resected patients, high SII was significantly associated with diminished overall [hazard ratio (HR) 1.3, 95% confidence interval (95% CI) 1.2-1.4; HR 1.2, 95% CI 1.2-1.3, respectively] and disease-free survival (HR 1.3, 95% CI 1.2-1.3; HR 1.2, 95% CI 1.2-1.3, respectively). In multivariable survival analysis, SII remained an independent prognostic factor for overall survival (HR 1.3, 95% CI 1.2-1.4; HR 1.2, 95% CI 1.2-1.3, respectively) and disease-free survival (HR 1.3, 95% CI 1.2-1.3; HR 1.2, 95% CI 1.2-1.3, respectively) in primarily resected and neoadjuvantly treated patients. Elevated SII is an independent adverse prognostic factor in patients with resectable gastroesophageal adenocarcinomas with and without neoadjuvant treatment.

344 The correlation between the diseases severity in children of Staphylococcal scalded skin syndrome and impetigo and serum levels of anti-Dsg1 antibodies and anti-Dsg3 antibodies

Objective:To explore the association of the serum levels of anti-Dsg1 antibodies and anti-Dsg3 antibodies with disease severity in children with Staphylococcal scalded skin syndrome and impetigo.Methods:Serum levels of anti-Dsg1 antibodies and anti-Dsg3 antibodies in 16 children with SSSS and 40 patients with impetigo by adopting the ELISA.Results:Serum anti-Dsg1 antibodies were positive in children with SSSS and impetigo, and the serum levels of anti-Dsg1 antibodies of children with SSSS were higher than those with impetigo; the difference was statistically significant. Serum anti-Dsg3 antibodies were negative in children with SSSS and those with impetigo. The serum levels of anti-Dsg1 antibodies were correlated with disease duration, body temperature, lesion area and peripheral neutrophil counts, but not correlated with the total number of the white blood cells in patients with SSSS. The serum levels of anti-Dsg1 antibodies with disease duration, body temperature and lesion area were correlated, but not correlated with the total number of the white blood cells and peripheral neutrophil counts in patients with impetigo.Conclusions:Serum anti-Dsg1 antibodies levels is positive in children with SSSS and impetigo, and the serum levels of anti-Dsg1 antibodies of children with SSSS is higher than those with impetigo. Serum anti-Dsg3 antibodies are negative in children with SSSS and impetigo. The serum levels of anti-Dsg1 antibodies are correlated with disease severity in patients with SSSS and impetigo. It suggests that serum anti-Dsg1 antibodies levels may be useful for illness monitoring.

Impact of early detection of acute invasive fungal rhinosinusitis in immunocompromised patients

BackgroundEarly diagnosis of acute invasive fungal rhinosinusitis (AIFRS) is vital to improving outcomes in immunocompromised patients. This study evaluated the impact of a systematic protocol with nasal endoscopy and biopsies to early detect AIFRS in immunocompromised patients. Additionally, we compared the accuracy of frozen-section biopsy and culture with formalin-fixed paraffin-embedded (FFPE) biopsy.MethodsRetrospective cohort in a Tertiary Referral Hospital. Patients with the suspected diagnosis of AIFRS were evaluated following a standardized protocol, including serial nasal endoscopies and biopsies when necessary. The sensitivity and specificity of frozen-section biopsy and culture were also compared with FFPE.ResultsThe mortality rate related to AIFRS of this standardized cohort (13/43) was 30.2%. Better outcomes were observed in patients with disease limited to the turbinates and in those with higher peripheral neutrophils count. Frozen-section biopsy positivity correlated with FFPE findings for fungi detection (p-value < 0.0001), with a sensitivity of 90.6%, specificity of 72.7%, and accuracy of 86.0%.ConclusionImplementation of this standardized protocol was related to a considerably low mortality rate among patients with suspected AIFRS at our Institution. Frozen-section biopsy revealed high accuracy to diagnose AIFRS. The current protocol including frozen-tissue biopsy improved the evaluation and survival rates of immunocompromised patients with presumed AIFRS.

The systemic inflammation response index predicts survival and recurrence in patients with resectable pancreatic ductal adenocarcinoma.

Purpose: The systemic inflammation response index (SIRI), based on peripheral neutrophil, monocyte, and lymphocyte counts, was recently emerged and used as a novel tool in predicting prognosis in different types of cancer. Our aim was to investigate the clinical significance of preoperative SIRI in patients with resectable pancreatic ductal adenocarcinoma (PDAC).Materials and methods: The SIRI was developed in a training cohort of 371 PDAC patients undergoing radical surgery between 2010 and 2013 and validated in a validation cohort of 310 patients from 2014 to 2015. Baseline clinicopathologic characteristics, preoperative laboratory parameters and follow-up information were collected. The optimal cutoff value of SIRI was determined by receiver operating characteristic curve. Univariate and multivariate analysis were performed to analyze the prognostic value of SIRI.Results: The optimal cutoff value of SIRI stratified patients into low SIRI group (≤0.69) and high SIRI group (>0.69). Survival analysis showed that the median overall survival (OS) and recurrence-free survival (RFS) were significantly better in patients with low SIRI. The SIRI was an independent predictor of OS and RFS in multivariate analysis. In addition, SIRI remained its prognostic significance both in patients with early-stage diseases and in patients with normal carbohydrate antigen 19-9 levels. High SIRI indicated poor treatment response for patients who received postoperative adjuvant chemotherapy.Conclusion: Preoperative SIRI was an independent prognostic indicator of poor outcomes in PDAC patients after radical resection. It might assist clinicians to identify high-risk patients and choose the optimal individualized treatment strategy.

Systemic Immune-Inflammation Index (SII) Predicts Poor Survival in Pancreatic Cancer Patients Undergoing Resection

BackgroundThe systemic immune-inflammation index based on peripheral neutrophil, lymphocyte, and platelet counts has shown a prognostic impact in several malignancies. The aim of this study was to determine the prognostic role of systemic immune-inflammation index in patients with pancreatic ductal adenocarcinoma undergoing resection. MethodsConsecutive patients who underwent surgical resection at the department of surgery at the Medical University of Vienna between 1995 and 2014 were included into this study. The systemic immune-inflammation index was calculated by the formula platelet*neutrophil/lymphocyte. Optimal cutoffs were determined using Youden’s index. Uni- and multivariate analyses were calculated by the Cox proportional hazard regression model for overall survival. ResultsThree hundred twenty-one patients were included in this study. Clinical data was achieved from a prospective patient database. In univariate survival analysis, elevated systemic immune-inflammation index was found to be significantly associated with shortened patients’ overall survival (p = 0.007). In multivariate survival analysis, systemic immune-inflammation index remained an independent prognostic factor for overall survival (p = 0.004). No statistical significance could be found for platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in multivariate analysis. Furthermore, area under the curve analysis showed a higher prognostic significance for systemic immune-inflammation index, compared to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio. ConclusionA high systemic immune-inflammation index is an independent, preoperative available prognostic factor in patients with resectable pancreatic ductal adenocarcinoma and is superior to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio for predicting overall survival in pancreatic ductal adenocarcinoma patients.

Prognostic Value of Preoperative Systemic Immune-Inflammation Index in Patients with Cervical Cancer

The systemic immune-inflammation index (SII) based on peripheral lymphocyte, neutrophil and platelet counts has been considered a good index that reflects the local immune response and systemic inflammation. However, the use of the SII has not been reported in cervical cancer. In this study, Kaplan-Meier survival analysis showed that a high SII was associated with poor prognosis in cervical cancer patients in the primary and validation cohorts. A higher SII had a significant correlation with larger tumours but had no correlation with other clinicopathological parameters. Among all systemic immune indexes, the SII is the only independent prognostic factor for cervical cancer patients. Compared with the area under the curve for the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR), the area for the SII was larger at 3 and 5 years. In addition, the SII still retains it prognostic values across all FIGO stages. The SII can independently predict the overall survival of patients with cervical cancer receiving radical resection and is thus superior to existing systemic inflammatory indexes. The prognostic nomogram based on the SII is a reliable model for predicting the postoperative survival of patients with cervical cancer.

Effect of hyperthermia on improving neutrophil restoration after intraperitoneal chemotherapy

Purpose: Intraperitoneal (IP) chemotherapy has several benefits but also can have severe hematologic side effects. We compared the effects of hyperthermic intraperitoneal chemotherapy (HIPEC) and conventional IP chemotherapy on bone marrow suppression and evaluated whether HIPEC increased neutrophil recovery.Methods: HIPEC or IP chemotherapy was administered to ovarian cancer–bearing mice. Bone marrow progenitor cell colony-forming unit (CFU) count, serum cytokine levels, and peripheral leukocyte count after HIPEC and IP chemotherapy were compared.Results: Peripheral neutrophil count, cytokine (G-CSF and CXCL1/KC) levels, and bone marrow progenitor cell CFU count were significantly higher after HIPEC than after IP chemotherapy.Conclusions: Hyperthermia increased the serum neutrophil-recruiting cytokine levels and reduced the magnitude of chemotherapy-induced neutropenia. Thus, HIPEC improved neutrophil and bone marrow recovery compared with conventional IP chemotherapy.

Neutrophils From Children With Systemic Juvenile Idiopathic Arthritis Exhibit Persistent Proinflammatory Activation Despite Long-Standing Clinically Inactive Disease.

Background: Systemic juvenile idiopathic arthritis (SJIA) is a chronic childhood arthropathy with features of autoinflammation. Early inflammatory SJIA is associated with expansion and activation of neutrophils with a sepsis-like phenotype, but neutrophil phenotypes present in longstanding and clinically inactive disease (CID) are unknown. The objective of this study was to examine activated neutrophil subsets, S100 alarmin release, and gene expression signatures in children with a spectrum of SJIA disease activity.Methods: Highly-purified neutrophils were isolated using a two-step procedure of density-gradient centrifugation followed by magnetic-bead based negative selection prior to flow cytometry or cell culture to quantify S100 protein release. Whole transcriptome gene expression profiles were compared in neutrophils from children with both active SJIA and CID.Results: Patients with SJIA and active systemic features demonstrated a higher proportion of CD16+CD62Llo neutrophil population compared to controls. This neutrophil subset was not seen in patients with CID or patients with active arthritis not exhibiting systemic features. Using imaging flow cytometry, CD16+CD62Llo neutrophils from patients with active SJIA and features of macrophage activation syndrome (MAS) had increased nuclear hypersegmentation compared to CD16+CD62L+ neutrophils. Serum levels of S100A8/A9 and S100A12 were strongly correlated with peripheral blood neutrophil counts. Neutrophils from active SJIA patients did not show enhanced resting S100 protein release; however, regardless of disease activity, neutrophils from SJIA patients did show enhanced S100A8/A9 release upon PMA stimulation compared to control neutrophils. Furthermore, whole transcriptome analysis of highly purified neutrophils from children with active SJIA identified 214 differentially expressed genes (DEG) compared to neutrophils from healthy controls. The most significantly upregulated gene pathway was Immune System Process, including AIM2, IL18RAP, and NLRC4. Interestingly, this gene set showed intermediate levels of expression in neutrophils from patients with long-standing CID yet persistent serum IL-18 elevation. Indeed, all patient samples regardless of disease activity demonstrated elevated inflammatory gene expression, including inflammasome components and S100A8.Conclusion: We identify features of neutrophil activation in SJIA patients with both active disease and CID, including a proinflammatory gene expression signature, reflecting persistent innate immune activation. Taken together, these studies expand understanding of neutrophil function in chronic autoinflammatory disorders such as SJIA.

Impact of malnutrition on febrile neutropenia in children with acute lymphoblastic leukemia during induction phase chemotherapy

Background Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and adolescents. Febrile Neutropenia (FN) is a medical emergency on ALL that often leads to death. Nutrition status assessment on ALL patient is important because malnutrition can reduce the tolerance of chemotherapy, increase incidence of infection and decrease survival rate.&#x0D; Objectives To assess malnutrition as a risk factor for FN in children with ALL.&#x0D; Methods This case-control study was performed at Sardjito Hospital, Yogyakarta on patients aged 1 month to 18 years diagnosed with ALL and undergoing induction phase chemotherapy between January 2013 and December 2015. The case and control subjects were children with and without FN, respectively. Febrile neutropenia was confirmed by patients temperature above 38ºC at one measurement and a peripheral neutrophil count of less than 1,000/mm3. Malnutrition was defined as body weight-for-height was between -2 and &lt;-3 standard deviation. Subjects were included using simple random sampling.&#x0D; Result Bivariate analysis showed a significant correlation between malnutrition and FN (OR 2.62; 95%CI 1.07 to 6.45; P=0.03). However, there was no inverse correlation between socioeconomic status and FN (OR 1.1; 95%CI 0.42 to 2.41; P=0.83). There was no correlation between nutritional status and duration of FN (P= 0.48). &#x0D; Conclusion Malnutrition is a risk factor for FN in children with acute lymphoblastic leukemia.

Preoperative systemic immune-inflammation index predicts prognosis of patients with oral squamous cell carcinoma after curative resection

BackgroundDeregulated inflammation and immune deficit both intricately associate with cancer initiation and progression, which have been increasingly exploited as prognostic biomarkers and therapeutic targets. Recently, systemic immune-inflammation index (SII) based on peripheral neutrophil, lymphocyte and platelet counts serves as a novel and powerful cancer biomarker with prognostic significance in multiple types of malignancies. Here, we sought to evaluate the prognostic value of preoperative SII in patients with primary oral squamous cell carcinoma (OSCC) after curative resection.MethodsTwo independent cohorts with a total number of 309 patients with OSCC from two tertiary referral hospitals were included and defined as training (Nanjing, 138) and validation (Wuxi, 171) cohort, respectively. Preoperative SII in both cohorts was calculated and its optimal cutoff value was initially determined by X-tile software in the training cohort and then verified in the validation cohort.ResultsOur data indicated that high SII (≥ 484.5) was significantly associated with larger tumor size (P < 0.05, Chi square test), reduced overall and disease-free survival (Kaplan–Meir, P < 0.05, Log-rank test). Univariate and multivariate analyses further revealed that SII was an independent prognostic predictor for patient survival. Moreover, the area under receiver operating characteristic curve of SII for survival was significantly greater or comparable to other well-established prognostic parameters, indicative of its satisfactory prediction accuracy and specificity.ConclusionsOur findings reveal that high preoperative SII associates with poor outcome and serves as a non-invasive, low-cost and powerful prognostic predictor for patients with OSCC. This inflammation/immune-related biomarker holds translational potentials to supplement currently prognostic regime to better stratification of patients and treatment planning.

Imatinib Protects Against Hypoxia/Reoxygenation Induced Lung and Kidney Injury in a Humanized Mouse Model for SCD

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by chronic hemolytic anemia in association with acute and chronic life-threatening complications mainly related to acute vaso-occlusive events (VOCs) due to amplified inflammatory response and defective pro-resolving events.Imatinib is an oral Tyrosine (Tyr)-kinase inhibitor, developed for the treatment of chronic myeloid leukemia (CML). Few case reports on SCD patients with CML undergoing imatinib treatment highlight the beneficial impact of imatinib on severity and recurrence of acute VOCs in SCD. In red blood cells (RBCs), Imatinib has been shown to interfere with Tyr-phosphorylation state of the integral membrane protein band 3, affecting RBC microparticle formation. Here, we study the actions of Imatinib on a model of acute VOCs using humanized SCD mice (Hbatm1(HBA)TowHbbtm2(HBG1,HBB*)Tow). We treated SCD and control healthy mice (AA, Hbatm1(HBA)Tow Hbbtm3(HBG1,HBB)Tow) (n=6-7 animals in each group) with Imatinib 50 mg/Kg/d for 2 weeks before hypoxia/Reoxygenation (H/R) stress used to mimic acute VOCs. Under normoxia, we found that in SCD mice Imatinib significantly reduced (i) Tyr-phosphorylation state of sickle red cell membrane proteins; (ii) the amount of phosphatidyl-serine (PS)+ sickle RBCs; and (iii) the release of erythroid microparticles, which was associated with accumulation of hemichromes and a more efficient erythrophagocytosis compared to vehicle treated animals. In SCD mice exposed to H/R stress, imatinib significantly decreased the H/R-induced (i) increase in peripheral neutrophil count; (ii) lung inflammatory cell infiltrate; (iii) kidney inflammatory cell infiltrate. In the lung of H/R SCD mice, Imatinib inhibited the H/R induced NF-kB activation and prevented the up-regulation of (i) pro-inflammatory cytokines such as ET-1; (ii) vascular endothelial activation markers (VCAM-1, ICAM-1); (iii) pro-fibrotic markers such as PDGF-B and (iv) the activation of UPR system. In the kidney of H/R SCD mice, Imatinib significantly reduced H/R induced expression of ET-1, VCAM-1 and E-selectin, which were again associated with inhibition of NF-kB. In addition, Imatinib significantly upregulated the expression of the microRNAs miR200a/b, which has been described to reduce renal fibrosis. Finally, in isolated aorta from Imatinib treated SCD exposed to H/R stress, a significant reduction in vascular activation markers was observed compared to vehicle treated animals. Collectively, our data indicate that Imatinib acts on multiple targets, modulating signal transduction and reducing inflammatory vasculopathy and extracellular matrix remodeling process related to VOC in SCD. Thus, Imatinib might represent a new therapeutic tool in clinical management of SCD patients. DisclosuresEl Nemer:Imara: Research Funding.

Tranexamic acid decreases rodent hemorrhagic shock-induced inflammation with mixed end-organ effects.

Beyond its anti-fibrinolytic mechanism, tranexamic acid has been suggested to have anti-inflammatory properties which may contribute to the survival benefit it provides to trauma patients. The objective of this study was to assess possible immunomodulatory effects of tranexamic acid as well as potential amelioration of end-organ injury in a rodent hemorrhagic shock model. Controlled hemorrhagic shock was induced in adult Sprague Dawley rats to a mean arterial pressure of 30 mmHg. Groups of 10 rats were administered intravenous tranexamic acid (300mg/kg) or vehicle control (normal saline) intravenously 15 minutes after the induction of shock. After 60 minutes of hemorrhagic shock, resuscitation was started. Animals were euthanized at six, 24, or 72 hours from the start of shock. Serum laboratory values to include inflammatory biomarkers were measured, and end organ histology was evaluated. Tranexamic acid treatment was associated with a significant decrease in serum IL-1β at six and 24 hours and IL-10 at 24 hours from start of shock compared to vehicle control. Histologic analysis demonstrated mild decreases in both perivascular pulmonary edema and follicular mesenteric lymph node hyperplasia in the tranexamic acid treatment group but also increased myocardial lymphocytic infiltration with necrosis and degeneration. Tranexamic acid was also associated with a small but significant increase in peripheral neutrophil count as well as a significant decrease in neutrophil aggregation in pulmonary tissue at six hours post-injury. These data thus demonstrate a mixed effect of tranexamic acid. While there was an improvement in pulmonary edema and a suppressive effect on several key inflammatory mediators, there was also increased myocardial degeneration and necrosis, which is possibly related to the pro-thrombotic effect of tranexamic acid.

Prognostic role of the systemic immune-inflammation index in brain metastases from lung adenocarcinoma with different EGFR mutations.

The prognostic value of the systemic immune-inflammation index (SII) has been shown in various types of cancers. We aimed to evaluate the predictive values in brain metastases from lung adenocarcinoma with status of EGFR mutations. We, retrospectively, examined 310 patients with brain metastases from lung adenocarcinoma with status of EGFR mutations. SII was calculated using P * N/L, where P, N, and L, respectively refer to peripheral blood lymphocyte, neutrophil, and platelet counts. The cut-off value of SII was assessed by area under the curve (AUC). The log-rank test and Cox proportional hazard model were used to confirm the impact of SII and other variables on survival. The SII value ≤ 1218.81 was associated with prolonged survival in patients with brain metastases from lung adenocarcinoma in both variable and multivariable analysis In patients with EGFR mutations, the SII had statistical effect on OS only in invariable test. While, for patients with wild-type EGFR, SII achieved statistically significant differences both in variable and multivariable analyses. SII is an independent prognostic factor in brain metastases from lung adenocarcinoma. SII may have varying prognostic effects on patients with and without EGFR mutations and is a promising variable for the future prognostic systems.

Systemic immune-inflammation index, SII, for prognosis of elderly patients with newly diagnosed tumors.

BackgroundCancer in the elderly has become a common problem due in part to the increase in life expectancy. Compared to younger counterparts, the biological characteristics of tumors and their responsiveness to therapy may differ in elderly patients, and the elderly also can have a decreased tolerance to anticancer therapy. In addition, there is less evidence from clinical trials to guide physicians in treating aged patients with solid tumors. Thus, we often face a dilemma as to how actively to treat these patients and it would be highly useful to have a simple and powerful indicator of their prognosis. In this paper we evaluated the predictive value of the Systemic Immune-inflammation Index, SII, in determining the one-year survival and tumor differentiation status in elderly patients with newly diagnosed solid tumors.ResultsA high SII > 390×109 cells/L was correlated with poor tumor differentiation (χ2 = 9.791, P = 0.002) and poor one-year survival (χ2 = 7.658, P = 0.006). Patients with low SII had improved survival and better tumor differentiation (Stage I-II). The SII was not associated with Ki-67 expression.Materials and MethodsData from 119 patients, 70 to 89 years of age with newly diagnosed solid tumors in 2014 were retrospectively analyzed. The patients were divided into two groups according to age: (1) 70-75 years of age and (2) over 75 years of age. We calculated SII from the equation, SII = P x N/L, where P, N and L are the preoperative peripheral blood platelet, neutrophil and lymphocyte counts per liter respectively. The optimum cutoff point for SII for a favorable prognosis was determined to be 390×109 cells/L. For evaluation of SII as a prognostic indicator, the patients were divided into high SII (> 390×109 cells/L) and low SII (≤ 390×109 cells/L) groups. Individual values were used to determine the relationship between SII and one-year survival, tumor differentiation and Ki-67 expression in the two age groups.ConclusionsSII was a robust indicator of tumor differentiation and one-year survival in elderly patients with newly diagnosed solid tumors. Patients in the high SII group showed poor tumor differentiation and poor prognosis compared to patients with a low SII score.

Adalimumab Associated Pancytopenia and Reversible Lymphadenopathy

Introduction: Adalimumab (Humira?) is a monoclonal antibody directed against TNF-a used for treatment of autoimmune conditions including Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing spondylitis, and Inflammatory Bowel Disease. Case Report: 70 year old female with a history of Ulcerative Colitis on adalimumab presented with a fever of 101? in the setting of progressive weakness over the last 6 months. Her last dose was 1 week prior, for a total duration of 15 months. Physical exam was significant for submandibular lymphadenopathy (left greater than right) without any rashes, bruises, or swelling. Labs showed pancytopenia with neutropenia (WBC 2.0, HgB 11.5, Plts 10, ANC 1.1). CT illustrated bilateral axillary lymphadenopathy and enlarged retroperitoneal lymph nodes from the level of the celiac axis to the groin. Adalimumab was discontinued, infectious workup was initiated, and cefepime was started for neutropenic fever. Soon after, with resolution of fever and negative infectious workup, cefepime was discontinued. Tbo-filgrastim was administered with an increase in the WBC count to 8.2 and ANC of 6.2. A lymph node biopsy revealed atypical lymphoid proliferation with necrotizing granulomas. Patient clinically remained stable with a concordant increase in all cell lines in the following days and was discharged. A repeat CT performed 2 weeks later illustrated complete resolution of the lymphadenopathy. Discussion: Anti-TNF-a therapies carry many potential adverse infectious and non-infectious consequences including hematological dyscrasias and lymphoma. This case highlights an uncommon potential side effect of Adalimumab, which has become a mainstay of treatment in patients with moderate-to-severe ulcerative colitis. In regards to the diffuse lymphadenopathy, lymphoma continues to be a debated association. Long term safety data from global clinical trials have recently illustrated that malignancy rates for adalimumab-treated patients are as expected for the general population. With respect to cases of cytopenias, TNF inhibitor therapy is associated with a significant reduction in peripheral blood neutrophil count. Currently there are no recommendations for monitoring of hematologic dyscrasias for those receiving adalimumab. It is prudent for monitoring to be standardized for prescribing clinicians, as subclinical abnormalities can be intervened on with discontinuation of therapy prior to presentation of sequelae requiring hospitalization.2064_A Figure 1. Lymphadenopathy2064_B Figure 2. No Lymphadenothapy2064_C Figure 3. Granulomatous Appearance