Immature Neutrophils Research Articles

A Case of Ambiguous Lineage Acute Leukemia Posing Diagnostic Challenge

Abstract Introduction/Objective N/A. Methods/Case Report Acute leukemias with ambiguous lineage encompass those leukemias that show no clear evidence of differentiation along a single lineage and account for less than 4% of all cases of acute leukemias and often poses diagnostic dilemma. We present a challenging case of an ambiguous lineage acute leukemia in a previously healthy 27-year-old male, who presented to the ED with acute fever, dyspnea on exertion, nausea and vomiting. A complete blood count (CBC) showed a white blood cell count of 323 × 109/L, Hemoglobin of 3.3 g/dl, Platelet count of 44 × 109/L and a differential count of Neutrophil: 11, Lymphocyte: 31, Monocyte: 02, Band Neutrophil:1, Myelocyte :1, Blast: 54. Bone marrow aspirate smears revealed a heterogenous population of small to large sized blasts comprising 83% of cellularity. They expressed scant to moderate basophilic cytoplasm, high N/C ratio, round to irregular nuclear contour, finely granular chromatin and some with nucleoli. Other lineages were markedly suppressed. Flow cytometric analysis revealed an abnormal blast population (~80% of total) expressing CD34, HLA-DR, Tdt (subset), CD71 (dim) and CD38. In addition, the blasts expressed myeloid associated antigens CD13, MPO (smaller subset), as well as B-cell associated antigens CD19 (dim), cytoplasmic CD22 and cytoplasmic CD79a. They also expressed T-cell associated antigens, CD2, CD3 (smaller subset), CD5 (subset) and CD7 (subset) but negative for cytoplasmic CD3. This unusual pattern of expression posed a challenge as to what type of mixed phenotype leukemia it should be with variable expressions from all three lineage of myeloid, B- and T-cell. Further work-up showed, scattered blasts are also positive for MPO by cytochemical (on aspirate smear) and immunohistochemical stain (on core). The latter also showed negativity for CD3. Based on all these findings, this mixed phenotype acute leukemia (MPAL) was best categorized as MPAL (B/myeloid) over so called “Triphenotypic (B/T/myeloid) acute leukemia”. We considered expression of myeloid and B cell markers as more lineage defining in this case as compared to small subset expressing T lineage marker CD3. This case exemplifies the importance of multimodal comprehensive analysis of acute leukemia, especially in the setting of MPAL with expression of multi- lineage markers posing a diagnostic challenge. Results (if a Case Study enter NA) N/A. Conclusion N/A.

A rapid and precise method of establishing age model for coral skeletal radiocarbon to study surface oceanography using coupled X-ray photos and ICP-AES measurement

A high-precision age model is a critical component of coral skeletology. Here we propose a rapid and precise method, coupling coral growth band counting based on X-ray photo and Sr/Ca measurement using inductively coupled plasma atomic emission spectroscopy (ICP-AES) to establish the high-resolution age model. We measured Sr/Ca ratio of the Kikai coral, southeast of Japan using ICP-AES and compared the results with a previous study using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Sr/Ca values in 1947–2009 obtained by ICP-AES measurement were well correlated with Sr/Ca values obtained by LA-ICP-MS. Therefore, our study once again proved the feasibility of establishing age models by using Sr/Ca of temperate corals, and a smaller sample amount was applied for ICP-AES measurement to obtain higher-resolution data. The age model established by both Sr/Ca ratio and X-ray photo of corals will be contributed to the high-resolution coral skeletology, such as reconstructing high-resolution paleoceanography using coral skeletal radiocarbon.

Classification of peripheral blood neutrophils using deep learning.

Deep learning has been used to classify the while blood cells in peripheral blood smears. However, the classification of developing neutrophils is rarely studied. Moreover, it is still unknown whether deep learning can work well on the data coming from different sources. In this study, we therefore investigate the classification performance of deep learning for immature and mature neutrophils. In particular, we used three open-access datasets obtained from different imaging systems: CellaVision DM 96, CellaVision DM 100, and iCELL ME-150. A total of 26,050 images identified by one laboratory technologist were randomly split into training, validation, and testing datasets. A total of 10 convolutional neural networks were trained to classify six blood cell types: myeloblast, promyelocyte, myelocyte, metamyelocyte, banded neutrophil, and segmented neutrophil. The experimental results showed that compared to any single model, the average ensemble model could achieve a better classification performance and provide a testing accuracy of 90.1%. The sensitivity and specificity of the average ensemble model for the six blood cell types were above 83.5% and 96.9%, respectively. Our results suggest that deep learning is a promising tool for the classification of developing neutrophils, but further improvement is required.

Remodeling of the osteoimmune microenvironment after biomaterials implantation in murine tibia: Single-cell transcriptome analysis.

Osseointegration seems to be a foreign body reaction equilibrium due to the complicated interactions between the immune and skeletal systems. The heterogeneity of the osteoimmune microenvironment in the osseointegration of implant materials remains elusive. Here, a single-cell study involving 40043 cells is conducted, and a total of 10 distinct cell clusters are identified from five different groups. A preliminary description of the osteoimmune microenvironment revealed the diverse cellular heterogeneity and dynamic changes modulated by implant properties. The increased immature neutrophils, Ly6C + CCR2hi monocytes, and S100a8hi macrophages induce an aggressive inflammatory response and eventually lead to the formation of fibrous capsule around the stainless steel implant. The enrichment of mature neutrophils, FcgR1hi and differentiated immunomodulatory macrophages around the titanium implant indicates favorable osseointegration under moderate immune response. Neutrophil-depletion mice are conducted to explore the role of neutrophils in osseointegration. Neutrophils may improve bone formation by enhancing the recruitment of BMSCs via the CXCL12/CXCR3 signal axis. These findings contribute to a better knowledge of osteoimmunology and are valuable for the design and modification of ‘osteoimmune-smart’ biomaterials in the bone regeneration field.

COVID-19 and antimicrobial therapy

BACKGROUND: One of the problems with managing patients with a new coronavirus infection is the irrational use of antibiotics. Antibacterial drugs are not active against viral infection, including COVID-19. Unfortunately, in actual clinical practice, the level of antibiotic use remains extremely high, reaching 7080%. Unwanted antibacterial therapy leads to a number of undesirable phenomena that can significantly worsen the patients condition, and sometimes lead to life-threatening consequences. In this context, the most important question is the formulation of the diagnosis. In particular, the reference to the term pneumonia, in the case of COVID-19, is neither scientifically or clinically feasible. The most correct would be to call this process viral or virus-associated lung damage. This term will allow you to set priorities in the choice of tactics leading the patient. That is, viral lesion (not pneumonia!) will induce the practical doctor to analyze the situation requiring prescription in the presence of indications of anti-inflammatory (monoclonal antibodies, glucocorticosteroids) and anticoagulation therapy, and will avoid unnecessary in the overwhelming number of antimicrobial prescription situations.
 AIM: Formulate criteria for prescribing antibacterial therapy in patients with COVID-19.
 MATERIALS AND METHODS: The study is based on a review and analysis of the literature on new coronavirus infection, drawing conclusions and recommendations.
 RESULTS: In actual Russian practice, the level of use of antibiotics remains extremely high, reaching 7080%.
 CONCLUSION: The prescription of antibacterial therapy in patients with COVID-19 is justified only if there are convincing signs of bacterial infection the appearance of purulent sputum, increased procalcitonin of blood more than 0,250.5 ng/ml, an increase in blood white count of more than 10 thousand/mcl with an increase in the number band neutrophils more than 10%.

Predictive value of complete blood count for early diagnosis of mixed infection of the non-erythema migrans form of Lyme borreliosis and tick-borne encephalitis

Objective: is to develop a model for early diagnosis of mixed infection of the non-erythema migrans form of Lyme borreliosis and tick-borne encephalitis using the assessment of the complete blood count and the blood leukocyte indices of patients in the first week of the disease.Materials and methods. The retrospective clinical study involved Group 1 of 27 patients with the mixed infection of the non-erythema migrans form of Lyme borreliosis and the febrile form of tick-borne encephalitis and Group 2 of 29 patients with the monoinfection of the non-erythema migrans form of Lyme borreliosis, who were hospitalized no later than in the 7th day of the disease. The average age of patients in Groups 1 and 2 was 50.6±3.4 and 49.9±2.3. We analyzed 14 parameters of the complete blood count as well as calculated the leukocyte intoxication index and the body resistance index. Statistical significance assessment was carried out using the chi-square test and ROC analysis. Logistic regression model was developed using STATISTICA 12.0 modules.Results. The levels of the band and polymorphonuclear neutrophils (<0,001 и p=0,002) and the leukocyte intoxication index (p<0,001) were significantly higher and the levels of the body resistance index (p<0.001), lymphocytes (p<0.001) and platelets (p=0.004) were lower in Group 1 than in Group 2. Informative predictors of mixed infection included the body resistance index (AUC=0.77), leukocyte intoxication index (AUC=0.75), the band and polymorphonuclear neutrophils (AUC=0.74), lymphocytes (AUC=0.77), and platelets (AUC=0.70). Logistic regression model has a “very good” predictive value (AUC=0.85) and include two parameters: body resistance index and platelets (×109/L).Conclusion. The developed model has a “very good” predictive value for early diagnosis of the mixed infection of the non-erythema migrans form of Lyme borreliosis and tickborne encephalitis before laboratory diagnosis confirmation.

Iron regulatory protein (IRP)-mediated iron homeostasis is critical for neutrophil development and differentiation in the bone marrow.

Iron is mostly devoted to the hemoglobinization of erythrocytes for oxygen transport. However, emerging evidence points to a broader role for the metal in hematopoiesis, including the formation of the immune system. Iron availability in mammalian cells is controlled by iron-regulatory protein 1 (IRP1) and IRP2. We report that global disruption of both IRP1 and IRP2 in adult mice impairs neutrophil development and differentiation in the bone marrow, yielding immature neutrophils with abnormally high glycolytic and autophagic activity, resulting in neutropenia. IRPs promote neutrophil differentiation in a cell intrinsic manner by securing cellular iron supply together with transcriptional control of neutropoiesis to facilitate differentiation to fully mature neutrophils. Unlike neutrophils, monocyte count was not affected by IRP and iron deficiency, suggesting a lineage-specific effect of iron on myeloid output. This study unveils the previously unrecognized importance of IRPs and iron metabolism in the formation of a major branch of the innate immune system.

Phagocytic and chemiluminescent activity of blood neutrophils in patients with bladder cancer

BACKGROUND: Tumor microenvironment modulates (including with the help of metabolites) the functional activity of the neutrophils that contribute to the reprogramming of the antitumor activity into a protumor one.
 AIMS: To study the phagocytic and chemiluminescent activity of neutrophils in patients with bladder cancer (BC) under the influence of metabolites of the tumor microenvironment in vitro.
 MATERIALS AND METHODS: We examined 37 patients with superficial BC (T1,а,isN0M0) and considered 32 healthy individuals as a control group. Neutrophils isolated from their blood were incubated in vitro with lactate, ADP, and glutamate. Phagocytic activity was examined using flow cytometry, and the intensity of the respiratory burst of neutrophils was evaluated via chemiluminescent analysis.
 RESULTS: In patients with BC, the phagocytic index (PhI) values are reduced compared to the control sample (without in vitro metabolite exposure) and when exposed to glutamate, while the effect of lactate on cells causes an increase in the phagocytic number and PhI. Moreover, under the influence of lactate in vitro, the activity of spontaneous and zymosan-induced chemiluminescence of neutrophils decreases. ADP causes a decrease in spontaneous chemiluminescence only. Finally, under the influence of glutamate, the indicators of spontaneous and induced chemiluminescence decrease.
 CONCLUSIONS: Under the influence of lactate and ADP (products of tumor cells), the phagocytic activity of a population of immature neutrophils is stimulated, which leads to myeloid suppressor cells that inhibit antitumor immunity. Thus, metabolites of the tumor microenvironment modulate the activity of the respiratory burst of neutrophils in patients with BC.

Atherosclerosis licenses for an exceeding immune response in COVID-19 disease

Abstract Background COVID-19 is characterized by emergency hematopoiesis with a dysregulated myeloid compartment, comprising proinflammatory and immunosuppressive immune cells. Preexisting cardiovascular disease (CVD) is a major risk factor for severe and fatal COVID-19 outcomes. Individuals with atherosclerosis are known to have a proinflammatory immune cell phenotype. However, the mechanisms of how CVD causes worse outcomes during SARS-Cov2 infection remain unknown. Purpose To investigate the mechanisms of how immune cells link atherosclerosis to worse COVID-19 outcomes Methods Single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) derived from hospitalized SARS-Cov2 infected patients in an uncomplicated phase of the disease not requiring intensive-care treatment with (n=5) and without (n=6) preexisting atherosclerosis was performed. Results Baseline characteristics between the two groups were similar (atherosclerosis vs. no atherosclerosis: mean age 75 vs. 70 years, oxygen requirement 2.2 vs. 3.2 l/min, CRP 10.7 vs. 6.6 mg/dl, IL-6 61.6 vs. 60.6 pg/ml, all p>0.05). In accordance with previous COVID-19 scRNA-seq studies, we found low-density neutrophils, immature neutrophils, neutrophil like plasmablasts and mostly classical monocytes in the myeloid compartment. Low-density neutrophils from patients with atherosclerosis demonstrated an increased expression of proinflammatory (IL18R1 fold change (fc) = 3.3, IL18RAP fc=1.9, HMGB2 fc=1.8, S100A12 fc=1.7, TLR2 fc=1.5, S100A9 fc=1.4 C3AR1 fc=1.8, TLR4 fc= 1.4, all adjusted p-values <1.3x10–98) and immunosuppressive genes (IL1R2 fc=2.6, ARG1 fc=1.7, ANXA1 fc= 1.6, all adjusted p-values <4.1x10–67). Interestingly, we found an enrichment of proinflammatory COVID-19 specific neutrophil like plasmablasts in patients with atherosclerosis (p=0.049) with an increased expression of inflammatory genes (S100A12 fc=2.5, S100A9 fc=2.5, S100A8 fc=1.8, HMGB2 fc=2.8, IL18R1 fc=3.9 S100A10 fc=2, all adjusted p-values <1.1x10–54). In accordance, monocytes from patients with atherosclerosis showed an enrichment of inflammatory (S100A9 fc=1.6, NEAT1 fc=1.8, C3AR1 fc= 1.5, TLR2 fc= 1.5, IL13RA1 q=1.3, CCR2 fc=1.2, all p-values <1.3x10–60) and immunomodulatory genes (IL1R2 fc=3.5, CD163 fc=2.2, all adjusted p-values <2.7x10–87). Conclusions Our data show for the first time that patients with atherosclerosis have a dysregulated myeloid immune response already in the uncomplicated phase of SARS-CoV-2 infection. Upregulated genes and cell populations found in this study have previously been associated with severe COVID-19. Therefore, the enhanced inflammatory response may contribute to the worse outcome of patients with CVD and might be addressed by antiinflammatory drugs. Further efforts are needed to understand how atherosclerosis may control chromatin accessibility to predispose for an enhanced inflammatory response. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Heart Foundation

Combining Complete Blood Count with Differential Count; C-Reactive Protein and Band Neutrophils in Diagnosis of Early onset Neonatal Sepsis

Aim: To assess the diagnostic accuracy of complete blood count with band versus total neutrophil ratio and C-reactive proteins as an efficient analytical procedure for determining early onset sepsis in neonates. Study design: Cross sectional analytical study Place and duration of study: Department of Paediatric Medicine, Abbas Institute of Medical Sciences Muzafarabad, AJ Kashmir from 01-02-2022 to 31-07-2022. Methodology: Fifty patients were enrolled. Coulter counter was used for analyzing leucocytes of the neonates. Thin film-smears were generated by the laboratory scientist for identifying band neutrophils separately from mature neutrophils. C-reactive proteins level <5mg/dl was considered as negative. Thio-glycate-oxide in liquid form was used for 2ml neonatal blood culture analysis mixed in the 20ml medium at 36 degree celsius. Results: There were 28 (56%) males and 22 (44%) females. The mean age of the neonates was 1.6± 0.77 days. The mean weight of the neonates was 2.4±0.51kg with a range of 4-1.2kg. A variance of band versus total neutrophil ratio was significantly higher in cultures which were positive than negative such as 70% vs 25%. There was also significant percentage of C-reactive proteins positive in positive sepsis cultures in comparison to negative blood culture. Conclusion: A combination of complete blood count with differential count, white blood cell analysis with band versus total neutrophil ratio and c-reactive proteins is an efficient early analytical procedure for determining early onset sepsis in neonates as gold standard test blood culture is time taking. Key Words: Complete blood count, C-reactive protein, Total neutrophils ratio, Early onset neonatal sepsis.

Using procalcitonin levels to predict infection and reduce unnecessary antibiotic usage in febrile children aged 3-36 months

High risk features including body temperature (BT) ≥ 39 °C, inactive appearance, white blood cells (WBC) ≥ 15,000 cells/mm3, or absolute band count (ABC) ≥ 1,500 cells/mm3 have low sensitivity and negative predictive value (NPV) to discriminate between bacterial and viral infections, leading to overuse of antibiotics. We aimed to determine whether procalcitonin (PCT) level ≥ 0.5 ng/mL can differentiate bacterial from viral infections. The medical data of children aged 3 to 36 months who presented with fever without localizing signs or having initially undetermined cause of respiratory tract infection and/or non-mucus bloody diarrhea for 1 to 7 days and were hospitalized between January 2017 and December 2018 with one of the high-risk features were recorded. Children with an immunocompromised condition, who had previously received antibiotics, and/or had clinical sepsis were excluded. Non-serious bacterial infection (SBI) and SBI (occult bacteremia) were found in 17.2% and 4.5%, respectively. The proportions of children with high-risk features were not significantly different between children with and without bacterial infection, except for absolute band count which was significantly higher in the bacterial infection group (419 cells/mm3, IQR [0, 1429]) than the non-bacterial group (76 cells/mm3, IQR [0,455]). A PCT level ≥ 0.5 ng/mL had the highest sensitivity and NPV (100%, 100%, respectively) to predict bacterial infection when compared with the other high-risk features. Antibiotics can be safely withheld while waiting for hemoculture in acute febrile children with one of the high-risk features of bacterial infection with PCT level < 0.5 ng/mL.

The effects of age, sex, breed, diet, reproductive status and housing condition on the amounts of 25(OH) vitamin D in the serum of healthy dogs: Reference values.

Optimal amount of vitamin D for the proper functioning of the immune system is different from the required vitamin D amount for bones to prevent rickets. However, reports on vitamin D reference values in dogs are minimal, and there is still not enough information regarding the relationship between vitamin D and various variables such as disease, age, breed, diet type, and so on, as well as its relationship with haematological and serum biochemical parameters. The present study aimed to determine reference values of 25(OH) Vit D in dogs and its concentration in different groups, categorized based on age, sex, breed, housing conditions, and diet, as well as 25(OH) Vit D relationship with hematology and serum biochemistry parameters. In this study, 90 healthy dogs were selected to determine the reference value of 25 (OH) Vit D of serum after evaluating of their haematological and biochemical parameters to assess their general health. Dogs were divided into different groups according to above-mentioned variables. Serum 25 (OH) Vit D was subsequently measured by the ELISA method. The median concentration of 25 (OH) Vit D was 52.50ng/ml with minimum and maximum amounts of 14.00 and 155.57ng/ml, respectively. No significant difference was observed between 25 (OH) Vit D levels in the studied dogs regarding their different age, sex, breed, diet, housing condition, and reproductive status. Serum 25 (OH) Vit D concentration is directly correlated with the number of band neutrophils (p<0.05). We also witnessed indirect correlations between serum 25 (OH) Vit D levels and the number of blood eosinophils and serum glucose (p<0.05). In the present study age, sex, breed, housing condition and age had no significant effects on the amounts of 25(OH) vitamin D. According to correlations of vitamin D with MCH, band and eosinophil numbers and glucose, vitamin D may have a role in erythropoiesis and leukocytes response and also in energy metabolism in dog.

The Immune Features of Neutrophil and Neutrophil Immune Deviation Induced by Human SARS-COV-2 Infections

Current published scientific works on human neutrophils have shown them to be heterogeneous in their immune functions. Activated neutrophil perform both up regulation and down regulation processes on other immune cells finalized by either tissue protection or tissue damage in virus human diseases. The objectives of the present opinion were to; I - make a show case analysis for the immune activities of neutrophil compartment both in children and adults with coviod-19 illness and ii - to deduce the possible existence of immune deviation mechanisms in this disease .The absolute numbers of circulating neutrophils in childhood and adulthood patients with sars-cov-2 infection were correlated with the infection severity .It was apparent that there was inhibition of T cell mediated immune responses with an elevated sars-cov-2 anti-spike antibodies in continuum with activated immature neutrophil phenotypes that might be induced by the virus antigens and can either preserve or damage the affected tissue. The antibody may directly inhibit T cells or activate neutrophil phenotype to inhibit T cell responses. The features of this immune deviation are; i – Conditional, ii – reversible, iii – associated with active functional state, iv – the virus antigen induced chemokine that orchestrate neutrophil and induce hyper-cytokinemia, v – acquisition of molecular surface markers variation and appearance of inhibitory markers, vi – the neutrophil/lymphocyte ration dis-proportionated, vii – activation consequences leaves tissue pathology at most, and viii – The inflammatory circuit stages may serve drug target identification and development. Thus the opinion suggest that the absolute number of circulating neutrophils is correlated with disease severity and the existence of neutrophil immune deviation in covid-19 human disease.

The Role of Neutrophils in Oncolytic Orf Virus-Mediated Cancer Immunotherapy.

Neutrophils are innate leukocytes with diverse effector functions that allow them to respond to pathogens rapidly. Accumulating evidence has highlighted these cells’ complex roles in the host’s response to viral infections and tumor progression. Oncolytic virotherapy is emerging as a promising treatment modality in the armamentarium of cancer therapeutics. Oncolytic viruses preferentially kill cancer cells and stimulate tumor-associated inflammation, resulting in tumor regression. Assessing the activity of individual effector cell subsets following oncolytic virotherapy is important in identifying their contribution to antitumor immunity. In this study, we investigated the role of neutrophils in oncolytic Orf-virus-mediated immunotherapy in a murine model of pulmonary melanoma metastases. The systemic administration of the Orf virus stimulated a dramatic increase in the number of leukocytes in circulation and within the tumor microenvironment, most of which were neutrophils. Analysis of tumor-burdened lungs shortly after therapy revealed significant numbers of phenotypically immature neutrophils, with the enhanced expression of molecules affiliated with activation, migration, and cytotoxicity. Neutrophils stimulated by Orf virus therapy were directly tumoricidal through tumor necrosis factor-α-mediated effects and were required for optimal antitumor efficacy following Orf virus therapy. Taken together, these data reveal neutrophils as a crucial innate effector to consider when investigating oncolytic virotherapy.

Frequency of Bacteremia and Urinary Tract Infection in Pediatric Renal Transplant Recipients.

Our primary goal was to determine the frequency of bacteremia and urinary tract infections (UTI) in pediatric renal transplant recipients presenting with suspected infection within 2 years of transplant and to identify clinical and laboratory factors associated with bacteremia. We conducted a retrospective cross-sectional study for all pediatric ( < 18 years old) renal transplant recipients seen at 3 large children's hospitals from 2011 to 2018 for suspected infection within 2 years of transplant date, defined as pyrexia ( > 38°C) or a blood culture being ordered. Patients with primary immunodeficiencies, nontransplant immunosuppression, intestinal failure, and patients who had moved out of the local area were excluded. The primary outcome was bacteremia or UTI; secondary outcomes included pneumonia, bacterial or fungal meningitis, respiratory viral infections, and antibiotic resistance. The unit of analysis was the visit. One hundred fifteen children had 267 visits for infection evaluation within 2 years of transplant. Bacteremia (with or without UTI) was diagnosed in 9/213 (4.2%) and UTIs in 63/189 (33.3%). Tachycardia and hypotension were present in 66.7% and 0% of visits with documented bacteremia, respectively. White blood cell (12,700 cells/mm 3 vs. 10,900 cells/mm 3 ; P = 0.43) and absolute neutrophil count (10,700 vs. 8200 cells/mm 3 ; P = 0.24) were no different in bacteremic and nonbacteremic patients. The absolute band count was higher in children with bacteremia (1900 vs. 600 cells/mm 3 ; P = 0.02). Among Gram-negative pathogens, antibiotic resistance was seen to 3rd (14.5%) and 4th (3.6%) generation cephalosporins, 12.7% to semisynthetic penicillins, and 3.6% to carbapenems. Bacteremia or UTIs were diagnosed in one-quarter of all pediatric renal transplant recipients presenting with suspected infection within 2 years of transplant. Evaluations were highly variable, with one-third of visits not having urine cultures obtained. No single demographic, clinical or laboratory variable accurately identified patients with bacteremia, although combinations of findings may identify a high-risk population.

1057P Baseline circulating immature neutrophils anticipate hyperprogressive disease (HPD) upon 1st-line PD-1/PD-L1 inhibitors (ICI) in non-small cell lung cancer (NSCLC) patients (pts) and are reduced by platinum-based chemotherapy (PCT) and ICI combinations

1057P Baseline circulating immature neutrophils anticipate hyperprogressive disease (HPD) upon 1st-line PD-1/PD-L1 inhibitors (ICI) in non-small cell lung cancer (NSCLC) patients (pts) and are reduced by platinum-based chemotherapy (PCT) and ICI combinations

Agranulocytosis following intravenous immunoglobulin administration in a patient with Guillain-Barré Syndrome triggered by COVID-19: A case report

Neutropenia during recovery after coronavirus disease 2019 (COVID-19), as well as neutropenia after intravenous immunoglobulin (IVIG) administration are very rare hematological abnormalities. We report the first case of agranulocytosis following IVIG administration in patients with Guillain-Barre syndrome (GBS) triggered by COVID-19. A 62-year-old female patient was admitted to the Emergency Department due to progressive limb weakness and sensory disturbances that began two weeks before admission. Five weeks before admission she was treated for COVID-19 and has fully recovered. She was diagnosed with Guillain-Barre syndrome (GBS), and treatment with IVIG was started. Twenty hours after the first dose of IVIG, blood analysis showed neutropenia and thrombocytopenia, and after the fifth dose she developed agranulocytosis followed by mild increase in body temperature. Granulocyte colony-stimulating factor (G-CSF) was administered and after 12 hours the leukocyte lineage recovered. According to the previous findings, neutropenia after IVIG administration might be related to CD11b, and COVID-19 is associated with an increase in immature neutrophil populations in the later stages of the disease defined by their expression of CD11b. Meanwhile, some finding suggests that corticosteroid pretreatment prevent neutropenia after IVIG administration, which might be important because many patients with post-COVID GBS have been treated with corticosteroids for COVID-19.

COMPARISON OF MEAN PLATELET VOLUME IN NEONATES WITH AND WITHOUT SEPSIS

ABSTRACT&#x0D; Objectives&#x0D; To compare mean platelet volume (MPV) in neonates with and without sepsis. &#x0D; Study design&#x0D; Cross sectional descriptive study.&#x0D; Place &amp; duration of study&#x0D; Neonatal Unit, Department of Paediatrics, Military Hospital, Rawalpindi from 2nd July 2017 to 22nd January 2018.&#x0D; Material and Methods&#x0D; 140 neonates, of either gender with ages between 0-28 days, suspected of neonatal sepsis presenting with any two of the signs: core body temperature of &gt; 38.5°C or &lt; 36°C at time of presentation, pulse rate beyond the range of 100-200 beats/minute, leukocyte count beyond the range of 4000 to 30,000/mm3 or &gt; 10% immature neutrophils on peripheral smear, tachypnea (&gt;60 breaths/minute) and oxygen saturation (&lt; 90%) on pulse oximeter, were included; while neonates having taken &gt; 2 doses of antibiotics in last 48 hours as per history and clinical record were excluded. 3ml of blood was drawn and sent for culture, while another 3ml of blood sent for peripheral smear and MPV. All the data along with demographic details of the patients were noted. Same laboratory was used for all samples and the peripheral smear was done by the same pathologist each time to eliminate bias.&#x0D; Results&#x0D; 31 neonates were culture positive for neonatal sepsis. Mean MPV(fl) was 7.31+0.92(fl). MPV was 8.52+0.51(fl) in septic neonates and 6.97+0.70(fl) in neonates without sepsis. The p value was significant (0.0001).&#x0D; Conclusion&#x0D; MPV was significantly raised in patients with sepsis.&#x0D; KEYWORDS&#x0D; &#x0D; Neonates, Sepsis, Mean Platelet Volume &#x0D; &#x0D;

A stratification strategy to predict secondary infection in critical illness-induced immune dysfunction: the REALIST score

BackgroundAlthough multiple individual immune parameters have been demonstrated to predict the occurrence of secondary infection after critical illness, significant questions remain with regards to the selection, timing and clinical utility of such immune monitoring tests.Research questionAs a sub-study of the REALISM study, the REALIST score was developed as a pragmatic approach to help clinicians better identify and stratify patients at high risk for secondary infection, using a simple set of relatively available and technically robust biomarkers.Study design and methodsThis is a sub-study of a single-centre prospective cohort study of immune profiling in critically ill adults admitted after severe trauma, major surgery or sepsis/septic shock. For the REALIST score, five immune parameters were pre-emptively selected based on their clinical applicability and technical robustness. Predictive power of different parameters and combinations of parameters was assessed. The main outcome of interest was the occurrence of secondary infection within 30 days.ResultsAfter excluding statistically redundant and poorly predictive parameters, three parameters remained in the REALIST score: mHLA-DR, percentage of immature (CD10− CD16−) neutrophils and serum IL-10 level. In the cohort of interest (n = 189), incidence of secondary infection at day 30 increased from 8% for patients with REALIST score of 0 to 46% in patients with a score of 3 abnormal parameters, measured ad D5–7. When adjusted for a priori identified clinical risk factors for secondary infection (SOFA score and invasive mechanical ventilation at D5–7), a higher REALIST score was independently associated with increased risk of secondary infection (42 events (22.2%), adjusted HR 3.22 (1.09–9.50), p = 0.034) and mortality (10 events (5.3%), p = 0.001).InterpretationWe derived and presented the REALIST score, a simple and pragmatic stratification strategy which provides clinicians with a clear assessment of the immune status of their patients. This new tool could help optimize care of these individuals and could contribute in designing future trials of immune stimulation strategies.Graphical

A retrospective observational study of biomarker levels and severity assessment in pediatric community-acquired pneumonia.

Multiple studies have investigated the role of biomarkers in predicting pneumonia severity in adults but minimal conclusive research exists for children. This study aimed to determine if the following biomarker levels, collected within 72 hours of hospital arrival: white blood cell count (WBC), platelet count, C-reactive protein (CRP), procalcitonin (PCT), neutrophil-lymphocyte ratio, neutrophil count, or band count associated with community-associated pneumonia (CAP) severity in children.Methods:A retrospective chart review was conducted on children (aged 60 days to 18 years) diagnosed with CAP, and admitted to a regional, tertiary hospital (Charleston, WV, USA) for 3 years (2015–2018). Patients were stratified into 2 severity cohorts, mild (no ICU care), and moderate/severe (required ICU care). Biomarker values were then compared between the severity cohorts and area under the curve (AUC), and cut-off values and performance characteristics were calculated.Results:A total of 108 patients met inclusion criteria with 46% having moderate/severe CAP. Elevated levels of CRP (51.7 mg/L in mild vs. 104.8 mg/L in moderate/severe, P = .003, PCT (0.29 ng/ml in mild vs. 4.02 ng/mL in moderate/severe, P = .001) and band counts (8% in mild vs. 15% moderate/severe, P = .009) were associated with increased pneumonia severity. In predicting moderate/severe CAP, PCT had the highest AUC of 0.77 (P = .001) followed by bands AUC of 0.69 (P = .009) and CRP AUC of 0.67 (P = .003). Cut-off for PCT of 0.55 ng/mL had a sensitivity of 83% and a specificity of 65%. Cut-off level of 53.1 mg/L for CRP had a sensitivity of 79% and specificity of 52%. Cut off level of 12.5% bands had a sensitivity of 61% and specificity of 71%. In a multivariable model controlled for patient demographics and other biomarker levels, only PCT levels significantly predicted moderate/severe CAP (adjusted odds ratio: 1.40 [95% CI, 1.14–1.73], P = .002).Conclusion:Biomarkers, in particular PCT, obtained early in hospitalization may perform as possible predictors for CAP severity in children and be beneficial in guiding CAP management. However, biomarkers in pneumonia should not drive severity assessment or patient management independent of clinical presentation.