Total White Cell Research Articles

Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study (update)

ObjectiveTo quantify the predictive value of unexpected weight loss for cancer according to patient’s age, sex, smoking status, and concurrent clinical features (symptoms, signs, and abnormal blood test results).DesignDiagnostic accuracy...

Effect of inflammatory factors on myocardial infarction

BackgroundCohort studies have increasingly shown associations between inflammatory markers and myocardial infarction (MI); however, the specific causal relationships between inflammatory markers and the development of MI remain unclear.Methods and resultsBy utilizing publicly accessible genome-wide association studies, we performed a two-sample Mendelian randomization (MR) analysis to explore the causal associations between inflammatory markers and myocardial infarction (MI). A random-effects inverse-variance weighted method was used to calculate effect estimates. The study included a total of 395,795 European participants for MI analysis and various sample sizes for inflammatory factors, ranging from 3,301 to 563,946 participants.Neutrophil count was found to increase the risk of MI (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.00–1.17; p = 0.04). C-reactive protein levels correlated positively with MI. No associations were observed with IL-1 beta, IL-6, IL-18, procalcitonin, TNF-α, total white cell count, or neutrophil percentage of white cells. Neutrophil count and C-reactive protein were inversely associated with lactate dehydrogenase: neutrophil cell count (OR 0.95; 95% CI, 0.93–0.98; p < 0.01) and C-reactive protein (OR 0.96; 95% CI, 0.92–1.00; p = 0.02). No associations of MI with myoglobin, troponin I, and creatine kinase-MB levels were found.ConclusionsThis two-sample MR analysis revealed a causal positive association of MI with neutrophil count, C-reactive protein level, and the myocardial injury marker lactate dehydrogenase. These results indicate that monitoring C-reactive protein and neutrophil counts may be useful in management of MI patients.

Machine Learning to Predict Interim Response in Pediatric Classical Hodgkin Lymphoma Using Affordable Blood Tests.

Response assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers. Changes in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL. DS 1-3 denoted rapid early response (RER) while DS 4-5 denoted slow early response (SER). Missing values were imputed using the k-nearest neighbor algorithm. Baseline and follow-up blood test values were combined into a single difference variable. Data were split into training and testing sets for analysis using Python scikit-learn 1.2.2 with logistic regression, random forests, naïve Bayes, and support vector machine classifiers. Random forest analysis achieved the best validated test accuracy of 73% when predicting RER or SER from blood samples. When applied to the full data set, the optimal model had a predictive accuracy of 80% and a receiver operating characteristic AUC of 89%. The most predictive variable was the differences in ALC, contributing 21% to the model. Differences in ferritin, LDH, and TWC contributed 15%-16%. Differences in ESR, hemoglobin, and albumin contributed 11%-12%. Changes in low-cost, widely available blood tests may predict chemosensitivity for pediatric cHL without access to PET-CT, identifying patients who may not require radiotherapy. Changes in these nonspecific blood tests should be assessed in combination with clinical findings and available imaging to avoid undertreatment.

Antibiotic use in a co-infection of respiratory syncytial virus and pathogenic bacteria in children in a resource-limited setting in northeast Peninsular Malaysia.

To investigate co-infection of bacterial isolates associated with respiratory syncytial virus (RSV) in children aged less than two years who were admitted to hospital with confirmed lower respiratory tract infection (LRTI) in Kelantan, Malaysia. The demographic data, clinical history, case management, haematological as well as infectious parameters (white blood cell differential and count, plus C-reactive protein, CRP) of the patients were systematically recorded. Less than one-third of cases were RSV-positive (21.03% and 26.23% were diagnosed as acute bronchiolitis or pneumonia, respectively). Blood cultures from approximately 10% of patients demonstrated growth of Haemophilus influenzae, Staphylococcus aureus, coagulase-negative Staphylococcus, Pseudomonas stutzeri, haemolytic Streptococcus group A, and Bacillus subtilis. Further analysis indicated that children with positive bacterial growth had an insignificant predictive value of CRP (2.32-7.16 mg/dl). The total white cell counts were 2.97-7.33 x 109sup>/L despite increased lymphocyte values in the bacteria-positive blood culture. Platelet counts were also within normal limits except for a single case of H. influenzae infection (685.50 x 109sup>/L). Interestingly, 95.01% of patients were treated with antibiotics; 66.23% of RSV infection cases were administered with a combination of antibiotics and 33.77% with only a single antibiotic. The data indicate that the use of antibiotics, either singly or in combination, is not always effective in treating LRTI in infants. Alternative therapeutic regimens should be considered, especially in Asian countries that may have limited resources.

Systemic Immune-Inflammation Indices Could Be Additional Predictive Markers for Cesarean Scar Pregnancy.

Cesarean scar pregnancy (CSP) is characterized by a gestational sac fully or partially implanted in the scar from a previous cesarean section. Systemic immune-inflammation indices (SIIs) have recently been discussed as additional diagnostic markers in placenta accreta and preeclampsia. CSP shares a similar pathogenesis with these diseases, suggesting that assessing the SIIs and neutrophil-to-lymphocyte ratio (NLR) could enhance additional predictability in diagnosing CSP. In this study, we analyzed the complete blood counts between 264 women who were confirmed with CSP by ultrasound and 295 women who underwent elective termination. The mean counts of total white cells and neutrophils were significantly higher, whereas the counts of monocytes, lymphocytes, and platelets were significantly lower in the CSP group compared to the control group (p<0.001). Additionally, the SII, systemic inflammation response index (SIRI), or NLR was significantly higher in the CSP group compared to the control group (p<0.0001). Given the limited effect of SII and SIRI on the increased risk of developing CSP, the optimal cut-off value for NLR in predicting CSP was 2.87 (area under the curve [AUC] 0.656, 68% sensitivity). The optimal cut-off value for NLR in predicting type 2 CSP was 2.91 (AUC 0.690, 71% sensitivity). Although ultrasound or magnetic resonance imaging images are a gold standard for visualizing the gestational sac's location in the diagnosis of CSP, assessing peripheral blood tests is cost-effective, and NLR may provide additional diagnosis value for CSP.

Neutrophil phagocytic activity in SCA subjects

Abstract Objectives Subjects with SCA are highly susceptible to life-threatening infections. The exact mechanism of immunodeficiency in this condition remains uncertain as different researchers have varying findings in their respective immunological studies. This study is aimed to comparatively determine the phagocytic competence of neutrophils of sickle cell subjects and immunological response in blood transfusion. Methods This study was carried out on 100 subjects in Calabar Municipality, Cross River State, Nigeria, comprising 41 SCA subjects and 59 subjects that were used as controls after confirming their Hb electrophoresis as “AA” in the laboratory. These subjects were within the ages of 2-25 years. The blood samples were analyzed for neutrophils, and some blood count parameters using standard methods and P &amp;lt; .05 were used to determine the level of confidence. Results Neutrophil function activity of SCA subjects was observed to be reduced significantly (P &amp;lt; .05) compared with the control subjects. The total white cell, packed cell volume, and relative differential counts were elevated significantly (P &amp;lt; .05) when compared with the control subjects except for lymphocytes, which was significantly reduced in SCA patients. Neutrophil function activity was significantly lower in the symptomatic subjects. Those transfused with blood revealed significantly higher total white cell and eosinophil counts, whereas their lymphocyte and monocyte counts significantly reduced. Conclusion This work has shown that SCA subjects have impaired neutrophil function activity as well as depressed immune cells as reflected in the blood count.

Neutropenic Sepsis in the Intensive Care Unit: Differences in Clinical Profile and Outcomes According to the Cause of Neutropenia.

Neutropenic sepsis frequently requires admission to an intensive care unit (ICU). Differences between subgroups of patients with neutropenic sepsis are not well characterized. To investigate clinical outcomes among patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis. Retrospective cohort study of all patients admitted to ICU in Australia or New Zealand between January 2000 and December 2022 with a primary admission diagnosis of sepsis and total white cell count <1.0 × 109 cells/L. We identified 8617 ICU admissions with neutropenic sepsis (hematological malignancy n = 4660; metastatic solid cancer n = 1034; no cancer n = 2800). Patients with hematological malignancy were younger (median, 61.5 years) with low rates of chronic comorbidities (4.7%) and were usually admitted to ICU from the ward (67.4%). Mechanical ventilation rates were 20.2% and in-hospital mortality was 30.6%. Patients with metastatic solid cancers were older (median, 66.3 years), with higher rates of chronic comorbidities (9.9%), and were usually admitted to the ICU from the emergency department (50.8%). Mechanical ventilation rates were 16.9% and in-hospital mortality was 42.4%. Patients with no documented cancer had highest rates of mechanical ventilation (41.7%) and mortality (46.3%). Neutropenia was independently associated with mortality among patients with solid cancers or no cancer but did not confer increased risk among patients with hematological malignancy (odds ratio, 0.98; 95% confidence interval, .90-1.06; P = .60). Patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis constitute 3 distinct clinical groups. Management approaches should be tailored accordingly.

P156 Type I interferon is raised across connective tissue diseases and is associated with haematological abnormalities and specific autoantibody profiles

Abstract Background/Aims The overlapping clinical and serological features among connective tissue diseases (CTDs) suggest a shared molecular aetiology. A molecular taxonomy of CTDs offers new opportunities in clinical trial design, which can potentially be translated into targeted treatment. In a previous study of 164 patients, we identified a type I interferon (IFN) positive subgroup within an unselected CTD cohort associated with specific clinical and serological features. Here, we aim to investigate the relationship between type I IFN and the clinical and immunological phenotype in a larger CTD cohort and determine whether a distinct subpopulation of patients can be identified. Methods Adult patients with at least 1 CTD clinical feature and CTD-related autoantibody were recruited from five rheumatology centres in North West England into the Lupus Extended Autoimmune Phenotype (LEAP) cohort. A 24-gene interferon-stimulated gene (ISG) score was calculated using NanoString as described by Neasens et al. 2022. Results Most patients had lupus (36%). 160 of 344 (46.5%) patients had a positive ISG score across all CTDs with 64/125 (51%) of lupus patients (Fig.1). Patients with positive ISG score were younger and had longer disease duration (p &amp;lt; 0.005 for both). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had significantly increased frequency of specific autoantibodies (anti-Smith, anti-Chromatin, anti-RNP, anti-Ro) and Rheumatoid Factor, and haematological abnormalities (lower haemoglobin, and lower total white cell and neutrophil counts) in an adjusted model including the CTD subtype. Conclusion In CTD patients, IFN type I positivity was identified across a subset of patients of all CTDs and is associated with specific autoantibodies and haematological parameters; these results support the findings of our previous smaller study. The identification of an IFN I-positive subgroup within an unselected CTD regardless of clinical diagnosis supports a molecular-based approach to treatment. Disclosure A. Madenidou: Grants/research support; Janssen and UCB. G.I. Rice: None. S. Dyball: Grants/research support; UCB, Novartis,Eli Lilly. B. Parker: Honoraria; Fresenius-Kabi and AbbVie. Member of speakers’ bureau; Eli Lilly and Roche. Grants/research support; Genzyme/Sanofi and GlaxoSmithKline. T.A. Briggs: Grants/research support; Janssen. I.N. Bruce: Consultancies; AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck Serono and UCB. Member of speakers’ bureau; AstraZeneca, GlaxoSmithKline and UCB. Grants/research support; Genzyme/Sanofi, GlaxoSmithKline, Roche, Novartis, Janssen and UCB.

Predictors of Treatment Failure and Mortality among Patients with Septic Shock Treated with Meropenem in the Intensive Care Unit.

The aim of the study was to determine the predictors of meropenem treatment failure and mortality in the Intensive Care Unit (ICU). This was a retrospective study, involving sepsis and septic shock patients who were admitted to the ICU and received intravenous meropenem. Treatment failure is defined as evidence of non-resolved fever, non-reduced total white cell (TWC), non-reduced C-reactive protein (CRP), subsequent culture negative and death in ICU. An Acute Physiology and Chronic Health Evaluation II (APACHE II) and duration of antibiotic treatment less than 5 days were associated with treatment failure with adjusted OR = 1.24 (95% CI: 1.15, 1.33; P < 0.001), OR = 65.43 (95% CI: 21.70, 197.23; P < 0.001). A higher risk of mortality was observed with higher APACHE and Sequential Organ Failure Assessment (SOFA) scores, initiating antibiotics > 72 h of sepsis, duration of antibiotic treatment less than 5 days and meropenem with renal adjustment dose with an adjusted OR = 1.21 (95% CI: 1.12, 1.30; P < 0.001), adjusted OR = 1.23 (95% CI: 1.08, 1.41; P < 0.001), adjusted OR = 6.38 (95% CI: 1.67, 24.50; P = 0.007), adjusted OR = 0.03 (95% CI: 0.01, 0.14; P < 0.001), adjusted OR = 0.30 (95% CI: 0.14, 0.64; P = 0.002). A total of 50 (14.12%) patients had a treatment failure with meropenem with 120 (48.02%) ICU mortality. The predictors of meropenem failure are higher APACHE score and shorter duration of meropenem treatment. The high APACHE, high SOFA score, initiating antibiotics more than 72 h of sepsis, shorter duration of treatment and meropenem with renal adjustment dose were predictors of mortality.

Risk Prediction of Diabetic Foot Amputation Using Machine Learning and Explainable Artificial Intelligence.

Diabetic foot ulcers (DFUs) are serious complications of diabetes which can lead to lower extremity amputations (LEAs). Risk prediction models can identify high-risk patients who can benefit from early intervention. Machine learning (ML) methods have shown promising utility in medical applications. Explainable modeling can help its integration and acceptance. This study aims to develop a risk prediction model using ML algorithms with explainability for LEA in DFU patients. This study is a retrospective review of 2559 inpatient DFU episodes in a tertiary institution from 2012 to 2017. Fifty-one features including patient demographics, comorbidities, medication, wound characteristics, and laboratory results were reviewed. Outcome measures were the risk of major LEA, minor LEA and any LEA. Machine learning models were developed for each outcome, with model performance evaluated using receiver operating characteristic (ROC) curves, balanced-accuracy and F1-score. SHapley Additive exPlanations (SHAP) was applied to interpret the model for explainability. Model performance for prediction of major, minor, and any LEA event achieved ROC of 0.820, 0.637, and 0.756, respectively, with XGBoost, XGBoost, and Gradient Boosted Trees algorithms demonstrating best results for each model, respectively. Using SHAP, key features that contributed to the predictions were identified for explainability. Total white cell (TWC) count, comorbidity score and red blood cell count contributed highest weightage to major LEA event. Total white cell, eosinophils, and necrotic eschar in the wound contributed most to any LEA event. Machine learning algorithms performed well in predicting the risk of LEA in a patient with DFU. Explainability can help provide clinical insights and identify at-risk patients for early intervention.

VISUALIZING HETEROGENEOUS TRAJECTORIES OF SUBJECTS WITH SURGICAL RELAPSE IN INFLAMMATORY BOWEL DISEASE FROM UK BIOBANK GENERAL PRACTICE DATA

Abstract BACKGROUND AND AIMS The United Kingdom (UK) Biobank (UKBB) is a large-scale biomedical database and research resource, containing in-depth health information from half a million participants in UK that have been used for detailed analyses of IBD. Using the UKBB, we examined the lab findings and prescription medication use in IBD subjects to identify trajectory patterns of disease with respect to surgical relapse. METHODS Of the 363 subjects in the UKBB with an established IBD diagnosis (UC, CD, or both) and an initial GI surgery, 116 had a subsequent surgery within 5 years of initial surgery and had follow up lab values of urine and serum creatinine, plasma and serum C-reactive protein, urine and serum albumin, urine albumin-creatinine ratio, total white blood count, urine microalbumin, total white cell count, hemoglobin estimation, and erythrocyte sedimentation rate. Additionally, data for the 9 most used IBD prescription medications: budesonide, sulfasalazine, methotrexate, hydrocortisone, balsalazide, olsalazine, prednisolone, azathioprine, and mesalamine was analyzed as well. Hidden Markov Models (HMM) using these variables and open-source packages were incorporated to label observations of each subject-visit until the subsequent surgery. Interactive visualizations using DPVis open-source package were then applied to identify individual trajectories and explore clinical characteristics. RESULTS Five hidden states were observed from HMM. The five states observed are based on differing prescription medication usage for the treatment of IBD and were assigned a color to allow for comparison (Figure 1). The majority of patients fell within the states labeled “blue” (azathioprine, sulfasalazine, and prednisone) “red” (mesalamine only) or “purple” (azathioprine, balsalazide, and prednisolone). The visualizer showed that while some transitions among states were observed, most patients fell into one of three major trajectory patterns as a factor of time to surgical relapse and were largely segregated by state. Based on the trajectories, a comparison of subjects with prescription of mesalamine-only vs. any immunosuppressive medications (azathioprine + sulfasalazine + balsalazide) in combination with prednisolone showed a significant difference in time to surgical relapse (P &amp;lt; 0.005) (Figure 2), with a shorter time to surgical relapse identified in patients who took mesalamine only. CONCLUSIONS We identified three distinct trajectories leading up to surgical relapse. These trajectories show distinctive medication prescription patterns (5-ASA vs. Azathioprine with steroid use), as well as significantly different times to surgical relapse. Furthermore, heterogeneity is shown within each trajectory pattern in terms of progression time and warrant further investigation. Figure 1 Three Trajectories of time to surgical relapse generated from 5-State HMM using lab values and prescription medications. Note that a patient can traverse multiple states so the summation of the observed subjects of those states exceeds the cohort size (N=116). Figure 2 Kaplan-Meier curves for the UC/CD subgroup with surgical relapse considering events from the first documented lab values and/or planned prescription at most 2 years prior to the baseline surgery up to the subsequent 5 years.

COVID 19 - Dengue Co-Infection: Socio-Demographic, Clinical and Laboratory Characterestics in a Tertiary Hospital In Bangladesh

Background: Since starting of the SARS-COV 2 pandemic till date, in dengue endemic countries co-infection of COVID -19 and Dengue co-infection remains a healthcare concern and cases have been reported from some Asian countries. Bangladesh being a high endemic region for dengue infection bears risk of significant healthcare burden of such co-infection cases. During the surge of dengue cases during monsoon season in 2021, the possibility of COVID19 - Dengue co-infection cases also increased. Method: This study was carried out in the Department of Internal Medicine and Pulmonology, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) General Hospital, Dhaka, Bangladesh from June 2021 to December 2021. Dengue and COVID 19 cases were confirmed as per Bangladesh National guidelines. Result: Total 12 cases including 8 males were diagnosed as dengue –COVID 19 co-infection during the study period. Mean age was 47.0 years. Majority of cases (10) were residing in Dhaka. Among risk factors, 5 cases were known diabetic and 4 cases were hypertensive while 1 case was congenital adrenal hyperplasia. Common presentations were fever (100%), headache (75%), bodyache (66.7%), dry cough (41.7%), nausea, vomiting, abdominal pain, and retro orbital pain were 25% while rash and shortness of breath occurred in 16.7%. Mean duration of fever was 5.8 days and mean recorded highest temperature was 102.5°F. Dengue manifestation was predominant in 8 cases (66.7%). Laboratory investigations revealed following mean values: baseline haematocrit (HCT) 39.9%, initial total white cell count 4.64x109/L, absolute neutrophil-lymphocyte ratio 2.4, lowest platelet count 100.4x109/L, C-Reactive Protein 143.8mg/L, serum ferritin 888.1 ng/ml, D dimer 2.0 µg/ml, LDH 668.1 U/L, serum Aspartate aminotransferase 88.1 U/ L, Alanine aminotransferase 73 U/L. Radiological findings were present in 7(58.3%) cases, among which pneumonitis was predominant (4 cases,57.1%). All cases were managed and followed up as per national guidelines till discharge and no one required critical care. Conclusion: Observation revealed that COVID -19 and Dengue co-infection may occur and if managed adequately fatal outcome can be avoided, even in high risk patients. Therefore, high degree of suspicion of co-infection should be considered in appropriate clinical scenario. J Bangladesh Coll Phys Surg 2023; 41: 44-50

Effect of Dolutegravir regimen against other regimens on some hematological parameters, CD4 count and viral load of people living with HIV infection in South Eastern Nigeria.

Appropriate usage of highly active antiretroviral therapy (HAART) suppresses human immunodeficiency virus (HIV) replication. One of such HAART is dolutegravir (DTG) containing regimen which Nigeria included in her national protocol, as the preferred first-line option, with particularly fixed dose combination of tenofovir/lamivudine/dolutegravir (TLD) in 2018. To access the impact of this regimen as against other regimens on some hematological parameters as well as cluster of differentiation 4 (CD4) count and viral load on people living with HIV infection. The study site is a health facility center supported by President Emergency Plan for acquired immunodeficiency syndrome (AIDS) Relief where people living with HIV infection (PLWHIV) visit for their routine management in Abakaliki, Ebonyi State. A hundred and twenty-two (122) subjects participated, 58 PLWHIV and 64 control subjects. CD4 + count by partec cyflow auto analyzer, while the Viral load assay was by Roche COBAS Ampriplep/COBAS TaqMan molecular systems. Full blood count determination was by Sysmex XE-2100 hematology auto analyzer, while the detection of antibody to HAART was by Petz and direct Coombs tests. Mean values of hemoglobin (Hb), Total white cell count, Lymphocytes, Monocytes and CD4 + counts of people living with HIV infection (PLWHIV) were significantly (P = .0001) lower than the control subjects. The Hb level of PLWHIV on Efavirenz combination (TDF/3TC/EFV) are comparable 123 ± 32g/l with those on Ritonavir combination (TDF/3TC/LPV/R) 136 ± 16g/l and Dolutegravir (TLD)134 ± 20.0g/l (P = .307). On the other hand, total white cell count (4.55 ± 1.99 × 109/L) of those on Efavirenz combination (TDF/3TC/EFV) and Dolutegravir (TLD) (4.53 ± 1.31 × 109/L) were significantly higher than those on Ritonavir combination (TDF/3TC/LPV/R) (4.09 ± 1.15 × 109/L). The Viral Load of PLWHIV on Dolutegravir (TLD) was significantly lower 171.57 ± 4.56 copies/mL than those on Efavirenz combination (TDF/3TC/EFV) (86,395.91 ± 27,476.57copies/mL) and Ritonavir combination (TDF/3TC/LPV/R) (81,188.83 ± 13,393.47 copies/mL), respectively. Some hematological parameters (such as Hb, total white cell counts and CD4 + count) were lower in people living with HIV than values seen in control group. The 3 regimens used in the management of HIV infection in the locality revealed comparable Packed cell volume and Hemoglobin levels. Total white cell count of those on Efavirenz and DTG is comparable with higher values than those on Ritonavir.

PB0249 Some Coagulation Profiles (PT, APTT, TT, FIB), Red Cell, Total White Cell, Platelet Counts and Their Indices Activity Levels in Persons Exposed to Wood Smoke (Firewood) in Calabar, Nigeria

PB0249 Some Coagulation Profiles (PT, APTT, TT, FIB), Red Cell, Total White Cell, Platelet Counts and Their Indices Activity Levels in Persons Exposed to Wood Smoke (Firewood) in Calabar, Nigeria

An outlook on the target-based molecular mechanism of phytoconstituents as immunomodulators.

The immune system is one of the essential defense mechanisms. Immune system inadequacy increases the risk of infections and cancer diseases, whereas over-activation of the immune system causes allergies or autoimmune disorders. Immunomodulators have been used in the treatment of immune-related diseases. There is growing interest in using herbal medicines as multicomponent agents to modulate the complex immune system in immune-related diseases. Many therapeutic phytochemicals showed immunomodulatory effects by various mechanisms. This mechanism includes stimulation of lymphoid cell, phagocytosis, macrophage, and cellular immune function enhancement. In addition increased antigen-specific immunoglobulin production, total white cell count, and inhibition of TNF-α, IFN-γ, NF-kB, IL-2, IL-6, IL-1β, and other cytokines that influenced the immune system. This review aims to overview, widely investigated plant-derived phytoconstituents by targeting cells to modulate cellular and humoral immunity in in vivo and in vitro. However, further high-quality research is needed to confirm the clinical efficacy of plant-based immunomodulators.

Clinical features and prognostic outcomes of angioimmunoblastic T cell lymphoma in an Asian multicenter study

In our Asian multicenter retrospective study, we investigated the clinical prognostic factors affecting the outcomes of AITL patients and identified a novel prognostic index relevant in the Asian context. In our 174-patient cohort, the median PFS and OS was 1.8 years and 5.6 years respectively. Age > 60, bone marrow involvement, total white cell count >12 × 109/L and raised serum lactate dehydrogenase were associated with poorer PFS and OS in multivariate analyses. This allowed for a prognostic index (AITL-PI) differentiating patients into low (0-1 factors, n = 64), moderate (2 factors, n = 59) and high-risk (3-4 factors, n = 49) subgroups with 5-year OS of 84.0%, 44.0% and 28.0% respectively (p < 0.0001). POD24 proved to be strongly prognostic (5-year OS 24% vs 89%, p < 0.0001). Exploratory gene expression studies were performed and disparate immune cell profiles and cell signaling signatures were seen in the low risk group as compared to the intermediate and high risk groups.

Complete blood and absolute CD4+ve T lymphocyte counts of whole blood donors at a hospital blood center in Nigeria

Background: Comprehensive routine screening and adequate selection of the prospective whole blood donor protects his health and safety as well as that of the recipient. Objectives: The main objective of this study was to determine the complete blood and absolute CD4+ T lymphocyte cell counts of apparently healthy prospective whole blood donors. Participants and Methods: This was a hospital based prospective study. A form was designed by the researchers for data collection. The socio demographic status, complete blood cells and absolute CD4+vel counts of apparently healthy whole blood donors who had tested seronegative for HIV, hepatitis B and C markers was captured . Obtained data was analysed with the statistical package for the social scientist software version 20 Results: One hundred male (97.1%) and three female (2.9%) apparently healthy prospective whole blood donors were studied. The median age of study subjects was 30 years. Obtained median blood cell values were 13g/dl, 40%, 4.9/nl and 203.9/nl for haemoglobin concentration, haematocrit, total white cell and platelet counts respectively. The median values for the mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) of studied blood donors were 32.6g/dl,27.7pg and 85.7fl respectively. Observed prevalence of subnormal blood cell counts for haemoglobin concentration, total white cells and platelets were 12.6%, 25.2%, 13.6% respectively. Also subnormal values for MCHC, MCH, and MCV were 11.7%, 26.2%, 16.5% respectively among studied whole blood donors. No higher than normal blood cell count values were observed. Median values for erythrocyte sedimentation rate and CD4+ T lymphocytes were 8.4mm/hr and 876.2cells/µl respectively. The percentage of subnormal CD4+T lymphocyte count was18.4% Conclusion: A significant percentage of apparently healthy prospective whole blood donors had subnormal blood cell and CD+ve T lymphocyte values. Obtained normal values were comparable with local reference range reports from previous studies in Nigeria and other parts of Africa.

Retrospective analysis of leukemoid reactions in extremely preterm infants in a tertiary NICU from 2018–2021

Background Neonatal leukemoid reaction is associated with higher risk of mortality, chronic lung disease and has been associated with chorioamnionitis. Literature on extremely low birth weight infants with leukemoid reaction is limited. Objectives The aim of our study was to characterize the maternal and placental factors associated with neonatal leukemoid reaction and to describe outcomes of these ELBW infants. Our objective was to assess if there were maternal factors that would assist the decision-making process regarding the delivery of preterm infants at risk of chorioamnionitis and the sequelae of this inflammatory process. Methods This was a retrospective case-control study performed in a single, tertiary Maternity Hospital in Dublin. Two matched controls were identified for each case based on gestation and year of birth and data was collected on both the infants and their mothers. Results 7 extremely preterm neonates were identified as having a leukemoid reaction, defined as a total white cell count of >50,000 or in the first seven days of life. Baseline characteristics between the groups were similar. The median gestational age in the cases group was 24 + 4 weeks and in the control group was 24 + 1. The mean birthweight was 650 g in the cases group vs. 655 g in the control group. There was a higher percentage of males in the control group, 42.9% vs 28.6% in the cases. The preterm infants with leukemoid reaction had a longer duration of ventilation with a median of 18 days (7.5–23.5 days) compared to 6.5 days (2.8–24.5 days) in the control group. More infants in the leukemoid reaction group required inotropes for hypotension in the first 72 h after delivery (42.9% vs 7.1% in the controls, p value .169). Death or Bronchopulmonary dysplasia (BPD) occurred in 85.7% of the cases identified with a leukemoid reaction vs 71.4% of the controls matched. Median maternal CRP was higher in cases prior to delivery vs the controls (66 vs 18.1 mg/L, p-value = .2151). There was histological evidence of maternal inflammatory response in all cases with fetal inflammatory response in 71% of cases. Conclusions Leukemoid reaction in ELBW infants with evidence of maternal and fetal inflammatory response syndrome on placental histology is associated with a longer duration of initial ventilation, increased need for inotropes in the first 72 h after birth, higher rates of death, and BPD. Prospective studies are required to identify potential biomarkers such as proinflammatory cytokines, IL-6, which might aid the decision-making process in delivery.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Angioimmunoblastic T cell Lymphoma (AITL) is a subtype of peripheral T cell lymphoma and prognosis is generally felt to be poor. Molecular characteristics differentiating good or poor risk AITL has not been identified. In our Asian multicentre study, we investigate the clinical prognostic factors affecting the outcomes of our AITL patients. We also interrogate the gene expression profiles in our patients to identify if there may be different immune and cell signalling signatures in different risk groups. Methods: Patients who were diagnosed with AITL and seen at National Cancer Centre Singapore, Singapore General Hospital and National University Cancer Institute, Singapore between June 1999 and December 2019 were retrospectively analysed. Relevant demographical and clinical characteristics were collected. Outcomes of interest were that of 5-year overall survival (OS) and 5-year progression free survival (PFS). Kaplan-Meier curves were plotted to estimate survival for each individual clinical parameter. Parameters found to be significant on univariate analysis were subsequently used in the generation of multivariate cox regression models. NanoString PanCancer IO360 panel (NanoString Technologies, Seattle, WA, USA) was used to interrogate gene expression on AITL FFPE tissue, following manufacturer’s protocol using the nCounter platform. Results: A total of 174 patients were identified. Median duration of follow up was 20.4 months. Median PFS and OS was 1.8 years and 5.6 years respectively. In multivariate analyses, Age >60, bone marrow Involvement, Total white cell count and serum Lactate dehydrogenase were associated with poorer PFS and OS. A prognostic index (AITL-PI) differentiated patients into low (0–1 factors, n = 64), moderate (2 factors, n = 59) and high-risk (3–4 factors, n = 49) subgroups with 5-year OS of 84.0%, 44.0% and 28.0% respectively (p < 0.0001). Gene expression studies performed in 23 patients found disparate immune cell type profiles and oncogenic signalling pathway signatures in the low risk as compared to the intermediate and high-risk groups. In the low risk group, neutrophilic, T-regulatory and Th-1 cell profiles were predominant whereas cytotoxic cell profile was predominant in the intermediate and high-risk groups. The low risk group was more active in the myeloid compartment, WNT, cytokine and chemokine, TGF-β and hedgehog signalling pathways whereas cytotoxicity, interferon and lymphoid compartment signalling signatures returned higher in the intermediate and high-risk groups. The research was funded by: NCCS Cancer Fund (Research) (NCCSCF-R-YR2021-JUN-SSD1), Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore Ministry of Health’s National Medical Research Council Research Transition Awards (TA21jun-0005 and TA20nov-0020), Large Collaborative Grant (OFLCG18May-0028), and Collaborative centre grant (TETRAD II). Keywords: Aggressive T-cell non-Hodgkin lymphoma, Diagnostic and Prognostic Biomarkers No conflicts of interests pertinent to the abstract.

An open-label multiyear study of sargramostim-treated Parkinson’s disease patients examining drug safety, tolerability, and immune biomarkers from limited case numbers

BackgroundThe clinical utility and safety of sargramostim has previously been reported in cancer, acute radiation syndrome, autoimmune disease, inflammatory conditions, and Alzheimer’s disease. The safety, tolerability, and mechanisms of action in Parkinson’s disease (PD) during extended use has not been evaluated.MethodsAs a primary goal, safety and tolerability was assessed in five PD patients treated with sargramostim (Leukine®, granulocyte–macrophage colony-stimulating factor) for 33 months. Secondary goals included numbers of CD4+ T cells and monocytes and motor functions. Hematologic, metabolic, immune, and neurological evaluations were assessed during a 5-day on, 2-day off therapeutic regimen given at 3 μg/kg. After 2 years, drug use was discontinued for 3 months. This was then followed by an additional 6 months of treatment.ResultsSargramostim-associated adverse events included injection-site reactions, elevated total white cell counts, and bone pain. On drug, blood analyses and metabolic panels revealed no untoward side effects linked to long-term treatment. Unified Parkinson’s Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were increased. In the initial 6 months of treatment, transcriptomic and proteomic monocyte tests demonstrated autophagy and sirtuin signaling. This finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile arms.ConclusionsTaken together, the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment. Confirmation in larger patient populations is planned in a future phase II evaluation.Trial registration: ClinicalTrials.gov: NCT03790670, Date of Registration: 01/02/2019, URL:https://clinicaltrials.gov/ct2/show/NCT03790670?cond=leukine+parkinson%27s&draw=2&rank=2.