Lymphocyte Levels Research Articles

The subsets of blood circulating T-cells associated with the development and prognosis of coinfection in patients with critical COVID-19

BackgroundA secondary bacterial infection, which has a high incidence in patients with critical coronavirus disease 2019 (COVID-19), has been proven to have an association with increased mortality. Adaptive immune responses have been detected in almost all COVID-19 cases. This study aimed to determine whether the levels of immune-inflammatory factors are associated with coinfection in patients with critical COVID-19.MethodsPatients with a confirmed critical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were enrolled in this single-center cohort study. Clinical data and venous blood samples were collected on the day of hospital admission. All patients were divided into two groups according to the presence of bacterial coinfection or absence of bacterial coinfection, which were then divided into two groups (survived group and deceased group) based on the outcome of the disease during hospitalization.ResultsPatients with coinfection had a higher mortality rate (83.3% VS 50.0%, P<0.001) and longer hospital stays (25.15 VS 13.80d, P<0.001). We observed that patients who developed coinfection tended to have a significantly lower number of CD4+ T cells (121.19 VS 207.83cells/µL, P=0.001) and CD8+ T cells (79 VS 158cells/µL, P=0.006) and a higher proportion of CD4+CD8+ double-positive T (DPT) cells (3.66% VS 1.91%, P=0.011) on the day of hospital admission. The tests for inflammatory cytokines showed a higher level of IL-4 (0.99 VS 0.42pg/mL, P<0.001) and IL-6 (109.60 VS 63.59pg/mL, P=0.009) in coinfection group. And the multivariant analyses also revealed that CD4+ cell counts < 199.5cells/µL, CD8+ cell counts < 124.5cells/µL, IL4 > 0.535pg/mL, IL6 > 388.9pg/mL could be independent risk factors for coinfection. Moreover, in the coinfection group, we observed that the deceased patients had a lower level of total lymphocytes, T cells, and albumin.ConclusionOur study found that lymphocyte subsets and cytokines play an important role in predicting bacterial coinfection in patients with critical COVID-19. Lower levels of CD4+ and CD8+ cells and higher level of IL4 and IL6 in patients on the day of admission were significantly correlated with the development of coinfection the following days in the hospital.

Single-cell and bulk transcriptome sequencing identifies circadian rhythm disruption and cluster-specific clinical insights in colorectal tumorigenesis.

Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive system worldwide, with its mortality ranking second among all cancers. Studies have indicated that disruptions in circadian rhythm (CR) are associated with the occurrence of various cancers; however, the relationship between CR and CRC requires further evidence, and research on the application of CR in CRC is still limited. In this study, we employed both bulk and single-cell RNA sequencing to explore the dysregulation of CR in patients with CRC. By constructing a CR subtype classifier, we conducted an in-depth analysis of the prognostic significance, the status of the tumor microenvironment, and response to immune checkpoint blockade (ICB) therapy between different CR clusters. Furthermore, we developed a CR scoring system (CRS) using machine learning to predict overall survival and identified several genes as potential targets affecting CRC prognosis. Our findings revealed significant alterations in CR genes and status between CRC and normal tissues using bulk and single-cell transcriptome sequencing. Patients with CRC could be categorized into two distinct CR clusters (CR cluster 1 and 2). The prognosis of CR cluster 2, with higher epithelial-mesenchymal transition (EMT) and angiogenesis scores, was significantly worser than that of CR cluster 1. These clusters exhibited distinct levels of tumor-infiltrating lymphocytes. CR cluster 2 with a notably higher proportion of patients with microsatellite-instability-high (MSI-H), potentially benefit from ICB therapy. The proportion of patients belonging to consensus molecular subtype 4 (CMS4) in CR cluster 2 was also notably higher than in CR cluster 1. Additionally, the CRS combined with tumor stage demonstrated superior overall survival prediction efficacy compared to traditional tumor stage. We revealed a potential link between model genes (LSAMP, MS4A2, NAV3, RAB3B, SIX4) and the disruption of CR and patient prognosis. This study not only provide new insights into the assessment of CR status in CRC patients but also develop a prognosis model based on CR-related genes, offering a new tool for personalized risk assessment in CRC.

Synthesis and Exploration of the Anti‐Inflammatory and Antioxidant Potential of Silver Nanoparticle of Propolis and GC–MS Profiling

ABSTRACTIn the current study, propolis aqueous extract was utilized as biological reducing agent to fabricate its silver nanoparticles (Prop‐AgNPs). First, the extract was subjected to GC–MS analysis to determine its chemical profile. After characterization, the Prop‐AgNPs were evaluated for its biological potential in comparison with parental raw extract. The SEM images revealed the NPs as spherical or somewhat spherical in shape with particle size distribution ranging from 80 to 100 nm. The antioxidant potentials of the extract and fabricated nanoparticles were determined against DPPH free radical producing substantial antioxidant activities with IC50 values of 55.07 and 46.62 μg/mL correspondingly, whereas for standard ascorbic acid, its value recorded was 30.35 μg/mL. The Prop‐AgNPs was then evaluated for in vivo anti‐inflammatory potentials in animal model. Inflammation was induced by administering turpentine oil to lower limb of rat, and subsequently, changes in biochemical and hematological parameters were monitored. Animals were administered with doses of extract and Prop‐AgNPs for 14 days, whereas biochemical parameters were monitored at day 7th and 14th of the study. Comparatively, the results were more promising on day 14th of the study. The creatinine level for the normal group were 0.55 ± 0.08 and 0.50 ± 0.04 at day 7th and 14th, whereas for negative control group, the results were 0.88 ± 0.04 (p < 0.001) and 0.94 ± 0.03 correspondingly; while for standard group, the recorded values were 0.57 ± 0.09 and 0.53 ± 0.07. Groups treated with 0.5 and 1 mg/kg body weight (b.w.) doses of extract has creatinine level 0.78 ± 0.23 (p < 0.05) and 0.69 ± 0.13 at day 7th while 0.69 ± 0.13 and 0.65 ± 1.15 at day 14th. Group treated with dose of 0.5 mg and 1 mg/kg b.w. of the synthesized nanoparticle has creatinine level 0.76 ± 0.03 and 0.63 ± 0.09 at day 7th while 0.71 ± 0.09 and 0.60 ± 0.05 at day 14th of the study. Both the extract and Prop‐AgNPs normalized the level of blood urea, SGPT, bilirubin, and alkaline phosphatase compared with normal control and negative control groups among which the results of blood urea, SGPT, and alkaline phosphatase were statistically significant (p < 0.001). The level of hemoglobin for the normal control, negative control, and standard groups was 10.4 ± 0.13, 12.5 ± 0.68 (p < 0.001) and 12.4 ± 0.43 (p < 0.001) at day 7th, whereas at day 14th, the results were 12.1 ± 00.52, 13.8 ± 0.57 (p < 0.001), and 12.6 ± 0.54 indicated more promising changes the studied parameter. The group treated with 0.5 and 1 mg/kg b.w. doses of propolis extract has hemoglobin levels 11.9 ± 0.27 (p < 0.001) and 11.8 ± 0.31 (p < 0.001) at day 7th, whereas at day 14th, the results were 12.9 ± 0.24, and 12.8 ± 0.54 while equivalent doses of nanoparticles resulted in hemoglobin level as 11.8 ± 0.38 (p < 0.001) and 12.7 ± 0.41 (at day 7th) and 13.9 ± 0.34 and 12.2 ± 0.74 (at day 14th). Similarly, levels of neutrophils, lymphocytes, monocytes, and eosinophils were statistically more significant (p < 0.001) for nanoparticles treated groups. This study found positive impact of Prop‐AgNPs on inflammation induced by turpentine oil by improving/reversing changes brought in biochemical and hematological parameters pointing toward its anti‐inflammatory potential that could be utilized in drug formulation.

The prognostic value of halp score in predicting the efficacy of nivolumab treatment in metastatic malignant melanoma patients: A real-life, retrospective, single center analysis.

Patients with metastatic malignant melanoma have a survival rate of less than one year. Nivolumab, a monoclonal antibody against programmed cell death 1 (PD-1) receptor, has improved survival in patients without BRAF mutations. The HALP score, calculated from hemoglobin, albumin, lymphocyte, and platelet levels, provides information about a patient immune and nutritional status. High HALP scores have been associated with a better prognosis in various cancers. This study aimed to investigate the effect of high HALP scores on response to nivolumab treatment in patients with metastatic malignant melanoma. A retrospective study was conducted on 44 patients with metastatic malignant melanoma treated with nivolumab at Adana City Training and Research Hospital between 2014 and 2021. Patients who received dabrafenib-trametinib before nivolumab treatment were excluded. The HALP scores were calculated using laboratory parameters before the first nivolumab treatment. Statistical analyses were performed using SPSS version 25.0. The study included 22 female and 22 male patients with a mean age of 61.4 ± 15.6 years. Of the patients, 10 (27.2%) had a positive BRAF mutation, whereas 34 (77.3%) did not. The HALP score cutoff value was determined as 30.1. Patients with high HALP scores had significantly longer progression-free survival (PFS) and overall survival (OS) compared to those with low HALP scores (PFS: median 5.8 vs 3.1 months, P = .041; OS: median 54.9 vs 14.4 months, P = .005). In this study, we found that high HALP scores were significantly associated with longer PFS and OS in metastatic malignant melanoma patients receiving nivolumab treatment. HALP score was associated with both PFS and OS in patients with metastatic malignant melanoma treated with nivolumab. This immuno-nutritional parameter may be useful in various cancers; however, further prospective studies with larger patient cohorts are needed for clinical application.

A nutritional prognostic model for hospitalized Belgian blue calves: The Calf-CONUT ratio for predicting survival.

A nutritional prognostic model for hospitalized Belgian blue calves: The Calf-CONUT ratio for predicting survival.

The relationship between inflammatory blood cells and executive functions in medication-free children with ADHD

Abstract Background: The aim of this study was to compare blood neutrophil, lymphocyte, platelet, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), erythrocyte and systemic inflammatory index levels in children with attention deficit hyperactivity disorder (ADHD) with typically developing (TD) healthy controls and to investigate the relationship between these levels and executive functions. Methods: In this study, 79 ADHD children aged 8-14 years who did not use medication and 34 healthy controls were included. Participants' blood levels were based on routine complete blood count analysis. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) was used for clinical diagnosis in children, and stroop colour test and serial digit learning test were applied to evaluate executive functions. Results: No significant difference was found between the groups in neutrophil, lymphocyte, platelet, NLR, PLR, erythrocyte and systemic inflammatory index levels. Compared to TDs, patients with ADHD were observed to perform significantly worse on executive function tests. Platelets, neutrophils and lymphocytes were positively correlated with stroop first section correction scores, platelets were positively correlated with stroop second section time scores, lymphocytes were positively correlated with stroop second section correction scores, NLR was negatively correlated with stroop second section correction scores and platelets were positively correlated with stroop third section time scores. Platelets and lymphocytes were positively correlated with stroop section fourth time scores and NLR was positively correlated with stroop section fourth error scores. Conclusion: This study suggests that serum lymphocyte, neutrophil, NLR and platelet levels may be associated with impaired executive tests in ADHD.

Potential Mechanisms for Immunotherapy Resistance in Adult Soft-Tissue Sarcoma.

Soft-tissue sarcomas represent a diverse group of rare malignancies originating from mesenchymal tissue, accounting for less than 1% of adult cancers in the USA. With over 13,000 new cases and around 5350 deaths annually, patients with metastatic soft-tissue sarcomas face limited therapeutic options and an estimated median overall survival of 18 months. While immunotherapy has demonstrated effectiveness in several cancers, its application in soft-tissue sarcomas remains challenging owing to the tumors' largely "cold" immunological environment, characterized by low levels of tumor-infiltrating lymphocytes and a lack of soft-tissue sarcoma-specific biomarkers. This review examines potential mechanisms underlying immunotherapy resistance in soft-tissue sarcomas, including the complex interplay between innate and adaptive immunity, the tumor microenvironment, and the role of immune-related genes. Despite preliminary findings suggesting correlations between immune profiles and histological subtypes, consistent biomarkers for predicting immunotherapeutic responses across soft-tissue sarcoma types are absent. Emerging strategies focus on converting "cold" tumors to "hot" tumors, enhancing their susceptibility to immunologic activation. While research is ongoing, personalized treatment approaches may offer hope for overcoming the inherent heterogeneity and resistance seen in soft-tissue sarcomas, ultimately aiming to improve outcomes for affected patients.

Abstract 6532: Higher Lachnoanaerobaculum abundance in the oral microbiome go along with higher levels of tumor-infiltrating lymphocytes and improved survival in head-and-neck cancer patients undergoing radiotherapy

Recent studies suggest a role for the microbiome in modulating anti-cancer treatment responses, but the impact of the oral microbiome on head-and-neck squamous cell carcinoma (HNSCC) treatment outcomes remains largely unexplored, prompting our analysis of its potential influence following definitive (chemo)radiation. Saliva samples of two independent prospective trials including HNSCC patients undergoing definitive (chemo)radiation were analyzed in terms of the oral microbiome composition before treatment initiation using V3-4 16S rRNA sequencing. Significant findings of the saliva microbiome were validated using information on the intratumoral HNSCC microbiome from The Cancer Genome Atlas (TCGA) database. Immunohistochemistry analyses of tumor-infiltrating lymphocytes (TILs) were carried out to reveal potential differences in the tumor microenvironment depending on microbiome findings. A subset of patients received serial [18F]FMISO-PET imaging as part of a prospective study (n=11) and were analyzed regarding a potential link between their oral microbiome and tumoral hypoxia. A total of 92 HNSCC patients treated with definitive (chemo)radiation were analyzed. Median age was 61 years (IQR, 56-66), most patients were male (n=77, 84%), and oropharyngeal cancer was the most common carcinoma (n=53, 58%). Higher salivary levels of Lachnoanaerobaculum spp. was associated with longer locoregional recurrence-free (p=0.0115) and overall survival (p=0.0417), which remained significant in the multivariable regression analysis (p=0.049974 [locoregional recurrence-free survival], p=0.0187 [overall survival]). Validation using intratumoral data from the TCGA cohort demonstrated an association of higher intratumoral Lachnoanaerobaculum levels with improved overall survival (p=0.0380). Neither the overall prevalence (p>0.9999) nor the time until occurrence of acute higher-grade mucositis (p=0.8414) was influenced by Lachnoanaerobaculum abundance. Patients with higher salivary Lachnoanaerobaculum levels had more CD4-positive stromal (p=0.0269) and CD8-positive intraepithelial TILs (p=0.0123). There was an inverse correlation between higher baseline salivary Lachnoanaerobaculum levels and a prognostically favorable early resolution of intratumoral hypoxia during chemoradiation (r = -0.6514, p=0.0229). High Lachnoanaerobaculum levels in the oral microbiome are associated with better locoregional control, overall survival, and factors predicting improved chemoradiation response in HNSCC patients, such as higher CD8-positive TILs levels and early hypoxia resolution. While Lachnoanaerobaculum may serve as a prognostic marker for improved treatment outcomes, further research is required on the mechanistic role of Lachnoanaerobaculum. Citation Format: Alexander Rühle, Maté Krausz, Elsa Beatriz Monroy Ordonez, Jannis Heyer, Andreas R. Thomsen, Henning Schäfer, Peter Bronsert, Rebecca Kesselring, Ali Al-Ahmad, Andreas Knopf, Anca-Ligia Grosu, Michele Proietti, Michael Henke, Christopher Berlin, Nils Henrik Nicolay. Higher Lachnoanaerobaculum abundance in the oral microbiome go along with higher levels of tumor-infiltrating lymphocytes and improved survival in head-and-neck cancer patients undergoing radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6532.

D-Dimer/Fibrinogen Ratio as a Prominent Predictor of Mortality in COVID-19 Patients Admitted To the Intensive Care Unit

Purpose: In this retrospective cohort study, evaluating the role of the D-dimer/fibrinogen ratio in predicting the in-hospital mortality rate of COVID-19 regardless of the presence of comorbidities was aimed. Materials and Methods: This retrospective cohort study included patients admitted to the intensive care unit. The demographic data of the patients (sex, age, body mass index, comorbidities), their prognostic clinical scores, laboratory results, and need for and duration of invasive mechanical ventilation (IMV) were recorded. Results: The rates of chronic renal diseases, acute renal failure, cardiac diseases, and severe sepsis were significantly higher in the exitus group. It was found that lower levels of lymphocytes were associated with increased mortality. Furthermore, neutrophil counts and the neutrophil to lymphocyte ratio (NLR) were associated with increased mortality. A higher D-dimer/fibrinogen ratio (DDFR) was a predictor of mortality but not a predictor of the duration of hospitalization in the ICU. Conclusion: DDFR has a potential impact in anticipating mortality rates in COVID-19 patients.

Abstract 1962: Detection of plasma circulating tumor DNA is not affected by kidney and liver function in patients with muscle-invasive bladder cancer

Abstract Introduction: Circulating tumor DNA (ctDNA) has demonstrated significant potential for early relapse detection and therapeutic monitoring in patients with muscle-invasive bladder cancer (MIBC). Advancing its clinical utility requires examining factors that may affect plasma ctDNA levels, including those influencing clearance. Here, we evaluated the association between plasma ctDNA detection and kidney and liver function markers in MIBC patients. Secondly, we explored the association between plasma ctDNA detection and immune markers, as well as the prognostic potential of the evaluated biochemical markers. Methods: Tumor-informed plasma ctDNA analysis was available for 276 MIBC patients undergoing radical cystectomy (RC), of which 174 patients received neoadjuvant chemotherapy (NAC). Biochemical measurements collected within 10 days of an available ctDNA test (median: 0 days [IQR: 0-2 days]) and clinical data were retrieved from the patients’ electronic health records. Immune marker measurements were confined to the pretreatment period. The median levels of all biochemical markers were within normal reference ranges, except for the neutrophil-to-lymphocyte ratio (NLR) which was above normal range in ctDNA positive patients. Wilcoxon rank-sum test, Spearman’s correlation and Bonferroni correction for multiple testing were applied. Results: The primary analysis indicated no correlation between kidney (plasma creatinine, eGFR) and liver (albumin, lactate dehydrogenase, alanine aminotransferase (ALAT), bilirubine, alkaline phosphatase) function markers in MIBC patients and plasma ctDNA detection or ctDNA variant allele frequencies (VAFs). Subgroup analyses of NAC-treated and NAC-naïve patients showed similar results, with no association observed, except for a weak positive correlation between ALAT and plasma ctDNA detection in NAC-naïve patients (P=0.036, n=72; not significant after multiple test correction). Levels of leukocytes (P=0.00098, n=146), neutrophils (P=0.0004, n=134), NLR (P=0.00016, n=77) and C-reactive protein (P=0.04, n=241), demonstrated positive correlations with plasma ctDNA detection. Multivariable logistic regression including tumor stage at diagnosis confirmed significant correlations between ctDNA detection and leukocytes (P=0.00322, n=146), neutrophils (P=0.00152, n=134) and NLR (P=0.00185, n=77). None of the biochemical parameters were associated with pathological downstaging after NAC. Reduced pretreatment plasma lymphocyte levels correlated with recurrence in the NAC-treated patients (P=0.012; not significant after multiple test correction). Conclusion: Clinical application of ctDNA can be implemented with minimal risk of detection being influenced by fluctuations in the patients’ kidney and liver function. Finally, biochemical parameters alone showed no strong prognostic value. Citation Format: Deema Radif, Sia V. Lindskrog, Iver Nordentoft, Karin Birkenkamp-Demtröder, Mads Agerbæk, Jørgen B. Jensen, Lars Dyrskjøt. Detection of plasma circulating tumor DNA is not affected by kidney and liver function in patients with muscle-invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1962.

Abstract 2152: NT-I7 increases lymphocytes and enhances chemotherapy and immunotherapy efficacy in HNSCC

Background: Lymphopenia is associated with poor outcomes and is exacerbated by conventional chemoradiation therapies in head and neck squamous cell carcinoma (HNSCC). NT-I7 (rhIL-7-hyFc, efineptakin alfa; NeoImmuneTech, Inc.), a long-acting human IL-7, has the potential to restore lymphocyte populations, modulate immune responses, and enhance anti-tumor activity. This study investigated NT-I7’s effects on lymphocyte populations and its synergy with cisplatin and immune checkpoint inhibitors (ICIs) in syngeneic, immunocompetent HNSCC mouse models. Methods: The impact of NT-I7 was studied in two syngeneic tumor models, MOC1 and MOC22. Flow cytometry and Cytometry by Time of Flight (CyTOF) analyses were used to evaluate NT-I7 effects on peripheral and intratumoral immune cells. Anti-tumor efficacy was assessed following NT-I7 treatment alone, in combination with cisplatin, or with anti-PD-1 therapy. Results: Mice bearing syngeneic MOC1 and MOC22 tumors exhibited significant lymphopenia, characterized by reductions in CD4+ and CD8+ T-cells, Tregs, NK cells, and NKT cells, resembling clinical observations in HNSCC patients. NT-I7 treatment significantly increased lymphocyte levels in both spleen and tumor, with notable induction of CD8+ T-cells and NKT cells, peaking at day 7 and day 4 post-treatment, respectively, and minimal impact on intratumoral Treg levels. NT-I7 modestly inhibited MOC1 tumor growth and potently suppressed MOC22 tumor growth. Combining NT-I7 with cisplatin significantly enhanced anti-tumor activity in MOC1 tumors, accompanied by increased numbers of peripheral and intratumoral CD4+, CD8+, and NKT cells. Furthermore, NT-I7 augmented the efficacy of anti-PD-1 therapy in MOC1 tumors, resulting in greater tumor growth inhibition compared to either treatment alone. CyTOF analysis revealed preferential expansion of CD8+ Tpex cells, a key subset of tumor-specific cells that expand in response to ICIs, highlighting NT-I7’s role in overcoming lymphopenia and potentiating anti-tumor immunity. Conclusions: NT-I7 effectively increases lymphocyte populations in HNSCC preclinical models that demonstrate tumor-associated lymphopenia, and enhances the efficacy of cisplatin and anti-PD-1 in HNSCC preclinical tumor models. Citation Format: Zhibin Cui, Jacqueline L. Yee, Hua Li, Yan Zeng, Liam Woerner, Alexandra A. Wolfarth, Sara Ferrando-Martinez, Hyunseok Kang, Jennifer R. Grandis, Matthew H. Spitzer, Daniel E. Johnson. NT-I7 increases lymphocytes and enhances chemotherapy and immunotherapy efficacy in HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2152.

Evaluation of blood-count-derived inflammatory markers in patients with idiopathic epiretinal membrane

BackgroundTo assess the role of inflammation in the pathogenesis of idiopathic epiretinal membrane (iERM) by evaluating blood-count-derived inflammatory marker levels.MethodsThe medical records of patients diagnosed with iERM and cataract patients with normal fundus examinations were analyzed retrospectively. Levels of neutrophils, monocytes, lymphocytes, and thrombocytes were obtained from blood samples. Systemic inflammatory markers, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammatory response index (SIRI) were calculated and compared between the two groups. The receiver operating characteristic curve (ROC) analysis was performed to determine the best cutoff value of NLR, PLR, SII, and SIRI in iERM.ResultsIn total, 91 iERM cases and 95 controls were included in the study. iERM patients had significantly higher NLR (2.25 vs. 1.91, p = 0.003), PLR (117.22 vs. 113.33, p = 0.042), SII (529.45 vs. 472.57, p = 0.003), and SIRI (1.25 vs. 0.90, p < 0.001). The area under the curve of NLR, PLR, SII, and SIRI in differentiating patients with iERM and controls was 0.637, 0.608, 0.645 and 0.660, respectively, according to ROC analysis. The best cutoff values (with sensitivity and specificity) were 1.95 (60.4% and 52.6%) for NLR, 116.7 (54.9% and 55.7%) for PLR, 498.03 (58.2% and 58.9%) for SII, and 1.07 (62.6% and 64.6%) for SIRI.No significant differences in inflammatory markers were found across iERM stages.ConclusionPatients with iERM exhibit higher levels of blood-count-derived inflammatory markers, suggesting a link between systemic subclinical inflammation and iERM development. However, these markers do not correlate with iERM severity. Further research with larger cohorts and broader inflammatory marker analysis is needed to elucidate the role of systemic inflammation in iERM pathogenesis.

Evaluation of a cost-effective gating strategy for CD4+ T lymphocyte enumeration in HIV-infected individuals via flow cytometry.

Evaluation of a cost-effective gating strategy for CD4+ T lymphocyte enumeration in HIV-infected individuals via flow cytometry.

Evaluation of Morphology and Biochemical Parameters of Young Adults Using Heated Tobacco Products in Poland: A Case-Control Study.

Background/Objectives: Little is currently known of the impact of heated tobacco on health. The aim of this study is to evaluate the impact of heated tobacco use on selected health assessment parameters among people aged 18-30 to determine the effect on health status. Methods: A case-control study was conducted from April 2022 to February 2025. A total of 195 young, healthy adult residents of Lodz, Poland, took part. The participants were divided into three groups: IQOS (I-Quit-Ordinary-Smoking) smokers who had never smoked or who had quit smoking six months previously (n = 65); daily smokers who had smoked at least five cigarettes per day for at least one year and had not used any other smoking substitutes for at least one year (n = 65); and people who have never smoked or used tobacco products (n = 65). Blood samples from 37 IQOS users (57%), 28 traditional cigarette smokers (43%), and 45 non-smokers (69%) were submitted for laboratory analysis. The tested parameters were determined in the diagnostic laboratory of the Bonifratów Hospital in Lodz. Results: No significant differences (p > 0.05) were found between the groups with regard to blood count (white blood cell count (WBC), red blood cell count (RBC), lymphocytes, monocyte number (MONO), hemoglobin concentration (HGB)), biochemical biomarkers (C-reactive protein (CRP), fibrinogen, apolipoprotein A1 (apo A1), apolipoprotein B (apo B), glucose), or lipid profile (total cholesterol, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL)). The cigarette smokers demonstrated significantly higher uric acid levels compared to the IQOS users and non-smokers: 5.22 vs. 4.77 vs. 4.40 mg/dL (p < 0.01). The IQOS users demonstrated significantly higher platelet count levels compared to cigarette smokers and non-smokers: 290.27 vs. 267.14 vs. 256.33 × 103/ μL (p < 0.05). Among the IQOS users (n = 37), the level of glucose (ρ = -0.47; p = 0.01), WBC (ρ = -0.36; p = 0.03), lymphocytes (ρ = -0.38; p = 0.02), and uric acid (ρ = -0.34; p = 0.04) was negatively correlated with the daily number of heated tobacco sticks. The HDL level was positively correlated (ρ = 0.39; p = 0.02) with the daily number of heated tobacco sticks. Conclusions: Further cohort studies assessing the health status of young users of heated nicotine products and prospective analyses are necessary.

Clinical characteristics and treatment response of chronic disseminated candidiasis in patients with hematological disorders

Chronic disseminated candidiasis (CDC) is an invasive fungal infection typically affecting patients with hematological diseases and severe neutropenia, associated with increased mortality. However, there is a global shortage of clinical evidence on CDC. We retrospectively analyzed clinical data from 49 CDC patients over the past decade. Clinical characteristics of primary hematological diseases, CDC diagnosis, treatment and response evaluations were included. Clinical factors associated with CDC remission and patients’ survival were analyzed. The majority of patients had hematological malignancies (n = 43, 87.8%), and 27 patients (55.1%) had persistent severe neutropenia for more than 10 days prior to CDC. CT scans revealed liver lesions in 44 patients, spleen lesions in 34 patients, and kidney lesions in 9 patients. Proven, probable and possible CDC was diagnosed in 5 (10.2%), 3 (6.1%) and 41 patients (83.7%), respectively, and treatment outcomes at 3 months included 5 complete response (CR, 10.2%), 34 partial response (PR, 69.4%) and 10 treatment failure (20.4%). Caspofungin treatment showed a trend towards improving CR/PR rate, while severe neutropenia > 20 days and proven diagnosis were significantly associated with 3-month treatment failure. Kaplan–Meier curve showed achieving CR/PR within 3 months did not significantly prolong OS compared to treatment failure patients (1197.6 days vs. 564.8 days, P = 0.074). Additionally, no patient deaths were directly attributed to CDC infection. Age > 45 years old and malignancy non-remission were prognostic factors of overall survival (OS). Furthermore, a prediction model identified severe neutropenia > 20 days, proven/probable diagnosis and concomitant bacteremia as risk factors to effectively predict treatment failure. Also, patients with a risk score < 0.203 in the model exhibited more rapid treatment response. After CDC symptoms onset, lymphocyte levels remained consistently higher in treatment failure patients, while the neutrophil-to-lymphocyte ratio was persistently higher in CR/PR patients. Our findings recommend CT scans for diagnosis and caspofungin as first-line therapy while continuing scheduled chemotherapy or bone marrow transplantation. Notably, risk factors identified by the prediction model could be used to predict treatment response.

A prospective cohort study on the association between neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and gestational diabetes mellitus in Chinese pregnant women.

This study investigated whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in early pregnancy correlate with subsequent development of gestational diabetes mellitus (GDM). This prospective cohort study enrolled 1,200 pregnant women during their first trimester at Peking University International Hospital between December 2017 and March 2019. All participants underwent oral glucose tolerance testing (OGTT) at 24-28 weeks gestation. Complete blood counts obtained in the first trimester were analyzed for NLR and PLR values. Participants were categorized into GDM (n=227) and non-GDM (n=973) groups based on International Association of Diabetes and Pregnancy Study Groups criteria. Women who developed GDM exhibited significantly higher first-trimester levels of neutrophils, lymphocytes, platelets, NLR, and PLR (all p<0.05) compared to women without GDM. First-trimester NLR and PLR values positively correlated with second-trimester blood glucose levels at 0, 60, and 120 minutes during OGTT (all p<0.05). The optimal cut-off values for predicting GDM were 3.89 for NLR (sensitivity 76.05%, specificity 36.56%) and 148.11 for PLR (sensitivity 68.72%, specificity 68.65%). A multivariate predictive model incorporating NLR, PLR, age, parity, BMI, blood lipids, and uric acid demonstrated 78.39% sensitivity, 73.83% specificity, and 78.87% accuracy with an area under the curve of 0.79 (95% CI: 0.71, 0.86). First-trimester NLR and PLR represent independent risk factors for GDM development. These readily available inflammatory markers may have value for early GDM risk assessment and aid in targeting preventive interventions.

Inflammatory Markers and Saphenous Vein Graft Stenosis: Insights into the Use of Glucose-to-Lymphocyte Ratio as a Prognostic Marker.

Background: Coronary artery bypass grafting (CABG) for the treatment of ischemic heart disease is still considered an effective treatment option to improve clinical outcomes and reduce mortality. However, the patency rates of saphenous vein grafts (SVGs) are significantly lower compared to those of arterial grafts. Atherosclerosis has emerged as one of the main causes of SVG stenosis (SVGS), especially stenoses that develop after one year. In this study, we aimed to investigate the association of glucose-to-lymphocyte ratio (GLR), a novel inflammatory biomarker, with LVG patency status in patients undergoing CABG surgery. Methods: A total of 778 patients who were diagnosed with chronic coronary syndromes (CCS) according to the 2019 ESC guidelines for the diagnosis and treatment of CCS; had undergone CABG more than one year previously; and had at least one SVG used during surgery were included in this study. GLR was calculated as blood glucose level (mg/dL) divided by lymphocyte count (K/uL). Results: SVGS was detected in 341 patients, while SVGs were intact in 437 patients. Patients with SVGS had a higher prevalence of diabetes mellitus (DM) (p = 0.002) and significantly higher blood glucose levels (p < 0.001). In addition, the interval between CABG operation and coronary angiography (CAG) was longer in the SVGS group (p < 0.001). Neutrophil levels were higher, and lymphocyte levels were lower in this group (p = 0.010 and p = 0.034, respectively). Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), glucose/lymphocyte ratio (GLR) and high-sensitivity C-reactive protein (CRP) levels were significantly higher in patients with SVGS (p < 0.001 for all). According to multivariate logistic regression analysis, DM, CRP level, time since CABG, and GLR were identified as independent predictors of SVGS (p = 0.004, p = 0.048, p < 0.001, and p < 0.001, respectively). ROC analysis showed that SVGS could be predicted with 75.8% sensitivity and 68.6% specificity when the cut-off value for GLR was >315.5 (area under the curve [AUC]: 0.801, 95% CI: 0.765-0.837, p < 0.001). Conclusions: Higher GLR levels are associated with SVGS in patients with coronary artery disease.

C-Reactive Protein, Ferritin and D-dimer as Predictors of Covid-19 Severity

Background: Coronavirus Disease 2019 (COVID 19) is a novel infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It emerged in Wuhan and has quickly spread across the world. In Bangladesh, the mortality rate in critically ill patients with COVID-19 is high. This study compares biochemical parameters between mild/moderate and severe patients, helping to identify severe or critical patients early. Objective: To identify severe or critical covid-19 patients early by analysis of biochemical parameters. Materials and Methods: This cross-sectional study was done in Intensive Care Unit (ICU) of Enam Medical College Hospital from April 2021 to August 2021. Total 60 Covid positive patients were enrolled. Among them 30 were severe (ICU) patients and 30 were mild/moderate (non–ICU) patients. Results: A comparison of the hematological parameters between the mild and severe groups showed significant differences in lymphocyte, neutrophil, ferritin, D-dimer and CRP levels. Conclusion: The findings suggest that ferritin, D-dimer and CRP levels can be used to detect the severity of COVID-19 patients. J Enam Med Col 2022; 12(3): 127−131

The single-cell spatial landscape of stage III colorectal cancers

We conducted a spatial analysis of stage III colorectal adenocarcinomas using Hyperion Imaging Mass Cytometry, examining 52 tumors to assess the tumor microenvironment at the single-cell level. This approach identified 10 distinct cell phenotypes in the tumor microenvironment, including stromal and immune cells, with a subset showing a proliferative phenotype. By focusing on spatial neighborhood interactions and tissue niches, particularly regions with tumor-infiltrating lymphocytes, we investigated how cellular organization relates to clinicopathological and molecular features such as microsatellite instability (MSI) and recurrence. We determined that microsatellite stable (MSS) colorectal cancers had an increased risk of recurrence if they had the following features: 1) a low level of stromal tumor-infiltrating lymphocytes, and 2) low interactions between CD4 + T cells and stromal cells. Our results point to the utility of spatial single-cell interaction analysis in defining novel features of the tumor immune microenvironments and providing useful clinical cell-related spatial biomarkers.

Metformin alleviates inflammatory response and severity rate of COVID-19 infection in elderly individuals

To evaluate the relationship between metformin and the outcome of coronavirus disease 2019 (COVID-19) infection. The study included 413 patients with type 2 diabetes among the 5217 patients enrolled in a COVID-19 study, and analyzed whether receiving metformin therapy prior to infection was associated with risk of ICU admission, development of pneumonia and length of hospital stay. The study also examined the correlation between metformin treatment and levels of IL-6, CRP, serum ferritin (SF), lymphocyte, CD4 at admission, as well as the increase in open reading frame 1ab gene cycle threshold (ORF1abCT) after one week of hospitalization. There were no differences in age, sex, BMI, comorbidities, number of vaccine doses or eGFR between patients receiving and not receiving metformin therapy. In the ICU group, the proportion of patients not receiving metformin was 92.5%, significantly higher than the 69.2% of patients not admitted to ICU (p = 0.010). In the pneumonia group, the proportion of patients not receiving metformin was 78.6%, significantly higher than the 67.2% in the non-pneumonia group (p = 0.020). Compared with patients receiving no treatment, those receiving metformin had a shorter hospital stay (12.1 ± 5.9 days vs. 14.5 ± 8.2 days, p = 0.001). In the patients ≥ 60 years old, those receiving treatment had significantly lower levels of IL-6 (median, 12.3 pg/ml vs. 4.0 pg/ml, p = 0.026) and significantly higher levels of Lymphocyte (median, 1.2 × 109/L vs. 1.4 × 109/L, p = 0.015) compared with those not receiving treatment. However, for the patients under 60, there were no significant differences observed in IL-6 and Lymphocyte levels between those receiving treatment and those not. Metformin can reduce the severity of COVID-19 infection and attenuate the inflammatory response associated with COVID-19 infection.