Absolute Monocyte Count Research Articles

Abstract 4136182: Usefulness of Lymphocyte-to-Monocyte Ratio in Predicting Late Recurrence of Atrial Fibrillation after Catheter Ablation and its Association With the Type of Atrial Fibrillation

Introduction: Leukocyte activation is reported to be an important inflammatory pathway underlying atrial fibrillation (AF). The lymphocyte-to-monocyte ratio (LMR) is a novel, cost-effective, and widely available marker of inflammation. Research Questions: The usefulness of LMR in predicting late recurrence of AF (LRAF) after catheter ablation (CA), and the impact of AF type on its usefulness, have not yet been elucidated. Goals: We aimed to elucidate the association between LMR measured just before CA and the risk of LRAF in patients who underwent CA for AF, and to investigate whether the type of AF impacts the predictability of LMR for LRAF. Methods: We enrolled 597 consecutive patients with AF (median age, 65 years; 32% female; 334 patients with paroxysmal AF [PAF] and 263 patients with persistent AF [PeAF]) who underwent initial radiofrequency CA. LMR was measured within 3 days prior to the date of CA, and calculated by dividing the absolute lymphocyte count by the absolute monocyte count using the same blood samples. Any detectable atrial tachyarrhythmia lasting for longer than 30 s beyond a 3-month blanking period after the procedure was considered as LRAF. Patients were followed-up for a maximum of 3 years. Results: During a median follow-up of 24 months, LRAF occurred in 215 patients (96 with PAF and 119 with PeAF). Although there was no significant difference in LMR between patients with and without LRAF in PAF (5.3 [4.1–6.7] vs 5.2 [4.0–6.6], p=0.403), LMR in patients with LRAF was significantly lower than those without LRAF in PeAF (4.7 [3.9–6.4] vs 5.6 [4.5–6.8], p=0.015). Multivariate Cox analysis showed that LMR was an independent predictor of LRAF in PeAF (p=0.008), but not in PAF (p=0.662). Receiver operating characteristic curve analysis revealed that an LMR of 4.8 was a fair discriminator for LRAF in PeAF. Although there was no significant difference in the risk of LRAF between the patients with lower (LMR<4.8) and higher LMR (LMR≥4.8) in PAF, patients with lower LMR had a significantly higher risk of LRAF than those with higher LMR in PeAF (Figure). Conclusions: Pre-ablation LMR was shown to be useful for predicting LRAF in patients with PeAF who underwent CA for AF, while not in patients with PAF.

The relationship between immune cells and prostate cancer, and the mediating role of metabolites: a Mendelian randomization study

Research has demonstrated the significant involvement of immune cells in the development and progression of prostate cancer (PCa). However, the precise causal relationship between immune cells and PCa remains unclear. This study utilized bidirectional Mendelian randomization (MR) analysis to investigate the causal link between immune cells and PCa. Additionally, employed mediation MR design to ascertain the potential mediating role of metabolites in the connection between immune cells and PCa outcomes. Unswitched memory B cell % lymphocyte and CD24 + CD27 + B cell % lymphocyte were positively related to PCa risk, while CD62L − monocyte absolute count and CD62L − monocyte % monocyte were negatively associated with PCa risk. Sensitivity analysis was conducted to validate these results. The mediation MR results indicate that 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) levels may be an independent risk factor for PCa, while the succinate to acetoacetate ratio (SA ratio) was found to be a mediator for the effect of CD62L − monocyte % monocyte on PCa, with a mediation proportion of 16.6% (mediation percentage: 16.6%, 95%CI − 163% − 196%). The research validates the genetic causality between particular immune cells and PCa, and has emphasized the potential intermediary function of SA ratio. These noteworthy discoveries provide fresh perspectives for the clinical management of PCa.

Monocyte Count as a Predictor of Major Adverse Limb Events in Aortoiliac Revascularization.

Background/Objectives: Atherosclerosis is a leading cause of death, especially in the developed world, and is marked by chronic arterial inflammation and lipid accumulation. As key players in its progression, monocytes contribute to plaque formation, inflammation, and tissue repair. Understanding monocyte involvement is crucial for developing better therapeutic approaches. The objective of this study is to assess the prognostic value of monocytes for limb-related outcomes following revascularization for complex aortoiliac lesions, thereby emphasizing the central role of monocytes in atherosclerosis. Methods: This prospective cohort study-enrolled patients who had undergone elective aortoiliac revascularization at two hospitals between January 2013 and December 2023. Patients with TASC II type D lesions were included, excluding those with aneurysmal disease. Demographic, clinical, and procedural data were gathered, and patients were monitored for limb-related outcomes. Preoperative complete blood counts were analyzed, and statistical analyses, including multivariable Cox regression, were conducted to identify predictors of major adverse limb events (MALE). Results: The study included 135 patients with a mean age of 62.4 ± 9.20 years and predominantly male (93%). Patients were followed for a median of 61 IQR [55.4-66.6] months. Smoking history (91%) was the most prevalent cardiovascular risk factor. Preoperative monocyte count >0.720 × 109/L was associated with worse 30-day limb-related outcomes (MALE: OR 7.138 95% CI: 1.509-33.764, p = 0.013) and long-term outcomes, including secondary patency (p = 0.03), major amputation (p = 0.04), and MALE (p = 0.039). Cox regression analysis confirmed an elevated monocyte count as an independent predictor of MALE (adjusted hazard ratio 2.149, 95% CI: 1.115-4.144, p = 0.022). Conclusions: This study demonstrated that patients with a higher absolute monocyte count may be more exposed to the risk of MALE in patients with aortoiliac TASC II type D lesions undergoing revascularization, with predictive accuracy in both the short and long term. Additionally, it was an independent predictor of major amputation. This new marker has the potential to serve as a cost-effective and easily available tool for risk stratification, helping identify patients at higher risk of MALE.

Diagnostic Value of Osteopontin, Lymphocyte-to-Monocyte Ratio, and CA-125 in Ovarian Carcinoma Suspect

Osteopontin (OPN) is an important protein in cancer development and progressivity. Lymphocyte-to-Monocyte Ratio (LMR) as a systemic immunity and inflammatory indicator could be an ideal predictor biomarker because of its method’s simplicity and availability. Elevated CA-125 and OPN as well as decreased LMR were reported as signs of ovarian malignancy. Limited studies about OPN and LMR as diagnostic biomarkers, as well as various specificity and sensitivity of CA-125 intrigued the researcher to prove OPN, LMR, and CA-125 as diagnostic biomarkers for ovarian carcinoma. This study aimed to measure the diagnostic value of OPN, LMR, and CA-125 levels against histopathology results for ovarian carcinoma diagnosis. Eighty patients involved with suspected ovarian carcinoma who were referred to Dr. Kariadi Hospital, Semarang. Osteopontin and CA-125 levels were measured using ELISA, and LMR was calculated from absolute lymphocyte and monocyte counts using an automated hematology analyzer. The receiver operating characteristics curve was used to determine the cut-off and 2x2 table. The cut-off values for OPN, LMR, and CA-125 were 124 ng/mL, 3.7 and 45.4 U/mL, respectively. The sensitivity for OPN, LMR, and CA-125 was 67.24%, 62.07% and 60.34%. Specificity for OPN, LMR, and CA-125 were 68.18%, 54.55% and 59.09%. Osteopontin is the best parameter for determining the diagnosis of ovarian carcinoma but it is still not sufficient because OPN cut-off was still within the normal reference value.

Mediation effect of plasma metabolites on the relationship between immune cells and the risk of prostatitis: A study by bidirectional 2-sample and Bayesian-weighted Mendelian randomization.

According to the findings of multiple observational studies, immune disorder was a risk factor for prostatitis. However, it remained unknown whether there was a direct causal relationship between immune cells and prostatitis or whether this relationship was mediated by plasma metabolites. Based on the pooled data of a genome-wide association study (GWAS), a genetic variant was used to predict the effects of 731 immunophenotypes on the risk of prostatitis and determine whether the effects were mediated by 1400 metabolites. The bidirectional 2-sample Mendelian randomization (MR) method was adopted to uncover the causal relationship between immunophenotypes and prostatitis. Subsequently, a 2-step MR method was employed to evaluate whether the metabolites mediated this causal relationship and quantify the mediating effects and the corresponding ratios. In addition, the Bayesian-weighted Mendelian randomization (BWMR) method was employed to verify the results. Among the 731 immunophenotypes analyzed, 16 had causal relationships with the risk of prostatitis, including 11 with positive correlations (P < .05, beta > 0) and 5 with negative correlations (P < .05, beta < 0). The MR analysis screened out 9 metabolites related to the risk of prostatitis. The X - 24344 levels mediated the causal relationship between CD3 on CD39+ activated Treg and prostatitis (mediation effect: 0.01; ratio: 9.82%). Both histidine betaine (hercynine) levels and the proline-to-glutamate ratio mediated the causal relationship between CD14-CD16+ monocyte absolute count and prostatitis, with the mediation effects of -0.016 (14.20%) and -0.008 (7.24%), respectively. The glutamine degradant levels mediated the causal relationship between HLA DR+ CD4+ %T cells and prostatitis, with a mediation effect of -0.012, accounting for 8.07% of the total. The present study indicated that the immune cell subsets predicted based on gene expression profiles were potentially beneficial or harmful risk factors of prostatitis, and plasma metabolites may serve as the mediating factors of the relationship. The study thus shed light on deciphering the immunologic mechanism of prostatitis.

Systemic Inflammatory Response Index and the Short-Term Functional Outcome of Patients with Acute Ischemic Stroke: A Meta-analysis.

The systemic inflammatory response index (SIRI) is a novel indicator of systemic inflammation derived from the absolute counts of neutrophils, monocytes, and lymphocytes. The aim of this meta-analysis was to evaluate the association between SIRI and functional outcome in patients with acute ischemic stroke (AIS). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in this meta-analysis. Relevant cohort studies were retrieved by a search of electronic databases including PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure from database inception to February 9, 2024. A poor functional outcome was defined as a modified Rankin Scale ≥ 3 within 3months after disease onset. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. The protocol of the meta-analysis was not prospectively registered in PROSPERO. Fourteen cohort studies were included. Pooled results showed that a high SIRI at admission was associated with increased risk of poor functional outcome within 3months (odds ratio [OR]: 1.57, 95% confidence interval: 1.39 to 1.78, p < 0.001; I2 = 0%). Results of the meta-regression analysis suggested that the cutoff for defining a high SIRI was positively related to the OR for the association between SIRI and the risk of poor functional outcome (coefficient = 0.13, p = 0.03), while other variables including sample size, mean age, severity of stroke at admission, percentage of men, current smokers, or patients with diabetes did not significantly modify the results. Subgroup analyses according to study design, main treatments, and study quality scores showed similar results. A high SIRI may be associated with a poor functional outcome in patients after AIS.

Comparing Absolute Eosinophil and Monocyte Counts in Critical and Non-Critical COVID-19 Patients

Emerging evidence suggests that variations in immune cell counts, particularly absolute eosinophil and monocyte counts may be important in predicting the clinical course and severity of the disease in COVID-19 patients. Objective: To compare the absolute eosinophil and monocyte counts ‘between critical and non-critical COVID-19 patients to elucidate potential associations with disease severity and prognosis. Methods: Between March 19th and June 6th, 2021, peripheral blood samples were taken from 26 ‘critical COVID-19 patients and 26 non-critical COVID-19 patients. Standard laboratory procedures were used to determine the immunological and haematological parameters for every participant. Whole blood samples were taken in ethylenediaminetetraacetic acid (EDTA) tubes and processed per the manufacturer's instructions using an automated haematology analyser (XN-1000, Sysmex, Japan). Results: Critical patients of COVID-19 exhibited significantly reduced absolute eosinophil, absolute monocyte, and lymphocyte count compared to non-critical patients. Additionally, critical patients were significantly older. However, there is no significant differences in the two groups' basophil counts, neutrophil counts, WBC counts, RBC counts, HCT percentage, HGB levels, MCH levels, MCV, MCHC levels, and MPV or platelet counts. Conclusions: Critical patients exhibited significantly reduced absolute eosinophil and monocyte counts suggesting a potentially weaker immune response in these subgroups. The significance of immune cell counts in assessing the severity of COVID-19 is highlighted by these results which may aid in developing targeted therapeutic interventions and prognostic indicators. Validating these results and clarifying their therapeutic significance will require more investigation.

The early prognostic value of the 1–4-day BCM/PA trend after admission in neurocritical patients

The purpose of this study was to investigate early stage dynamic changes in relevant indicators in neurocritical patients to identify biomarkers that can predict a poor prognosis at an early stage (1–4 days after admission). This study retrospectively collected clinical data, inflammatory indicators, and nutritional indicators from 77 patients at the neurology intensive care unit. The 3-month modified Rankin scale score was used as the outcome indicator. A linear mixed model was used to analyze changes in inflammatory indicators and nutritional indicators in neurocritical patients over time from 1–4 days after admission. Logistic regression was used to determine the independent risk factors for a poor prognosis in neurocritical patients and to construct a predictive model. The predictive efficacy of the model was verified using leave-one-out cross-validation and decision curve analysis methods. The analysis results showed that 1–4 days after admission, the inflammatory indicators of white blood cell and absolute monocyte counts and the nutritional indicators of body cell mass(BCM), fat-free mass, body cell mass/phase angle (BCM/PA), intracellular water, extracellular water, and skeletal muscle index increased overall, while the nutritional indicators of albumin and visceral fat area decreased overall. The logistic multivariate regression model showed that the Charlson comorbidity index (CCI) (odds ratio (OR) = 2.526, 95% CI [1.202, 5.308]), hemoglobin (Hb)(on admission)-Hb(min) (OR = 1.049, 95% CI [1.015, 1.083), BCM(on admission) (OR = 0.794, 95% CI [0.662, 0.952]), and the change in BCM/PA 1–4 days after admission (OR = 1.157, 95% CI [1.070, 1.252]) were independent risk factors for a poor prognosis in neurocritical patients. The predictive analysis showed that the predictive power of Model 1 with BCM/PA (area under the curve (AUC) = 0.95, 95% CI (0.90, 0.99)) was 93%, 65%, 141%, and 133% higher than that of Model 2 without BCM/PA, the CCI, the APACHE II score, and the NRS2002 score (all P < 0.05), respectively. The CCI, Hb(on admission)-Hb(min), BCM(on admission), and an increase in BCM/PA 1–4 days after admission were independently associated with a poor prognosis in neurocritical patients. Of these variables, BCM/PA may be a valid indicator for early stage prediction of a poor prognosis in neurocritical patients.

Baseline immune state and T-cell clonal kinetics are associated with durable response to CAR-T therapy in large B-cell lymphoma

AbstractEngineered cellular therapy with CD19-targeting chimeric antigen receptor T cells (CAR-Ts) has revolutionized outcomes for patients with relapsed/refractory large B-cell lymphoma (LBCL), but the cellular and molecular features associated with response remain largely unresolved. We analyzed serial peripheral blood samples ranging from the day of apheresis (day –28/baseline) to 28 days after CAR-T infusion from 50 patients with LBCL treated with axicabtagene ciloleucel by integrating single-cell RNA and T-cell receptor sequencing, flow cytometry, and mass cytometry to characterize features associated with response to CAR-T. Pretreatment patient characteristics associated with response included the presence of B cells and increased absolute lymphocyte count to absolute monocyte count ratio (ALC/AMC). Infusion products from responders were enriched for clonally expanded, highly activated CD8+ T cells. We expanded these observations to 99 patients from the ZUMA-1 cohort and identified a subset of patients with elevated baseline B cells, 80% of whom were complete responders. We integrated B-cell proportion ≥0.5% and ALC/AMC ≥1.2 into a 2-factor predictive model and applied this model to the ZUMA-1 cohort. Estimated progression-free survival at 1 year in patients meeting 1 or both criteria was 65% vs 31% for patients meeting neither criterion. Our results suggest that patients’ immunologic state at baseline affects the likelihood of response to CAR-T through both modulation of the T-cell apheresis product composition and promoting a more favorable circulating immune compartment before therapy. These baseline immunologic features, measured readily in the clinical setting before CAR-T, can be applied to predict response to therapy.

Clinical and biochemical factors for bacteria in bile among patients with acute cholangitis.

Acute cholangitis is a clinical syndrome caused by a bacterial infection in the biliary system. The bacteria could exist in the bile before bile drainage despite empirical antibiotic treatment. Patients with acute cholangitis admitted to a tertiary hospital in Southeastern China from August 2011 to September 2021 were involved when bile cultures were performed. Patient information before bile cultures and during hospitalization was extracted from the clinical record database. The risk factors related to bacteria in bile were assessed by univariable and multivairable logistic regression analysis, respectively. A total of 533 patients (66.05%) had bacterial growth in bile. Alanine aminotransferase concentration [odds ratio (OR) = 0.998, P < 0.001], absolute monocyte count (OR = 0.335, P = 0.001), and duration of antibiotic use (OR = 0.933, P = 0.026) were negatively correlated with bacteria in bile. In contrast, C-reactive protein (OR = 1.006, P = 0.003), thrombin time (OR = 1.213, P = 0.033), prothrombin time (OR = 1.210, P = 0.011), and age (OR = 1.025, P < 0.001) were positively correlated with bacteria in bile. Based on an area under the receiver operating characteristic curve of 0.737 (95% CI, 0.697-0.776, P < 0.001), combining these seven variables could efficiently predict the presence of bacteria in bile among patients with acute cholangitis. The combination of clinical indicators before bile drainage could predict the risk of bacteria in bile for patients with acute cholangitis.

Clonal monocytosis of renal significance

Clonal monocytosis reflects a preneoplastic or neoplastic sustained increase in the absolute monocyte count in the absence of reactive causes. Causes of clonal monocytosis include clonal cytopenias with monocytosis and acute and chronic myeloid neoplasms. Chronic myelomonocytic leukemia is a prototypical myelodysplastic/myeloproliferative overlap neoplasm in adults, characterized by sustained peripheral blood monocytosis. Renal abnormalities, including acute kidney injury and chronic kidney disease, are frequent in patients with chronic myelomonocytic leukemia and are predictors of worse outcomes. In addition, acute kidney injury/chronic kidney disease often limits eligibility for allogeneic stem cell transplantation or enrollment in clinical trials. In this review, we highlight clonal monocytosis-related etiologies that give rise to acute kidney injury and chronic kidney disease, with special emphasis on chronic myelomonocytic leukemia and lysozyme-induced nephropathy. Monocytes produce lysozyme, which, in excess, can accumulate in and damage the proximal renal tubular epithelium. Early identification of this etiology and a timely reduction in monocyte counts can salvage renal function. Other etiologies of renal injury associated with clonal monocytosis include direct renal infiltration by monocytes, renal extramedullary hematopoiesis, myeloproliferative neoplasm-associated glomerulopathy, autoimmune (membranous nephropathy, minimal change disease) and paraneoplastic manifestations, thrombotic microangiopathy, obstructive nephropathy due to myeloproliferation, and urate nephropathy due to tumor lysis syndrome. We propose to group these mechanistic etiologies of renal injury as clonal monocytosis of renal significance and provide guidance on their diagnosis and management.

Circulating monocytes decrease significantly following disease-directed therapy and may reflect disease expansion in Langerhans Cell Histiocytosis.

We aimed to examine the association between relative monocytosis and the recurrence of pulmonary Langerhans Cell Histiocytosis. Clinical, laboratory, radiographic and treatment data for 86 patients with a histopathological diagnosis of Langerhans Cell Histiocytosis over a 20-year duration. Parameters such as biological sex, age at diagnosis, time to diagnosis, molecular diagnostic data and imaging were collected. Treatment responses were assessed predominantly through radiography, with RECIST 1.1 criteria applied to MRI or CT scans and PERCIST utilized for serial PET imaging. Investigators also assessed peripheral blood absolute monocyte count at various time points, including initial diagnosis and the most recently available value. While peripheral blood absolute monocyte count between the earliest assessed timepoint and latest value did not differ, the mean value on progression (0.94K/µL), however, was significantly higher than that following re-institution of therapy (0.31, p = 0.000794. Our observation of relative monocytosis on LCH disease progression may be related to an increase in circulating LCH on disease progression or from increased monocyte production for later differentiation into mature dendritic cells that participate in MHC Class 1 upregulation. This trend is especially evident in pulmonary LCH which is incited by tissue trauma and irritation by environmental factors. The phenomena observed in our study parallel other non-LCH cohorts, specifically in published findings from our own group in patients with Rosai Dorfman and Erdheim Chester Disease. To further elucidate the molecular underpinnings of LCH and explore the etiology of this monocyte trend, expanded integrated genomic-transcriptomic sequencing analyses to evaluate the molecular character of LCH and ultimately clarify the origin of this monocyte trend are in progress. These studies are poised to offer invaluable insight to the molecular mechanisms underlying LCH, specifically as they pertain to monocyte signaling and differentiation.

Absolute counts of leukocyte subsets in peripheral blood in pregnancies complicated by preterm prelabour rupture of membranes

Background This study aimed to assess variations in the absolute counts of various leukocyte subsets in the peripheral blood of women with pregnancies affected by preterm prelabour rupture of membranes (PPROM), in relation to the presence of intra-amniotic inflammation (IAI). Methods The study included fifty-two women with singleton pregnancies experiencing PPROM. Absolute counts of different leukocyte subpopulations, such as granulocytes, monocytes, lymphocytes, T cells and their subsets, B cells and their subsets, and NK cells and their subsets, were measured in maternal peripheral blood samples using multicolour flow cytometry. IAI was identified by elevated concentrations of interleukin 6 (IL-6) in the amniotic fluid, which was collected through transabdominal amniocentesis. Results Women with IAI exhibited higher absolute counts of leukocytes (p = 0.003), granulocytes (p = 0.008), and monocytes (p = 0.009). However, the presence of IAI did not significantly affect the absolute counts of lymphocytes or their subpopulations. Conclusions The study found that IAI is associated with changes in the absolute counts of leukocytes from the innate immunity compartment in the peripheral blood of women with pregnancies complicated by PPROM. Conversely, it does not significantly alter the counts of cells from the adaptive immune system. The changes observed may reflect the natural, temporal, and localised characteristics of IAI.

Autopsy findings from patients diagnosed with COVID-19 demonstrate unique morphological patterns in bone marrow and lymph node

AimsThe identification of haemophagocytosis in bone marrow (BM) is recurrently identified in patients with severe COVID-19. These initial COVID-19 autopsy studies have afforded valuable insight into the pathophysiology of this...

Blood absolute monocyte count trends in preterm infants with suspected necrotizing enterocolitis: an adjunct tool for diagnosis?

We investigated the trends of blood absolute monocyte count (AMC) over 72 h after suspecting necrotizing enterocolitis (NEC). A single center, retrospective study, the AMC was plotted over 72 h after NEC evaluation. Receiver operating characteristic (ROC) curve analysis assessed change in AMC to identify absence of NEC and different NEC stages. In 130 infants, the AMC decreased in patients with NEC stage 2 or 3. Stages 2 and 3 NEC experienced a drop in AMC compared to an increase in no NEC, possible NEC, or positive culture (p < 0.05). AMC increase 24% or less can differentiate NEC stage 2/3 from possible NEC with an area under the curve (AUC) of 0.78. While decrease of more than 32% can differentiate stage 2/3 vs. possible or no NEC with AUC of 0.71. A decrease in AMC can be an adjunct biomarker to confirm the diagnosis of NEC.

ROLE OF HAEMATOLOGY BIOMARKERS IN URINARY BLADDER AND RENAL CELL CANCER PATIENTS TREATED WITH IMMUNE-ONCOLOGICAL DRUGS

Background: Urinary bladder (UB) and Renal Cell Cancer (RCC) are common in men than women with poor outcome. The novel immunotherapy drugs like Immune Check Point Inhibitors (ICIs) are effective but expensive. However, a cost-effective and reliable biomarker to predict response and clinical outcomes is lacking. Objective: To study the association of pre-treatment haematological parameters with clinical outcome in urinary bladder and renal cell cancer patients treated with ICIs. Method: In a retrospective study, we included 52 patients with urinary bladder and RCC treated with ICIs from Jan 2008 to Dec 2019. Clinical evaluation and laboratory investigations were performed as a part of standard protocol. CBC parameters such as WBC, TLC, DLC, Hb, Platelet, Neutrophil:Lymplocyte Ratio(NLR), Platelet:Lymphocyte Ratio (PLR), Lymphocyte:Monocyte Ratio(LMR) were studied at the time of TMC enrolment(first) and before the start (pre-treatment) of the ICIs therapy(io). Results: Amongst the CBC parameters, WBC count, when categorized based on cut off from ROC at the time of TMC enrolment(first) and the pre-treatment of the ICIs therapy(io) were found to be significantly associated with progression of disease with p- value 0.012 with Hazard Ratio (HR) - 2.52 (95% C.I. - 1.2-5.31) &amp; p- value 0.060 with Hazard Ratio (HR) – 1.99 (95% C.I. – 0.96-4.12) respectively. The ROC - based cut off for WBC at the time of TMC enrolment(first) and the pre-treatment of the ICIs therapy(io) were found to be 7.16 X10e3/µL (AUC of 72%) with 71% sensitivity and 72% specificity and 6.48 X10e3/µL (AUC of 74%) with 67% sensitivity and 72% specificity respectively to predict progressed cases with respect to non-progressed cases. Along with WBC, the pre-treatment Absolute Neutrophil Count (ANC) (&gt;3.67)&amp; Absolute Monocyte count (AMC)(&gt;0.42) pre-treatment of the ICIs therapy(io)) showed a significance with Hazard Ratio (HR) – 3.09(95% C.I.– 1.26-7.6) with p-value 0.010, Hazard Ratio (HR) – 3.48(95% C.I. - 1.6-7.57)and p-value &lt;0.001 respectively. The ROC- based cut off for ANC at the pre-treatment of the ICIs therapy(io) were found to be 3.67 X10e3/µL (AUC of 68.4%) with 82.4% sensitivity and 50% specificity. Similarly The ROC- based cut off for AEC at the time of TMC enrolment(first) and AMC at the pre- treatment of the ICIs therapy(io) were found to be 0.22 X10e3/µL (AUC of 69.6%) with 55.9% sensitivity and 82.3% specificity and 0.42 X10e3/µL (AUC of 74.7%) with 72.7% sensitivity and 72.2% specificity respectively to predict progressed cases compared to non-progressed cases. Of 52 patients, 34 (65.4%) had progression. The median (m) PFS was 8.67 months (95% CI 2.26 - 15.09).The one year PFS rate was 46.5 (95% CI 31.2 -60.5). The mPFS in WBC &lt;=7.16 was 26.48 months (95% CI 0 - 53.08) higher than the mPFS of 5.75 (95% CI 0.21 - 11.29) in WBC &gt;7.16 with P value 0.012 at the time of TMC enrolment. Similarly, the mPFS in WBC pre- treatment of the ICIs therapy(io))&lt;=6.48 was13.11 months (95% CI 0 – 28.95) higher than the mPFS of 6.18 (95% CI 2.67-9.68) in WBC &gt;6.48 with P value 0.060.Along with WBC, the mPFS in ANC at the pre- treatment of the ICIs therapy(io)&lt;=3.67 was 27.4(95% CI 0-55.21) higher than the mPFS of 6.18(95% CI 1.47-10.88)in ANC &gt;3.67 with p value 0.010. The mPFS in AMC at the pre-treatment of the ICIs therapy(io)&lt; =0.415 was 27.4 (95% CI 9.41-45.39) higher than the mPFS of 3.91 (95% CI 0.06-7.76) in AMC &gt;0.415with p- value &lt;0.001.We observed mPFS in immunotherapy cycles &gt;=6 to be 15.9 (95% CI 6.98-24.82) was higher than the mPFS of 2.23 (95% CI 0.99-3.481) in immunotherapy cycles&lt;6 with p value 0.025. The patients were followed for a period of 40.35 months (95% CI 26.98 - 53.71). Of 52 patients, 32(61.5%) patients deceased with median OS of 18.46 months (95% CI 10.12 - 26.80) and the one year OS rate was 57.6 (95% CI 41.6 - 70.6). Conclusion: Simple, routinely available and cost effective WBC (TLC), Absolute Neutrophil Count (ANC) ,Absolute Monocyte Count (AMC) and Absolute Eosinophil Count (AEC) from CBC test has a great potential to be used as a biomarker to predict response and clinical outcomes in patients with urinary bladder cancer and RCC patients treated with ICIs.

Effects of Oral Nutritional Supplement with β-Hydroxy-β-methylbutyrate (HMB) on Biochemical and Hematological Indices in Community-Dwelling Older Adults at Risk of Malnutrition: Findings from the SHIELD Study.

Malnutrition may result in abnormal biochemical and hematological indices. This planned prespecified analysis investigated the effects of a specialized oral nutritional supplement (ONS) on biochemical and hematological indices in community-dwelling older adults at risk of malnutrition. In the Strengthening Health in ELDerly through nutrition (SHIELD) study, 811 older adults aged 65 years and above took part in this randomized, double-blind, placebo-controlled, multi-center study. Participants were randomly allocated to either a complete and balanced specialized ONS (each serving provides 262 kcal, 10.5 g protein, 7.75 µg vitamin D3, and 0.74 g calcium β-hydroxy-β-methylbutyrate) and dietary counselling (intervention group) or a placebo and dietary counselling (placebo group). Both groups consumed study products twice a day for 180 days. Data were collected at baseline, day 90, and day 180. Blood analysis results at follow-up visits were analyzed using repeated measures analysis of covariance with adjustments for confounders. Overall, when compared with the placebo group, the intervention group showed significantly greater urea (6.0 mmol/L vs. 5.4 mmol/L, p < 0.001), urea to creatinine ratio (4.39 vs. 4.26, p < 0.001), prealbumin (24.9 mg/dL vs. 24.0 mg/dL, p < 0.001), vitamin B12 (480.0 pmol/L vs. 420.1 pmol/L, p < 0.001), and globulin levels (26.8 g/L vs. 26.5 g/L, p = 0.032). The intervention group also had a significantly higher absolute reticulocyte count (62.0 × 103/µL vs. 58.2 × 103/µL, overall p < 0.001) and mean platelet volume (10.0 fL vs. 9.9 fL, overall p = 0.003). Furthermore, significant improvements were seen in total protein at day 90 (71.7 g/L vs. 71.1 g/L, p = 0.017) and in absolute monocyte count at day 90 (0.50 × 103/µL vs. 0.47 × 103/µL, p = 0.009) in the intervention group. In conclusion, daily consumption of a specialized ONS for six months led to significant improvements in biochemical and hematological indices in community-dwelling older adults at risk of malnutrition.

Differential decline of SARS-CoV-2-specific antibody levels, innate and adaptive immune cells, and shift of Th1/inflammatory to Th2 serum cytokine levels long after first COVID-19.

SARS-CoV-2 has triggered a pandemic and contributes to long-lasting morbidity. Several studies have investigated immediate cellular and humoral immune responses during acute infection. However, little is known about long-term effects of COVID-19 on the immune system. We performed a longitudinal investigation of cellular and humoral immune parameters in 106 non-vaccinated subjects ten weeks (10 w) and ten months (10 m) after their first SARS-CoV-2 infection. Peripheral blood immune cells were analyzed by multiparametric flow cytometry, serum cytokines were examined by multiplex technology. Antibodies specific for the Spike protein (S), the receptor-binding domain (RBD) and the nucleocapsid protein (NC) were determined. All parameters measured 10 w and 10 m after infection were compared with those of a matched, noninfected control group (n = 98). Whole blood flow cytometric analyses revealed that 10 m after COVID-19, convalescent patients compared to controls had reduced absolute granulocyte, monocyte, and lymphocyte counts, involving T, B, and NK cells, in particular CD3+CD45RA+CD62L+CD31+ recent thymic emigrant T cells and non-class-switched CD19+IgD+CD27+ memory B cells. Cellular changes were associated with a reversal from Th1- to Th2-dominated serum cytokine patterns. Strong declines of NC- and S-specific antibody levels were associated with younger age (by 10.3 years, p < .01) and fewer CD3-CD56+ NK and CD19+CD27+ B memory cells. Changes of T-cell subsets at 10 m such as normalization of effector and Treg numbers, decline of RTE, and increase of central memory T cell numbers were independent of antibody decline pattern. COVID-19 causes long-term reduction of innate and adaptive immune cells which is associated with a Th2 serum cytokine profile. This may provide an immunological mechanism for long-term sequelae after COVID-19.

Baseline monocyte count predicts symptom improvement during intravenous ketamine therapy in treatment-resistant depression: a single-arm open-label observational study.

Neuroinflammatory processes in depression are associated with treatment resistance to conventional antidepressants. Ketamine is an effective new therapeutic option for treatment-resistant depression (TRD). Its well-established immunomodulatory properties are hypothesized to mediate its antidepressant effect. In this context, higher levels of inflammation may predict a better treatment response. However, conclusive evidence for this hypothesis is lacking. We thus investigated whether standard peripheral inflammatory cell markers and C-reactive protein (CRP) levels could predict symptom improvement during intravenous ketamine therapy in TRD patients. 27 participants with TRD were treated with six weight-adjusted intravenous ketamine infusions (0.5 mg/kg bodyweight) over three weeks. Baseline assessments included CRP, absolute monocyte count (AMC), and absolute neutrophil count (ANC). Depression severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline (D1), after the first (D3) and before the last ketamine infusion (D18). Raters were blinded for the baseline laboratory assessments. 13 participants responded to ketamine treatment, and 8 participants partially responded. Baseline AMC showed a strong negative correlation with MADRS change at D3 (r=-0.57, p=0.002) and at D18 (r =-0.48, p=0.010), indicating that a high baseline AMC was associated with greater symptom improvement. A generalized linear model confirmed the association of baseline AMC with symptom improvement during ketamine treatment when additionally accounting for age, sex, and body mass index. Specifically, baseline AMC demonstrated predictive value to discriminate responders and partial responders from non-responders, but lacked discriminative ability between partial responders and responders. Baseline ANC correlated with the MADRS changes at D3 (r=-0.39, p=0.046), while CRP values did not correlate at all. Our prospective single-arm open-label observational study demonstrated that baseline AMC reliably predicted symptom improvement during intravenous ketamine treatment in TRD patients. AMC could therefore serve as a simple and easily accessible marker for symptom improvement during ketamine therapy in daily clinical practice. Future studies with larger sample sizes and a more detailed longitudinal assessment of AMC subtypes are needed to better understand the specific relationship between monocytes and the neuromodulatory effects of ketamine.

Clinical characteristics and prognostic marker for hospitalization in children with influenza infection in an emergency setting

BackgroundInfluenza is a main cause of illnesses during seasonal outbreaks. Identifying children with influenza who may need hospitalization may lead to better influenza outcomes.ObjectiveTo identify factors associated with the severity of influenza infection, specifically among children who were admitted to the hospital after being diagnosed with influenza at the emergency department.MethodsA retrospective cohort study was conducted among pediatric patients (age < 18 years) with a positive influenza rapid test who visited the emergency department at Srinagarind hospital between January2015-December2019. The dependent variable was hospital admission, while the independent variables included clinical parameters, laboratory results, and emergency severity index(ESI). The association between these variables and hospital admission was analyzed.ResultsThere were 542 cases of influenza included in the study. The mean age was 7.50 ± 4.52 years. Males accounted for 52.4% of the cases. A total of 190(35.05%) patients, needed hospitalization. Patients with pneumonia, those who required hospitalization or were admitted to the critical care unit, consistently exhibited an elevated absolute monocyte count and a reduced lymphocyte-to-monocyte ratio (LMR). Various factors contribute to an increased risk for hospitalization, including ESI level 1–2, co-morbidity in patients, age < 1 year old, and an LMR below 2.ConclusionsESI level 1–2 and co-morbidity in patients represent significant risk factors that contribute to higher hospitalization admissions. A LMR below 2 can be used as a prognostic marker for hospitalization in children with influenza infection.