Lymphocyte Count Research Articles

Real world experience with cladribine tablets in the management of relapsing multiple sclerosis in Qatar

ObjectivesTo study the 30-month safety and effectiveness of Cladribine tablets (CladT) in relapsing multiple sclerosis (RMS) months in a real-world setting. MethodsRetrospective single-centre observational study in Qatar (January 2018–Feb 2023). Clinical and MRI data, lymphocyte counts and adverse events (AE) were recorded for patients with RMS who received at least one course of CladT. ResultsForty-six patients were included (mean follow-up 22 months); 34 (74%) were female, 22 (48%) were disease-modifying therapy (DMT) naïve, 16 (35%) had switched from platform DMT and 8 (17%) from high efficacy (HE) DMD. Mean age was 26.7±7.2y, mean disease duration was 7.2±6.0y. Common reasons for treatment with CladT were MS activity (91%), pregnancy planning (17%), AE (20%), compliance (9%). 44/46 ( 96%) received the year 2 course of CladT. Annualised relapse rate (ARR) fell from 1.02 (baseline) to 0.1, 0, 0.1, 0.1 and 0.1 for years 1–5 post-treatment, respectively; 87.5–100% were free of relapses at these times, vs. 21% at baseline. There were no relapses in year 2; 78%, 100%, 84%, 80% and 100%, respectively, were free of GD+ MRI lesions at years 1–5, vs. 31% at baseline. Most clinical AE were mild (1 moderate, no severe AE); 12 contracted Covid-19 (no hospitalisations). Grade 3 lymphopenia occurred in 5 patients. ConclusionsCladT appeared to be effective and safe in our retrospective study, irrespective of prior treatments, consistent with other real world data that support the early use of CladT in the management of RRMS.

Reevaluation of prognostic and severity indicators for COVID-19 patients in the emergency department.

This study aimed to re-evaluate whether the scoring systems, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were effective in predicting prognosis and severity of COVID-19 patients in the emergency department (ED). COVID-19 patients enrolled in this retrospective study divided into the death (DEA) and survival (SUR) groups, the severe/critical (SC) and non-severe/critical (non-SC) groups. The Acute Physiology and Chronic Health Evaluation (APACHE) II, Sequential Organ Failure Assessment (SOFA), National Early Warning Score (NEWS) and CCEDRRN COVID-19 Mortality Score were calculated. The neutrophil, lymphocyte and platelet counts were extracted from the first routine blood examination, and NLR and PLR were calculated accordingly. Receiver Operating Characteristic (ROC) curve and logistic regression were performed. All the scoring systems, as well as NLR and PLR, significantly increased in both the DEA and SC groups. The ROC curve showed that the CCEDRRN COVID-19 Mortality Score had the highest predictive value for mortality and severity (AUC 0.779, 0.850, respectively), which outperformed the APACHE II, SOFA and NEWS. NLR presented better predictive ability for severity (AUC 0.741) than death (AUC 0.702). The APACHE II, NEWS and CCEDRRN COVID-19 Mortality Score were positively correlated with both prognosis and severity, whereas NLR only with severity. The NEWS and CCEDRRN COVID-19 Mortality Score were reconfirmed for early and rapid predicting the poor prognosis and severity of COVID-19 patients in ED, especially the CCEDRRN COVID-19 Mortality Score with the highest discrimination capacity, and NLR was more appropriate for predicting the severity.

Evaluation of Treatments with Radiotherapy Alone and Radiotherapy Plus Chemo-immunotherapy in Patients with Primary Liver Cancer based on Blood Biomarkers.

It is critical to assess primary liver cancer patients likely to benefit from radiotherapy (RT) or RT plus chemo-immunotherapy. Many potential peripheral biomarkers from blood samples have been proposed for clinical application. Therefore, the aim of this study was to evaluate treatments with radiotherapy alone and radiotherapy plus chemo-immunotherapy in patients with unresectable primary liver cancer based on blood biomarkers. From January, 2017, to February, 2022, 63 unresectable primary liver cancer patients receiving radiotherapy alone (RT, n = 21) or radiotherapy plus chemo-immunotherapy (RT plus C/IT, n = 42) were included in this study. We compared the clinical outcomes and adverse effects of these two groups. Also, distant metastasis-free survival (DMFS), overall survival (OS), and progress- free survival (PFS) were retrospectively analyzed. Finally, univariable and multivariable Cox analyses were used to explore the prognostic role of blood biochemical biomarkers. In this study, 1, 2, and 3 years of OS after RT treatment were 63.9%, 27.0%, and 13.5%, and after RT plus C/IT were 68.2%, 37.0%, and 24.7%, respectively (p = 0.617). Compared with baseline, white blood cells (WBC) and lymphocytes were significantly decreased after RT (p = 0.002 and p = 0.001, respectively) or RT plus C/IT therapy (p = 0.135 and p<0.001, respectively). In multivariable Cox regression analyses, higher lymphocyte counts before RT (pre-Lymphocyte) were associated with better OS and PFS (HR=0.439, p = 0.023; HR=0.539, p = 0.053; respectively), and higher lymphocyte counts before RT (pre- Platelets) were a poor prognostic factor associated with DMFS (HR=1.013, p = 0.040). Importantly, OS and PFS were significantly better for patients (pre-Lymphocyte ≥1.10 x 109/L) (p = 0.006; p = 0.066, respectively). The DMFS was significantly better for patients (pre-platelets < 233.5 ×109/L) (p<0.001). Our evaluation of blood biomarkers before and after radiotherapy or plus chem-immunotherapy for primary liver cancer revealed a potential marker for clinics to decide on precise treatment strategies.

Analysis of Concentrations of Monomethyl Fumarate in Patients with Multiple Sclerosis: Result from Routine Health Care

Dimethyl fumarate is used to treat patients with relapsing-remitting multiple sclerosis. After ingestion, it is rapidly hydrolyzed to the active primary metabolite monomethyl fumarate. The main objective of our study was to analyze serum concentrations of monomethyl fumarate during routine health care in patients with multiple sclerosis treated with a fixed dose of dimethyl fumarate. In the pilot cross-sectional study, data from 42 patients treated with dimethyl fumarate at a dose of 240 mg twice daily were collected. Concentrations of the active metabolite monomethyl fumarate were determined at 1-8 h (median, 3 h) or 10-14 h (median, 13 h) after taking the dose. The relationship between monomethyl fumarate concentrations and absolute lymphocyte count was evaluated. Concentrations of monomethyl fumarate ranged from 2.5-3177.9 μg/L, with most concentrations being undetectable approximately 10 hours after administration. In the 1-8 h (median, 3 h) post-dose subgroup, the concentration/dose ratio ranged widely from 0.04-6.62. The median concentration of monomethyl fumarate in the group with the absolute lymphocyte count <0.8 x 10^9/l was more than four times higher than in the group with the absolute lymphocyte count ≥0.8 x 10^9/l (median 440.1 μg/L versus 98.4 μg/L). The wide interindividual variability in monomethyl fumarate pharmacokinetics could contribute to the differential response to dimethyl fumarate in multiple sclerosis patients. A nonsignificant but noticeable trend was observed in the relationship of higher serum monomethyl fumarate concentrations to absolute lymphocyte counts.

Prognostic value of the cholesterol-dependent nutritional prognostic index in patients receiving adjuvant chemotherapy after radical esophageal cancer treatment.

Esophageal cancer is the 6th most common cancer in terms of incidence and the 4th most common cause of mortality in China. Given the limited survival outcomes observed in patients with locally advanced disease managed exclusively with surgical intervention, postoperative treatment is critically important. This study sought to assess the prognostic value of total cholesterol (TC) levels and the prognostic nutritional index (PNI) in patients undergoing postoperative chemotherapy for esophageal cancer. A total of 101 patients who underwent postoesophagectomy chemotherapy were included in this retrospective analysis. PNI values for prechemotherapy were calculated for each patient [PNI = albumin + 5 × lymphocyte count] and TC. The optimal cutoff values for these indices were calculated from the receiver operating characteristic (ROC) curve. Patients were stratified into three groups on the basis of their PNI and TC levels. A novel nutritional prognostic index, termed the cholesterol-dependent nutritional prognostic index (CPNI), was developed on the basis of the PNI and TC. Univariate and multivariate Cox analyses were employed to determine the associations between each indicator and clinical outcomes. The prechemotherapy PNI, TC level, and TNM stage became independent risk factors for OS (p < 0.05). Patients in the high PNI-high TC group had significantly improved DFS and OS compared with those in the low PNI-low TC group (p < 0.001) and had a lower early recurrence rate (P = 0.008). In contrast, patients with a high CPNI had a higher mortality rate. The prechemotherapy PNI combined with TC is an accurate and useful predictor of patient prognosis.

Prognostic significance of early nk cell recovery in pediatric t-cell replete allogeneic hematopoietic stem cell transplantation.

Early immune reconstitution, particularly of natural killer (NK) cells with strong graft-versus-leukemia effects, is crucial for the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective study examined 122 pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who underwent T-cell replete allo-HSCT at the Children's Hospital of Soochow University from 2019 to 2021. Peripheral blood lymphocyte counts on days 30 and 60 post-transplant were analyzed, focusing on NK cell recovery and its impact on overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), relapse, graft-versus-host disease, and CMV reactivation. Patients were categorized into high and low NK cell groups by the median NK cell counts at day 30 (NK30) and day 60 (NK60) after HSCT. Patients with high NK30 and NK60 levels had significantly better 3-year OS rates compared to their respective low NK count groups (86.8% ± 4.7% versus 67.6% ± 7.0%, P = 0.046; 95.7% ± 3.0% versus 63.7% ± 8.7%, P < 0.001, respectively). NK60 was found to be an independent predictor for 3-year OS and RFS in multivariate analysis. Early NK reconstitution was also related to lower NRM rates. However, this correlation disappeared in patients with ALL and those undergoing haploidentical transplantation. In addition, A positive association between early T cell and NK cell reconstitution was found in our study. Higher NK cell counts on days 60 can predict superior OS, RFS and lower NRM in pediatric AML allo-HSCT patients.

Association of the Preoperative Controlling Nutritional Status (CONUT) Score with Clinicopathological Characteristics in Patients with Papillary Thyroid Carcinoma.

The Controlling Nutritional Status (CONUT) score is an immunonutritional test tool based on serum albumin, total cholesterol, and lymphocyte counts. It has been studied as a simple prognostic predictor for various carcinomas. This study aimed to investigate the association between preoperative CONUT scores and the clinicopathological characteristics in papillary thyroid carcinoma (PTC) patients. This study included 2,403 PTC patients who underwent total thyroidectomy between 2012 and 2016 at a single tertiary medical center. The CONUT scores were calculated based on preoperative blood tests. The clinicopathological characteristics were retrospectively reviewed. The patients were categorized by the CONUT score (relatively low, 0-2; relatively high, 3-5). Among the 2,997 PTC patients who underwent total thyroidectomy at Pusan National University Hospital between 2012 and 2016, those without preoperative blood test were excluded (n=149). Finally 2,403 patients were analyzed after excluding 439 patients taking lipid-lowering drugs and six patients without available T stage data after surgery. Based on the CONUT score, the relatively high score group had a lower body mass index (23.7±3.3 kg/m2 vs. 21.9±2.9 kg/m2, P<0.001), more advanced T stage (T stage 3/4, 5.9% vs. 11.4%, P=0.045), and higher extrathyroidal extension (2.1% vs. 7.6%, P=0.005). Patients included in this large, single-center study all had a preoperative CONUT score of 0-5, but this study demonstrated that higher preoperative CONUT scores were significantly associated with advanced T stage and extrathyroidal extension. The CONUT score, which can be easily used in clinical practice, is thought to be helpful in predicting the aggressiveness of PTC.

Bilateral Sialadenitis as an Uncommon Initial Manifestation of Infectious Mononucleosis: A Case Report.

Sialadenitis has rarely been reported in patients with infectious mononucleosis (IM). Our patient was a 22-year-old man who presented with bilateral swelling of the parotid and submandibular glands, a fever, malaise, and splenomegaly. Laboratory tests revealed an increased percentage of atypical lymphocytes in the leukocyte fraction. Serological testing for antibodies against Epstein-Barr virus (EBV) revealed an acute infection pattern. The patient was diagnosed with sialadenitis associated with IM caused by EBV infection. With symptomatic treatment, the salivary gland swelling completely resolved within a week. This case suggests that EBV-induced IM should be included in the differential diagnosis of diffuse sialadenitis with elevated atypical lymphocyte counts.

Factor analysis for assessing the etiopathogenesis of facial boils in military personnel

Background: Boils are the most prevalent non-odontogenic inflammatory condition of the head and neck. The treatment of skin and subcutaneous tissue inflammations in the Russian Armed Forces (RAF) is a pressing issue. We were unable to find any data on the etiopathogenesis of facial boils in otherwise healthy RAF members, as well as the factors that contribute to the development of this condition. Aim: To examine the causes of facial boils in military personnel, the factors that contribute to their development, and the association between them using factor analysis. Materials and Methods: Between 2019 and 2021, 53 patients aged 18 to 25 years were examined and treated for abscess-forming face boils. Of these, 38 (72%) were conscripts and 15 (28%) were contract servicemen. At admission, clinical examinations (complaints, history taking, status localis, facial skin type and status) and laboratory tests (complete blood count, blood chemistry, immunoassay, and bacterial tests, including the composition and antibiotic sensitivity of microflora) were performed. The control group included 30 otherwise healthy individuals aged 18 to 25 years. A mathematical model for predicting maxillofacial boil development in military personnel was generated using binomial regression analysis (logistic regression). The following variables were considered: age, length of service, season of disease development, serum glucose level, lymphocyte count, white blood cell count, CD3+, CD4+, CD8+, IgA, IgG, IgM, immunosuppressive regulatory T cells (CD4+CD25brightCD45+; % of all T helper cells), skin type, and microbial composition of maxillofacial skin. Results: The mathematical model revealed that oily skin in combination with specific blood lymphocyte (20.30±1.03%) and IgG parameters (10.15±0.70%) increases the risk of maxillofacial boils in military personnel. Conclusion: The study revealed the cumulative effect of general and local factors on the development and progression of facial boils in military personnel, allowing for more accurate prevention and treatment strategies.

Relative Factor Analysis of Postoperative Complications in Infants Below 1 Year Undergoing Repair of Ventricular Septal Defect Combined with Other Procedures through a Right Axillary Incision

Background: Compared to the traditional surgical repair of isolated ventricular septal defects, the proportion of complex congenital heart diseases has been increasing due to advancements in diagnostic capabilities and surgical techniques. Concomitant surgeries to correct multiple congenital heart diseases have become the preferred choice. Therefore, the evaluation of the safety of the combined correction of ventricular septal defects with other cardiac anomalies in young children through a right axillary incision and the analysis of related factors of perioperative complications needs to be investigated. Methods: A retrospective study was conducted on a single-center patient sample from January 2018 to December 2022 to compare outcomes between infants undergoing isolated ventricular septal defect (VSD) repair via a right axillary thoracotomy (control group) and those undergoing VSD repair combined with other cardiac procedures (experimental group). Results: A total of 397 eligible infants were included. After baseline data were matched using propensity score matching, the experimental group (n = 181) and the control group (n = 107) showed no significant differences in intraoperative blood loss, postoperative total drainage, length of hospital stay, duration of ICU monitoring, Vasoactive-Inotropic Score (VIS), pre-discharge left ventricular ejection fraction, fractional shortening (FS), postoperative severe pulmonary infection, reoperation, mortality, postoperative atrioventricular block, chylothorax, cardiac arrest, pericardial effusion, pneumothorax, pulmonary atelectasis, tricuspid regurgitation, myocardial injury, abdominal effusion, and metabolic acidosis. However, the control group had shorter surgical time [28.00 (90.00, 196.00) vs. 140.00 (95.00, 658.00) min, p &lt; 0.05], shorter cardiopulmonary bypass time [58.00 (24.00, 114.00) vs. 66.00 (33.00, 422.00) min, p &lt; 0.05], shorter aortic cross-clamp time [32.00 (17.00, 62.00) vs. 37.00 (15.00, 142.00) min, p &lt; 0.05], and shorter postoperative mechanical ventilation time [22.00 (0, 99.00) vs. 23.00 (3.00, 193.00) h, p &lt; 0.05]. The rate of abdominal effusion was lower in the experimental group than in the control group (p = 0.044). In the analysis of postoperative complication-related factors, the preoperative grade of tricuspid regurgitation, postoperative mechanical ventilation time, and VIS were positively correlated with abdominal effusion and satisfied the variable (p &lt; 0.05) in each of three established models. In the single-factor analysis, both VIS and preoperative lymphocyte count were (p &lt; 0.1) related to pericardial effusion; however, in the multi-factor analysis, only VIS met the threshold (p &lt; 0.05). Gender, height, and VIS were each associated with pleural effusion (p &lt; 0.05). Conclusion: The combination of ventricular septal defect repair with other cardiac procedures via a right axillary thoracotomy did not significantly differ from isolated VSD repair in terms of postoperative complications, monitoring, and length of hospital stay. However, increased surgical complexity was associated with longer surgical and mechanical ventilation times. Factors such as tricuspid regurgitation severity, duration of postoperative mechanical ventilation, and VIS were identified as relative factors for postoperative effusion. Additionally, the risk of postoperative pericardial effusion increased with higher VIS, while gender, height, and VIS were identified as relative factors for postoperative chylothorax.

The Roles of Vitamin D Levels, Gla-Rich Protein (GRP) and Matrix Gla Protein (MGP), and Inflammatory Markers in Predicting Mortality in Intensive Care Patients: A New Biomarker Link?

Objectives: Identifying reliable biomarkers to predict mortality in critically ill patients is crucial for optimizing management in intensive care units (ICUs). Inflammatory and metabolic markers are increasingly recognized for their prognostic value. This study aims to evaluate the association of various inflammatory and metabolic markers with ICU mortality. Methods: This prospective observational study was conducted from January 2023 to January 2024 in the City Hospital’s ICU. A total of 160 critically ill patients were enrolled. Laboratory parameters, including white blood cell (WBC) count, red cell distribution width (RDW), platelet count, neutrophil count, mean platelet volume (MPV), monocyte count, lymphocyte count, procalcitonin (PCT), C-reactive protein (CRP), calcium (Ca++), and vitamin D levels, were analyzed. Additionally, ratios such as the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory index (SII), and pan-immune-inflammation value (PIV) were calculated. Plasma levels of Gla-rich protein (GRP) and dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) were measured using ELISA. Results: The mean age of the patients included in the study was 60.5 ± 15.8 years. Cardiovascular disease was present in 72 patients (45%), respiratory system disease in 58 (36%), and chronic kidney disease (CKD) in 38 (24%). Additionally, 61 patients (38%) had diabetes, and 68 (42%) had hypertension. Inflammatory markers, including PLR, NLR, and PIV, were all significantly higher in non-survivors, while calcium and vitamin D levels were lower (p &lt; 0.05). Higher WBC, RDW, neutrophil count, PLR, NLR, PIV, CRP, procalcitonin, GRP, and dp-ucMGP levels were positively correlated with longer hospital stays and increased mortality. In contrast, platelet and lymphocyte counts were negatively correlated with both outcomes (p &lt; 0.05). Vitamin D levels showed an inverse relationship with both hospital stay and mortality, indicating that lower levels were associated with worse outcomes (p &lt; 0.05). In multiple logistic regression analysis, elevated WBC count (OR = 1.20, p = 0.02), RDW (OR = 1.35, p = 0.01), neutrophil count (OR = 1.25, p = 0.01), MPV (OR = 1.20, p = 0.02), PLR (OR = 1.30, p = 0.01), NLR (OR = 1.40, p = 0.001), PIV (OR = 1.50, p = 0.001), CRP (OR = 1.32, p = 0.01), procalcitonin (OR = 1.45, p = 0.001), GRP (OR = 1.40, p = 0.001), and dp-ucMGP (OR = 1.30, p = 0.001) levels were significantly associated with increased mortality. Conclusions: Inflammatory and metabolic markers, particularly NLR, PLR, PIV, GRP, and dp-ucMGP, are strong predictors of mortality in ICU patients. These markers provide valuable insights for risk stratification and early identification of high-risk patients, potentially guiding more targeted interventions to improve outcomes.

Relation of CXCL10 and CXCR3 Gene Polymorphisms with COVID-19 Severity and its Serum Biochemical Markers

CXCL10 (rs201830102) is a chemokine involved in immune cell recruitment, while its receptor, CXCR3 (rs779120264), mediates immune responses through the activation of T cells. These genes are critical in the immune response to viral infections, including COVID-19. The study aimed to explore the relationship between polymorphisms in the CXCL10 gene and CXCR3 receptor with disease severity in COVID-19 patients. In this cross-sectional analytical study, 100 COVID-19 patients were enrolled after ethical approval, and written informed consent was obtained from each participant. Polymorphisms in CXCL10 and CXCR3 were analyzed by sequencing, while biochemical and hematological parameters were assessed using appropriate methods. Descriptive and inferential statistics were employed to analyze continuous and categorical data. Significant associations were observed between severe COVID-19 cases and elevated levels of serum D-dimer, ferritin, random blood sugar (RBS), neutrophils, and erythrocyte sedimentation rate (ESR), along with reduced hemoglobin levels. Lymphocyte and platelet counts were significantly lower with increased disease severity. The wild genotype of CXCL10 was notably associated with elevated ferritin levels, suggesting that certain gene variants may offer protective effects. However, no significant correlation was found between CXCR3 and CXCL10 polymorphisms and other serum biomarkers. Our study confirmed a significant rise in serum D-dimer, ferritin, RBS, neutrophils, and ESR, along with a reduction in hemoglobin, lymphocyte, and platelet counts in severe COVID-19 cases compared to mild ones. Notably, mutations in the CXCL10 gene were linked to less severe COVID-19 outcomes.

Hematological Changes in Newly Diagnosed Pulmonary Tuberculosis Patients on Standard Anti-TB Treatment Regimen and their Influence on Smear Conversion

Pulmonary tuberculosis (PTB) mortality remains high despite the availability of effective anti-TB therapy. Disease and treatment-associated hematological derangements at diagnosis and during therapy might contribute to this high TB mortality rate. This paper aims to determine hematological changes in newly diagnosed pulmonary tuberculosis patients on standard anti-TB treatment regimen and their influence on smear conversion. The study adopted a longitudinal design in which 55 newly diagnosed HIV negative PTB patients were followed up to the fifth month of anti-TB therapy. Blood samples (5ml) were collected for diagnosis during the second and fifth months and analyzed using automated HumaCount 5D hematology analyzer. Data was analyzed using Kruskal-wallis test with Dunn’s multiple comparisons test in Graph-Pad prism version 6.0. Throughout therapy, there was a statistically significant time-dependent decrease in median total white blood cell counts from 6.82x103/ uL at diagnosis to 5.87x103/ uL at the fifth month (P=0.0358). This decrease in total WBC count was majorly driven by significant decrease in the neutrophil numbers from 4.31x103/ uL at diagnosis to 2.97x103/ uL at the fifth month. The proportion of patients who had anemia at the fifth month of treatment increased compared to the second month post intensive phase. There was also a significant decrease in MCV, MCH and MCHC at the second month compared to diagnosis. Moreover, the median platelet count, MPV, PDW and PCT% decreased from 314x103/ uL, 8.9 fL, 10.4 fL and 0.273 at diagnosis to 232x103/ uL, 10.15 fL, 12.5 fL and 0.235 at the fifth month, respectively. High WBC count, high platelet count, low lymphocyte count and low HGB at the end of month two of therapy were shown to increase the likelihood of sputum non-conversion (OR-2.42 (95% Ci 2.07-2.82)), (OR-1.5 (95% Ci 1.01-2.22)), (OR-1 (95% Ci 1-1)) and (OR-2.58 (95% Ci 1.68-3.95)), respectively (P&lt;0.05). A significant number of PTB patients presented with anemia, thrombocytosis and leukocytosis. The proportion of patients with anemia increased over time. The study recommends screening for hematological abnormalities in patients for tailored patient interventions for better clinical outcomes.

Risk factors for surgical site infection after general surgery in HIV-infected patients: a retrospective study.

As the number of HIV-infected patients increased, the number of patients requiring general surgery has subsequently increased. However, impairment of immune function due to HIV infection increases the risk of postoperative surgical-site infection and significant harm to patient health. This study aimed to examine the risk factors for surgical-site infection after general surgery. The patients' data were from Zunyi fourth hospital medical information system. Machine learning based Boruta algorithm were used for variable screening. Univariable and multivariable logistic regression and restricted cubic spline analysis were performed to examine the relationship between significant variables and surgical-site infection. A total of 125 general surgery postoperative HIV-infected patients participated in the study. Surgical-site pathogen culture identified Escherichia coli, Klebsiella pneumoniae, and mixed bacteria as the three most common pathogens causing Surgical-site infection. Univariable and multivariable logistic regression analysis to adjust for risk factors identified type III surgical incision (OR = 9.92, 95% CI = 1.28-76.75) and elevated preoperative white blood cell (WBC) count (OR = 1.30, 95% CI = 1.12-1.51) as independent risk factors for postoperative surgical-site infection, whereas CD4 + T lymphocyte count greater than 400 cells/µL was identified as a protective factor (OR = 0.23, 95% CI = 0.09-0.60) while. The restricted cubic spline analysis results directly reflected the dose-response relationship between continuous variables and postoperative surgical-site infection. Type III incision and an elevated WBC count pose a higher risk of postoperative surgical-site infection. A CD4 + T lymphocyte counts greater than 400 cells/µL provided a protective effect of lower risk of surgical site infection. Preoperative serum neutrophil percentage, albumin level, red blood cell count, and serum urea level within a specific range were beneficial in reducing the risk of incisional infections. Our research provides a theoretical basis for clinical practice.

Abstract 4119517: Association of Systemic Inflammatory Response Syndrome with Cardiovascular Events after Mitral Transcatheter Edge-to-edge Repair

Background: Systemic inflammatory response syndrome (SIRS) following cardiovascular interventions is associated with adverse events during hospitalization and follow-up. Mitral transcatheter edge-to-edge repair (M-TEER) is increasingly utilized for treatment of mitral regurgitation (MR). Hypothesis: It is unknown whether SIRS following M-TEER may occur and be associated with adverse clinical outcomes. Goals: to investigate the frequency and impact of SIRS following M-TEER on major cardiovascular events (MACE) and MR recurrence. Methods: A total of 158 consecutive patients with severe MR undergoing M-TEER were studied. SIRS was defined by leukocytosis (≥12×10 9 /L) and fever (T≥38 °C) within 48 hours after intervention. Baseline inflammation was measured by absolute neutrophil and lymphocyte counts and neutrophil: lymphocyte ratio (NLR). The primary endpoint of MACE was the composite of non-fatal myocardial infarction (MI), non-fatal stroke, and all-cause death. Recurrent MR at follow-up was also recorded. Results: The mean patient age was 80.8±8.8 years. 44 (27.9%) developed SIRS. NLR correlated with onset of leukocytosis and fever (p=0.04). During a median follow-up of 12.5±8.2 months, the primary endpoint occurred in 27 (17.1%) patients (6 MI, 5 strokes and 16 deaths). Patients with SIRS more often had severe MR (79.5% vs. 62.7%, p=0.02) and adverse left ventricular (LV) remodeling indicated by lack of reduction in end-diastolic diameter (LVEDD) at follow-up (p=0.12 for SIRS-patients vs. p=0.0012 for non-SIRS patients). After adjustment for pertinent variables, SIRS (HR 3.24, CI 1.13-9.31, p=0.03) was independently associated with MACE. Conclusion: SIRS after M-TEER is a strong independent predictor of MACE. Closer follow-up is warranted as patients with SIRS have more severe MR and unfavorable LV remodeling at follow-up.

Abstract 4136280: Inflammation and Cancer Mortality among CVD Individuals: NHANES-Continuous study

Background: Both cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. While previous research showed a relationship between CVD and cancer incidence, limited evidence is available regarding the relationship between inflammation and cancer mortality in CVD patients. Methods: A prospective cohort study using data from the continuous National Health and Nutrition Examination Survey (NHANES) (1999-2016) merged with Medicare and National Death Index (NDI) mortality data until December 31, 2018. We included CVD individuals with no history of cancer at baseline to investigate the relationship between inflammatory markers, including Neutrophil-to-Lymphocyte ratio (NLR), as the main exposure and cancer mortality as the main outcome. Results: We included 4,089 adult individuals representing 127,809,316 individuals (47% females, 72% non-Hispanic Whites, and 5% Hispanics). The risk factor analysis (Table) using the competing risk modeling showed that while inflammatory markers did not show significant associations with cancer mortality in the overall analysis, upon stratification by race/ethnicity, NH-Blacks showed higher cancer mortality with higher WBC count (aHR 5.61, 95% CI 1.66-18.91, p=0.007) and NLR (aHR 2.97, 95% CI 1.19-7.42, p=0.02), but lower cancer mortality with higher neutrophil (aHR 0.08, 95% CI 0.01-0.60, p=0.02) and lymphocyte (aHR 0.34, 95% CI 0.15-0.80, p=0.02) counts. Notably, our NH-Blacks showed lower neutrophils at baseline than others which could be explained by a phenomenon called “Benign Ethnic Neutropenia -BEN-” that still brings more complexity when interpreting NLR. Conclusions: Our study highlights the close relationship between cardiovascular health, inflammation, and cancer mortality. The findings also suggest that race/ethnicity may play a significant role in the relationship between inflammation and cancer mortality among individuals with CVD. Yet, further research is still needed to underpin the biological pathways influencing this relationship.

Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial.

Pancreatic ductal adenocarcinoma (PDA) is characterized by low cytotoxic lymphocytes, abundant immune-suppressive cells, and resistance to immune checkpoint inhibitors (ICI). Preclinical PDA models showed the HDAC inhibitor entinostat reduced myeloid cell immunosuppression, sensitizing tumors to ICI therapy. This phase II study combined entinostat with nivolumab (PD1 inhibitor) in patients with advanced PDA (NCT03250273). Patients received entinostat 5 mg orally once weekly for 14-day lead-in, followed by entinostat and nivolumab. The primary endpoint was the objective response rate (ORR) by RECIST v1.1. Secondary endpoints included safety, duration of response, progression free-survival and overall survival. Between November 2017 and November 2020, 27 evaluable patients were enrolled. Three showed partial responses (11% ORR, 95% CI, 2.4%-29.2%) with a median response duration of 10.2 months. Median progression-free survival (PFS) and overall survival (OS) were, respectively, 1.89 (95% CI, 1.381-2.301) and 2.729 (95% CI, 1.841-5.622) months. Grade ≥3 treatment-related adverse events occurred in 19 patients (63%), including decreased lymphocyte count, anemia, hypoalbuminemia, and hyponatremia. As exploratory analysis, peripheral and tumor immune profiles changes were assessed using CyTOF, mIHC, and RNA-seq. Entinostat increased dendritic cell activation and maturation. Gene expression analysis revealed an enrichment in inflammatory response pathways with combination treatment. Although the primary endpoint was not met, entinostat and nivolumab showed durable responses in a small subset of PDA patients. Myeloid cell immunomodulation supported the preclinical hypothesis, providing a basis for future combinatorial therapies to enhance clinical benefits in PDA.

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&lt;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.

Bevacizumab as a mitigating factor for the impact of high systemic immune-inflammation index on chemorefractory in advanced epithelial ovarian cancer.

Predicting chemorefractory disease in advanced epithelial ovarian cancer (EOC) remains challenging. This study aimed to identify clinicopathological factors and hemogram data as predictive markers for chemorefractory EOC and to explore potential therapeutic approaches that may mitigate these unfavorable conditions. We conducted a retrospective analysis of patients with advanced EOC treated with chemotherapy. Hemogram data and clinicopathological variables were collected. We employed logistic regression to assess factors associated with chemorefractory EOC and used the Kaplan-Meier method for survival analysis. Among the 191 patients analyzed, suboptimal surgery, lymphocyte count < 1440/mm3, systemic immune-inflammation index (SII) ≥ 2350, and lack of bevacizumab therapy were independently associated with chemorefractory EOC (OR 19.30, 95% CI 7.01-53.12; OR 9.07, 95% CI 2.76-29.82; OR 12.45, 95% CI 3.87-40.07; OR 6.61, 95% CI 2.01-21.78, respectively). Elevated SII was also identified as a risk factor for poor progression-free (PFS) and overall survival (OS). Specifically, patients with high SII who did not receive bevacizumab had a significantly higher probability of chemorefractory EOC and poorer survival outcomes compared to those who received bevacizumab. Our findings suggest that hemogram parameters and clinicopathological factors such as suboptimal surgery, lymphocyte count, SII, and bevacizumab therapy status are predictive markers for chemorefractory disease in advanced EOC. Elevated SII emerged as a predictor for poorer PFS and OS outcomes, particularly in the absence of bevacizumab therapy.

DISP-16. EXPLORING SEX-BASED DIFFERENCES IN RESPONSE TO IMMUNOTHERAPY IN GLIOBLASTOMA: A RETROSPECTIVE REVIEW

Abstract BACKGROUND The prognostic implication of sex is unclear in glioblastoma. A recent preclinical study suggested that T-cell exhaustion in males confers improved response to anti-PD1 therapy (PMID: 37378557). We conducted a retrospective study of patients with newly diagnosed (nGBM) and recurrent (rGBM) glioblastoma enrolled on immunotherapy trials at Dana-Farber Cancer Institute from 2014 to 2022 to determine whether sex influences the response to immunotherapy. METHODS Clinical, molecular, and radiographic data were collected, and their association with progression-free survival (PFS) and overall survival (OS) was evaluated using log-rank. RESULTS We evaluated 299 subjects with nGBM (172 male, 127 female) and 539 with rGBM (329 male, 210 female). In the nGBM cohort, median PFS for males vs females was 9.1 [7.2, 13.8] months vs 8.8 [6.5, 10.1] months (p=0.59) among subjects on immunotherapy trials (N=106), and 6.9 [6.1, 8.0] vs 6.5 [5.8, 8.1] months (p=0.44) in those on non-immunotherapy trials (N=193). Median OS was 18.6 [15.4, 24.0] in males vs 18.8 [15.9, 23.1] months in females (p=0.85) in immunotherapy trials and 15.6 [14.7, 17.3] vs 15.3 [13.1, 16.9] months (p=0.77) in non-immunotherapy trials. There was also no statistically significant difference in OS and PFS between sexes in the rGBM cohort: median PFS was 3.6 [3.0, 4.1] months in males vs 4.1 [3.8, 5.2] months in females and median OS was 8.4 [7.4, 9.6] vs 9.6 [8.2, 12.1] months in immunotherapy trials (N=254); median PFS was 1.8 [1.7, 2.1] vs 1.9 [1.8, 2.4] months and median OS was 8.6 [7.5, 9.6] vs 8.5 [7.3, 9.6] months in non-immunotherapy trials (N=285). CONCLUSION Sex did not have a prognostic impact on survival outcomes, regardless of the treatment modality. The impact of other clinical variables such as corticosteroid use, performance status, lymphocyte counts, and tumor burden will be reported.