Lymphocyte Count Research Articles

Dynamic changes in peripheral blood lymphocyte trajectory predict the clinical outcomes of sepsis

BackgroundSepsis induces profound derangements in the immune system, including lymphopenia, which correlates with immunosuppression and poor prognosis. However, most evaluations of immunosuppression in sepsis patients rely on static, sporadic lymphocyte counts, lacking dynamic modeling over the disease course. This study aimed to apply latent class mixed modeling on longitudinal lymphocyte counts to uncover heterogeneous trajectory phenotypes in sepsis patients and assess their predictive value for clinical outcomes.ResultsFour lymphocyte trajectory phenotypes were identified in the retrospective cohort (n=2,149) and externally validated (n=2,388): high–declining (α, 3.8%), stable–medium (β, 69.3%), high–increasing (γ, 3.2%), and stable–low (δ, 23.8%). The α phenotype exhibited the highest disease severity and mortality (25.9%) compared with other phenotypes in both cohorts. In the prospective cohort (n=1,056), all lymphocyte subset counts differed among phenotypes on admission (P <.001) and were lower in non-survivors (P<.05). Multivariable regression demonstrated that age, Acute Physiology and Chronic Health Evaluation-II score, heart rate, natural killer cell count, infection source, and lymphocyte trajectory phenotype were independent predictors of 28-day mortality. A nomogram combining these variables provided individualized risk estimations.ConclusionsThe lymphocyte trajectories delineated novel dynamic phenotypes associated with divergent sepsis outcomes. Incorporating longitudinal trajectory modeling and lymphocyte subsets may improve prognostic risk assessment and guide the selection of immunotherapies tailored to specific immune phenotypes in sepsis patients.Clinical trial registrationhttps://www.chictr.org.cn/showproj.aspx?proj=18277, identifier ChiCTR-40 ROC-17010750.

Cell Population Data Parameters in Dengue-Is There Any Significance? A Single-Center Study.

To assess the significance of cell population data parameters (CPD) in dengue positive individuals. A retrospective cross-sectional study was conducted at the National Institute of Blood Disease and Bone Marrow Transplantation (NIBD and BMT), Karachi, Pakistan from July 2022 to September 2022 (in a period of 3 months of peak dengue fever outbreak). Dengue fever is a viral infection that is transmitted from mosquitoes to humans. It is more prevalent in tropical and subtropical environments. A total of 389 individuals, who presented with febrile illness at the NIBD clinics, were screened for dengue and malaria with Complete Blood Count (CBC), Dengue nonstructural protein 1 (NS1) antigen test and Malaria Parasite Immunochromatographic test (MP-ICT). Whole blood samples were collected and analyzed for CBC on Sysmex XN hematology analyzers. All 65 CPD and standard CBC parameters were analyzed. Statistical analysis was performed using SPSS version 25.0. Descriptive analysis of all the parameters was performed and a p value < 0.001 was considered significant. Positive and negative correlation was also evaluated within the parameters to assess their significance. Furthermore, cut-off values of CPD parameters were evaluated plotting their receiver operating characteristic (ROC) curves. Out of the 389 febrile patients, 137 were diagnosed as dengue-positive. Descriptive analysis for mean and median values of parameters revealed statistically significant difference for seven parameters (namely WBC, PLT-F, NEUT, LYMP, MONO, HFLC, and LY-WY) in the comparison of the two groups which were then further assessed for positive and negative correlation. Multivariate logistic regression analysis revealed High Fluorescence Lymphocyte Count (HFLC) to be the distinguishing parameter among dengue positive and negative cases. Compared to all the CPD parameters of our data set, the area under curve for lymphocytes cell size and the width of dispersion (LY-WZ) displayed a borderline value of 0.582. Sysmex XN hematology analyzers can provide extensive information about CPD parameters, allowing for the prompt differentiation among febrile illnesses and dengue infection. HFLC and other significant parameters demonstrate promise as rapid, adjunctive diagnostic tools. Further research is needed to validate these findings and optimize the clinical utility of CPD parameters in dengue management.

Hospital malnutrition and stroke: a study of nutritional risk and patient outcomes.

Introduction: Hospital malnutrition is a prevalent issue among stroke patients, with significant impacts on immune function and clinical outcomes. Malnutrition is associated with poor outcomes such as increased complications, prolonged recovery, and higher mortality. This study aims to assess the prevalence of malnutrition using the Malnutrition Screening Tool (MST) and its association with clinical outcomes, including length of stay (LOS), inflammatory markers, and mortality. Methods: A retrospective cohort study was conducted, including 230 stroke patients who were admitted between January 2022 and January 2024. Nutritional status was assessed using the MST, with key outcomes including LOS, Total Lymphocyte Count (TLC), Neutrophil-to-Lymphocyte Ratio (NLR), serum albumin, Prognostic Nutritional Index (PNI), and mortality. Statistical analyses were performed using chi-square tests for categorical variables and t-tests or Mann-Whitney U tests for continuous variables, with a p-value of &lt;0.05 considered statistically significant. Result: The study found that 26.5% of patients had an MST score of 2 or higher, indicating a high risk of malnutrition. Patients with high MST scores had significantly lower TLC (p = 0.017), indicating a weakened immune response. No significant differences were observed in LOS (p = 0.63), mortality (p = 0.404), or other inflammatory markers such as NLR, albumin, and PNI between the high-risk and low-risk groups. Conclusion: Malnutrition is common among stroke patients and is associated with impaired immune function, as evidenced by lower TLC in malnourished patients. Although no significant differences were observed in LOS or mortality, the findings underscore the importance of routine nutritional screening and timely intervention to improve patient outcomes.

COVID-19 Vaccine Response in Pediatric Oncology Patients.

Pediatric oncology and hematopoietic stem cell transplant (HSCT) patients may fail to mount an appropriate immune response to COVID-19 vaccinations. The immunologic response to initial SARS-CoV-2 vaccination was studied in 93 pediatric patients with hematologic malignancy, solid tumors, or post-HSCT. The majority of patients who were not receiving chemotherapy showed a positive humoral and cell-mediated response to COVID-19 vaccination. In contrast, variable responses to vaccination were seen in patients receiving chemotherapy. Patients with a normal lymphocyte count showed higher rates of seroconversion than their lymphocytopenic counterparts. This report details pediatric oncology and HSCT patients' immunologic responses to COVID-19 vaccination during all phases of treatment.

Comparison between patients who have undergone cancer surgery based on MST value: a retrospective study.

Abstract Introduction: Malnutrition is a prevalent concern in oncologic surgery patients, often exacerbated by the effects of cancer and its treatments. Malnutrition is associated with poor clinical outcomes, including higher mortality rates, longer hospital stays, and increased complications. The Malnutrition Screening Tool (MST) is a valuable method for identifying malnutrition risk at hospital admission. This study aims to assess the prevalence of malnutrition using the MST and evaluate its prognostic value in relation to clinical outcomes, such as length of stay (LOS), inflammatory markers, and mortality in oncologic surgery patients. Methods: A retrospective cohort study was conducted at Dr. Wahidin Sudirohusodo Hospital in Makassar, Indonesia, from January 2022 to January 2024. Nutritional status was assessed using the MST, and key clinical outcomes—LOS, inflammatory markers (Neutrophil-to-Lymphocyte Ratio [NLR]), serum albumin, total lymphocyte count (TLC), and Prognostic Nutritional Index (PNI)—were analyzed. Statistical comparisons were performed using chi-square tests and t-tests, with statistical significance set at p &lt; 0.05. Results: Among the 284 patients, 33.8% were classified as malnourished (MST ≥2). Patients with higher MST scores had significantly worse clinical outcomes, including higher mortality (33.3% vs. 12.3% for MST &lt;2, p &lt; 0.001). Malnourished patients exhibited poorer inflammatory and nutritional markers, with higher NLR (6.13 vs. 4.68, p = 0.05), lower albumin (3.0 g/dL vs. 3.3 g/dL, p = 0.004), and lower PNI (36.4 vs. 41.8, p &lt; 0.001). No significant difference was found in LOS between the two groups (median 10 days vs. 9 days, p = 0.732). Conclusion: Malnutrition, as identified by the MST, is strongly associated with increased mortality and worsened inflammatory and nutritional markers in oncologic surgery patients. These findings underscore the need for routine nutritional screening and timely interventions to improve clinical outcomes in this high-risk population.

Hospital malnutrition in gastro-entero-hepatology (GEH) patients and its relationship to clinical outcomes: a retrospective cohort study.

Background: Hospital malnutrition remains a significant global health burden, particularly among gastro-entero-hepatology patients. It adversely impacts clinical outcomes, prolongs hospital stays, and raises healthcare costs. Despite its relevance, recent data on malnutrition among Indonesia’s gastro-entero-hepatology (GEH) patients are limited. Objective: To determine the prevalence of malnutrition and its associated risk factors and clinical outcomes, inflammatory markers, and Prognostic Nutritional Index (PNI) in GEH patients at Wahidin Sudirohusodo General Hospital. Methods: A retrospective cohort study was conducted among 569 GEH inpatients aged 18–59 years with hospital stays exceeding 7 days. Nutritional risk was assessed using the Malnutrition Screening Tool (MST), while Neutrophil-Lymphocyte Ratio (NLR), Total Lymphocyte Count (TLC), and Prognostic Nutritional Index (PNI) were measured as inflammatory markers. Statistical analyses evaluated correlations between malnutrition risk, clinical outcomes, and laboratory values. Results: Of the 569 patients, 7.4% were at high risk of malnutrition, 38.7% at moderate risk, and 54% at low risk. High-risk patients showed significantly elevated NLR (p = 0.000) and lower TLC (p = 0.000), reflecting an impaired immune response. These patients also had a lower PNI (p = 0.000) and more extended hospital stays (p = 0.000). No significant difference in mortality was found between different malnutrition risk groups. Conclusion: Malnutrition is prevalent among GEH patients, particularly those with malignancies. Early nutritional screening and appropriate interventions are essential to improving clinical outcomes and reducing hospital stay durations. A multidisciplinary approach is necessary to optimize patient care.

Assessment of Spinster homologue 2 (Spns2)-dependent transport of sphingosine-1-phosphate as a therapeutic target.

Sphingosine-1-phosphate (S1P) receptor modulator (SRM) drugs suppress immune system function by disrupting lymphocyte trafficking, but SRMs are broadly immunosuppressive with on-target liabilities. Another strategy to modulate the immune system is to block S1P transport. This study tests the hypothesis that blockers of S1P transport (STBs) mediated by Spinster homologue 2 (Spns2) approximate the efficacy of SRMs without their adverse events. We have discovered and optimized STBs to enable investigations of S1P biology and to determine whether S1P transport is a valid drug target. The STB SLF80821178 was administered to rodents to assess its efficacy in a multiple sclerosis model and to test for toxicities associated with SRMs or Spns2-deficient mice. Further, potential biomarkers of STBs, absolute lymphocyte counts (ALCs) in blood and S1P concentrations in plasma and lymph, were measured. SLF80821178 resembles SRMs in that it is efficacious in a standard multiple sclerosis model but does not evoke bradycardia or lung leakage, common to the SRM drug class. Also, chronic SLF80821178 administration does not affect auditory responses in adult mice despite the neurosensorial hearing defect observed in Spns2-null mice. While both SRM and STB administration decrease ALCs, the maximal effect is less with an STB (45% vs. 90%). STBs have minimal effects on S1P concentration in plasma or thoracic duct lymph. We found nothing to invalidate Spns2-dependent S1P transport as a drug target. Indeed, STBs could be superior to SRMs as a therapy to modulate immune system function.

The sex differences in diseases progression and prognosis among persons with HIV and HBV coinfection

To investigate sex differences in liver disease development and prognosis in individuals with HIV and HBV co-infection. This study comprised 752 HIV/HBV co-infected people who were diagnosed with HIV and started on combination antiretroviral therapy (cART) between January 31st, 2015 and January 31st, 2023. Their clinical data, including CD4+ T lymphocyte counts, HBV-DNA, and FIB-4 scores, were tracked once a year. The prognosis was determined during the long-term surveillance period. Risk factors related with the progression of liver diseases were included in both univariable and multivariable logistic regression. Then, sex differences in CD4+ T lymphocyte counts, HBV-DNA, FIB-4 scores, changes in liver fibrosis levels, and prognosis were investigated. Multivariable logistic regression analysis identified male as an independent risk factor for liver disease progression. Compared to the male group, the female group had a significantly greater decline of HBV DNA levels at years 1, 2, 3, 3–5, and > 5 post-cART. At each assessment point, the female group showed a significantly greater rise in CD4+ T lymphocyte counts than the male group based on their respective baseline values. Furthermore, females had greater CD4+ T lymphocyte counts and a lower prevalence of liver cirrhosis than males throughout the study period. Compared to female, higher incidence of end-stage-liver disease (1.190/100 person-years vs 0.714/100 person-years), higher all-cause mortality (0.440/100 person-years vs 0.148/100 person-years) and higher mortality associated with end-stage-liver diseases (0.273/100 person-years vs 0.074/100 person-years) were found in male. Among individuals with HIV and HBV coinfection, males had a worse therapeutic effect of HBV-active therapy and poorer prognosis than females.

Severe Lymphopenia Predicts Poorer Survival in Patients With Rectal Cancer Undergoing Neoadjuvant Chemoradiation.

Chemoradiation-induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. However, the association between chemoradiation-related lymphopenia and survival outcomes in rectal cancer is yet unclear. The objective of this study was to evaluate the prognostic impact of lymphopenia and its predictors in patients with rectal cancer undergoing neoadjuvant chemoradiation. The inclusion criteria for this single-institution retrospective study were as follows: (1) biopsy-proven diagnosis of rectal adenocarcinoma, (2) receipt of neoadjuvant chemoradiation followed by surgery, and (3) absolute lymphocyte count available prior to and within 12 weeks of chemoradiation. In general, chemoradiation consisted of 5-fluorouracil or capecitabine and radiotherapy with 50.4 Gy over 28 fractions. Lymphopenia was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The primary variable of interest was absolute lymphocyte count nadir within 12 weeks of chemoradiation, dichotomized by <500/μL (grade 3 or worse lymphopenia). The primary endpoint was overall survival. Cox modeling and Kaplan-Meier methods were used to perform survival analyses. A total of 193 patients were identified with a median follow-up of 68 months. Overall clinical stage was 2 in 21% and 3 in 76%. Median baseline lymphocyte count for the entire cohort was 1700/μL. One hundred ten patients (57%) experienced chemoradiation-related severe lymphopenia. Pathologic complete response rate was 21%; 83% received adjuvant chemotherapy. Lower baseline lymphocyte count was significantly associated with increased risk for chemoradiation-related severe lymphopenia (odds ratio, 1.71). On multivariable Cox regression analysis, chemoradiation-related severe lymphopenia was significantly associated with worse disease-free survival (hazard ratio, 2.64) and overall survival (hazard ratio, 4.32). Five-year overall survival was 79% versus 92%, and 5-year disease-free survival was 70% versus 86% in the cohort that experienced versus did not experience severe lymphopenia, respectively. Chemoradiation-induced lymphopenia is common and a prognostic marker of poorer survival in rectal cancer. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating treatment-related lymphopenia. Our findings also suggest an important role of the host immunity in rectal cancer outcomes and support future studies investigating ways to reduce treatment-induced lymphopenia.

The value of CSF diagnostic and prognostic biomarkers in NMOSD and MOGAD in real-life use.

Diagnosing neuromyelitis optica spectrum disorder (NMOSD) may be challenging owing to overlapping clinical features with multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), particularly in AQP4-IgG seronegative NMOSD patients. We evaluated cerebrospinal fluid (CSF) biomarkers, specifically glial fibrillary acidic protein (GFAP) and albumin quotient (QAlb), to improve diagnostic accuracy in NMOSD. In this retrospective study, we analyzed CSF samples for biomarkers GFAP, QAlb, neurofilament light, and total-Tau, from patients with AQP4-NMOSD, DNNMOSD, MOGAD, and MS in the Region Västra Götaland, Sweden. Receiver operating characteristic (ROC) analysis with calculation of the area under the curve (AUC) was used to identify optimal cut-off levels for discriminating AQP4-NMOSD from the other groups. Logistic regression models assessed the diagnostic power of GFAP and QAlb combined. Patients with AQP4-NMOSD (N = 19) had significantly higher CSF GFAP levels than the others: median 2470 ng/L vs 330 ng/L (p < 0.001). The GFAP cutoff >715 ng/L gave a sensitivity of 81 % and specificity of 92 %. Combining GFAP and QAlb further increased the diagnostic accuracy (AUC = 0.96). MOGAD patients (N = 29) had the highest CSF lymphocyte counts, with elevated lymphocyte counts correlating with polyphasic MOGAD (R = 0.63; p = 0.016). CSF GFAP is a valuable biomarker for distinguishing AQP4-NMOSD from other demyelinating diseases: Combining GFAP with QAlb enhances diagnostic precision.

NRG-GI007: Secondary endpoints of safety assessment and clinical complete response (cCR) of chemoradiation with endoscopically injected oncolytic virus OBP-301 in medically inoperable esophageal cancer.

435 Background: Definitive chemoradiation (CRT) is a standard-of-care for patients (Pts) with medically inoperable esophageal cancer (EC). The NRG/RTOG 0436 study of cisplatin/paclitaxel and RT (+/- cetuximab) as definitive therapy showed that 58% of control arm Pts have locally persistent disease. OBP-301 is a conditionally-restricted, replication-competent adenovirus derived from human adenovirus type 5 that adds a human Telomerase Reverse Transcriptase gene promoter, replicating only in tumor cells to cause lysis.It may cause immunogenic cell death, enhance RT increasing radiosensitization by blocking DNA repair and improve local control. Methods: In NRG-GI007, a phase 1 study (NCT04391049), OBP-301 was added to weekly carboplatin/paclitaxel and RT (50.4 Gy/28 fxs) for medically inoperable EC Pts with pathologically proven adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus or Siewert Type I/II gastroesophageal junction. Pts receive 1-2mL of intratumoral OBP-301 1×10 12 virus particles/ml via endoscopy 3 days prior to and then at days 12 and 26 of CRT. The primary endpoint was protocol-defined dose-limiting toxicity, already reported. Secondary endpoints reported here are treatment-related (definitely or probably related to any protocol treatment) AEs - all and grade 4+ non-hematologic, and cCR in the primary tumor, defined as negative EGD/biopsy 6-8 weeks post-CRT. Per the protocol design, no statistical testing is done for these endpoints. Results: Initially, 6 evaluable (eligible and started protocol treatment) Pts were enrolled from June 2020 to April 2023. As initial dose level was deemed safe, an additional 9 Pts were enrolled from August 2023 to July 2024, totaling 15 evaluable Pts for secondary endpoints. Median age was 74 years, 9 Pts (60%) with ECOG PS 1. 11 Pts (73%) had adenocarcinoma and 4 had SCC; 11 Pts had N+ disease. 14 Pts (93%) received all planned OBP-301 injections and received 50.4 Gy RT. The most common treatment-related grade 3/4 AEs were decreased neutrophil (6 Pts; 40%) and lymphocyte counts (5 Pts; 33%), expected with CRT. No grade ≥3 OBP-301-related non-hematologic AEs were reported. 2 Pts died prior to restaging neitherdefinitely or probably related to OBP-301: 1 Pt developed grade 5 respiratory failure 6 weeks after CRT (suspected RT pneumonitis), while a 2 nd Pt had an unrecognized tumor invasion of the bronchus at baseline, which worsened during week 3 of CRT, resulting in a grade 5 tracheo-esophageal fistula. 2 Pts have not yet reached time for restaging. All 11 Pts who have been restaged had a cCR, for a preliminary cCR rate of 100% (95% CI: 74.1%, 100%). Conclusions: OBP-301 + CRT is safe and the preliminary cCR rate compares favorably to the historical control from NRG/RTOG 0436. Updated safety and cCR data will be presented. A randomized study is being planned. Clinical trial information: NCT04391049 .

Complete blood count and systemic inflammation indices in individuals with Alzheimer's disease: A case-control study.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive cognitive and functional decline and is associated with aging. Chronic inflammatory processes are also involved in its the etiology, as the consequence or cause of proteinopathy (amyloid and tau load in the brain). This study aimed to investigate the complete blood count and systemic inflammation indices in 61 individuals with AD, compared to 59 cognitively healthy individuals as controls. The diagnosis of AD dementia was based on the NIA-AA criteria and patients presented biomarkers in the cerebrospinal fluid compatible with the diagnosis of AD. The complete blood count (CBC) was conducted using an automated system. The neutrophil count (p=0.011), neutrophil-to-lymphocyte ratio (p=0.023), and Systemic Inflammation Response Index (SIRI) (p=0.044) were significantly higher, whereas the lymphocyte count (p=0.018) and platelet count (p=0.038) were significantly lower in the AD group compared to the control group. After a multivariategeneralized linear model analyses, neutrophils count and SIRI maintained significant difference between the groups, even after correcting for age, sex, body mass index and ApoE ε4 carrier status. The overall results suggest that AD is associated with a low-grade pro-inflammatory profile, characterized by alterations in blood inflammatory and immune cells, leading to a higher systemic inflammatory index. The CBC and its derived inflammatory indices, routinely obtained in clinical practice, have potential utility in the context of AD.

The role of TRECs/KRECs as immune indicators that reflect immunophenotypes and predict the risk of infection in systemic autoimmune diseases

T cell receptor rearrangement excision circles (TRECs) and immunoglobulin κ-deleting recombination excision circles (KRECs) represent the lymphopoiesis capacity, widely used for newborn screening of inborn errors of immunity. To clarify the significance of TRECs and KRECs as immune indicators in patients with systemic autoimmune diseases, we prospectively evaluated TREC and KREC levels with qPCR, lymphocyte phenotypes with flow cytometry, along with lymphocyte counts and serum immunoglobulin levels in peripheral blood samples from newly diagnosed patients. Each variable was assessed before immunosuppressive treatments (baseline), 3-, 6-, and 12-months after the treatment. Severe infections were recorded until 6 months after treatment. Among 35 patients, TREC and KREC levels were associated positively with the proportion of recent thymic emigrants, naïve T and B cells at all the timepoints. TREC and KREC levels decreased after treatment. The ratios of TREC and KREC levels under treatment to baseline were significantly lower in patients with severe infection than those without. In conclusion, TREC and KREC levels reflect peripheral blood immunophenotypes, specifically recent-emigrated T and B cells, in patients under treatment-naïve and immunosuppressive conditions. The longitudinal changes in TREC and KREC levels were beneficial markers for predicting the risk of severe infection during immunosuppressive treatments.

The impact of nutritional status on recurrence-free survival (RFS) in patients with locally advanced oesophagogastric adenocarcinoma (LA-OGA) treated with FLOT therapy.

388 Background: Malnutrition and weight loss were reported as poor prognostic factors in operable OGA. This study examines the relationship between oncological outcomes and nutritional status in LA-OGA patients under the current standard of care, perioperative FLOT therapy. Methods: From 2017 to 2023, 423 patients who had radical resection at Royal Marsden Hospital were screened. Inclusion criteria included LA-OGA (cT2≤ and Nany or Tany and N+), at least one cycle of neoadjuvant chemotherapy (NAC), and ECOG PS 0–2. Nutritional status was assessed by body weight and prognostic nutritional index (PNI), with significant weight loss defined as a 5% loss within six months before diagnosis or during NAC. PNI was calculated as serum albumin (g/L) + 0.005 × lymphocyte count /μL, with categories of severe (&lt;45), mild to moderate (45–49.9), and normal (≥50). The primary endpoint was 3-year recurrence-free survival (3y-RFS). Restricted mean survival time (RMST) at 36 months was calculated to analyze survival time. Multivariate analyses were performed to identify prognostic factors for RFS. The pathological response was assessed using tumour regression grade (TRG) (Mandard criteria). Results: Of the 423 patients, 210 met the inclusion criteria. Primary tumour sites were the oesophagus (52.4%), the oesophagogastric junction (18.1%), and the stomach (29.5%). The median follow-up was 26.5 months. Weight loss at baseline and after NAC, as well as PNI, did not significantly impact RFS (p=0.13, p=0.91, p=0.69, p=0.45). However, a PNI decrease from baseline was associated with significantly shorter 3y-RFS (46% vs. 69%, p&lt;0.001), and the RMST difference was 5.46 months (p&lt;0.001). Multivariable analyses showed ypN positivity (p&lt;0.001), R1 resection (p&lt;0.001), and PNI decrease (p=0.03) as negative prognostic factors for RFS. Pathological response did not differ regardless of PNI change (28.2% vs. 30.4%, p=0.75). Conclusions: A decrease of PNI is a significant poor prognostic factor for RFS in LA-OGA patients undergoing FLOT, suggesting that maintaining nutritional status during NAC could enhance survival outcomes.

Correlation of newer inflammatory markers in patients with type 2 diabetes mellitus: A cross-sectional study

Background: Globally, diabetes mellitus (DM) is a major health concerns and has reached alarming levels. DM is a group of metabolic disorders characterized by hyperglycemia leading to micro- and macro-vascular complications. Chronic low-grade inflammation is associated with the pathophysiology of DM. Aims and Objectives: The present study aimed to assess the levels of neutrophil-to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and other inflammatory markers in T2DM patients and their correlation with blood sugar and HbA1c. Materials and Methods: This cross-sectional study was conducted in Department of Biochemistry in association with Department of General Medicine and Pathology, NRI Institute of Medical Sciences (NRIIMS), Visakhapatnam, Andhra Pradesh, India. In this study, 90 T2DM patients and 90 non-diabetic subjects were recruited. Fasting and post-prandial blood samples were collected and used for the estimation of blood sugar, urea, creatinine, and lipid profile parameters. Whole blood (EDTA) samples were used for analysis of complete blood count (CBC) and HbA1c. NLR, PLR, SII, SIRI, MHR, NHR, LHR, and PHR were calculated from CBC values. Demographic details were collected. Results: In this study, significant increase in blood pressure (systolic [120.4±8.1 mmHg], diastolic [80.2±4.8 mmHg]), fasting blood sugar (FBS) (162.5±53.7 mg/dL), post-prandial blood sugar (238.3±78.8 mg/dL), HbA1c (8.5±2.2%), urea (28.6±8.6 mg/dL), creatinine (1.1±0.2 mg/dL), total cholesterol (186.8±46.1 mg/dL), triglycerides (168.9±61.2 mg/dL), LDLC (115.0±36.3 mg/dL), VLDL (33.8±12.4 mg/dL), and neutrophil count (66.6±11.4%) was observed in T2DM cases. Inflammatory markers such as NLR (4.2±1.1), PLR (0.17±0.01), SII (12.6±3.6), SIRI (25.7±5.2), MHR (0.15±0.08), NHR (1.9±0.72), and PHR (0.07±0.02) were significantly increased in T2DM cases than non-diabetic subjects. FBS was positively correlated with SIRI (r=0.180), MHR (r=0.257), NHR (r=0.418), and PHR (r=0.212). Similarly, HbA1c positively correlated with NHR (r=0.353) and PHR (r=0.177) in T2DM subjects. In this study, HDLC level and lymphocyte count was significantly decreased in T2DM cases. Conclusion: The study may conclude that increased levels of NLR, PLR, SII, SIRI, MHR, NHR, and PHR in T2DM and their positive correlation with blood sugar and HbA1c may serve as alternate markers of inflammation and are useful to assess the impact of systemic inflammatory response in T2DM patients.

Weight and Blood-Based Markers of Cachexia Predict Disability, Hospitalization and Worse Survival in Cancer Immunotherapy Patients.

Cancer-associated cachexia can inhibit immune checkpoint inhibitor (ICI) therapy efficacy. Cachexia's effect on ICI therapy has not been studied in large cohorts of cancer patients aside from lung cancer. We studied associations between real-world routinely collected clinical cachexia markers and disability-free, hospitalization-free and overall survival of cancer patients. A retrospective study was conducted of electronic health records (EHR) of patients with lung, renal cell, melanoma and other cancers treated with ICI therapy at Northwestern Medicine of Chicago, IL, United States, between March 2011 and January 2022. Weight, body mass index, absolute neutrophil and lymphocyte counts, albumin and C-reactive protein (CRP) measures were analysed to calculate the Fearon consensus criteria for cachexia, weight loss grading system (WLGS) score, neutrophil-lymphocyte ratio (NLR), Prognostic Nutritional Index (PNI) and modified Glasgow Prognostic Score (mGPS) at ICI therapy initiation. Kaplan-Meier and Cox proportional hazards analyses were used to determine associations between these metrics and disability-free, hospitalization-free and overall survival. EHR analysis uncovered 3285 cancer patients on ICI therapy (54% > 65 years of age, 50.7% male, 77.7% White). At ICI therapy initiation, 1282 (39.0%) patients had cachexia (consensus criteria), 1641 (50.0%) had a WLGS score ≥ 2, 1806 (55.0%) had an NLR > 3, 1087 (33.1%) had albumin < 3.5 g/dL and 1318 (40.1%) had a PNI < 44. Missing measurements included CRP missing for 98.2% and mGPS missing for 98.6% of patients. Disability-free (n = 1373), hospitalization-free (n = 2374) and overall survival (n = 1599) events were analysed with 1-year rates of 65% (64%-67%), 35% (34%-37%) and 65% (63%-66%), respectively. Multivariate Cox model analyses showed hazard ratios (HR) for cachexia at 1.58 (95% CI 1.38-1.80), 1.47 (95% CI 1.33-1.63) and 1.97 (95% CI 1.75-2.23) for disability, hospitalization and death, respectively. HRs for WLGS ≥ 2 were 1.45 (95% CI 1.28-1.66), 1.37 (95% CI 1.24-1.51) and 1.91 (95% CI 1.69-2.17). HRs for NLR > 3 were 1.57 (95% CI 1.35-1.83), 1.40 (95% CI 1.25-1.58) and 1.95 (95% CI 1.67-2.27). HRs for albumin < 3.5 g/dL were 1.33 (95% CI 1.15-1.54), 1.67 (95% CI 1.50-1.86) and 2.09 (95% CI 1.84-2.36). HRs for PNI < 44 were 1.60 (95% CI 1.39-1.84), 1.46 (95% CI 1.31-1.63) and 2.07 (95% CI 1.80-2.37). Fearon consensus criteria, WLGS, NLR, albumin and PNI were routinely collected at ICI initiation in regular clinical practice and predictive of worse disability-free, hospitalization-free and overall survival in cancer patients receiving ICI therapy. These routine clinical measures may aid prognostication and decision-making in cancer patients with cachexia.

Evaluating systemic immune-inflammation indices as predictive markers for endometriosis diagnosis: A retrospective observational study.

Endometriosis is a chronic inflammatory disease for which there is currently no accurate screening test to identify or predict the probability of the disease in individuals. This can often lead to delays in diagnosis. Several systemic immune-inflammation indices are currently used as predictive or supportive markers for several inflammation-associated diseases. In this study, we investigated whether these immune-inflammation indices, such as systemic immune inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), and pan-immune inflammation value (PIV) could serve as predictive or supplementary markers for diagnosing endometriosis. A total of 434 women with confirmed endometriosis and 517 controls were included in this study. Data on peripheral blood tests, including total counts of white cells, neutrophils, monocytes, lymphocytes, and platelets, were collected, and systemic immune-inflammation indices were calculated. SII, SIRI, NLR, and PIV values were significantly higher in women diagnosed with endometriosis compared to controls. Using the cut-off values of 538 for SII, 0.814 for SIRI, 2.03 for NLR, and 210 for PIV, we achieved 76 % sensitivity and 70 % specificity. When the four indices were combined, the area under the ROC curve (AUC) was 0.796 (95 % CI: 0.766, 0.827), with 76 % sensitivity and 70 % specificity. In conclusion, while ultrasonography or MRI remains the gold standard for visualizing the lesions in diagnosing endometriosis, followed by laparoscopy and histologic verification, routine peripheral blood tests in combination with clinical symptoms, could provide additional clinical diagnostic value for endometriosis as a non-invasive and cost-effective test.

Anlotinib plus benmelstobart as adjuvant therapy in patients with esophageal squamous cell carcinoma: A phase II clinical trial (ALTER-E005).

459 Background: Surgery represents a primary radical treatment for esophageal cancer, However, the risk of recurrence remains noteworthy after surgical resection, underscoring the need for more effective and tolerable postoperative regimens for esophageal squamous cell carcinoma (ESCC). Benmelstobart, a novel PD-L1 blockade, demonstrated promising antitumor activity when combined with anlotinib, an antiangiogenic agent, in the treatment of various tumors including advanced ESCC (NCT05038813) and biliary tract cancer (NCT03996408). Therefore, ALTER-E005 study aimed to evaluate the efficacy and safety of combining anlotinib with benmelstobart as adjuvant therapy in patients (pts) with ESCC. Methods: This was a single-arm, multi-center phase Ⅱ clinical trial. Thirty pts (≥18 years) with histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC who had undergone radical (R0) resection with no recurrence 6 to 12 weeks after surgery and an ECOG PS ≤ 1 were eligible for enrollment. Enrolled pts received oral anlotinib (12 mg, days 1-14) and intravenous benmelstobart (1200 mg, day 1) every 3 weeks for up to 16 cycles or until disease recurrence. The primary endpoint was disease recurrence free (DFS). while secondary endpoints included safety, 1-year DFS rate, 3-year DFS rate, 1- year overall survival (OS) rate, and 3-year OS rate. Results: As of the data cut-off date (September 20, 2024), a total of 30 patients were enrolled with a median age of 67. Among the 30 surgically resected patients with ESCC, 26 (86.7%) had an ECOG score of 1, and 25 (83.3%) were male. According to the eighth edition of the AJCC Cancer Staging Manual, 9 (30.0%) were classified as stage Ⅱ, and 21 (70.0%) were classified as stage Ⅲ. As of the data cut-off date, the median follow-up time was 8.9 months (95% CI: 7.9-12.3). Four pts experienced disease recurrence, and the median duration of DFS has not yet been reached, with 6-month and 1-year DFS rates of 95.7% (95% CI, 72.9%-99.4%), 84.0% (95% CI, 57.7%-94.6%) respectively. Currently, 13 pts are still undergoing therapy. Out of the total 30 patients, 9 (30%) experienced grade 3 treatment-emergent adverse events (TEAEs). No grade 4 or higher TEAEs were observed. The grade 3 TEAEs included hand-foot syndrome (10.0%), hypertension (3.3%), abnormal liver function (3.3%), immune-related hepatitis (3.3%), pneumonia (3.3%), hyperglycemia (3.3%) Lymphocyte count decreased (3.3%), acute cholecystitis (3.3%) and syncope (3.3%). Conclusions: This study highlighted the promising efficacy and safety preliminarily of combining anlotinib with benmelstobart as adjuvant therapy in patients with ESCC who underwent radical (R0) resection and showed no recurrence 6 to 12 weeks after surgery. Clinical trial information: NCT05252078 .

Neoadjuvant Clinical Trials in Adults with Newly Diagnosed High-Grade Glioma: A Systematic Review.

High-grade gliomas are devastating cancers that remain incurable with standard surgical resection and radiochemotherapy. Although beneficial against neoplasms, radiation lowers lymphocyte counts, weakens immune activation, and recruits suppressive myeloid cells impairing immune responses. Tumor environments treated with radiation experience long-term immunosuppression, reducing immunotherapy effectiveness and contributing to recurrence. Investigating pre-radiation treatments in newly diagnosed patients could identify active agents, assess immunotherapy impact, and enable multiomic analyses without radiation-induced confounding factors. This literature review was conducted to describe the feasibility, safety, and outcomes of postsurgical, pre-radiation clinical trials for adults with newly diagnosed high-grade glioma. A systematic review was performed of the English-language literature reporting results of clinical trials for adults with newly diagnosed high-grade glioma administered postsurgical treatment prior to radiation therapy. A search was conducted in PubMed and references cited in research and review articles were also considered. From 1991 to 2024, 52 clinical trials were identified: 3 phase I, 38 phase II, 4 phase III, and 7 of unknown phase. Nine trials were randomized, 24 were multicenter trials, 21 investigated temozolomide-containing regimens, and 12 focused on inoperable tumors, involving a total of 2,737 patients. Pre-radiation neoadjuvant studies are feasible and may identify active drugs. This is particularly relevant in the era of personalized medicine with brain-penetrant drugs, targeted therapy, and immuno-oncology advancements. Investigating pre-radiation treatments in newly diagnosed high-grade glioma is a viable approach to rapidly identify active and inactive regimens while the immune system and tumor microenvironment remain intact.

Short-course radiotherapy (SCRT) followed by fruquintinib plus adebrelimab and CAPOX in the total neoadjuvant therapy of locally advanced rectal cancer (LARC): A multicenter, single-arm, open-label, phase II study (UNION TNT).

192 Background: We have demonstrated that neoadjuvant SCRT followed by PD-1 inhibitor plus CAPOX for LARC patients (pts) showed a higher pCR rate and a well-tolerated safety profile in phase III UNION study. Fruquintinib is a potent and highly selective VEGFR inhibitor, which had been approved for previously treated mCRC pts. This study aimed to investigate the efficacy and safety of SCRT followed by fruquintinib plus adebrelimab and CAPOX as a total neoadjuvant therapy for high-risk LARC pts. Methods: In this prospective, open-label, multi-centers, single-arm phase 2 study (NCT06234007), pts diagnosed with newly diagnosed and high risk LARC were recruited. Pts received SCRT (25Gy/5f) followed by six cycles of fruquintinib (4mg, qd, po, q3w,for the initial 6 pts in the safety run-in period, dosage would be adjusted based on dose-limited toxicities in the 1st cycle) combined with adebrelimab (1200mg, iv, d1, q3w) and CAPOX (q3w). Primary endpoint was CR rate (including clinical CR &amp; pathologic CR). Secondary endpoints included 3-year EFS rate, OS, R0 resection rate and safety. Results: As of 30 Aug 2024, 45 pts were enrolled (median age 59 years [range: 24-75], 26 males, 23 clinical T4 stage and 20 clinical N2 stage, 36 with EMVI positive, 31 with MRF positive, 22 tumor located ≤5cm from the anal verge). Up to 20 Sep 2024, all pts completed SCRT, 73.33% (33/45), 57.78% (26/45) and 31.11% (14/45) pts completed two, four and six cycles of combination therapy, respectively. At data cut-off, of 33 pts included in the efficacy analysis, 28 pts underwent MRI examination and mrTRG results were available, the remaining 5 pts had early surgery due to AEs/serious AEs. 35.7% (10/28) and 46.43% (13/28) pts were classified as mrTRG1 and mrTRG2, respectively. Of 19 pts who underwent surgery, R0 rate was achieved in all 19 pts (100%) and pCR was achieved in 12 pts (63.16%). Moreover, 1 pt achieved cCR during neoadjuvant therapy, thus the treatment strategy provided a CR rate of 65% (1 cCR plus 12 pCR divided by 20). Grade 3/4 adverse effects (AEs) occurred in 16 pts (47.06%), and most commonly were lymphocyte count decreased (n=6, 18.18%), diarrhea (n=5, 15.15%) and AST increased (n=2, 6.06%). 4 serious AEs reported with intestinal perforation and all achieved pCR after surgery therapy. No treatment related death was reported. Conclusions: SCRT followed by fruquintinib combined with adebrelimab and CAPOX as a total neoadjuvant therapy showed promising CR rate and favorable pCR for high-risk LARC pts, and the safety profile was generally manageable. This treatment strategy might be a potential option as neoadjuvant therapy for high-risk LARC pts. Updated data will be presented in the future. Clinical trial information: NCT06234007 .