Preoperative Peripheral Blood Research Articles

Different biomarker ratios in peripheral blood have limited value in diagnosing periprosthetic joint infection after total joint arthroplasty: a single-center, retrospective study

BackgroundPeriprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA).MethodsWe performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated.ResultsCompared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688–0.823), 0.758 (95% CI: 0.687–0.821), 0.714 (95% CI: 0.639–0.781), 0.709 (95% CI: 0.634–0.777), 0.723 (95% CI: 0.649–0.789), and 0.728 (95% CI: 0.654–0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499–0.653) and 0.694 (95% CI: 0.619–0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790–0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015).ConclusionOur study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.

Preoperative peripheral inflammatory markers are predictors of postoperative central diabetes insipidus in craniopharyngioma patients: a retrospective study

BackgroundPostoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs.MethodsThe clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis.ResultsPreoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups.ConclusionsPreoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.

Prognostic value of preoperative combined neutrophil, monocyte, and lymphocyte scores in patients with renal cell carcinoma undergoing laparoscopic nephrectomy: A retrospective study.

In a multi-institutional clinical study, we assessed the prognostic significance of a novel indicator preoperative peripheral blood immune (PBIS) scores that combined ratios of preoperative lymphocyte, monocyte, and neutrophil of renal cell carcinoma (RCC) patients undergoing laparoscopic nephrectomy. Between January 2014 and December 2019, 438 patients with RCC were retrospectively analyzed in three centers. We used X-tile software to obtain the optimum cut-off values for neutrophils, monocytes, and lymphocytes to classify the patients. To assess the relationship between PBIS score and overall survival (OS), and cancer-specific survival (CSS) in patients with RCC by Kaplan-Meier survival curves and Cox regression analyses. In addition, predictive OS and CSS nomograms were constructed. The discriminative ability of nomogram and predictive performance accuracy were verified with consistency index (C-index), calibration curves, receiver operating curve (ROC) curves, decision curve analysis (DCA) curves, and time-dependent ROC curves. The optimum cutoff values for monocytes, lymphocytes, and neutrophils were 0.46, 1.01, and 4.50, respectively. We divided patients into four subgroups according to PBIS scores, which were significantly associated with M-stage (p = 0.008), T-stage (p < 0.001), N-stage (p = 0.006), and AJCC stage (p < 0.001). Multivariate Cox regression analysis revealed that RCC patients with lower PBIS scores showed a worse postoperative prognosis and served as an independent predictor of OS (p = 0.002) and CSS (p < 0.001). Ultimately, the nomograms based on PBIS scores demonstrated excellent predictive performance for OS (C-index: 0.770) and CSS (C-index: 0.828) through the analysis of calibration curves, ROC curves, DCA curves, and time-dependent ROC curves. PBIS score served as novel and effective predictor to accurately predict OS and CSS in patients with RCC receiving laparoscopic nephrectomy.

Comparison of Long-Term Postoperative Outcomes of the Subtypes of Chronic Rhinosinusitis with Nasal Polyps.

(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition that significantly impacts the health-related quality of life (HRQOL) of patients. This study aims to investigate the disparities in preoperative examination findings, postoperative HRQOL, and disease control status based on CRSwNP subtypes. (2) Methods: A retrospective analysis was conducted on 202 patients who underwent endoscopic sinus surgery for CRSwNP. The study assessed clinical characteristics, blood eosinophil and immunoglobulin E (IgE) levels, modified Lund-Kennedy and Lund-Mackay scores, and Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scores. HRQOL was evaluated using the Sino-nasal Outcome Test (SNOT-22) scores, and disease control status was assessed based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 guidelines. (3) Results: Of the 202 patients, Eosinophilic CRSwNP patients exhibited significantly higher preoperative peripheral blood eosinophil ratios and IgE levels, and JESREC scores (p < 0.05). Two years postoperatively, patients in the non-eosinophilic group showed significantly improved SNOT-22 scores compared to preoperative scores (p = 0.007). Notably, the proportion of patients with uncontrolled disease was significantly higher in the eosinophilic group (p = 0.035). Logistic regression analyses identified preoperative SNOT-22 scores and eosinophilic CRSwNP subtype as influential factors on disease control status (p < 0.05). (4) Conclusions: Patients with more severe preoperative symptoms and eosinophilic CRSwNP demonstrated poorer long-term treatment outcomes.

Risk factors and related miRNA phenotypes of chronic pain after thoracoscopic surgery in lung adenocarcinoma patients.

Chronic postsurgical pain may have a substantial impact on patient's quality of life, and has highly heterogenous presentation amongst sufferers. We aimed to explore the risk factors relating to chronic pain and the related miRNA phenotypes in patients with lung adenocarcinoma after video-assisted thoracoscopic lobectomy to identify potential biomarkers. Our prospective study involved a total of 289 patients with early invasive adenocarcinoma undergoing thoracoscopic lobotomy and a follow-up period of 3 months after surgery. Blood was collected the day before surgery for miRNA detection and patient information including operation duration, duration of continuous drainage of the chest, leukocyte count before and after operation, and postoperative pain scores were recorded. Using clinical and biochemical information for each patient, the risk factors for chronic postsurgical pain and related miRNA phenotypes were screened. We found that chronic postsurgical pain was associated with higher body mass index; greater preoperative history of chronic pain; longer postoperative drainage tube retention duration; higher numerical rating scale scores one, two, and three days after surgery; and changes in miRNA expression, namely lower expression of miRNA 146a-3p and higher expression of miRNA 550a-3p and miRNA 3613-3p in peripheral blood (p < 0.05). Of these factors, patient body mass index, preoperative history of chronic pain, average numerical rating scale score after operation, and preoperative peripheral blood miRNA 550a-3P expression were independent risk factors for the development of chronic postsurgical pain. Identification of individual risk markers may aid the development and selection of appropriate preventive and control measures.

Phenotypic and functional exhaustion of circulating CD3+ CD56+ NKT-like cells in colorectal cancer patients.

CD3+ CD56+ NKT-like cells are crucial to antitumor immune surveillance and defense. However, research on circulating NKT-like cells in colorectal cancer (CRC) patients is limited. This investigation selected 113 patients diagnosed with primary CRC for preoperative peripheral blood collection. The blood from 106 healthy donors at the physical examination center was acquired as a healthy control (HC). The distribution of lymphocyte subsets, immunophenotype, and functional characteristics of NKT-like cells was comprehensively evaluated. Compared to HC, primary CRC patients had considerably fewer peripheral NKT-like cells in frequency and absolute quantity, and the fraction of NKT-like cells was further reduced in patients with vascular invasion compared to those without. The NKT-like cells in CRC patients had a reduced fraction of the activating receptor CD16, up-regulated expression of inhibitory receptors LAG-3 and NKG2A, impaired production of TNF-α and IFN-γ, as well as degranulation capacity. Moreover, the increased frequency of NKG2A+ NKT-like cells and the decreased expression of activation-related molecules were significantly correlated with tumor progression. In detail, NKG2A+ NKT-like cells indicated increased PD-1 and Tim-3 and reduced TNF-α than NKG2A- subgroup. Blocking NKG2A invitro restored cytokine secretion capacity in NKT-like cells from CRC patients. Altogether, this research revealed that circulating NKT-like cells in CRC patients exhibited suppressive phenotype and functional impairment, which was more pronounced in NKG2A+ NKT-like cells. These findings suggest that NKG2A blockade may restore anti-tumor effector function in NKT-like cells, which provides a potential target for immunotherapy in CRC patients.

Should we consider Systemic Inflammatory Response Index (SIRI) as a new diagnostic marker for rectal cancer?

The Systemic Inflammatory Response Index (SIRI), which depends on peripheral neutrophil, monocyte, and lymphocyte count, was found to be an effective prognostic indicator for various malignancies. In this study, we aimed to investigate the diagnostic value and the prognostic impact of SIRI on rectal cancer patients. The medical records of patients underwent sphincter-sparing rectal cancer surgery at general surgery between 2017 and 2022 were examined retrospectively. Patient demographics, operation types, neoadjuvant chemo/radiotherapies, pathological results, and complications were recorded. A total number of 99 patients who operated with diagnoses other than cancer were conducted as a control group. SIRI was calculated from preoperative peripheral blood samples' neutrophil, lymphocyte, and monocyte count. The optimal cut-off value for SIRI was found to be 1.38. The clinicopathological outcomes and Overall Survival (OS) were analyzed under two groups according to the SIRI values lower or higher than 1.38. The number of eligible patients was 104. The median age of the entire cohort was 62 (31-89). The median follow-up time was 33 (1-62) months. The median SIRI value in the study group was significantly higher compared with the control group. The study group was examined under two groups: SIRI 1.38 and SIRI > 1.38. The male gender was significantly more frequent in the high SIRI group. The remaining patient demographics and operation types were similar between the groups. The pathological outcomes were similar between the two groups. Overall Survival rate was better in the low SIRI group than those higher. The higher group had significantly higher complication rates than the lower SIRI group (p: 0.004). SIRI may be a valuable diagnostic marker in rectal cancer patients. Higher SIRI levels were also associated with poorer prognosis and increased complication rates. Still, further prospective studies with a larger number of patients are needed.

Screening and identification of serum exosomal protein ZNF587B in liquid biopsy for ovarian cancer diagnosis.

Addressing the critical challenge of early ovarian cancer (OC) detection, our study focuses on identifying novel biomarkers by analyzing preoperative peripheral blood exosomes from high-grade serous ovarian cancer (HGSC) patients and healthy controls. Utilizing high-performance liquid chromatography-mass spectrometry-based quantitative proteomics, we isolated and analyzed peripheral blood exosomes to identify differentially expressed proteins (DEPs). This comprehensive analysis, supported by gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) database assessments, revealed 28 proteins with decreased abundance and 33 with increased abundance in HGSC patients compared to controls. Notably, Zinc Finger Protein 587B (ZNF587B) exhibited a significant reduction in abundance, confirmed by decreased mRNA and protein levels in HGSC and normal ovarian tissues, consistent with omes exosomal protein expression levels. Immunohistochemical staining further confirmed reduced ZNF587B protein levels in HGSC tissues. The significant correlation between ZNF587B expression levels and tumor stage underscores its potential as a valuable biomarker for early liquid biopsy screening of OC. Our findings suggest ZNF587B plays a crucial role in early HGSC detection, highlighting the importance of further research to validate its clinical utility and improve ovarian cancer patient outcomes.

Preoperative risk stratification for patients with ≤ 1cm papillary thyroid carcinomas based on preoperative blood inflammatory markers: construction of a dynamic predictive model.

The aim of this study was to investigate the relationships and predictive value of preoperative peripheral blood inflammatory markers as a means by which to assess risk for patients with ≤ 1cm papillary thyroid carcinomas (PTCs). In addition, a preoperative risk stratification predictive model was constructed and validated. Clinical and pathologic data, as well as preoperative blood specimens, were collected from patients who underwent initial thyroid cancer surgery at the Hangzhou First People's Hospital, from January 2014 to January 2023. Risk assessment was performed based on postoperative pathology according to the 2015 ATA guidelines for recurrence risk stratification. Using univariate analysis and multivariate logistic regression, we identified independent risk factors associated with risk stratification. A predictive model was established and its discriminative and calibration abilities were validated. An independent validation dataset was used to verify the model, and the model was deployed as an online calculator. A total of 1326 patients were included in the study, with 1047 cases (79.0%) classified as low risk and 279 cases (21.0%) classified as intermediate to high risk. The modeling group consisted of 981 cases, through univariate analysis and multivariate logistic regression analysis, preoperative blood Neutrophil/Lymphocyte Ratio (NLR), gender, tumor diameter, and multifocality were identified as independent risk factors that distinguished between low and intermediate to high risk patients with ≤ 1cm PTCs. The clinical predictive model exhibited an AUC of 0.785, specificity of 70.6%, and sensitivity of 75.8%. For the independent validation group of 345 patients, the AUC was 0.813, specificity was 83.8%, and sensitivity was 70.4%. The calibration curve and clinical decision curve indicate that the model demonstrates excellent calibration performance. A dynamic clinical predictive model based on preoperative blood NLR and clinical information for patients with ≤ 1cm PTCs was established. The model is useful for preoperative risk assessment of patients with ≤ 1cm PTCs.

Correlation between preoperative peripheral blood NLR, PLR, LMR and prognosis of patients with head and neck squamous cell carcinoma

BackgroundMarkers that can be used to evaluate the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) remain undefined.ObjectiveThis study aimed to investigate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in patients with HNSCC who underwent surgery-based treatment for the first time.MethodsThis retrospective study included patients HNSCC who underwent surgery-based treatment at our institution between January 2018 and December 2020. Specificity and sensitivity were analyzed using receiver operating characteristic (ROC) curves and the critical value was determined. Patients were divided into low and high groups according to NLR, PLR, and LMR the critical value. Log-rank and Cox proportional hazards models were used to evaluate the associations between preoperative NLR, PLR, LMR, and overall survival (OS).ResultsA total of 304 patients with HNSCC were included, of whom 190 (62.5%) and 114 (37.5%), 203 (66.8%) and 101 (33.2%), 98 (32.2%), and 206 (67.8%) cases were classified as low NLR and high NLR groups, low PLR and high PLR groups, and low LMR and high LMR groups, respectively. Univariate analysis showed that white blood cell count (WBC), neutrophil count (NEU), platelet count (PLT), NLR, pathologic N stage (pN stage), TNM stage and postoperative complications were significantly associated with OS (p < 0.05). Multivariate analysis showed that NEU, NLR, TNM stage and postoperative complications were independent negative prognostic factors for HNSCC (p < 0.05).ConclusionPreoperative NLR is an independent negative prognostic factor for HNSCC. Patients with an increased NLR may have a poor OS.

BIOM-36. PREOPERATIVE IMMUNE AND INFLAMMATORY FACTORS IN PERIPHERAL BLOOD PREDICT PROGNOSIS OF GLIOMA AND CORRELATE WITH GRADES AND SUBTYPES: A PROSPECTIVE MULTI-INSTITUTIONAL STUDY OF 1282 PATIENTS

Abstract BACKGROUND Peripheral blood immune and inflammatory factors can reflect glioma patients' immune status and inform anti-tumor immunotherapy, but research in this field is limited compared to tumor microenvironment studies. We aim to investigate the relationship between these circulating factors and glioma grades, subtypes, and prognosis. METHODS From October 2006 to April 2022, 1282 patients with primary gliomas were enrolled in this study, and their preoperative peripheral blood was collected. Correlations between immune and inflammatory factors and different glioma grades and subtypes were analyzed using ANOVA, t-test, and Ordinal Logistic Regression. ROC curve analysis was used to evaluate the diagnostic efficiency of these factors. In addition, the Cox regression model, K-M survival analysis, and other methods were used to study the relationship between these factors and the prognosis and survival of patients. RESULTS The results showed that with the higher clinical grade, the percentage of NK cells in peripheral blood increases while the percentage of Th and T lymphocytes decreases. C4 levels and percentage of B lymphocytes were higher in grade I gliomas than in other grades. The percentage of NK and Th cells also correlated with glioma subtypes. Immunoglobulin light chains were associated with a favorable prognosis, whereas a higher percentage of peripheral B lymphocytes in grade IV patients was associated with a poor prognosis. CONCLUSIONS The relationship between immune and inflammatory factors and the grades and subtypes of glioma can offer potential opportunities to intervene in these factors that could improve the prognosis of glioma patients. Additionally, it may be helpful to screen glioma and anti-tumor immunotherapy.

A Novel Filtration Membrane for Clustered Circulating Tumor Cell Extraction: A Prospective Feasibility Study.

Circulating tumor cells (CTCs) have garnered attention as biomarkers for therapeutic response and prognosis in malignant neoplasms. Nonetheless, existing literature predominantly relies on surrogate markers of tumor cells or focuses on single-cell CTC, failing to adequately address the challenge of detecting cluster-forming CTCs, which bear considerable prognostic implications. This prospective study aims to validate the efficacy of a novel filtration membrane, namely Soft Micro Pore Filter (S-MPF®), for rare cell recovery in detecting CTCs through the analysis of clinical samples. Patients with confirmed lung cancer or highly suspected lung cancer based on specific criteria (solid tumor size >2.0 cm, serum carcinoembryonic level >7.5 ng/ml, maximum standard uptake value derived from fluorodeoxyglucose-position emission tomography >2.9) were included in the study. CTCs were extracted from preoperative peripheral arterial blood samples using S-MPF®, and the validity of the filtration system was positively verified. Out of the 25 enrolled patients, 23 had lung cancer. CTC positivity was observed in 17 cases (73.9%), whereas cluster CTC positivity was observed in 16 cases (69.6%), with a median count of two clusters. Single CTC positivity was observed in 11 cases (52.1%), with a median count of one cell. The utilization of the newly developed S-MPF® filtration membrane exhibited a high rate of CTC identification, demonstrating its suitability for clinical applications.

ICOSLG-associated immunological landscape and diagnostic value in oral squamous cell carcinoma: a prospective cohort study.

Background: We previously reported that stroma cells regulate constitutive and inductive PD-L1 (B7-H1) expression and immune escape of oral squamous cell carcinoma. ICOSLG (B7-H2), belongs to the B7 protein family, also participates in regulating T cells activation for tissue homeostasis via binding to ICOS and inducing ICOS+ T cell differentiation as well as stimulate B-cell activation, while it appears to be abnormally expressed during carcinogenesis. Clarifying its heterogeneous clinical expression pattern and its immune landscape is a prerequisite for the maximum response rate of ICOSLG-based immunotherapy in a specific population. Methods: This retrospective study included OSCC tissue samples (n = 105) to analyze the spatial distribution of ICOSLG. Preoperative peripheral blood samples (n = 104) and independent tissue samples (n = 10) of OSCC were collected to analyze the changes of immunocytes (T cells, B cells, NK cells and macrophages) according to ICOSLG level in different cellular contents. Results: ICOSLG is ubiquitous in tumor cells (TCs), cancer-associated fibroblasts (CAFs) and tumor infiltrating lymphocytes (TILs). Patients with high ICOSLGTCs or TILs showed high TNM stage and lymph node metastasis, which predicted a decreased overall or metastasis-free survival. This sub-cohort was featured with diminished CD4+ T cells and increased Foxp3+ cells in invasive Frontier in situ, and increased absolute numbers of CD3+CD4+ and CD8+ T cells in peripheral blood. ICOSLG also positively correlated with other immune checkpoint molecules (PD-L1, CSF1R, CTLA4, IDO1, IL10, PD1). Conclusion: Tumor cell-derived ICOSLG could be an efficient marker of OSCC patient stratification for precision immunotherapy.

B-383 Exosomal PRPSAP1 in Plasma Predicts Microvascular Invasion in Hepatocellular Carcinoma

Abstract Background Microvascular invasion (MVI), a critical predictor of postoperative tumor recurrence in hepatocellular carcinoma (HCC), is only detectable by histopathological examination of the surgical specimen. Prediction of MVI before surgery is of great significance to prognosis, especially by non-invasive means. Here, we report that exosome-derived mRNA in plasma can be promising biomarkers for MVI preoperatively. Methods Patients with initially suspected HCC who were undergoing hepatectomy were prospectively recruited with preoperative peripheral blood collection and followed up. Exosomal mRNA profiling was performed using RNA sequencing in the discovery cohort, and the edgeR package in R software was used to screen out significantly differential expression exosomal mRNAs between MVI and non-MVI groups. Multiplex droplet digital PCR (ddPCR) technology was utilized to verify filtered exosomal mRNAs in the validation cohort. Results A total of 131 HCC patients were enrolled with 37 in the discovery cohort and 94 in the validation cohort. RNA-sequencing data identified six candidate exosomal mRNAs (ZC3H3, RSAD2, PRPSAP1, HOXA2, CHPM4A and KCTD10) as potential predictors for MVI. In the validation cohort, expression levels of PRPSAP1 and HOXA2 were slightly higher and the expression level of CHMP4A was slightly lower in the MVI group than the non-MVI one, which were consistent with the discovery cohort though without statistically significant difference (P &amp;gt; 0.05). Further analysis between MVI number&amp;gt;5 and non-MVI patients validated that the expression level of exosomal PRPSAP1 was significantly higher in MVI number&amp;gt;5 patients (0.147 vs 0.070, P = 0.035). Altogether, exosomal PRPSAP1 in plasma was a promising biomarker predicting MVI for HCC patients. Conclusion We validated for the first time that high level expression of exosome-derived PRPSAP1 can preoperatively predict MVI, especially with the number &amp;gt;5, to improve prognosis.

Preoperative elevated eosinophils in peripheral blood for prediction of postoperative recurrence of chronic subdural hematoma.

Chronic subdural hematoma (CSDH) is a common neurological disease with a significant postoperative recurrence rate. There are numerous reported studies of the development of CSDH. In recent years, fibrinolysis, angiogenesis, and inflammation have all been identified as relevant factors in the development of CSDH. While several authors have reported risk factors associated with CSDH recurrence, differential blood count of leukocytes has not yet been discussed. Therefore, in this study the authors aimed to retrospectively investigate the association between differential blood leukocyte count and the rate of CSDH recurrence. The authors retrospectively reviewed 476 patients with 529 CSDHs who underwent surgery at a single institution between January 2011 and December 2021. After exclusion of patients who had not undergone a differential blood test of leukocytes preoperatively, CSDHs in 517 cerebral hemispheres of 466 patients were included in the study. Peripheral blood eosinophil counts ≥ 100/µL were considered eosinophil rich. CSDHs in 494 cerebral hemispheres of 445 patients were followed up postoperatively for at least 3 months or until resolution indicated by CSDH disappearance. Postoperative recurrence of CSDH was observed in 46 cerebral hemispheres (9.3%). Among the preoperative differential blood counts of all leukocytes, eosinophils alone were significantly associated with CSDH recurrence (median [IQR] 76/µL [30-155/µL] vs 119/µL [39-217/µL]; p = 0.03). Multivariable regression analysis showed thrombocytopenia (adjusted OR [aOR] 5.23, 95% CI 1.85-14.79; p = 0.002), use of anticoagulant drugs (aOR 2.51, 95% CI 1.17-5.38; p = 0.02), hematoma volume (10 mL per increase) (aOR 1.08, 95% CI 1.00-1.16; p = 0.04), and eosinophil-rich peripheral blood (aOR 2.22, 95% CI 1.17-4.23; p = 0.02) were all independent predictors for CSDH recurrence. This study showed that preoperative peripheral blood eosinophil count was an independent risk factor for CSDH recurrence. Therefore, patients with CSDH who have elevated eosinophils preoperatively in peripheral blood require careful follow-up.

Effect of preoperative peripheral blood platelet volume index on prognosis in patients with invasive breast cancer.

Aim: This study was designedto investigate the prognostic value of the platelet volume index in patients with invasive breast cancer (IBC). Methods: A total of 524 patients with IBC were enrolled in this study, with a median follow-up time of 6.76years. The relationship between platelet volume indices and breast cancer prognosis was analyzed. Results: There is a strong correlation between a higher platelet distribution width-to-platelet count ratio (PDW/P) and poorer disease-free survival (DFS)in patients with IBC. The DFS rate was significantly lower among individuals with elevated PDW/P ratios compared with those with lower ratios. Conclusion: The PDW/P ratio is an independent risk factor for predicting DFS in patients with IBC.

A prospective study of the effect of functional endoscopic sinus surgery on the recovery of olfactory function in patients with chronic rhinosinusitis with nasal polyposis

Objective:To investigate the efficacy of functional endoscopic sinus surgery（FESS） in the treatment of olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyps （CRSwNP） , at the same time, it provides an evidence for the prognosis evaluation of olfaction and the clinical application of oERPs to evaluate the plasticity of olfaction cortex. Methods:From October 2021 to October 2022, 45 patients with CRSwNP who underwent FESS nine-step standardized treatment in our department were recruited as the research subjects, divided into 22 patients with eosinophilic CRSwNP（ECRS）and 23 patients with non-eosinophilic CRSwNP（nECRS）. VAS-olfactory dysfunction （VAS-OD） score, SNOT-22 olfactory score, Sniffin' Sticks test and oERPs collection and processing were performed before the operation. All items were evaluated again 3 months after the operation. Results:VAS-OD and SNOT-22 olfactory score were significantly lower in all CRSwNP patients after the operation than those before the operation[F（1, 43） =357.429, P<0.001; F（1, 43） =185.657, P<0.001], the scores of T, D, I and TDI scores in Sniffin' Sticks test were significantly higher than those before the operation[F（1, 43） =126.302, P<0.001; F（1, 43） =311.301, P<0.001; F（1, 43） =131.401, P<0.001; F（1, 43） =295.885, P<0.001]; The decrease of VAS-OD and SNOT-22 olfactory score in the ECRS group was smaller than that in the nECRS group[F（1, 43） =4.825, P=0.033; F（1, 43） =9.916, P=0.003], T, D and TDI scores were significantly lower in nECRS group than those in nECRS group[F（1, 43） =6.719, P=0.013; F（1, 43） =4.890, P=0.032; F（1, 43） =4.469, P=0.040]; There was a positive correlation between preoperative eosinophil-to-lymphocyte ratio（ELR） and SNOT-22 olfactory score and how much it changes（r=0.455, P=0.002; r=-0.414, P=0.005）, a negative correlation between T, TDI score and how much they change respectively（r=-0.431, P=0.003; r=-0.385, P=0.009; r=-0.383, P=0.010; r=-0.316, P=0.035）. The latency of P3 was significantly shorter after operation than that before operation in all CRSwNP patients[F（1, 14） =24.840, P<0.001], however, the amplitude has no significant surgical effect. Conclusion:FESS could significantly improve the olfactory function of CRSwNP patients, while changes in plasticity may occur in the olfactory cortex. In addition, the preoperative peripheral blood eosinophil granulocyte level can predict the postoperative olfactory improvement.

A machine learning–based multidimensional model integrating clinical, radiomics, and cell-free DNA methylation biomarkers for the classification of pulmonary nodules.

3070 Background: Patients with pulmonary nodules undergoing excessive invasive procedures is a pressing clinical problem. We sought to develop a noninvasive, machine learning-based multidimensional tool combining clinical, radiomic, and cell-free DNA (cfDNA) methylation biomarkers for improving accuracy of pulmonary nodules classification. Methods: This prospectively collected and retrospective blinded evaluation trial enrolled a total of 1,276 subjects at 24 hospitals in China. All patients with a 5-30 mm pulmonary nodule at high risk of lung cancer had undergone surgical resection with definitive pathological diagnosis. Clinical information, preoperative peripheral blood, and chest CT scans were collected. The regions of interest (ROIs) containing target nodule on the CT images were automatically segmented by a deep-learning based model. 2,153 radiomics features were extracted from ROIs using PyRadiomics. Based on clinical and radiomics features, four classification models were constructed using LightGBM, Lasso, Random Forest, and Logistic Regression algorithms. Subsequently, the predicted probabilities of the above four models were averaged to obtain a final score of the combined clinical and radiomic biomarkers model (CRBM) in a training set (n=797). Then we integrated CRBM model with our previously established cfDNA methylation model (PulmoSeek; DOI: 10.1172/JCI145973) to create a new combined model using logistic regression (n=201), PulmoSeek Plus V2.0, and verified it independently (n =278). The ROC curves were compared to evaluate the diagnostic performance among the CRBM, PulmoSeek, and PulmoSeek Plus V2.0 model, pathologic diagnosis as the gold standard. Results: The CRBM model achieved AUCs of 0.81(95%CI 0.73-0.90) and 0.80 (0.74-0.86) in the two validation sets (n1=201, n2=278), respectively. In the training set (n=201) and validation set (n=278), the PulmoSeek Plus V2.0 obtained AUCs of 0.93 (0.90-0.97) and 0.91 (0.88-0.95), and accuracies of 0.89 (0.84-0.93) and 0.84 (0.79-0.88), respectively. In the combined set (n=479), when compared with CRBM and PulmoSeek, PulmoSeek Plus V2.0 yielded improved AUCs of 11% and 6%, and accuracies of 6% and 3%, respectively. PulmoSeek Plus V2.0 model for rule-out at the fixed specificity of 50%, had an overall sensitivity of 0.98 (0.96-0.99), PPV of 0.86 (0.82-0.89), and NPV of 0.998 (0.988-1.000, at 5% prevalence). It maintains good diagnostic performance in early-stage lung cancer (0-I, n=328) and 5-10 mm nodules (n=92), with sensitivities of 0.98 (0.96-0.99) and 0.98 (0.92-0.99), respectively. Conclusions: PulmoSeek Plus V2.0, as a novel machine learning-based multidimensional model, improves the accuracy of pulmonary nodules classification, and potentially reduces the unnecessary invasive procedures among individuals with benign nodules. Clinical trial information: NCT03181490 , NCT03651986 .

Prognostic value of preoperative hematological markers in patients with glioblastoma multiforme and construction of random survival forest model

ObjectiveIn recent years, an increasing number of studies have revealed that patients’ preoperative inflammatory response, coagulation function, and nutritional status are all linked to the occurrence, development, angiogenesis, and metastasis of various malignant tumors. The goal of this study is to determine the relationship between preoperative peripheral blood neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), platelet to lymphocyte ratio (PLR), and platelet to fibrinogen ratio (FPR). Prognostic nutritional index (PNI) and the prognosis of glioblastoma multiforme (GBM) patients, as well as establish a forest prediction model that includes preoperative hematological markers to predict the individual GBM patient’s 3-year survival status after treatment.MethodsThe clinical and hematological data of 281 GBM patients were analyzed retrospectively; overall survival (OS) was the primary endpoint. X-Tile software was used to determine the best cut-off values for NLR, SII, and PLR, and the survival analysis was carried out by the Kaplan–Meier method as well as univariate and multivariate COX regression. Afterward, we created a random forest model that predicts the individual GBM patient’s 3-year survival status after treatment, and the area under the curve (AUC) is used to validate the model’s effectiveness.ResultsThe best cut-off values for NLR, SII, and PLR in GBM patients’ preoperative peripheral blood were 2.12, 537.50, and 93.5 respectively. The Kaplan–Meier method revealed that preoperative GBM patients with high SII, high NLR, and high PLR had shorter overall survival, and the difference was statistically significant. In addition to clinical and pathological factors. Univariate Cox showed NLR (HR = 1.456, 95% CI: 1.286 ~ 1.649, P < 0.001) MLR (HR = 1.272, 95% CI: 1.120 ~ 1.649, P < 0.001), FPR (HR = 1.183,95% CI: 1.049 ~ 1.333, P < 0.001), SII (HR = 0.218,95% CI: 1.645 ~ 2.127, P < 0.001) is related to the prognosis and overall survival of GBM. Multivariate Cox proportional hazard regression showed that SII (HR = 1.641, 95% CI: 1.430 ~ 1.884, P < 0.001) is also related to the overall survival of patients with GBM. In the random forest prognostic model with preoperative hematologic markers, the AUC in the test set and the validation set was 0.907 and 0.900, respectively.ConclusionHigh levels of NLR, MLR, PLR, FPR, and SII before surgery are prognostic risk factors for GBM patients. A high preoperative SII level is an independent risk factor for GBM prognosis. The random forest model that includes preoperative hematological markers has the potential to predict the individual GBM patient’s 3-year survival status after treatment,and assist the clinicians for making a good clinical decision.

Is Systemic Inflammatory Response Index (SIRI) a Reliable Tool for Prognosis of Gastric Cancer Patients Without Neoadjuvant Therapy?

The systemic inflammatory response index (SIRI), which depends on peripheral neutrophil, monocyte, and lymphocyte count, was found as an effective prognostic indicator for various malignancies. This study aims to investigate the predictive value of preoperative SIRI in the prognosis of gastric cancer patients without neoadjuvant therapy. The patients who underwent gastric cancer surgery in Marmara University Hospital's General Surgery Department between 2019 and 2021 were analyzed retrospectively. SIRI was calculated from preoperative peripheral blood samples' neutrophil, lymphocyte, and monocyte count. The optimal cut-off value for SIRI was calculated by the receiver operating characteristics (ROC) curve and was found to be 1.35. The clinicopathological outcomes and overall survival (OS) were analyzed under two groups according to the SIRI values lower or higher than 1.35. The number of eligible patients was 199. The median follow-up time was 25 (1-56) months. The higher SIRI was associated with male gender (p = 0.044), lower serum albumin (0.002) level, and Clavien-Dindo (CD) Grade III and higher complications (p = 0.018). However, there was no significant difference between the groups regarded pathological tumor, nodes, and metastases (TNM) stages, histological grade, and Lauren Type. In addition, OS and stage-specific OS were similar between the groups. SIRI may be a valuable and effective predictive indicator for postoperative morbidity. The prognostic performance of SIRI on long-term OS is still controversial. Further investigations are needed into this topic.