Predictive Marker Research Articles

Biomarkers associated with progression of infantile hemangioma: Exploratory study.

To identify patients with infantile hemangioma (IH) in need of early-stage treatment in this multicenter, prospective, observational study, we investigated the potential of plasma cytokines as a clinically useful marker. Plasma samples were collected at three time points from 41 patients with infantile hemangioma: baseline (days 14-60 after delivery), visit 1 (days 61-150, the proliferative phase), and visit 2 (days 151-395, the involuting phase). With a twofold or more increase in tumor volume during the baseline-visit 1 period regarded as progression, progression was seen in 15 cases (36.6%). In the first step, cytokine arrays were performed using plasma samples in five progressive and five non-progressive cases. Plasma levels of six cytokines at baseline were selected for a prediction marker of change in tumor volume during baseline-visit 1. Validation enzyme-linked immunosorbent assay indicated that the baseline growth differentiation factor 1 (GDF1) concentration tended to correlate with the proliferation ratio of total lesions or target lesion during baseline-visit 1, although without statistical significance. However, the plasma GDF1 concentrations were significantly lower in patients with a fourfold or more increase in total volume (p = 0.013). Furthermore, changes in plasma interleukin (IL)-7Rα levels showed a statistically significant inverse correlation between volume change of the target lesion during baseline-visit 1 (p = 0.0069). Our results suggest that plasma GDF1 measurement after birth is a useful marker for progression of IH. Additionally, the downregulation of IL-7Rα that begins several months after birth may also contribute to tumor growth. (UMIN-CTR: UMIN000038574).

Problematic aspects of assessing predictive markers for gastric cancer based on endoscopic biopsy samples. Review

Problematic aspects of assessing predictive markers for gastric cancer based on endoscopic biopsy samples. Review

Inflammatory Markers as Predictors of Diabetic Nephropathy in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Background and Objectives: Diabetic nephropathy (DN) is a major complication of diabetes mellitus and a leading cause of end-stage renal disease. Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and red cell distribution width (RDW) have been proposed as potential predictors of DN progression. This study systematically reviews and meta-analyzes the role of these markers in DN. Materials and Methods: A comprehensive literature search was conducted to identify studies evaluating NLR, PLR, SII, and RDW in type 2 diabetes patients with normoalbuminuria, microalbuminuria, and macroalbuminuria. Five databases were searched: PubMed, Scopus, Embase, Web of Science, and LILACS. The Newcastle Ottawa Scale was used to assess the risk of bias in selected articles. Results: Out of 1556 records that were identified through searches, 40 were selected for the review. Finally, 35 were included for meta-analyses, including 13,519 patients. Higher levels of NLR, PLR, SII, and RDW were observed in macro- and microalbuminuria compared to normoalbuminuria, with significantly elevated NLR in microalbuminuria. Meta-analyses showed that NLR and RDW were significantly associated with higher odds of DN (NLR: OR 1.84, p < 0.001; RDW: OR 1.9, p = 0.023). However, PLR and SII were not significantly associated with DN. A longitudinal study confirmed SII as a significant predictor of DN progression (hazard ratio: 3.24, p = 0.023). Conclusions: This study highlights the potential of NLR and RDW as predictive markers for diabetic nephropathy.

Secretome and Proteome of Extracellular Vesicles Provide Protein Markers of Lung and Colorectal Cancer

Colorectal cancer (CRC) and lung cancer (LC) are leading causes of cancer-related mortality, highlighting the need for minimally invasive diagnostic, prognostic, and predictive markers for these cancers. Proteins secreted by a tumor into the extracellular space directly, known as the tumor secretome, as well as proteins in the extra-cellular vesicles (EVs), represent an attractive source of biomarkers for CRC and LC. We performed proteomic analyses on secretome and EV samples from LC (A549, NCI-H23, NCI-H460) and CRC (Caco2, HCT116, HT-29) cell lines and targeted mass spectrometry on EVs from plasma samples of 20 patients with CRC and 19 healthy controls. A total of 782 proteins were identified across the CRC and LC secretome and EV samples. Of these, 22 and 44 protein markers were significantly elevated in the CRC and LC samples, respectively. Functional annotation revealed enrichment in proteins linked to metastasis and tumor progression for both cancer types. In EVs isolated from the plasma of patients with CRC, ITGB3, HSPA8, TUBA4A, and TLN1 were reduced, whereas FN1, SERPINA1, and CST3 were elevated, compared to healthy controls. These findings support the development of minimally invasive liquid biopsy methods for the detection, prognosis, and treatment monitoring of LC and CRC.

Assessment of Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMDV) as Complementary Biomarkers to Torquetenovirus (TTV)

Recent studies have identified Torquetenovirus (TTV) as a promising biomarker of immune competence, particularly in assessing the vaccine response of solid organ transplant (SOT) recipients. However, given the individual variability of viral load, it is not yet possible to define "normal levels”. Nevertheless, TTV is just one component of the broader Anelloviridae family, which also includes Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMDV). This study explores whether the viremia of TTMV and TTMDV offers a stronger predictive marker for vaccine efficacy in SOT recipients. A cohort of 168 SOT patients (142 kidney and 26 lung transplant recipients) who received the BNT162B2 mRNA vaccine was examined, with viral loads quantified through virus-specific real-time PCR. While TTV remains a potentially useful biomarker for evaluating immune response, the combined analysis of all anelloviruses viremia provides deeper insights, particularly in cases where TTV is undetectable. Notably, only TTMV exhibited a pattern similar to TTV, suggesting its potential as an alternative biomarker when TTV is absent from the patient’s virome.

Construction of a prognostic signature based on T-helper 17 cells differentiation-related genes for predicting survival and tumor microenvironment in head and neck squamous cell carcinoma.

T-helper 17 (Th17) cells significantly influence the onset and advancement of malignancies. This study endeavor focused on delineating molecular classifications and developing a prognostic signature grounded in Th17 cell differentiation-related genes (TCDRGs) using machine learning algorithms in head and neck squamous cell carcinoma (HNSCC). A consensus clustering approach was applied to The Cancer Genome Atlas-HNSCC cohort based on TCDRGs, followed by an examination of differential gene expression using the limma package. Machine learning techniques were utilized for feature selection and model construction, with validation performed using the GSE41613 cohort. The interplay between the predictive marker, immune landscape, immunotherapy response, drug sensitivity, and clinical outcomes was assessed, and a nomogram was constructed. Functional evaluations of TCDRGs were conducted through colony formation, transwell invasion, and wound healing assays. Two distinct HNSCC subtypes with significant differences in prognosis were identified based on 87 TCDRGs, indicating different levels of Th17 cell differentiation. Thirteen differentially expressed TCDRGs were selected and used to create a risk signature, T17I, using the random survival forest algorithm. This signature was associated with grade, chemotherapy, radiotherapy, T stage, and somatic mutations. It was revealed that there were differences in the immune response-related pathways between the high- and low-risk groups. Inflammatory pathways were significantly activated in the low-risk group. The T17I signature was associated with immune infiltration. Specifically, there was a higher infiltration of immune activation cells in the low-risk group, whereas the high-risk group had a higher infiltration of M2 macrophages. In addition, the T17I signature was significantly associated with drug sensitivity. A nomogram combining age, radiotherapy, and the T17I signature accurately predicted the prognosis of patients with HNSCC. Finally, in vitro experiments confirmed that knockdown of LAT gene expression promotes proliferation, metastasis, and invasion of HNSCC cells. In conclusion, this study successfully identified molecular subtypes and constructed a prognostic signature and nomogram based on TCDRGs in HNSCC, which may aid in personalized treatment strategies.

Evaluation of treatment for diffuse large B-cell lymphoma using plasma D-dimer levels

It has been documented that D-dimer levels have potential utility as a measure of tumor activity in diffuse large B-cell lymphoma (DLBCL), however whether it can be used as a predictive marker of treatment outcome has not been established. This study means to retrospectively evaluate the role of D-dimer in prediction of treatment efficacy in patients with DLBCL. 151 patients with newly diagnosed DLBCL were enrolled. Blood samples were taken from those patients during the initial visit to our hospital and again after two cycles of chemotherapy to measure D-dimer levels. The link between plasma D-dimer concentrations and patients’ clinical characteristics was explored before and after treatment. D-dimer levels within the range of 0–1 µg/mL were considered negative, while readings above this range were considered positive. D-dimer difference percentage (Ddp) represents the percentage change in D-dimer levels before and after chemotherapy, calculated as (post-chemotherapy D-dimer minus pre-chemotherapy D-dimer) / pre-chemotherapy D-dimer × 100. Patients showed statistically different plasma D-dimer levels at initial consultation across treatment-response groups: CR (0.63 µg/mL [0.43–1.27]), PR (1.39 µg/mL [0.73–2.46]), SD (0.89 µg/mL [0.59–1.24]), and PD (1.34 µg/mL [0.67–2.62]). After chemotherapy, the PR group exhibited a mean D-dimer level of -0.38 µg/mL (range − 1.64 to -0.11), which was significantly lower than that of the PD group (mean 0.04 µg/mL, range − 0.40 to 0.79; p < 0.05). The CR group revealed significantly lower initial D-dimer levels (median 0.63 µg/mL) and greater reductions after chemotherapy compared to the non-CR group (median 1.17 µg/mL, p < 0.05). Patients with coagulation disorders such as DIC, DVT, or PE were excluded to minimize confounding factors. While this study demonstrates the utility of D-dimer in predicting short-term treatment response, the relationship with long-term outcomes such as PFS and OS requires further investigation. Patients who respond well to chemotherapy typically exhibit lower D-dimer levels at the initial diagnosis. Those in the SD or PD groups usually experience a greater increase in D-dimer levels following chemotherapy. Consequently, variations in plasma D-dimer levels before and after treatment may offer valuable insights for evaluating the efficacy of chemotherapy treatment.

Association of single nucleotide polymorphisms rs7459185 of the HSPβ1 gene and the risk of hematological toxicity in lung cancer.

Hematological toxicities (HTs) in lung cancer (LCa) may compromise the delivery of Radio-Chemotherapy (RTCT), and consequently affect the control of the disease. The aim of this study is to evaluate the association of Single nucleotide polymorphisms (SNPs) with HT. In this prospective multicentre study, 264 patients with primary LCa treated with RTCT between 2012 and 2018 were included. Genotyping analysis was performed on DNA isolated from peripheral blood samples by real-time polymerase chain reaction (PCR) using TaqMan. HTs were scored using the Common Toxicity Criteria (CTCAE) version 5.0. An increased risk of HT≥grade 2 was observed in patients with the GG genotype of the SNP rs7459185 (HSPβ1) with a hazard ratio (HR) of 1.462 (95%CI 1.054-2.029, p=0.007). Similarly, those patients had an increased risk of overall HT≥grade 3 with a HR of 1.531 (95%CI 1.016-2.30, p=0.007). The patients with the GG genotype experienced an acute lymphopenia≥Grade 3 (HR 1.590 [95%CI 1.004-2.517; p 0.045]) and acute anemia≥Grade 2 (HR 1.886 [95%CI 1.060-3.356; p 0.032]), compared to the GC/CC genotypes. Our findings show a relationship between the functional GG genotypic of the SNP rs7459185 (HSPβ1) and heightened risk the development of HT, including anemia and lymphopenia in patients with LCa. This genetic variant could be utilized as a predictive marker to tailor treatment intensity, contributing to the advancement of individualized therapeutic approaches.

Quantitative assessment of the academic adaptability of first-year students of higher education institutions

The article analyzes the factors that cause educational stress, the prerequisites for the formation of the ability of first-year students to adapt to the educational process and its importance in the formation of future specialists, identifies predictive markers of educational adaptation and resistance to educational stress, reveals gender-specific features of the body's adaptation to stresses, including those related to education. It is shown that the process of adaptation to the educational process has a biopsychosocial nature, identifies predictive markers of educational adaptation and resistance to educational stress. An integral assessment of students' educational adaptability is proposed based on indicators of psychosocial adaptability of the individual and the functional potential of the body. The scale for assessing the integral indicator of students' educational adaptability is modified based on the sum of points for indicators of psychosocial adaptability (P. Kuznetsov's questionnaire) and adaptive capabilities of the cardiovascular system of the body (R. Baievskyi method). The psychophysiological prerequisites of the adaptive reactions of the body of first-year students to the educational process were studied. It was established that the female body is more resistant to physiological stresses due to a higher level of vitality, however, the course and symptoms of psycho-emotional stress, adaptation to new conditions in men are easier due to lower emotional lability, higher balance and self-regulation. It was confirmed that the level of social adaptability in young men is higher, and the level of functional adaptability is lower than in girls. At the same time, it was recorded that almost every fifth young man and every third girl have a low level of the integral indicator of educational adaptability. Quantitative assessment of students' integral educational adaptability will allow for the differentiation of the parameters of motor loads in the educational process of physical education in order to increase the psychofunctional resources of the body of student youth.

Optimizing Appendectomy in Ulcerative Colitis: Predictive Markers and Mechanistic Insights

Abstract Background and aims Two recent studies from our group have demonstrated a beneficial effect of appendectomy in ulcerative colitis (UC): the ACCURE and COSTA trial show a 20% reduced recurrence rate and &amp;gt;20% increase in induction of remission when compared to medical treatment. However, like for all therapeutic interventions in IBD, not all patients respond equally, leaving room for optimisation. Preliminary RNA sequencing results suggested two subtypes of appendices. Clustering within subtype was seen based on inflammatory pathways which was associated with response. This was confirmed by histology, where patients with a more pro-inflammatory profile were more likely to respond. The aim of the current project is to improve efficacy of appendectomy by better patient selection through predictive markers and to elucidate the biological mechanisms of action of appendectomy in UC. Methods We will validate our preliminary data regarding gene signatures predictive for response to appendectomy and extend these results to the coecal base, enabling prediction of response from endoscopic biopsies and thus improving applicability. In addition, we will focus on the mechanisms of action of appendectomy by targeting the two theories: Firstly, using single cell RNA sequencing we will identify the cellular compartment expressing the genesets associated with response and determine the role of host cells. Secondly, using 16S sequencing of the microbiome of appendix and coecum will allow evaluation of the role of the microbiome. During the ACCURE and COSTA trial, appendiceal samples (n&amp;gt;100) have been stored for future analysis. This enables the direct start of this experimental study and completion within the 1 year timeframe. Anticipated impact This project aims to predict response and clarify the mode of action of appendectomy in UC, contributing to patient stratification. As a simple, safe, and low-cost procedure, appendectomy has significant potential for UC treatment in both high- and low/middle-income countries.

P0806 Monitoring of vedolizumab therapy using fecal calprotectin, abdominal ultrasound, and drug levels in ulcerative colitis: a predictive algorithm

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a relapsing course. Vedolizumab, an anti-integrin, induces clinical remission in UC, but response is typically evaluated after 14 weeks. Earlier predictive markers could optimize treatment. This study aimed to develop an algorithm using baseline and week 6 data (especially abdominal ultrasound, fecal calprotectin, and drug levels) to predict clinical response and remission at week 14. Methods In this prospective study, 37 UC patients were recruited from 2018 to 2024, and 17 were included in the final analysis. The primary endpoint was clinical response or remission at week 14, based on significant changes from baseline to week 6 in at least two markers (vedolizumab ≥ 24 µg/ml, ≥ 25% reduction in colon wall thickness, or ≥ 50% reduction in fecal calprotectin). Secondary endpoints included outcomes at week 22. Statistical methods included among others Mann-Whitney U-tests, Fisher’s exact tests, and logistic regression. Results Vedolizumab levels at week 6 were the most reliable individual marker for predicting clinical response at week 14, with 0.67 sensitivity and 0.62 specificity. In addition, leukocytes and pancreatic elastase were negatively associated with clinical response, while zonulin showed a positive association (p &amp;lt; 0.001). For clinical remission, colon wall thickness reduction and the combined predictive marker demonstrated perfect sensitivity (1.00) and negative predictive value (1.00). A significant association was found between reduced colon wall thickness and clinical remission (OR = 13.91, 95% CI: 1.13–1986.85). Conclusion Early changes in vedolizumab levels, fecal calprotectin, and colon wall thickness can predict clinical response and remission in UC. Colon wall thickness proved the strongest predictor of remission. Larger studies are needed to validate and refine this algorithm for personalized vedolizumab therapy.

P0937 Role of Interleukin-8 in Predicting Long-Term Response to Vedolizumab in Ulcerative Colitis Patients

Abstract Background Vedolizumab is effective for moderate-severe Ulcerative Colitis (UC), but predictive markers for long-term response are limited. This study aimed to profile circulating cytokines linked to inflammatory bowel disease (IBD) pathophysiology to identify immune predictive markers of vedolizumab response in UC patients. Secondary objectives included analyzing associations between baseline characteristics—such as smoking, disease duration, prior biologic exposure, and initial faecal calprotectin (FCP) and C-reactive protein (CRP) levels—and treatment response. Methods This retrospective, single-centre cohort study included 28 UC patients with inflammation objectified by clinical and biochemical data who initiated vedolizumab from 2015 to 2022. Blood samples were collected before treatment, and responses were evaluated at follow-up. Clinical remission (pMAYO &amp;lt; 3 with no subscore &amp;gt;1) with biochemical response (≥50% reduction in FCP and/or CRP) defined positive response. Endoscopic response was assessed in patients with available colonoscopy (endoscopic Mayo 0-1). Cytokines were measured via Magpix® Luminex with a Milliplex® T Cell Magnetic Bead Panel including 13 cytokines (IFN-gamma, IL8, IL12, IL13, IL17A, IL10, IL2, IL21, IL23, IL7, TNF-alpha, IL6, IL-1β). Results Twenty-eight patients with UC (100% pancolitis or left colitis) and S2+S3 94.7% were included in the study. 85.2% werebioexposed (infliximab in 75%). 50% of patients received concomitant corticosteroid therapy at the start of vedolizumab. Vedolizumab response was seen in 13 patients (46.4%) after a median overall treatment duration in both cohorts of 2.79 years (IQR7.55). The responder group was on vedolizumab treatment for a median of 5.58 (IQR 6.9) years vs 1.17 (IQR 5.13) years in the nonrespondergroup, p=0.005. There were no baseline differences between responders in pMayo or in FCP and CRP values. Activesmoking, disease duration until vedolizumab initiation and previous exposure to other biologics were not associated withresponse/non-response to vedolizumab treatment. Vedolizumab responders had significantly lower median interleukin 8 (IL8) levels at baseline than vedolizumab non-responders(median IL8 1.67 pg/mL versus 3.03 pg/mL, p=0.016). No statistically significant differences in baseline concentrations were found inany of the other interleukins analysed. Conclusion In our series of UC patients treated with vedolizumab, patients with long-term response to the drug show lower plasma IL8 levels than non-responders at baseline. Therefore, IL8 could serve as a predictive marker of long-term response to vedolizumab inUC patients. These results should be confirmed in prospective studies with larger sample sizes.

P0565 Spatial Metabolic Profiles in Ulcerative colitis patients determine response to therapy

Abstract Background Ulcerative Colitis (UC) is an heterogenous debilitating disease without a cure. The step-up therapy approach aims at controlling and alleviating intestinal inflammation by achieving and maintaining clinical and endoscopic remission. However, the rate of primary non-response or loss of response to therapies is still high. Predictive markers that accurately guide decisions about the best therapeutic choice are an unmet need. This study aims to determine the intestinal metabolic profiles of UC patients and explore differences in response groups of given treatments, thus helping a better patient stratification. Methods Mucosal biopsies collected from active UC patients (N=26) at week 0 and 14 after treatment (vedolizumab, tofacitinib and filgotinib) were sectioned at 10 µm thickness. Patients were classified as non-responders (NR), responders (R) and super responders (SR) based on both endoscopic and partial Mayo scores. Sections were processed by matrix-assisted laser desorption/ionization (MALDI) coupled with Orbitrap Exploris™ 120 Mass Spectrometer. Raw spectral data was processed with MSConverter and MSIpixel for metabolite quantification and annotation. Comprehensive statistical analyses including quantitative metabolite distributions, Moran’s I spatial correlations and pathway enrichment analysis were performed via an in-house developed computational pipeline. Results Spatial metabolomic analysis revealed different metabolite patterns between R and NR across all drugs. Notably, all non-responders exhibited a dysregulated lipid metabolism. In the Vedolizumab group, a fragmented pattern distribution of metabolites was found in NR characterized by an increase of canavalmine, N1-acetylspermidine and heptanenitrile at week 0, whereas SR showed a significant tissue reorganization environment, with increased number of metabolites such as LysoPA, LysoPE and 5alpha-Cholesta-7,24dien-3beta-ol, involved in anti-inflammatory pathways, as well as glutathione and purine metabolism. Additionally, SR showed histamine- and IgE-related pathways supporting cellular regeneration. Conclusion Overall, these data depicted the alteration of mucosal lipid metabolism as a hallmark of non-response to therapies, and evidenced that the effectiveness of a specific treatment in UC is impacted by the initial mucosal metabolic state conditioned by diet and medications. The validation of these results in a larger sample size will aid the prediction of therapy response. References ImmUniverse project: this project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 853995. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The content provided in this abstract reflects only the author's view and neither the IMI JU nor the European Commission are responsible for any use that may be made of the information it contains.

P0470 Albumin as a prognostic marker in IBD : Insights from a Tertiary Care Hepato-Gastroenterology Center Experience

Abstract Background Chronic inflammatory bowel diseases (IBD) are persistent conditions characterized by alternating phases of flare-ups and remissions, ranging from mild exacerbations to severe cases, such as those in ulcerative colitis (UC), which may require colectomy and significantly affect patients’ functional and vital outcomes. Over time, several predictive markers, particularly in Crohn’s disease (CD), have been identified at diagnosis. This raises an essential question: could hypoalbuminemia be considered a prognostic factor in the clinical course of IBD? Methods This retrospective descriptive and analytical study spanned 5 years and 2 months (January 2018 to March 2023) and included all IBD patients monitored in our department. Data analysis was conducted using SPSS, with chi-square tests and multivariate logistic regression employed to evaluate relationships Results 302 IBD patients were analyzed, with a mean age of 40.7 years and a female predominance ( sex ratio = 0.7).165 had Crohn’s disease (CD), and 143 had ulcerative colitis (UC), categorized as pancolitis (61 cases), UC E2 (46 cases), and UC E1 (30 cases). In the CD cohort, 30% (50 patients) underwent ileocecal resection. Smoking and alcoholism were reported in 14.9% and 6.6% of cases, respectively, while NSAID and PPI use were noted in 11.5% and 3.3%. Additionally, 8.6% reported phytotherapy use. Hypoalbuminemia was defined as serum albumin ≤35 mg/L, with 32% (97 patients) meeting this criterion. Patients with hypoalbuminemia were treatment-naïve and had serum albumin levels assessed at diagnosis, with follow-up for at least one year. Key findings included • Steroid Use: 78.35% of hypoalbuminemic patients required at least two courses of corticosteroids, compared to 12.68% with normal albumin levels (P=0.003). • Thiopurines and Anti-TNF: Thiopurines were used in 81% of hypoalbuminemic patients vs. 45.8% (P=0.001), and anti-TNF therapy in 42.2% vs. 16.58% (P=0.006). • Colectomy: Rates were higher in hypoalbuminemic patients (17.52%) compared to those with normal albumin (0.4%, P=0.009). • Anemia: Observed in 92.78% of hypoalbuminemic cases vs. 18.53% with normal albumin levels (P=0.001). Notably, only 7.2% of hypoalbuminemic patients were treated with combined oral and rectal 5-ASA, achieving sustained clinical and endoscopic remission over three years. Conclusion In conclusion, our study highlights hypoalbuminemia as a critical prognostic marker in the progression of IBD. Assessing albumin levels at diagnosis, particularly in UC, provides valuable insight for identifying patients at higher risk of severe disease, guiding the need for intensified treatment and closer follow-up. This reinforces the importance of early, comprehensive evaluation in optimizing IBD management strategies

Identification of circulating Tfh/Th subsets as a biomarker of developed hospital-acquired pneumonia

BackgroundThis study aimed to explore the possible value of follicular helper T (Tfh) cells in hospital-acquired pneumonia (HAP).MethodsFlow cytometry was used to measure circulating Tfh and helper T cell (Th) cells in 62 HAP patients and 16 healthy individuals. HAP patients were further categorized into uncontrolled and controlled groups, in accordance with relevant guidelines. Subgroup analyses were additionally conducted based on the pathogen and the presence of bloodstream infections (BSIs) and the incidence of septic shock. Kaplan-Meier survival analysis and ROC analysis were performed to estimate the prognostic value of the combination of Tfh/Th ratios and PCT levels.ResultsThe Tfh/Th ratio was notably higher in uncontrolled HAP patients than in controls (P&amp;lt;0.05). Specifically, either the Klebsiella pneumoniae (K.p) -positive HAP or BSIs subgroups or septic shock subgroups showed significantly increased Tfh/Th ratios (P&amp;lt;0.05). PCT level in BSIs and septic shock subgroups was significantly increased. However, there were no significant differences in PCT level between K.p-infected and non-K.p-infected patients. So, the Tfh/Th ratio is a good supplement to PCT for distinguishing between the K.p and non-K.p groups. The Tfh/Th ratio also demonstrated a strong correlation with procalcitonin (PCT) levels (P&amp;lt;0.05). Accordingly, the combination of Tfh/Th and PCT could serve as a more effective predictive marker for HAP deterioration and survival prediction. HAP patients with a high Tfh/Th ratio along with high PCT levels had a lower 28-day survival rate.ConclusionThe circulating Tfh/Th ratio, instrumental in gauging the severity of patients with HAP, could be employed as a prognostic biomarker for HAP.

Uric acid to albumin ratio is a novel predictive marker for all-cause and cardiovascular death in diabetic patients: a prospective cohort study

BackgroundDiabetes is one of the leading causes of death with an increasing prevalence worldwide. Diabetes-related premature mortality is largely preventable and reversible if identified and managed early. Accordingly, we intend to investigate the predictive value of uric acid to albumin ratio (UAR) for all-cause and cardiovascular death in diabetic patients.MethodsUnivariate and multivariate Cox regression analyses were performed to identify risk factors for all-cause death of diabetic patients. The receiver operating characteristic (ROC) curves and nomogram model were used to evaluate the predictive ability of variables. Kaplan-Meier survival analysis was used to display the progression risks of diabetic patients.ResultsA total of 804 diabetic patients were enrolled in the study. During the 5-year follow-up, all-cause death was found in 80 participants (9.95%) and cardiovascular death was found in 24 participants (2.99%). Age, UAR, and hsCRP were independent risk factors for all-cause death in diabetic patients after adjusting for potential confounding factors. Age and UAR had good predictive value for 1-, 3-, and 5-year all-cause death in diabetic patients, and the combination of UAR and age had the highest predictive value. An easy and intuitive prognostic nomogram model with good predictive accuracy was constructed based on age and UAR. Patients in higher quantiles of age and UAR had more rapid progression to all-cause death and higher mortality risk than patients in the lower quantiles. UAR also had good predictive value for cardiovascular death in diabetic patients.ConclusionsUAR may be a simple, cost-effective, and reliable predictive marker for all-cause and cardiovascular death in U.S. diabetic patients. The clinical utility of UAR and nomogram based on age and UAR can help physicians identify individuals at higher risk and therefore promote prevention strategies.

P0528 Leukocyte Adhesive Function as Potential Predictive Marker for Treatment Response to Vedolizumab Among Bio-naive Patients with Crohn’s Disease

Abstract Background Vedolizumab (VDZ) is approved for the treatment of Crohn’s diseases (CD), but around 60% of patients fail to respond. Predicting response to VDZ, especially prior to treatment, is desirable but remains challenging. In this study, we investigated if α4β7 and α4β1 integrin activity may be used to predict response to VDZ. Methods Both α4β7 and α4β1 integrin activity were assessed using Leukocyte adhesive function assay (LAFA). LAFA uses microfluidic techniques to mimic blood circulation in vitro. Blood samples were fluorescently labelled and then pulled into microfluidic channels precoated with either MAdCAM-1 or VCAM-1 as substrates. Interactions between leukocytes and substrates was recorded and analysed by cell tracking software. Cell kinetic parameters were calculated and used for the assessment of α4β7 and α4β1 integrin activity. Mn2+ was applied as activator to assess the full potential of integrin activity. Bio-naive CD patients were recruited and all received VDZ as treatment. Treatment response was assessed at week 14 by endoscopy. Patients were classified as primary loss of response to VDZ if the simplified endoscopic score for CD at week 14 failed to decrease by 25% compared to baseline. Blood samples were collected at weeks 0 (prior to VDZ infusion), 2, 6 and 14 and then applied for LAFA. The differences in α4β7 and α4β1 integrin activity between VDZ responders and non-responders were prospectively assessed and a prediction model was subsequently established. Results A total of 27 patients were recruited and received VDZ. Twenty patients were classified as responders and seven as non-responders. No difference was found in α4β7 integrin activity on CD4 and CD8 cells between responders and non-responders, either before or after VDZ treatment. However, a lower α4β1 integrin activity was found on CD4 and CD8 cells among VDZ non-responders at week 0 compared with responders in the presence of Mn2+. Using the best LAFA-derived markers, a model to predict VDZ non-responders at week 0 was developed, in which a sensitivity of 0.90 and a specificity of 0.73 were achieved, a substantially better performance than the existing prediction tool CDST. In addition, α4β1 integrin activity on CD4 and CD8 cells among non-responders was gradually enhanced following subsequent VDZ treatment, which was not detected in responders (figure), implying a possible mechanism underlining primary loss of response to VDZ. Conclusion Patients with a low α4β1 integrin activity at week 0 which can be enhanced after VDZ, is likely to be primary non-responders to VDZ. Integrin activity measured by LAFA prior to treatment may be used as new diagnostic tool for the prediction VDZ response in bio-naïve CD patients. References Dulai PS, Boland BS, Singh S, et al. Development and Validation of a Scoring System to Predict Outcomes of Vedolizumab Treatment in Patients With Crohn’s Disease. Gastroenterology. 2018;155(3):687-695.e10. doi:10.1053/j.gastro.2018.05.039

Protocol for prognosticating PPD using EEG changes during labor pain by uterine contractions: a prospective cohort study in the first stage of labor

BackgroundLack of motivation and behavioral abnormalities are the hallmarks of postpartum depression (PPD). Severe uterine contractions during labor are pain triggers for psychiatric disorders, including PPD in women during the puerperium. Creating biomarkers to monitor PPD may help in its early detection and treatment. It has been suggested that uterine contraction-induced labor pain plays a role in the emergence of this syndrome. Therefore, abnormal electroencephalography (EEG) patterns during the first stage of labor may provide useful information. Here, we propose that aberrant EEG patterns caused by painful uterine contractions may be predictive markers for PPD.MethodsThis study is a single-centre prospective cohort planned for 331 parturients for vaginal delivery in the maternity ward of Zhujiang Hospital from 2022 to 2023. At baseline, online or paper-based questionnaires, including the Edinburgh Postnatal Depression Scale (EPDS) and demographic data, will be collected when the parturient is admitted to labor. EEG, electrocardiography (ECG) and electrohysterography (EHG) signals will be monitored and recorded during the first stage of labor in the ward. Follow-up will be taken at the postpartum timepoints of day 3, day 42, and 3, 6 and 12 months, respectively. Power spectral density and functional connections will be quantified. The connections between PPD severity and EEG measurements as a function of time will be assessed using linear mixed-effects models. Maternal age, parity, and whether oxytocin is used during labor, all have an impact on the incidence of PPD, hence a stratified analysis will be carried out.DiscussionWe expect EEG changes caused by painful uterine contractions in the first labor may predict early PPD. The results from this study may act as a predictor for the development of PPD which may enhance long-term quality of life for the parturient and her offspring.Trial registration.Name of registry: EEG Alterations of Uterine Contractions in the First Stage of Labor Predicting PPD. Trial registration number: NCT05217251; registration date on the ClinicalTrial.gov platform: February, 1/2022.

P0918 Identification of a serum proteomics signature linked with anti-TNF therapy response outcomes in Inflammatory Bowel Disease

Abstract Background While treatment options for active disease in IBD become diverse, the choice of therapies is mostly based on patient characteristics, disease course and severity but restrained by economic rationales. To maximize treatment effectiveness, predictive biomarkers are needed to guide therapies either ex ante or at the earliest possible time point after therapy initiation. Previously, we identified dynamic blood-based RNA and DNA methylation signatures that are linked with therapy response to anti-TNF in IBD1. Here, we aim to identify serum proteome biomarkers associated with therapeutic outcomes in IBD patients receiving anti-TNF treatment. Methods 31 ulcerative colitis (UC) and 27 Crohn’s disease (CD) patients with active clinical and endoscopic disease were recruited and followed at baseline (W0) and at weeks 2 (W2), 6 (W6), and 14 (W14) after initiating infliximab therapy. The clinical endpoint of interest was defined as a combination of clinical remission (partial Mayo ≤ 2/CDAI &amp;lt; 150) and endoscopic response (reduction in endoscopic Mayo ≥ 1/SES-CD ≥ 50%) at W14. Serum was collected at each time point and subjected to proximity extension assays (Olink® Explore 3072 panel) to screen for 2,944 proteins. Linear mixed models (LMM) were applied to identify differentially expressed proteins (DEPs) between endpoint achievers/non-achievers over time. Additionally, post-analysis of DEPs was performed using cv.glmnet with least absolute shrinkage and selection operator (LASSO) regression to identify candidate predictive marker sets. Results A total of 229 DEPs were identified over time between UC responders and non-responders: 8 at W0, 22 at W2, 181 at W6, and 78 at W14. In CD patients, 23 DEPs were identified: 9 at W0, 7 at W2, 13 at W6, and 13 at W14. These DEPs were disease-specific and linked to Gene Ontology (GO) terms related to inflammatory response and cell differentiation. Using LMM and machine learning, we identified 5 baseline proteins in UC and 6 in CD patients that differentiated combined endpoint achievers from non-achievers (AUROC: UC: 0.958, CD: 0.800). Additionally, we identified dynamic changes from W0 to W2 in 7 proteins associated with immune regulation in UC patients (1 in CD), which were linked to therapeutic outcomes at W14. Conclusion Detecting specific ex ante biomarkers or early dynamic molecular signatures are critical for precision medicine in IBD. Our data suggest that serum proteomics profiling enables the differentiation of patients who will attain therapeutic success under anti-TNF therapy from those who will not. This study warrants further investigations in larger, independent datasets to confirm the potential clinical utility of the proteomics signature. References (1) Mishra N, et al. Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease. Genome Med. 2022 Sep 24;14(1):110. doi: 10.1186/s13073-022-01112-z. PMID: 36153599; PMCID: PMC9509553. This project has received funding from the DFG Cluster of Excellence 2167 "Precision medicine in chronic inflammation", the BMBF (e:Med Network iTREAT 01ZX2202A, and GUIDE-IBD 031L0188A), and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 831434 (3TR) and No 853995 (ImmUniverse).The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The content provided in this publication reflects the author’s views only. Neither the Innovative Medicines Initiative (IMI JU) nor the European Commission are responsible for any use that may be made of the information it contains.

Can the monocyte/HDL ratio predict ear effusion in adenoid vegetation patients?

BackgroundSince monocytes secrete cytokines, high monocyte counts may indicate subclinical inflammation. HDL-C, a significant component of total cholesterol, may reduce inflammation.ObjectivesThis study investigated whether the monocyte/HDL ratio (MHR) could be an independent predictive marker in patients with adenoid vegetation, both with and without otitis media with effusion (OME).MethodsThis cross-sectional study included patients diagnosed with adenoid vegetation, with or without OME, who underwent surgery. The groups consisted of patients who underwent adenoidectomy alone for adenoid vegetation and those who underwent adenoidectomy + ventilation tube for adenoid vegetation with OME (Group 2). Monocyte counts, HDL-C levels, and MHR values were calculated for both groups.ResultsThe mean age of Group 1 was 6.95 ± 2.77 years, while Group 2 had a mean age of 6.61 ± 2.98 years. No significant difference was found in monocyte count or percentage between the groups. The HDL-C ratios were lower in Group 2, which OME accompanied, and the difference between the groups was significant (p: 0.027). The MHR was not significantly different between Groups 1 and 2, with values of 10.47 (4.22–29.23) and 12.29 (5.43–99.6), respectively.ConclusionReduced MHR ratios may indicate elevated inflammatory levels in the body and may be linked to certain medical conditions. However, we found no significant difference in the parameters’ ability to predict OME in children with adenoid vegetation. Therefore, a simple, low-cost marker to predict middle ear effusion in children is needed.